colistin and Pseudomonas-Infections

Respiratory tract infections with Pseudomonas aeruginosa occur in most people with cystic fibrosis (CF). Established chronic P aeruginosa infection is virtually impossible to eradicate and is associated with increased mortality and morbidity. Early infection may be easier to eradicate. This is an updated review.. Does giving antibiotics for P aeruginosa infection in people with CF at the time of new isolation improve clinical outcomes (e.g. mortality, quality of life and morbidity), eradicate P aeruginosa infection, and delay the onset of chronic infection, but without adverse effects, compared to usual treatment or an alternative antibiotic regimen? We also assessed cost-effectiveness.. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and conference proceedings. Latest search: 24 March 2022. We searched ongoing trials registries. Latest search: 6 April 2022.. We included randomised controlled trials (RCTs) of people with CF, in whom P aeruginosa had recently been isolated from respiratory secretions. We compared combinations of inhaled, oral or intravenous (IV) antibiotics with placebo, usual treatment or other antibiotic combinations. We excluded non-randomised trials and cross-over trials.. Two authors independently selected trials, assessed risk of bias and extracted data. We assessed the certainty of the evidence using GRADE.. We included 11 trials (1449 participants) lasting between 28 days and 27 months; some had few participants and most had relatively short follow-up periods. Antibiotics in this review are: oral - ciprofloxacin and azithromycin; inhaled - tobramycin nebuliser solution for inhalation (TNS), aztreonam lysine (AZLI) and colistin; IV - ceftazidime and tobramycin. There was generally a low risk of bias from missing data. In most trials it was difficult to blind participants and clinicians to treatment. Two trials were supported by the manufacturers of the antibiotic used. TNS versus placebo TNS may improve eradication; fewer participants were still positive for P aeruginosa at one month (odds ratio (OR) 0.06, 95% confidence interval (CI) 0.02 to 0.18; 3 trials, 89 participants; low-certainty evidence) and two months (OR 0.15, 95% CI 0.03 to 0.65; 2 trials, 38 participants). We are uncertain whether the odds of a positive culture decrease at 12 months (OR 0.02, 95% CI 0.00 to 0.67; 1 trial, 12 participants). TNS (28 days) versus TNS (56 days) One trial (88 participants) comparing 28 days to 56 days TNS treatment found duration of treatment may make little or no difference in time to next isolation (hazard ratio (HR) 0.81, 95% CI 0.37 to 1.76; low-certainty evidence). Cycled TNS versus culture-based TNS One trial (304 children, one to 12 years old) compared cycled TNS to culture-based therapy and also ciprofloxacin to placebo. We found moderate-certainty evidence of an effect favouring cycled TNS therapy (OR 0.51, 95% CI 0.31 to 0.82), although the trial publication reported age-adjusted OR and no difference between groups. Ciprofloxacin versus placebo added to cycled and culture-based TNS therapy One trial (296 participants) examined the effect of adding ciprofloxacin versus placebo to cycled and culture-based TNS therapy. There is probably no difference between ciprofloxacin and placebo in eradicating P aeruginosa (OR 0.89, 95% CI 0.55 to 1.44; moderate-certainty evidence). Ciprofloxacin and colistin versus TNS We are uncertain whether there is any difference between groups in eradication of P aeruginosa at up to six months (OR 0.43, 95% CI 0.15 to 1.23; 1 trial, 58 participants) or up to 24 months (OR 0.76, 95% CI 0.24 to 2.42; 1 trial, 47 participants); there was a low rate of short-term eradication in both groups. Ciprofloxacin plus colistin versus ciprofloxacin plus TNS One trial (223 participants) found there may be no difference in positive respiratory cul. We found that nebulised antibiotics, alone or with oral antibiotics, were better than no treatment for early infection with P aeruginosa. Eradication may be sustained in the short term. There is insufficient evidence to determine whether these antibiotic strategies decrease mortality or morbidity, improve quality of life, or are associated with adverse effects compared to placebo or standard treatment. Four trials comparing two active treatments have failed to show differences in rates of eradication of P aeruginosa. One large trial showed that intravenous ceftazidime with tobramycin is not superior to oral ciprofloxacin when inhaled antibiotics are also used. There is still insufficient evidence to state which antibiotic strategy should be used for the eradication of early P aeruginosa infection in CF, but there is now evidence that intravenous therapy is not superior to oral antibiotics.

Topics: Anti-Bacterial Agents; Azithromycin; Ceftazidime; Child; Child, Preschool; Ciprofloxacin; Colistin; Cystic Fibrosis; Humans; Infant; Monobactams; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin

Pseudomonas aeruginosa is a pathogen that has a high propensity to develop antibiotic resistance, and the emergence of multidrug-resistant strains is a major concern for global health. The mortality rate associated with infections caused by this microorganism is significant, especially those caused by multidrug-resistant strains. The antibiotics used to treat these infections include quinolones, aminoglycosides, colistin, and β-lactams. However, novel combinations of β-lactams-β-lactamase inhibitors and cefiderocol offer advantages over other members of their family due to their better activity against certain resistance mechanisms. Selecting the appropriate empiric antibiotic treatment requires consideration of the patient's clinical entity, comorbidities, and risk factors for multidrug-resistant pathogen infections, and local epidemiological data. Optimizing antibiotic pharmacokinetics, controlling the source of infection, and appropriate collection of samples are crucial for successful treatment. In the future, the development of alternative treatments and strategies, such as antimicrobial peptides, new antibiotics, phage therapy, vaccines, and colonization control, holds great promise for the management of P. aeruginosa infections.

Topics: Anti-Bacterial Agents; beta-Lactamase Inhibitors; beta-Lactams; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

Pseudomonas aeruginosa is an opportunistic pathogen that infects the lungs of people with cystic fibrosis (CF) and is the most common cause of chronic respiratory infections with high morbidity and mortality in CF patients. This study aimed to evaluate the pattern of antibiotic resistance of P. aeruginosa strains from patients with CF using a systematic review and meta-analysis.. A comprehensive and systematic search was performed for relevant articles until August 2021 in the following database: PubMed, Scopus, Embase, and Web of Science. Finally, 122 articles with appropriate criteria were included in the meta-analysis. To estimate weighted pooled proportions Freeman-Tukey double arcsine transformation was performed using Metaprop command in Stata software version 17.1.. 122 studies evaluated the pattern of P. aeruginosa antibiotic resistance from different antibiotic classes in patients with CF. Cefotaxime had the highest resistance rate of 67% (95% CI 53_80%), while colistin had the lowest 5% (95% CI 2-8%).. High resistance to most of the studied antibiotics was observed. The high antibiotic resistance observed is worrying and it indicates the need to monitor using of antibiotics. In addition, colistin is the most appropriate treatment choice, but more randomized controlled trial studies are recommended.

Topics: Anti-Bacterial Agents; Colistin; Cystic Fibrosis; Drug Resistance, Microbial; Humans; Persistent Infection; Prevalence; Pseudomonas aeruginosa; Pseudomonas Infections

Ceftolozane-tazobactam is currently the most active antipseudomonal agent, including multidrug-resistant extensively drug-resistant strains. Tazobactam provides additional activity against many extended-spectrum beta-lactamases Enterobacterales. Ceftolozane-tazobactam is formally approved for complicated urinary tract infection, complicated intra-abdominal infection, and hospital-acquired and ventilator-associated bacterial pneumonia. The clinical and microbiological success is over 70-80% in many series. However, resistant mutants to ceftolozane-tazobactam have been already described. Combination therapies with colistin or meropenem could be among the strategies to avoid the resistance emergence.

Topics: Anti-Bacterial Agents; Cephalosporins; Colistin; Humans; Intraabdominal Infections; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Tazobactam

Over the last decades, there has been a dramatic global increase in multidrug-resistant (MDR) pathogens particularly among Gram-negative bacteria (GNB).

Topics: Africa, Northern; Anti-Bacterial Agents; Antimicrobial Stewardship; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Genome, Bacterial; Microbial Sensitivity Tests; Middle East; Prevalence; Pseudomonas aeruginosa; Pseudomonas Infections

Several recent cases associating cleaned and high-level disinfected duodenoscopes with outbreaks of carbapenem-resistant Enterobacteriaceae (CRE) and related multidrug-resistant organisms (MDROs) may cause bronchoscopists, pulmonologists, and other stakeholders to inquire about the effectiveness of today's practices for reprocessing flexible bronchoscopes. The primary objectives of this study were to address this question and investigate the risk of bronchoscopes transmitting infections of CRE and related MDROs. The published literature and the US Food and Drug Administration's medical device database of adverse events were searched beginning in 2012, when endoscopy first emerged as a recognized risk factor for transmission of CRE. The Internet was also searched during this same time frame to identify other relevant cases. Several cases associating reprocessed bronchoscopes with infections of CRE or a related MDRO were identified. This study's findings suggest that bronchoscopes may pose an underrecognized potential for transmission of CRE and related MDROs, warranting greater public awareness, enhanced preventive measures, and updated reprocessing guidance. This study's data also suggest that the cleaning and high-level disinfection of bronchoscopes performed in accordance with published guidelines and manufacturer instructions may not always be sufficiently effective to eliminate this risk. Several factors were identified that can adversely affect a bronchoscope's reprocessing and pose a risk of transmission of these multidrug-resistant bacteria, including use of a damaged or inadequately serviced bronchoscope, and formation of an inaccessible biofilm. Recommendations are provided to improve the safety of flexible bronchoscopes, including supplementing their reprocessing with an enhanced measure such as sterilization when warranted, and strict adherence to a periodic servicing and maintenance schedule consistent with the bronchoscope manufacturer's instructions.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; Bronchoscopes; Bronchoscopy; Carbapenem-Resistant Enterobacteriaceae; Colistin; Cross Infection; Disinfection; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Equipment Contamination; Equipment Reuse; Humans; Klebsiella Infections; Klebsiella pneumoniae; Pseudomonas aeruginosa; Pseudomonas Infections

A two-stage approach to total knee arthroplasty (TKA) using an antibiotic-impregnated articulating cement spacer is an option for an infected arthritic knee. Vancomycin combined with broad-spectrum antibiotics can be used to make an antibiotic-impregnated articulating cement spacer. Causative organisms are sometimes not confirmed before surgery. Joint infections of multidrug-resistant organisms are increasing. Therefore, routine combinations of antibiotics may not be effective.. We present a case of a patient who developed vancomycin-resistant Pseudomonas aeruginosa infection in an arthritic knee. A 71-year-old man was initially diagnosed with pyogenic arthritis caused by Staphylococcus aureus. He underwent arthroscopic debridement elsewhere. However, the infection persisted. He was referred to our hospital, and we performed a two-stage TKA using a vancomycin-based antibiotic-impregnated articulating cement spacer. Vancomycin-resistant P. aeruginosa was identified after surgery. Intravenous colistin was added. However, this failed, either because vancomycin was not effective against P. aeruginosa, or because insufficient systemic colistin due to colistin-induced acute kidney injury. Therefore, debridement was repeated, and colistin-loaded cement spacer was inserted. The spacer delivered high concentrations of colistin to the infected joint with decreased systemic effects. Thus, less systemic colistin was used. The infection was controlled without recurrent acute kidney injury. One year after surgery, conversion to TKA was successfully performed.. A two-stage approach to TKA using a colistin-loaded articulating cement spacer can be used for an arthritic knee infected by vancomycin-resistant P. aeruginosa. Furthermore, local administration of colistin using a cement spacer can reduce the systemic side effects of colistin.

Topics: Aged; Anti-Bacterial Agents; Arthritis, Infectious; Arthroplasty, Replacement, Knee; Bone Cements; Colistin; Debridement; Humans; Male; Pseudomonas aeruginosa; Pseudomonas Infections; Reoperation; Staphylococcal Infections; Vancomycin Resistance

Inhaled colistin is becoming increasingly popular against respiratory tract infections caused by multidrug resistant (MDR) Gram-negative bacteria because it may overcome the problems associated with intravenous (IV) administration.. To investigate the effectiveness and safety of inhaled colistin as monotherapy (without concomitant IV administration of colistin) in the treatment of respiratory tract infections caused by MDR or colistin-only susceptible Gram-negative bacteria.. PubMed and Scopus databases were searched. A systematic review and meta-analysis were conducted.. Twelve studies (373 patients receiving inhaled colistin for respiratory tract infection) were included. Ten studies evaluated patients with pneumonia (including 8 studies with ventilator-associated pneumonia) and 2 studies evaluated patients with ventilator-associated tracheobronchitis. Patients with infections due to MDR Acinetobacter baumannii and Pseudomonas aeruginosa were mainly studied. Daily dose of inhaled colistin and treatment duration varied in the individual studies. The pooled all-cause mortality was 33.8% (95% CI 24.6% - 43.6%), clinical success was 70.4% (58.5% - 81.1%) and eradication of Gram-negative bacteria was shown in 71.3% (57.6% - 83.2%) of cases.. Inhaled colistin monotherapy may deserve further consideration as a mode for colistin administration for the treatment of respiratory tract infections caused by MDR A. baumannii and P. aeruginosa.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Nebulizers and Vaporizers; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; Treatment Outcome

Respiratory tract infection with Pseudomonas aeruginosa occurs in most people with cystic fibrosis. Once chronic infection is established, Pseudomonas aeruginosa is virtually impossible to eradicate and is associated with increased mortality and morbidity. Early infection may be easier to eradicate.This is an update of a Cochrane review first published in 2003, and previously updated in 2006, 2009 and 2014.. To determine whether antibiotic treatment of early Pseudomonas aeruginosa infection in children and adults with cystic fibrosis eradicates the organism, delays the onset of chronic infection, and results in clinical improvement. To evaluate whether there is evidence that a particular antibiotic strategy is superior to or more cost-effective than other strategies and to compare the adverse effects of different antibiotic strategies (including respiratory infection with other micro-organisms).. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 10 October 2016.. We included randomised controlled trials of people with cystic fibrosis, in whom Pseudomonas aeruginosa had recently been isolated from respiratory secretions. We compared combinations of inhaled, oral or intravenous antibiotics with placebo, usual treatment or other combinations of inhaled, oral or intravenous antibiotics. We excluded non-randomised trials, cross-over trials, and those utilising historical controls.. Both authors independently selected trials, assessed risk of bias and extracted data.. The search identified 60 trials; seven trials (744 participants) with a duration between 28 days and 27 months were eligible for inclusion. Three of the trials are over 10 years old and their results may be less applicable today given the changes in standard treatment. Some of the trials had low numbers of participants and most had relatively short follow-up periods; however, there was generally a low risk of bias from missing data. In most trials it was difficult to blind participants and clinicians to treatment given the interventions and comparators used. Two trials were supported by the manufacturers of the antibiotic used.Evidence from two trials (38 participants) at the two-month time-point showed treatment of early Pseudomonas aeruginosa infection with inhaled tobramycin results in microbiological eradication of the organism from respiratory secretions more often than placebo, odds ratio 0.15 (95% confidence interval (CI) 0.03 to 0.65) and data from one of these trials, with longer follow up, suggested that this effect may persist for up to 12 months.One randomised controlled trial (26 participants) compared oral ciprofloxacin and nebulised colistin versus usual treatment. Results after two years suggested treatment of early infection results in microbiological eradication of Pseudomonas aeruginosa more often than no anti-pseudomonal treatment, odds ratio 0.12 (95% CI 0.02 to 0.79).One trial comparing 28 days to 56 days treatment with nebulised tobramycin solution for inhalation in 88 participants showed that both treatments were effective and well-tolerated, with no notable additional improvement with longer over shorter duration of therapy. However, this trial was not powered to detect non-inferiority or equivalence .A trial of oral ciprofloxacin with inhaled colistin versus nebulised tobramycin solution for inhalation alone (223 participants) failed to show a difference between the two strategies, although it was underpowered to show this. A further trial of inhaled colistin with oral ciprofloxacin versus nebulised tobramycin solution for inhalation with oral ciprofloxacin also showed no superiority of the former, with increased isolation of Stenotrophomonas maltophilia in both groups.A recent, large trial in 306 children aged between one and 12 years compared cycled nebulised tobramycin solution for inhalation to culture-based therapy and also ciprofloxacin to placebo. The primary analysis showed no difference in time to pulmonary exacerbation. We found that nebulised antibiotics, alone or in combination with oral antibiotics, were better than no treatment for early infection with Pseudomonas aeruginosa. Eradication may be sustained for up to two years. There is insufficient evidence to determine whether antibiotic strategies for the eradication of early Pseudomonas aeruginosa decrease mortality or morbidity, improve quality of life, or are associated with adverse effects compared to placebo or standard treatment. Four trials comparing two active treatments have failed to show differences in rates of eradication of Pseudomonas aeruginosa. There have been no published randomised controlled trials that investigate the efficacy of intravenous antibiotics to eradicate Pseudomonas aeruginosa in cystic fibrosis. Overall, there is still insufficient evidence from this review to state which antibiotic strategy should be used for the eradication of early Pseudomonas aeruginosa infection in cystic fibrosis.

Topics: Administration, Inhalation; Administration, Oral; Adult; Anti-Bacterial Agents; Child; Ciprofloxacin; Colistin; Cystic Fibrosis; Humans; Pseudomonas aeruginosa; Pseudomonas Infections; Randomized Controlled Trials as Topic; Respiratory System; Tobramycin

To provide an update on efficacy and safety of antibiotic treatments for stable non-cystic fibrosis (CF) bronchiectasis (BE). Systematic review based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines was done. Twenty-six studies (1.898 patients) fulfilled the inclusion criteria. Studies of inhaled tobramycin have revealed conflicting results regarding quality of life (QoL), exacerbations and admissions, but may result in sputum cultures negative for Pseudomonas aeruginosa, whereas studies investigating the effect of inhaled gentamycin have shown positive effects on sputum bacterial density, decrease in sputum cultures positive for P. aeruginosa, QoL and exacerbation rate, but no improvement in forced expiratory volume in first second (FEV

Topics: Aminoglycosides; Anti-Bacterial Agents; Aztreonam; Bronchiectasis; Ciprofloxacin; Colistin; Disease Progression; Forced Expiratory Volume; Humans; Macrolides; Pseudomonas aeruginosa; Pseudomonas Infections; Quality of Life; Sputum

Historically, the polymyxin antibacterial colistin has been administered as intravenous or nebulized colistimethate sodium in patients with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa infection. More recently, colistimethate sodium has been formulated as a dry powder (Colobreathe(®)) to be administered via a hand-held Turbospin(®) inhaler. Compared with nebulized colistimethate sodium, the colistimethate sodium dry powder for inhalation (DPI) formulation reduces treatment time and improves patient convenience. Colistimethate sodium DPI is approved in the EU for the treatment of chronic P. aeruginosa infections in patients with CF aged ≥6 years. In a phase III clinical trial in this patient population, it was determined that the change in percent predicted forced expiratory volume in 1 s with colistimethate sodium DPI 1.6625 MIU (125 mg) twice daily was noninferior to that with nebulized tobramycin 300 mg/5 mL twice daily. Moreover, patients found colistimethate sodium DPI easier to use than nebulized tobramycin. Colistimethate sodium DPI was generally well tolerated, with a similar adverse event profile to that of nebulized tobramycin, except for a numerically higher incidence of cough and abnormal taste. Most adverse events diminished after 28 days in patients receiving colistimethate sodium DPI, with an occurrence similar to that in nebulized tobramycin recipients. In conclusion, colistimethate sodium DPI administered via the Turbospin® inhaler is a useful option for the treatment of chronic P. aeruginosa infection in patients with CF aged ≥6 years.

Topics: Chronic Disease; Colistin; Cystic Fibrosis; Drug Resistance, Bacterial; Dry Powder Inhalers; Humans; Lung; Pseudomonas aeruginosa; Pseudomonas Infections

Antimicrobial resistance to Pseudomonas aeruginosa is on the rise. In the absence of new anti-pseudomonal drugs, clinicians have had to resort to older antimicrobials such as colistin for the treatment of multi-drug resistant (MDR) strains. This polymyxin compound acts on the outer membrane of the bacteria resulting in its permeability and cell-death. Its bactericidal action is concentration-dependant. This antibiotic is mainly used as salvage therapy in the treatment of often life-threatening infections due to MDR P. aeruginosa blood-stream infections (BSI). Its potential nephrotoxicity and neurotoxicity have been overestimated and have limited the use in its intravenous form. A better understanding of its pharmacokinetics and pharmacodynamics, has facilitated more appropriate dosing strategies with a standard 9 million-unit daily-dose that should be adapted to kidney function. Combination treatment that involves the association of colistin with classical anti-pseudomonal treatment has rarely been clinically tested. In vitro synergy has been reported for certain combinations that could be used to prevent or limit the risk of induced resistance in MDR strains. Positioning colistin in antimicrobial strategies especially as a first-line treatment remains to be properly assessed.

Topics: Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Pseudomonas aeruginosa; Pseudomonas Infections; Salvage Therapy

Inhaled medications play an important role in the daily treatment of patients with cystic fibrosis (CF). The classic route of administration was nebulisation via jet nebulisers. Respiratory delivery of fluid particles should loosen the viscid respiratory secretions, making airway clearance via cough or physiotherapy more efficient. Until recently, only jet nebulisers allowed to administer high doses of aerosolised antipseudomonal antibiotics. Powder inhalers for the treatment of cystic fibrosis have recently been made available. The newly developed powders and inhalers differ considerably from conventional dry powder inhalers used for the treatment of chronic obstructive airway disease. The present article will review two inhaled antibiotics, i. e. tobramycin and colistin, and the hyperosmotic agent mannitol, which increases the hydration of the airways. Topics are particle engineering, efficacy and tolerability results from clinical trials, as well as functional and practical aspects related to these new drugs.

Topics: Administration, Inhalation; Aerosols; Anti-Bacterial Agents; Colistin; Cystic Fibrosis; Diuretics, Osmotic; Drug Compounding; Dry Powder Inhalers; Humans; Mannitol; Powders; Pseudomonas Infections; Tobramycin

Inhaled antibiotic therapy, targeting Pseudomonas aeruginosa, is a fundamental component of cystic fibrosis (CF) management. Tobramycin inhalation solution (TIS) was approved in the United States (US) in 1998. Subsequent research efforts focused on developing products with a reduced treatment time burden. Aztreonam for inhalation solution (AZLI), administered via a more efficient nebulizer than TIS, was approved in the US in 2010. Dry powder for inhalation (DPI) formulations provide alternatives to nebulized therapy: tobramycin powder for inhalation (also known as TIP™) was approved in the US in 2013, and colistimethate sodium DPI received European approval in 2012. Other aerosolized antibiotics and regimens combining inhaled antibiotics are in development. Inhaled antibiotic rotation (e.g., TIS alternating with AZLI) is an important concept being actively tested in CF.

Topics: Administration, Inhalation; Amikacin; Anti-Bacterial Agents; Aztreonam; Colistin; Cystic Fibrosis; Equipment Design; Humans; Levofloxacin; Nebulizers and Vaporizers; Pseudomonas aeruginosa; Pseudomonas Infections; Randomized Controlled Trials as Topic; Tobramycin

Newer 'innovative' formulations of antibiotics for Pseudomonas aeruginosa lung infection in patients with cystic fibrosis include colistimethate sodium and tobramycin in the form of dry powders for inhalation (DPIs). Whilst these DPIs are anticipated to improve patient adherence because of increased convenience and ease of administration, questions remain concerning whether they are as clinically effective, safe and cost-effective as nebulized antibiotics.. This review describes the recent findings of a health technology assessment of the clinical effectiveness and cost-effectiveness of colistimethate sodium and tobramycin DPIs with regard to how innovative treatments may be judged to be incrementally better than existing treatments. The original assessment was undertaken to inform the National Institute for Health and Care Excellence's Technology Appraisal Programme to inform national clinical guidance on the use of these new treatments in the National Health Service.. Three trials were included in the systematic review. Issues surrounding the clinical effectiveness and cost-effectiveness of colistimethate sodium DPI and tobramycin DPI are discussed in light of the considerable uncertainties associated with the available evidence.

Topics: Administration, Inhalation; Anti-Bacterial Agents; Colistin; Cost-Benefit Analysis; Cystic Fibrosis; Dry Powder Inhalers; Humans; Medication Adherence; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin; Treatment Outcome

Colistin (polymyxin E) binds to the cell wall of gram-negative bacteria, leading to osmotic destruction of the cell. Since its introduction in 1959, colistin has been little used parenterally due to a high incidence of reversible nephrotoxicity and, to a lesser extent, neurotoxicity. Colistin use remained limited to combating Pseudomonas aeruginosa in cystic fibrosis patients. In addition, oral colistin is part of the recently introduced regime of selective digestive tract decontamination in ICU patients. Intravenous administration of colistin is now increasingly prescribed for the control of multi-resistant microorganisms. Colistin monotherapy, however, rapidly selects resistant subpopulations. Therefore, only combination therapy is advised. The prodrug colistimethate sodium is less toxic and is hydrolyzed in vivo to active colistin; colistin is renally cleared. Clinical practice remains hampered by lack of uniformity and standardization of names, dosage units, dosing recommendations and methods of concentration and susceptibility testing.

Topics: Anti-Bacterial Agents; Colistin; Cystic Fibrosis; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Gastrointestinal Tract; Humans; Practice Guidelines as Topic; Pseudomonas aeruginosa; Pseudomonas Infections

Respiratory tract infection with Pseudomonas aeruginosa occurs in most people with cystic fibrosis. Once chronic infection is established, Pseudomonas aeruginosa is virtually impossible to eradicate and is associated with increased mortality and morbidity. Early infection may be easier to eradicate.This is an update of a Cochrane review first published in 2003, and previously updated in 2006 and 2009.. To determine whether antibiotic treatment of early Pseudomonas aeruginosa infection in children and adults with cystic fibrosis eradicates the organism, delays the onset of chronic infection, and results in clinical improvement. To evaluate whether there is evidence that a particular antibiotic strategy is superior to or more cost-effective than other strategies and to compare the adverse effects of different antibiotic strategies (including respiratory infection with other micro-organisms).. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 08 September 2014.. We included randomised controlled trials of people with cystic fibrosis, in whom Pseudomonas aeruginosa had recently been isolated from respiratory secretions. We compared combinations of inhaled, oral or intravenous antibiotics with placebo, usual treatment or other combinations of inhaled, oral or intravenous antibiotics. We excluded non-randomised trials, cross-over trials, and those utilising historical controls.. Both authors independently selected trials, assessed risk of bias and extracted data.. The search identified 49 trials; seven trials (744 participants) with a duration between 28 days and 27 months were eligible for inclusion. Three of the trials are over 10 years old and their results may be less applicable today given the changes in standard treatment. Some of the trials had low numbers of participants and most had relatively short follow-up periods; however, there was generally a low risk of bias from missing data. In most trials it was difficult to blind participants and clinicians to treatment given the interventions and comparators used. Two trials were supported by the manufacturers of the antibiotic used.Evidence from two trials (38 participants) at the two-month time-point showed treatment of early Pseudomonas aeruginosa infection with inhaled tobramycin results in microbiological eradication of the organism from respiratory secretions more often than placebo, odds ratio 0.15 (95% confidence interval 0.03 to 0.65) and data from one of these trials, with longer follow up, suggested that this effect may persist for up to 12 months.One randomised controlled trial (26 participants) compared oral ciprofloxacin and nebulised colistin versus usual treatment. Results after two years suggested treatment of early infection results in microbiological eradication of Pseudomonas aeruginosa more often than no anti-pseudomonal treatment, odds ratio 0.12 (95% confidence interval 0.02 to 0.79).One trial comparing 28 days to 56 days treatment with nebulised tobramycin solution for inhalation in 88 participants showed that both treatments were effective and well-tolerated, with no notable additional improvement with longer over shorter duration of therapy. However, this trial was not powered to detect non-inferiority or equivalence .A trial of oral ciprofloxacin with inhaled colistin versus nebulised tobramycin solution for inhalation alone (223 participants) failed to show a difference between the two strategies, although it was underpowered to show this. A further trial of inhaled colistin with oral ciprofloxacin versus nebulised tobramycin solution for inhalation with oral ciprofloxacin also showed no superiority of the former, with increased isolation of Stenotrophomonas maltophilia in both groups.A recent, large trial in 306 children aged between one and 12 years compared cycled nebulised tobramycin solution for inhalation to culture-based therapy and also ciprofloxacin to placebo. The primary analysis showed no difference in time to pulmonary e. We found that nebulised antibiotics, alone or in combination with oral antibiotics, were better than no treatment for early infection with Pseudomonas aeruginosa. Eradication may be sustained for up to two years. There is insufficient evidence to determine whether antibiotic strategies for the eradication of early Pseudomonas aeruginosa decrease mortality or morbidity, improve quality of life, or are associated with adverse effects compared to placebo or standard treatment. Four trials of two active treatments have failed to show differences in rates of eradication of Pseudomonas aeruginosa. There have been no published randomised controlled trials that investigate the efficacy of intravenous antibiotics to eradicate Pseudomonas aeruginosa in cystic fibrosis. Overall, there is still insufficient evidence from this review to state which antibiotic strategy should be used for the eradication of early Pseudomonas aeruginosa infection in cystic fibrosis.

Topics: Administration, Inhalation; Administration, Oral; Adult; Anti-Bacterial Agents; Child; Ciprofloxacin; Colistin; Cystic Fibrosis; Humans; Pseudomonas aeruginosa; Pseudomonas Infections; Randomized Controlled Trials as Topic; Tobramycin

Inhaled antibiotics are probably the safest and most effective therapy for Pseudomonas aeruginosa chronic lung infection in cystic fibrosis (CF) patients.. To summarise the available evidence, a systematic review of the three currently available inhaled antibiotics (aztreonam lysine (AZLI), colistin (COL) and tobramycin (TOB)) was performed. The three AZLI placebo-controlled studies showed that the improvements in FEV1 and mean sputum P. aeruginosa density were statistically significant better than with placebo. The two COL placebo-controlled studies involved few patients but showed that COL was better than placebo in terms of maintenance of some pulmonary function parameters. The tobramycin inhalation solution (TIS) and tobramycin inhalation powder studies showed that the efficacy of both formulations was similar but significantly better than placebo. In the comparative studies, TIS showed more efficacy than COL solution, colistin inhalation powder showed non-inferiority to TIS and AZLI was superior to TIS.. Placebo-controlled and comparative clinical trials have shown that clinical evidence of inhaled antibiotics is very different. The choice of treatment for each individual CF patient must be based on the features of the drug (clinical evidence on efficacy and safety), the inhalation system and the patient characteristics. Development of new inhaled antibiotics will allow new end points of efficacy and therapy regimens to be assessed.

Topics: Administration, Inhalation; Anti-Bacterial Agents; Aztreonam; Chronic Disease; Colistin; Cystic Fibrosis; Humans; Lung Diseases; Pseudomonas aeruginosa; Pseudomonas Infections; Randomized Controlled Trials as Topic; Tobramycin

A 77-year-old man had undergone left-lobe liver resection and a choledochojejunostomy six years previously, and thereafter he suffered from a postoperative relapse of cholangitis. He was admitted to our hospital due to liver abscesses and bacteremia caused by multidrug-resistant Pseudomonas aeruginosa. Empirical treatment with piperacillin/tazobactam was started, and the patient initially recovered. However, he developed a second case of sepsis caused by piperacillin/tazobactam-resistant P. aeruginosa bacteremia originating from a new liver abscess. We changed the piperacillin/tazobactam to colistin and flomoxef and continued the two antibiotics for one month. During the antibiotic therapy, the patient successfully underwent bile duct stent placement.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Cephalosporins; Cholangitis; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Kidney; Liver Abscess, Pyogenic; Male; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections

Cystic fibrosis (CF) is an inherited condition characterised by the abnormal transport of chloride ions across transporting epithelia. This leads to the production of thick sticky mucus in the lungs, pancreas, liver, intestine and reproductive tract, and an increase in the salt content in sweat. Among other problems, people with CF experience recurrent respiratory infections and have difficulties digesting food. CF affects over 9000 individuals in the UK. CF shortens life expectancy and adversely affects quality of life. In 2010, CF was recorded as the cause of 103 deaths in England and Wales.. To evaluate the clinical effectiveness and cost-effectiveness of colistimethate sodium dry powder for inhalation (DPI) (Colobreathe(®), Forest Laboratories) and tobramycin DPI (TOBI Podhaler(®), Novartis Pharmaceuticals) for the treatment of Pseudomonas aeruginosa lung infection in CF.. Electronic databases were searched in February and March 2011 [MEDLINE, MEDLINE In-Process & Other Non-Indexed citations, EMBASE, The Cochrane Library databases, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, Conference Proceedings Citation Index (CPCI) and Bioscience Information Service (BIOSIS) Previews]. Relevant databases were searched for ongoing and unpublished studies, and bibliographies of relevant systematic reviews and the manufacturers' submissions were also hand-searched.. A systematic review of the clinical effectiveness and cost-effectiveness of colistimethate sodium DPI and tobramycin DPI for the treatment of chronic P. aeruginosa lung infection in CF was conducted. Existing economic evidence within the literature was reviewed and a de novo health economic model was also developed.. Three randomised controlled trials (RCTs) were included in the clinical effectiveness review. Both colistimethate sodium DPI and tobramycin DPI were reported to be non-inferior to nebulised tobramycin for the outcome forced expiratory volume in first second percentage predicted (FEV1%). It was not possible to draw any firm conclusions as to the relative efficacy of colistimethate sodium DPI compared with tobramycin DPI. The economic analysis suggests that colistimethate sodium DPI produces fewer quality-adjusted life-years (QALYs) than nebulised tobramycin. Given the incremental discounted lifetime cost of tobramycin DPI compared with nebulised tobramycin, it highly unlikely that tobramycin DPI has an incremental cost-effectiveness ratio that is better than £30,000 per QALY gained.. The uncertainty surrounding the short-term evidence base inevitably results in uncertainty surrounding the long-term clinical effectiveness and cost-effectiveness of colistimethate sodium DPI.. Both DPI formulations have been shown to be non-inferior to nebulised tobramycin as measured by FEV1%. The results of these trials should be interpreted with caution owing to the means by which the results were analysed, the length of follow-up, and concerns about the ability of FEV1% to accurately represent changes in lung health. Although the increase in QALYs is expected to be lower with colistimethate sodium DPI than with nebulised tobramycin, a price for this intervention had not been agreed at the time of the assessment. Depending on the price of colistimethate sodium DPI, this results either in a situation whereby colistimethate sodium DPI is dominated by nebulised tobramycin or in one whereby the incremental cost-effectiveness of nebulised tobramycin compared with colistimethate sodium DPI is in the range of £24,000-277,000 per QALY gained. The economic analysis also suggests that, given its price, it is unlikely that tobramycin DPI has a cost-effectiveness ratio of < £30,000 per QALY gained when compared with nebulised tobramycin. A RCT to assess the longer-term (≥ 12 months) efficacy of colistimethate sodium DPI and tobramycin DPI in comparison with nebulised treatments would be beneficial. Such a study should include the direct assessment of HRQoL using a relevant preference-based instrument. Future studies should ensure that the European Medicines Agency guidelines are adhered to. In addition, high-quality research concerning the relationship between forced expiratory volume in first second % (FEV1%) predicted or other measures of lung function and survival/health-related quality of life (HRQoL) would be useful.. PROSPERO CRD42011001350.. The National Institute for Health Research Health Technology Assessment programme.

Topics: Administration, Inhalation; Child; Colistin; Cost-Benefit Analysis; Cystic Fibrosis; Disease Progression; Humans; Outcome Assessment, Health Care; Pseudomonas aeruginosa; Pseudomonas Infections; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Therapeutic Equivalency; Tobramycin; United Kingdom

This systematic review evaluated evidence for two dry powder formulations, colistimethate sodium and tobramycin, for the treatment of chronic Pseudomonas aeruginosa in cystic fibrosis, as part of the UK national recommendation process for new technologies. Electronic bibliographic databases were searched in May 2012 (MEDLINE, MEDLINE in-Process, EMBASE, Cochrane Library databases, CINAHL, Web of Science, Conference Proceedings Citation Index and BIOSIS Previews). Relevant outcomes included rate and extent of microbial response (e.g. sputum density of P. aeruginosa), lung function (e.g. forced expiratory volume in 1 s (FEV1)), frequency, severity of acute exacerbations and adverse events. Three trials were included, and both dry powder formulations were reported to be non-inferior in the short term to nebulised tobramycin for FEV1. However, long-term follow-up data were missing and the effect on exacerbation rates was not always reported. Whilst short-term results showed that both dry powder drugs were non-inferior to nebulised tobramycin, there was no long-term follow-up and no phase 3 trials compared nebulised and dry powder colistimethate sodium. The use of FEV1 as the primary end-point may not accurately represent changes in lung health. This review illustrates the difficulty in assessing new technologies where the evidence base is poor.

Topics: Administration, Inhalation; Anti-Bacterial Agents; Colistin; Cystic Fibrosis; Disease Progression; Dry Powder Inhalers; Evidence-Based Medicine; Forced Expiratory Volume; Humans; Lung; Powders; Pseudomonas aeruginosa; Pseudomonas Infections; Research Design; Time Factors; Tobramycin; Treatment Outcome

Lower respiratory tract infections, due to Pseudomonas aeruginosa or Acinetobacter baumannii, are frequently encountered in patients with cystic fibrosis (CF) or in patients developing nosocomial pneumonias. Both of these conditions bear a high mortality risk and aggressive antibiotic therapy is necessary. Inhaled antibiotics might represent an effective therapeutic approach for these diseases as it has demonstrated good bactericidal efficacy and safety in both preclinical and clinical studies. This colistin formulation might be useful particularly in patients with respiratory tract infections due to multidrug-resistant Gram-negative bacteria. Its main advantages are a better safety profile with a minimal or absent risk of nephrotoxicity.. This paper discusses the available systemic formulations of colistin, with pharmacokinetic and safety profiles, followed by an overview of inhaled antibiotics in lower respiratory tract infections.. Inhaled colistin should be used selectively as monotherapy in chronic infections with P. aeruginosa in CF patients, whereas in patients with hospital/ventilator-acquired pneumonia (HAP/VAP), it should be used in a combined regimen with systemic antibiotics.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Animals; Anti-Bacterial Agents; Bronchiectasis; Colistin; Cross Infection; Cystic Fibrosis; Drug Synergism; Drug Therapy, Combination; Humans; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections

Various inhaled antibiotics are currently used for treating chronic Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) patients, however their relative efficacies are unclear. We compared the efficacy of the inhaled antibiotics tobramycin (TIP, TIS-T, TIS-B), colistimethate sodium (colistin) and aztreonam lysine for inhalation (AZLI) based on data from randomised controlled trials.. In the base case, efficacies of antibiotics were compared using a network meta-analysis of seven trials including change from baseline in forced expiratory volume in 1 second (FEV(1)) % predicted, P. aeruginosa sputum density and acute exacerbations.. The tobramycin preparations, AZLI and colistin, showed comparable improvements in efficacy in terms of FEV1% predicted at 4 weeks; the difference in % change from baseline (95%CrI) for TIP was compared to TIS-T (-0.55, -3.5;2.4), TIS-B (-0.64, -7.1;5.7), AZLI (3.64, -1.0;8.3) and colistin (5.77, -1.2;12.8).. We conclude that all studied antibiotics have comparable efficacies for the treatment of chronic P. aeruginosa lung infection in CF.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Bacterial Agents; Aztreonam; Bacterial Load; Bayes Theorem; Biological Availability; Chronic Disease; Colistin; Cystic Fibrosis; Disease Progression; Female; Forced Expiratory Volume; Humans; Information Services; Male; Pseudomonas aeruginosa; Pseudomonas Infections; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Tobramycin; Treatment Outcome

'Old' colistin and polymyxin B are increasingly used as last-line therapy against multidrug-resistant Gram-negative bacteria Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. For intravenous administration, colistin is dosed as its inactive prodrug colistin methanesulfonate (sodium), while polymyxin B is used as its sulfate (active antibacterial). Over the last decade, significant progress has been made in understanding their chemistry, pharmacokinetics (PK), and pharmacodynamics (PD). The first scientifically based dosing suggestions are now available for colistin methanesulfonate to generate a desired target steady-state plasma concentration of formed colistin in various categories of critically ill patients. As simply increasing polymyxin dosage regimens is not an option for optimizing their PK/PD due to nephrotoxicity, combination therapy with other antibiotics has great potential to maximize the efficacy of polymyxins while minimizing emergence of resistance. We must pursue rational approaches to the use of polymyxins and other existing antibiotics through the application of PK/PD principles.

Topics: Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Therapy, Combination; Humans; Klebsiella Infections; Polymyxin B; Polymyxins; Pseudomonas Infections

The emergence of multidrug-resistant Gram-negative bacteria that cause nosocomial infections is a growing problem worldwide. Colistin was first introduced in 1952 and was used until the early 1980s for the treatment of infections caused by Gram-negative bacilli. In vitro, colistin has demonstrated excellent activity against various Gram-negative rod-shaped bacteria, including multidrug-resistant Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae. Recent clinical findings regarding colistin activity, pharmacokinetic properties, clinical uses, emerging resistance, toxicities and combination therapy have been reviewed. Recent approaches to the use of colistin in combination with other antibiotics hold promise for increased antibacterial efficacy. It is probable that colistin will be the 'last-line' therapeutic drug against multidrug-resistant Gram-negative pathogens in the 21st century.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cell Membrane; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Klebsiella Infections; Klebsiella pneumoniae; Polymyxin B; Pseudomonas aeruginosa; Pseudomonas Infections; Treatment Outcome

Pseudomonas aeruginosa is a major hospital-associated pathogen that can cause severe infections, most notably in patients with cystic fibrosis or those hospitalized in intensive care units. In this context, the current increase in incidence of multi-drug resistant (MDR) isolates of P. aeruginosa (MDRPA) raises serious concerns. MDR in P. aeruginosa is defined as the resistance to 3 or 4 of the following antibiotic classes: penicillins/cephalosporins/monobactams, carbapenems, aminoglycosides, and fluoroquinolones. These strains constantly cumulate several resistance mechanisms as a consequence of multiple genetic events, i.e., chromosomal mutations or horizontal transfers of resistance genes. Involved mechanisms may include active efflux, impermeability resulting from porins loss, plasmid-encoded b-lactamases/carbapenemases or aminoglycosides-modifying enzymes, and enzymatic or mutation-associated changes in antibiotics targets. Antibiotic selection pressure represents the leading risk factor for MDRPA acquisition. Colistin (polymyxin E) remains active on virtually all MDRPA isolates, and increasingly appears as the last available option to treat infections caused by these strains. However, the emergence of colistin resistance has been reported in P. aeruginosa, which may announce the spread of pan-resistant strains in a close future.

Topics: Anti-Bacterial Agents; Ciprofloxacin; Colistin; Cross Infection; Drug Resistance, Multiple; Humans; Pseudomonas aeruginosa; Pseudomonas Infections

Based on the worldwide prevalence of multidrug-resistant strains of Pseudomas aeruginosa and the fact that no newer antipseudomonal agents are available, this article aims to investigate therapeutic solutions for combating infections caused by P aeruginosa, including multidrug-resistant strains. The article focuses mainly on colistin, the re-emerging old antibiotic that possesses prominent antipseudomonal activity in vitro and on doripenem, a newer carbapenem that seems to be close to its global marketing. Regarding older antipseudomonal antibiotics that have been reviewed extensively, only newer aspects on their use are considered in this article.

Topics: Anti-Bacterial Agents; Carbapenems; Colistin; Cross Infection; Doripenem; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Randomized Controlled Trials as Topic

The spectrum of available therapeutic options has become drastically narrowed in recent years, particularly for nosocomial multidrug-resistant gram-negative pathogens. This therapeutic void has created a resurgence of interest in colistin. In 5 published series since 1999, clinical response rates for pneumonia due to Pseudomonas aeruginosa or Acinetobacter baumannii treated with intravenous colistin have ranged from 25% to 62%, despite high severity of illness at baseline. De novo nephrotoxicity was observed in 8%-36% of patients, despite close attention to both appropriate dosing and duration of treatment. Neurotoxicity, which was commonly described in the old colistin era, has been exceedingly rare in recent experience. Aerosolized therapy as an adjunct to systemic treatment appears promising, but the current published data are much too limited to allow determination of the incremental benefit of the addition of aerosolized treatment to systemic treatment. Colistin is a reasonably safe last-line therapeutic alternative for pneumonia due to multi- or panresistant P. aeruginosa or A. baumannii.

Topics: Acinetobacter; Acinetobacter Infections; Administration, Inhalation; Anti-Bacterial Agents; Colistin; Cross Infection; Humans; Infusions, Parenteral; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Treatment Outcome; Ventilators, Mechanical

Nosocomial infections with organisms resistant to multiple antibiotic agents represent an evolving challenge in the intensive care setting, particularly in patients requiring surgical diversion of cerebrospinal fluid. The authors present the case of a 51-year-old woman who endured protracted hospitalization and required multiple surgeries including placement of a ventriculoperitoneal shunt. The shunt subsequently became colonized with Pseudomonas aeruginosa, which demonstrated intermediate sensitivity to amikacin and full resistance to all other antibiotics tested 'After failing to respond to intravenous imipenem as well as intravenous and intrathecal amikacin, the patient was successfully treated with intravenous and intrathecal colistin. Colistin is a polymyxin-type antibiotic, rarely used outside of topical application because of reported nephrotoxicity associated with parenteral administration. With activity limited to Gram-negative organisms, colistin is bactericidal by directly disrupting the structure of cell membranes. Authors of a few case reports in the literature have described successful treatment of various ventriculitis with the intrathecal administration of colistin. With bacterial resistances outpacing the pharmaceutical industry's ability to develop novel antibiotics, colistin represents an important alternative in situations involving multidrug-resistant organisms.

Topics: Anti-Bacterial Agents; Cerebral Ventricles; Cerebrospinal Fluid Shunts; Colistin; Cross Infection; Drug Resistance, Multiple; Encephalitis; Female; Humans; Injections, Spinal; Middle Aged; Postoperative Complications; Pseudomonas Infections

Chronic pulmonary infection with Pseudomonas aeruginosa is responsible for most of the morbidity and mortality in cystic fibrosis (CF). Once established as a biofilm, chronic P. aeruginosa infection caused by the mucoid phenotype cannot be eradicated. However, a period of intermittent colonization with P. aeruginosa precedes the establishment of the chronic infection. This window of opportunity can be utilized to eradicate P. aeruginosa from the respiratory tract of CF patients by means of oral ciprofloxacin in combination with nebulized colistin for 3 weeks or, even better, for 3 months or by means of inhaled tobramycin as monotherapy for 4 weeks or longer. This early, aggressive eradication therapy has now been used for 15 years without giving rise to resistance to the antibiotics and without serious side effects. The therapeutic results have been very successful and have completely changed the epidemiology in the Danish Cystic Fibrosis Center and a few other centers which have used this strategy for several years. The chronic P. aeruginosa lung infection is not seen in CF infants and children anymore due to the aggressive therapy, and no other bacteria have replaced P. aeruginosa in these young patients. The aggressive therapy has been shown to very cost-effective, and a European Consensus report recommends this approach.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Chronic Disease; Ciprofloxacin; Colistin; Cystic Fibrosis; Denmark; Humans; Incidence; Pseudomonas Infections

Pseudomonas aeruginosa colonisation has a negative effect on pulmonary function in cystic fibrosis patients. The organism can only be eradicated in the early stage of colonisation, while reduction of bacterial density is desirable during chronic colonisation or exacerbations. Monthly, or at least 3-monthly, microbiological culture is advisable for patients without previous evidence of P. aeruginosa colonisation. Cultures should be performed at least every 2-3 months in patients with well-established colonisation, and always during exacerbations or hospitalisations. Treatment of patients following the first isolation of P. aeruginosa, but with no clinical signs of colonisation, should be with oral ciprofloxacin (15-20 mg/kg twice-daily for 3-4 weeks) plus inhaled tobramycin or colistin (intravenous treatment with or without inhaled treatment can be used as an alternative), while patients with acute infection should be treated for 14-21 days with high doses of two intravenous antimicrobial agents, with or without an inhaled treatment during or at the end of the intravenous treatment. Maintenance treatment after development of chronic P. aeruginosa infection/colonisation (pathogenic colonisation) in stable patients (aged>6 years) should be with inhaled tobramycin (300 mg twice-daily) in 28-day cycles (on-off) or, as an alternative, colistin (1-3 million units twice-daily). Colistin is also a possible choice for patients aged<6 years. Treatment can be completed with oral ciprofloxacin (3-4 weeks every 3-4 months) for patients with mild pulmonary symptoms, or intravenously (every 3-4 months) for those with severe symptoms or isolates with ciprofloxacin resistance. Moderate and serious exacerbations can be treated with intravenous ceftazidime (50-70 mg/kg three-times-daily) or cefepime (50 mg/kg three-times-daily) plus tobramycin (5-10 mg/kg every 24 h) or amikacin (20-30 mg/kg every 24 h) for 2-3 weeks. Oral ciprofloxacin is recommended for patients with mild pulmonary disease. If multiresistant P. aeruginosa is isolated, antimicrobial agents that retain activity are recommended and epidemiological control measures should be established.

Topics: Amikacin; Anti-Bacterial Agents; Anti-Infective Agents; Bronchopneumonia; Cefepime; Ceftazidime; Cephalosporins; Ciprofloxacin; Colistin; Cystic Fibrosis; Drug Therapy, Combination; Humans; Inhalation; Injections, Intravenous; Lung Diseases; Pneumonia, Bacterial; Practice Guidelines as Topic; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin

Pseudomonas aeruginosa is one of the leading gram-negative organisms associated with nosocomial infections. The increasing frequency of multi-drug-resistant Pseudomonas aeruginosa (MDRPA) strains is concerning as efficacious antimicrobial options are severely limited. By searching MEDLINE from January 1966-February 2005 and relevant journals for abstracts, we reviewed the frequency, risk factors, and patient outcomes of MDRPA nosocomial infections in critically ill patients, determined the available antimicrobial therapies, and then provided recommendations for clinicians. The definition of MDRPA was established as isolates intermediate or resistant to at least three drugs in the following classes: beta-lactams, carbapenems, aminoglycosides, and fluoroquinolones. Reported rates of MDRPA varied from 0.6-32% according to geographic location and type of surveillance study. Risk factors for MDRPA infection included prolonged hospitalization, exposure to antimicrobial therapy, and immunocompromised states such as human immunodeficiency virus infection. Emergence of MDRPA isolates during therapy was reported in 27-72% of patients with initially susceptible P. aeruginosa isolates. Patients with severe MDRPA infections should be treated with combination therapy, consisting of an antipseudomonal beta-lactam with an aminoglycoside or fluoroquinolone rather than aminoglycoside and fluoroquinolone combinations, to provide adequate therapy and improve patient outcomes. Synergy has been observed when resistant antipseudomonal drugs were combined in vitro against MDRPA with successful clinical application reported in two centers. Colistin with adjunctive therapy, such as a beta-lactam or rifampin, may be a useful agent in MDRPA when antimicrobial options are limited, but patients should be monitored closely for toxicities associated with this agent. Standardization of terminology for MDRPA isolates is needed for consistency and comparability of surveillance and institutional reports. Clinical studies are needed to identify risk factors for MDRPA development and to determine the economic impact of these infections, as well as to determine the most efficacious antimicrobial regimens and duration of therapy to maximize outcomes in the treatment of MDRPA infections.

Topics: Anti-Bacterial Agents; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Meropenem; Polymyxin B; Pseudomonas aeruginosa; Pseudomonas Infections; Thienamycins

Aerosol delivery of antibiotics offers the potential to achieve high antibiotic concentrations at the site of infection while reducing the risk of systemic untoward effects because of minimal resorption into the bloodstream. We reviewed knowledge acquired in this field over the two latter decades. While the earliest data were obtained with gentamycin, the most conclusive evidence presently regards aminoglycosides and colistin. Aerosol delivery of tobramycin was recently improved with the development of a new formulation for inhalation. Coupled with an adequate nebulization system, intermittent treatment with tobramycin for inhalation has been evaluated in randomized placebo-controlled studies. These studies have demonstrated a significant improvement of respiratory function.

Topics: Administration, Inhalation; Adolescent; Aerosols; Anti-Bacterial Agents; Carbenicillin; Child; Colistin; Cystic Fibrosis; Drug Therapy, Combination; Gentamicins; Humans; Nebulizers and Vaporizers; Penicillins; Placebos; Polymyxins; Pseudomonas Infections; Randomized Controlled Trials as Topic; Time Factors; Tobramycin

Colistin is a cationic polypeptide antibiotic from the polymyxin family that was first introduced in 1962 but abandoned in the early 1970s because of initial reports of severe toxicities. However, a recent increase in the prevalence of multidrug resistant (MDR) Pseudomonas aeruginosa and the lack of novel agents in development calls for a need to re-examine the role of colistin therapy in patients with cystic fibrosis. Current data supports the use of intravenous colistimethate for the treatment of acute pulmonary exacerbations involving MDR P. aeruginosa and inhaled therapy for initial colonization. The frequency of nephrotoxicity and severity of neurotoxicity seem to be substantially less than previously believed. In addition, recent pharmacokinetic and pharmacodynamic data suggests new intravenous dosing regimens may enhance efficacy while minimizing toxicities; such regimens deserve further evaluation. Pre- and post-treatment spirometry is recommended at initiation of inhaled colistin therapy to identify sensitized individuals. Judicious use of colistin where the benefits have been clearly documented will retain this as a useful agent in the management of P. aeruginosa infections in patients with cystic fibrosis.

Topics: Anti-Bacterial Agents; Colistin; Cystic Fibrosis; Drug Resistance, Microbial; Humans; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Administration, Inhalation; Anti-Bacterial Agents; Chronic Disease; Colistin; Community Health Centers; Cystic Fibrosis; Drug Resistance, Microbial; Humans; Injections, Intravenous; Prognosis; Pseudomonas aeruginosa; Pseudomonas Infections

Treating chronic Pseudomonas infection of the bronchial tree is a very important part of the treatment strategy in patients with cystic fibrosis. There are only a few antibiotics which are effective against pseudomonas. Many of them soon lead to bacterial resistance (e.g. fluoro-quinolones). Inhaling antibiotics produces high sputum concentrations and low systemic toxicity. Tolerance is good and resistance rare. Several clinical studies, some of them doubleblind placebo controlled, have shown a positive effect of inhaled antibiotics on symptoms, on frequency of necessary i.v. therapies and also on pulmonary function. Most commonly aminoglycosides (tobramycin) and colistin, which is not yet registered in Switzerland, are used. The main indication is chronic therapy of Pseudomonas infection.

Topics: Administration, Inhalation; Anti-Bacterial Agents; Bronchitis; Colistin; Cystic Fibrosis; Humans; Microbial Sensitivity Tests; Pseudomonas Infections; Tobramycin

The literature on the clinical use of rifampicin in combination for the treatment of non-mycobacterial diseases is reviewed. From the published evidence, the most promising associations are, for staphylococcal infections, gentamicin, erythromycin, kanamycin and fusidic acid. In the field of Gram-negative infections, Psuedomonas-induced sepsis in particular, data are not so impressive but promising results have been obtained with the associated use of rifampicin and gentamicin or colistin. Some systemic fungal diseases may be successfully treated with rifampicin in combination with amphotericin-B. Although only few reports are available on this subject, the importance of such an application is stressed in view of the severity of these diseases and of the lack of appropriate treatments.

Topics: Amphotericin B; Cephalosporins; Chloramphenicol; Colistin; Drug Therapy, Combination; Endocarditis, Bacterial; Erythromycin; Gentamicins; Humans; Kanamycin; Lincomycin; Mycoses; Nalidixic Acid; Penicillins; Pseudomonas Infections; Respiratory Tract Infections; Rifampin; Staphylococcal Infections; Sulfamethoxazole; Tetracyclines; Trimethoprim; Urinary Tract Infections; Vancomycin

Topics: Animals; Antibodies, Bacterial; Antineoplastic Agents; Arthritis, Infectious; Bone Diseases; Burns; Carbenicillin; Carrier State; Colistin; Cross Infection; Cystic Fibrosis; Disease Models, Animal; Drug Therapy, Combination; Gentamicins; Humans; Immunologic Deficiency Syndromes; Leukemia; Lung Diseases; Pneumonia; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Therapy; Skin Diseases, Infectious; Surgical Wound Infection; Transplantation, Homologous

Topics: Antibody Formation; Cell Membrane Permeability; Chloramphenicol; Colistin; Drug Resistance, Microbial; Drug Synergism; Gentamicins; Humans; Pneumonia; Pseudomonas aeruginosa; Pseudomonas Infections; Sex Factors; Sputum; Time Factors; Virulence

Topics: Bacteriological Techniques; Colistin; Corneal Transplantation; Fluorescent Antibody Technique; Humans; Intraocular Pressure; Keratitis; Male; Polymyxins; Pseudomonas; Pseudomonas Infections; Staining and Labeling

Intravenous colistimethate sodium (CMS) is used to treat infections with multiresistant Gram-negative bacteria. Optimal dosing in patients undergoing continuous renal replacement therapy (CRRT) is unclear. In a prospective study, we determined CMS and colistin pharmacokinetics in 10 critically ill patients requiring CRRT (8 underwent continuous venovenous hemodialysis [CVVHD]; median blood flow, 100 ml/min). Intensive sampling was performed on treatment days 1, 3, and 5 after an intravenous CMS loading dose of 9 million international units (MU) (6 MU if body weight was <60 kg) with a consecutive 3-MU (respectively, 2 MU) maintenance dose at 8 h. CMS and colistin concentrations were determined by liquid chromatography with mass spectroscopy. A model-based population pharmacokinetic analysis incorporating CRRT settings was applied to the observations. Sequential model building indicated a monocompartmental distribution for both CMS and colistin, with interindividual variability in both volume and clearance. Hematocrit was shown to affect the efficacy of drug transfer across the filter. CRRT clearance accounted for, on average, 41% of total CMS and 28% of total colistin clearance, confirming enhanced elimination of colistin compared to normal renal function. Target colistin steady-state trough concentrations of at least 2.5 mg/liter were achieved in all patients receiving 3 MU at 8 h. In conclusion, a loading dose of 9 MU followed after 8 h by a maintenance dose of 3 MU every 8 h independent of body weight is expected to achieve therapeutic colistin concentrations in patients undergoing CVVHD using low blood flows. Colistin therapeutic drug monitoring might help to further ensure optimal dosing in individual patients. (This study has been registered at ClinicalTrials.gov under identifier NCT02081560.).

Topics: Adult; Aged; Anti-Bacterial Agents; Chromatography, Liquid; Colistin; Continuous Renal Replacement Therapy; Escherichia coli; Escherichia coli Infections; Female; Humans; Male; Mass Spectrometry; Middle Aged; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections

This study assessed the ease of use of tobramycin inhalation powder (TIP) administered via T-326 inhaler versus tobramycin inhalation solution (TIS) and colistimethate sodium (COLI), both administered via nebulizers, for the treatment of chronic pulmonary Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF).. A real-world, open-label, crossover, interventional phase IV study was conducted in CF patients aged ⩾6 years with forced expiratory volume in 1 second (FEV. A total of 60 patients [mean (standard deviation) age, 27.6 (8.4) years] were allocated to three treatment arms [TIS/TIP ( n = 14); COLI/TIP ( n = 28); TIP/TIP ( n = 18)] in Cycle 1. The mean total administration time, which included device setup and cleaning, in Cycle 1 versus Cycle 2 for TIS/TIP, COLI/TIP, and TIP/TIP arms were 37.0 versus 5.0 min, 16.4 versus 3.8 min, and 4.2 versus 3.4 min, respectively. The difference in mean total administration time was significantly shorter in Cycle 2 than in Cycle 1 for TIS/TIP ( p = 0.0112) and COLI/TIP ( p = 0.0016) arms. Overall, 12 patients were found to have contaminated devices across the two treatment cycles. In the TIP/TIP arm, no contamination of the T-326 inhaler was observed in either cycle. Treatment satisfaction, assessed by the Treatment Satisfaction Questionnaire for Medication and ACCEPT® questionnaire, was better overall for TIP compared with TIS and COLI. There were no unexpected adverse events and most were mild or moderate in intensity.. The T-326 inhaler used to deliver TIP was easy to use, required shorter total administration time, and was much less frequently contaminated than the nebulizers. The safety findings observed for TIP were generally consistent with its established safety profile.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Bacterial Agents; Child; Colistin; Cross-Over Studies; Cystic Fibrosis; Equipment Contamination; Equipment Design; Europe; Female; Forced Expiratory Volume; Humans; Lung; Male; Nebulizers and Vaporizers; Patient Satisfaction; Powders; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections; Time Factors; Tobramycin; Treatment Outcome; Young Adult

Chronic infection with Pseudomonas aeruginosa is associated with an increased exacerbation frequency, a more rapid decline in lung function, and increased mortality in patients with bronchiectasis.. To perform a randomized placebo-controlled study assessing the efficacy and safety of inhaled colistin in patients with bronchiectasis and chronic P. aeruginosa infection.. Patients with bronchiectasis and chronic P. aeruginosa infection were enrolled within 21 days of completing a course of antipseudomonal antibiotics for an exacerbation. Participants were randomized to receive colistin (1 million IU; n = 73) or placebo (0.45% saline; n = 71) via the I-neb twice a day, for up to 6 months.. The primary endpoint was time to exacerbation. Secondary endpoints included time to exacerbation based on adherence recorded by the I-neb, P. aeruginosa bacterial density, quality of life, and safety parameters. All analyses were on the intention-to-treat population. Median time (25% quartile) to exacerbation was 165 (42) versus 111 (52) days in the colistin and placebo groups, respectively (P = 0.11). In adherent patients (adherence quartiles 2-4), the median time to exacerbation was 168 (65) versus 103 (37) days in the colistin and placebo groups, respectively (P = 0.038). P. aeruginosa density was reduced after 4 (P = 0.001) and 12 weeks (P = 0.008) and the St. George's Respiratory Questionnaire total score was improved after 26 weeks (P = 0.006) in the colistin versus placebo patients, respectively. There were no safety concerns.. Although the primary endpoint was not reached, this study shows that inhaled colistin is a safe and effective treatment in adherent patients with bronchiectasis and chronic P. aeruginosa infection. Clinical trial registered with http://www.isrctn.org/ (ISRCTN49790596).

Topics: Administration, Inhalation; Adult; Aged; Anti-Bacterial Agents; Bronchiectasis; Chronic Disease; Colistin; Double-Blind Method; Female; Humans; Male; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Quality of Life; Russia; Surveys and Questionnaires; Time Factors; Treatment Outcome; Ukraine; United Kingdom

In patients with cystic fibrosis (CF), treatment of new Pseudomonas aeruginosa (Pa) infection postpones the occurrence of chronic infection, but the best eradication regimen is unknown .. Compare 2 Pa eradication regimens in children with new Pa infection.. Children with CF (0-18 years) and a new isolation of Pa from sputum, cough swab or BAL were randomized to treatment with tobramycin inhalation solution for 28 days (TIS) or inhaled sodiumcolistimethate (2×2millU/day) plus oral ciprofloxacin (30 mg/kg/day) for 3 months (CC). Airway cultures were taken for 6 consecutive months, then every 3 months. The primary outcome was Pa eradication at the end of treatment. Secondary outcome parameters were: time to Pa relapse from end of treatment, total and Pa specific IgG, FEV(1), BMI and Pa status at 2year follow-up.. 58 patients with new Pa isolation were randomized. Their median age was 9 years (IQR 4.7-13.1) and their median FEV(1) 98% predicted (IQR 87-107). Eighteen treatments concerned the first Pa isolation 'ever' (TIS: 8; CC: 10). For the remaining, median time since previous Pa was 19 months (IQR 9-41). Eradication at end of treatment was similar for both treatments: 26/29 CC and 23/29 in TOBI treated patients (p=0.47). Median time to recurrence of Pa was 9 months (95% CI 0.0-19.0) for CC and 5 months (95% CI 1.7-8.3) for TIS (p=0.608). After 1 year, the 2 groups did not differ in change in total and Pa specific IgG, FEV(1) and BMI. After 2 years, 10% of patients had chronic Pa infection.. In children with CF and new Pa infection, inhalation of TIS (28 days) or CC (3 months) resulted in similar eradication success at the end of treatment (80 and 90% respectively) and similar clinical evolution during the first 2 years of follow-up.

Topics: Administration, Inhalation; Adolescent; Anti-Bacterial Agents; Anti-Infective Agents; Child; Child, Preschool; Ciprofloxacin; Colistin; Cystic Fibrosis; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Infant; Male; Prospective Studies; Pseudomonas Infections; Sputum; Tobramycin; Treatment Outcome

To assess efficacy and safety of a new dry powder formulation of inhaled colistimethate sodium in patients with cystic fibrosis (CF) aged ≥6 years with chronic Pseudomonas aeruginosa lung infection.. A prospective, centrally randomised, phase III, open-label study in patients with stable CF aged ≥6 years with chronic P aeruginosa lung infection. Patients were randomised to Colobreathe dry powder for inhalation (CDPI, one capsule containing colistimethate sodium 1 662 500 IU, twice daily) or three 28-day cycles with twice-daily 300 mg/5 ml tobramycin inhaler solution (TIS). Study duration was 24 weeks.. 380 patients were randomised. After logarithmic transformation of data due to a non-normal distribution, adjusted mean difference between treatment groups (CDPI vs TIS) in change in forced expiratory volume in 1 s (FEV1% predicted) at week 24 was -0.98% (95% CI -2.74% to 0.86%) in the intention-to-treat population (n=373) and -0.56% (95% CI -2.71% to 1.70%) in the per protocol population (n=261). The proportion of colistin-resistant isolates in both groups was ≤1.1%. The number of adverse events was similar in both groups. Significantly more patients receiving CDPI rated their device as 'very easy or easy to use' (90.7% vs 53.9% respectively; p<0.001).. CDPI demonstrated efficacy by virtue of non-inferiority to TIS in lung function after 24 weeks of treatment. There was no emergence of resistance of P aeruginosa to colistin. Overall, CDPI was well tolerated. TRIAL REG NO: EudraCT 2004-003675-36.

Topics: Administration, Inhalation; Adult; Anti-Bacterial Agents; Clinical Trials, Phase III as Topic; Colistin; Cystic Fibrosis; Female; Forced Expiratory Volume; Humans; Male; Powders; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin; Treatment Outcome; Young Adult

Pseudomonas aeruginosa chronic pulmonary infection is an unfavourable event in cystic fibrosis. Bacterial clearance is possible with an early antibiotic treatment upon pathogen isolation. Currently, no best practice exists for early treatment. The efficacy of two different regimens against initial P. aeruginosa infection was assessed.. In a randomised, open-label, parallel-group study involving 13 centres, the superiority of inhaled tobramycin/oral ciprofloxacin compared with inhaled colistin/oral ciprofloxacin (reference treatment) over 28 days was evaluated. Patients were eligible if they were older than 1 year with first or new P. aeruginosa isolation. Treatments were assigned equally by centralised balanced randomisation, stratified by age and forced expiratory volume in 1 s values. The participants and those giving the intervention were not masked to arm assignments. The primary endpoint was P. aeruginosa eradication, defined as three successive negative cultures in 6 months. Analysis was by intention to treat. This trial was registered with EudraCT, number 2008-006502-42.. 105 patients were assigned to inhaled colistin/oral ciprofloxacin (arm A) and 118 to inhaled tobramycin/oral ciprofloxacin (arm B). All patients were analysed. P. aeruginosa was eradicated in 66 (62.8%) patients in arm A and in 77 (65.2%) in arm B (OR 0.90, 95% CI 0.52 to 1.55, p=0.81). Following treatment, an increase in Stenotrophomonas maltophilia was noted (OR 3.97, 95% CI 2.27 to 6.94, p=0.001) with no differences between the two arms (OR 0.89, 95% CI 0.44 to 1.78, p=0.88).. No superiority of treatment under study was demonstrated in comparison to the reference treatment. Early eradication treatment was associated with an increase in S maltophilia.

Topics: Administration, Inhalation; Administration, Oral; Anti-Bacterial Agents; Chi-Square Distribution; Child; Child, Preschool; Ciprofloxacin; Colistin; Cystic Fibrosis; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Infant; Male; Pseudomonas aeruginosa; Pseudomonas Infections; Stenotrophomonas maltophilia; Tobramycin; Treatment Outcome

Antibiotic combination therapy might be more efficient than single antibiotics to combat Pseudomonas aeruginosa biofilms in the airways of patients with cystic fibrosis. We tested the ability of colistin sulphate-tobramycin combinations and single antibiotics to kill P. aeruginosa biofilms.. P. aeruginosa biofilms were generated in vitro and in rat lungs. In a pilot study, 5 patients with cystic fibrosis inhaled colistin and then tobramycin for 4 weeks. The changes in P. aeruginosa counts and lung function were assessed before and after therapy.. Antibiotic combination therapy significantly reduced the number of P. aeruginosa cells in P. aeruginosa biofilm models in vitro. When rats were challenged with 1 x 10(7) cfu of P. aeruginosa, which was embedded in alginate beads, mortality rates, lung pathologic findings, and bacterial colony-forming unit counts were significantly lower after 7 days in animals receiving antibiotic combination than in animals receiving single antibiotics. In patients with cystic fibrosis, inhaled colistin-tobramycin was well tolerated and resulted in a mean decrease of 2.52 + /- 2.5 log(10) cfu of P. aeruginosa per milliliter of sputum (P = .027). Measurements of forced expiratory volume in 1 s, obtained both before and after the study, did not differ significantly.. Colistin-tobramycin combinations are more efficient than respective single antibiotics for killing P. aeruginosa in biofilms in vitro, and they significantly reduced P. aeruginosa cell counts in a rat lung infection model and in patients with cystic fibrosis.

Topics: Administration, Inhalation; Adult; Animals; Anti-Bacterial Agents; Biofilms; Colistin; Cystic Fibrosis; Drug Therapy, Combination; Female; Humans; Lung; Male; Microbial Sensitivity Tests; Pilot Projects; Pseudomonas aeruginosa; Pseudomonas Infections; Rats; Rats, Inbred Lew; Tobramycin; Treatment Outcome

The nosocomial spread of pan-antibiotic-resistant nonfermentative bacteria is an increasing concern. This study investigated the microbiologic and epidemiologic characteristics of a hospital outbreak due to alginate-producing, pan-antibiotic-resistant Pseudomonas aeruginosa (PAR-Pa).. All patients with infection with a P. aeruginosa strain that was resistant to all Clinic Laboratory Standards Institute-suggested antimicrobial agents between November 2004 and May 2005 were included in the study. Alginate production detection and pulsed-field gel electrophoresis (PFGE) typing were done for the patient and environmental surveillance isolates. A matched case-control study was performed to identify risk factors and evaluate outcomes.. PFGE analysis of a total of 35 PAR-Pa isolates (28 patient and 7 environmental surveillance isolates) identified a single epidemic clone as responsible for the outbreak. All epidemic isolates were alginate-producing and susceptible only to colistin. The Student t-test demonstrated that a longer stay in the intensive care unit (ICU) (6.64 days vs 1.83 days; P < .05) significantly increased the risk of PAR-Pa infection. Systemic PAR-Pa infection resulted in higher mortality (85.7% vs 27.8%; P < .05). Multivariate analysis determined that therapeutic failure (odds ratio = 24.7; 95% confidence interval = 4.144 to 147.221; P < .05) was the independent risk factor related to this high mortality. Localized PAR-Pa infections were associated with longer hospital stays (46.2% vs 14.4%; P < .05) and higher rates of surgery (85.7% vs 15.4%; P < .05) and amputation (42.8% vs 0%; P < .05). The recovery of the pathogen from staff hands and frequently handled surfaces suggests possible handborne transmission. Improved hygienic standards and application of strict contact precautions, including isolation, reduced the spread of the pathogen.. This study illustrates the ability of pan-antibiotic-resistant P. aeruginosa to cause an outbreak with significant mortality and stresses the need for precautions to prevent the spread of such highly resistant strains.

Topics: Alginates; Anti-Bacterial Agents; APACHE; Case-Control Studies; Colistin; Confidence Intervals; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Hospital Bed Capacity, 500 and over; Hospitals, University; Humans; Infection Control; Intensive Care Units; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Risk Factors; Turkey

The emergence of multidrug-resistant nosocomial pathogens, such as Pseudomonas aeruginosa and Acinetobacter baumannii, has led to the revival of the systemic use of antimicrobial agent colistin in critically ill patients, but only limited data are available to define its pharmacokinetic profile in these patients.. The aim of this study was to assess steady-state serum concentrations of colistin after i.v. administration of colistin methanesulfonate (CMS) in critically ill patients with stable kidney function.. This prospective, open-label, uncontrolled study was conducted at 2 intensive care units in the Athens Trauma Hospital, KAT, Athens, Greece. Adult patients were nonconsecutively enrolled if they were critically ill and had stable kidney function (<0.5 mg/dL change in serum creatinine prior to and until the day of sample collection) and had been receiving CMS as part of a treatment regimen for sepsis irrespective of site of infection with multidrug-resistant, gram-negative bacilli. After i.v. administration of 225-mg CMS (with the exception of 1 patient who received 150 mg) every 8 or 12 hours for at least 2 days, blood samples were collected just before and at 10 minutes and 1, 2, 4, 6, and 8 hours after i.v. infusion (duration, 30 minutes) of the colistin dose on the sampling day.. Fourteen nonconsecutive patients were enrolled in the study (13 male, 1 female; mean [SD] age, 62.0 [19.2] years; mean [SD] estimated weight, 72.5 [8.5] kg; mean [SD] Acute Physiology And Chronic Health Evaluation II score on admission, 17.1 [6.0]). At steady state, mean (SD) colistin maximum and minimum concentrations were 2.93 (1.24) and 1.03 (0.44) mg/L, respectively, while mean (SD) apparent total body clearance, apparent volume of distribution, and t(1/2) were 13.6 (5.8) L/h, 139.9 (60.3) L, and 7.4 (1.7) hours, respectively. Colistin-related nephrotoxicity was not observed in the study patients.. CMS dosage regimens administered to these critically ill adult patients were associated with suboptimal Cmax/MIC ratios for many strains of gram-negative bacilli currently reported as sensitive (MIC, < or = 2 microg/mL).

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Humans; Infusions, Intravenous; Intensive Care Units; Male; Middle Aged; Prospective Studies; Pseudomonas Infections; Sepsis

To determine the efficacy and safety of colistin (colistimethate sodium) produced by a local pharmaceutical company in Thailand for the treatment of infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa and Acinetobacter baumannii.. Patients hospitalized at Siriraj Hospital between January 2005 and April 2006, who had infections caused by MDR P. aeruginosa or A. baumannii, were enrolled in the study. Colistin (colistimethate sodium) at a dosage of 5 mg/kg/day was given intravenously in two divided doses. Primary outcomes were the clinical response and 30-day mortality; secondary outcomes were microbiological response and adverse events.. Ninety-three patients infected with MDR P. aeruginosa and A. baumannii were enrolled. Seventy-eight patients (71 with A. baumannii and seven with P. aeruginosa) received colistin, whereas 15 patients (12 with A. baumannii and three with P. aeruginosa) received other antibiotics. The mean age, gender, underlying conditions and severity of illness of the patients in both groups were not significantly different. In the colistin group, 63 patients (80.8%) had a favorable clinical response and 94.9% had a microbiological response. The overall mortality of the patients in the colistin group was 46.2% and that in the non-colistin group was 80%. Nephrotoxicity was found in 24 patients (30.8%) in the colistin group and 17 of them had predisposing factors contributing to their renal dysfunction. No neurotoxicity was observed among the 78 patients.. Locally produced colistin appears to be safe and effective for the treatment of infections caused by MDR P. aeruginosa and A. baumannii in Thai adult patients.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Thailand; Treatment Outcome

A previous study of tobramycin nebuliser solution (TNS) compared with colistin [C] in cystic fibrosis (CF) patients, chronically infected with pseudomonas, showed benefit for the TNS treated patients over one treatment cycle only. The current report is of an extension of that study. An open randomised cross-over study of TNS compared with C was conducted on 21 patients who had previously been on the 1 cycle study. They continued for a further 5 months and then crossed over to the alternate treatment. There was an advantage for TNS over C in FEV(1) % predicted change over time. The C slope was -0.88% per month and the TNS slope 0.35% per month (p=0.0002). This suggests advantages of TNS over C in a study with a small number of patients. Larger studies are required.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Chronic Disease; Colistin; Cross-Over Studies; Cystic Fibrosis; Female; Follow-Up Studies; Humans; Male; Pseudomonas Infections; Tobramycin

We retrospectively evaluated the safety and effectiveness of colistin alone or in combination with other antimicrobials in eight diabetic patients with severe diabetic foot infections due to multidrug resistant (MDR) Pseudomonas aeruginosa, complicated in 4 cases by osteomyelitis. All patients received colistin after other ineffective antimicrobial treatment, when MDR P. aeruginosa strains were isolated by cultural examination and together with a multidisciplinary care approach including revascularization, surgical debridement and adequate offloading. The mean duration of therapy was 72 +/- 52.9 days. Six out of 8 patients (75%) successfully benefited from colistin therapy, while 2 patients failed and/or experienced side effects that led to discontinuation of therapy. Serious adverse events (i.e. acute renal failure and pulmonary edema) were observed in 1 patient. Our data allow us to conclude that colistin, alone or in combination with other antimicrobials, is safe and effective when administered as part of a multidisciplinary approach, to promote healing of diabetic foot infection due to MDR P. aeruginosa.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Combined Modality Therapy; Debridement; Diabetic Foot; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Female; Humans; Imipenem; Male; Middle Aged; Osteomyelitis; Pseudomonas Infections; Retrospective Studies; Rifampin; Treatment Outcome

Inhaled colistin is used for the treatment of Pseudomonas aeruginosa infection in cystic fibrosis (CF) patients despite reports of chest tightness and bronchospasm. The main objective of the study was to assess whether bronchospasm occurred in pediatric CF patients with or without clinical evidence of airway hyperreactivity.. A prospective placebo-controlled clinical trial with crossover design was devised using challenge tests with 75 mg colistin in 4 mL saline solution and a placebo solution of the same osmolarity using a breath-enhanced nebulizer for administration. Subjects were recruited as follows: high risk (HR) for bronchospasm due to a personal history of recurrent wheezing, a family history of asthma and/or atopy, or bronchial lability, as demonstrated in pulmonary function tests; or low risk (LR) without these characteristics.. The mean FEV(1) (expressed as the mean [+/- SD] fall from baseline) of the HR group (n = 12) fell 12 +/- 9% after placebo was administered, and fell 17 +/- 10% after colistin was administered. For the LR group (n = 8), the mean FEV(1) fell 9 +/- 4% following placebo administration and 13 +/- 8% following colistin administration. There was a greater number of subjects in the HR group compared to the LR group, which had a mean fall in FEV(1) of >/= 15% (p < 0.01) after inhaling colistin. The differences between placebo and colistin therapy in the LR group were not significant.. The results demonstrated that colistin can cause bronchospasm, particularly in those patients with coexisting CF and asthma.

Topics: Administration, Inhalation; Adolescent; Asthma; Bronchial Spasm; Bronchitis; Bronchoconstriction; Child; Colistin; Comorbidity; Cross-Over Studies; Cystic Fibrosis; Female; Forced Expiratory Volume; Humans; Male; Nebulizers and Vaporizers; Prospective Studies; Pseudomonas Infections; Risk Factors; Spirometry

To assess renal dysfunction and outcome in patients treated exclusively with colistin vs. other antibiotics.. Prospective cohort study in a mixed ICU in a university-affiliated hospital.. 185 patients infected with Acinetobacter baumannii and Pseudomonas aeruginosa after an ICU stay longer than 48 h: 55 in the colistin group and 130 in the noncolistin group, similar in age, APACHE II, medical status, and SOFA score.. We recorded data on epidemiology and severity of illness, site of infection, renal function before and after treatment, clinical cure, and mortality. Clinical cure was defined as simultaneous normalization of central temperature (< or = 38 degrees), leukocyte count (< or = 10,000/mm3), and PaO2/FIO2 ratio (>187). Before treatment creatinine was 0.9+/-0.2 in the colistin group and 0.9+/-0.1 in the noncolistin group; after treatment the value was 1.0+/-0.3 in both groups. The most frequent infection was ventilator-associated pneumonia: 53% vs. 66% in colistin and noncolistin groups, respectively, Acinetobacter was the cause in 65% and 60% and Pseudomonas in 35% and 53%. In the noncolistin group 81% of patients were treated with carbapenems. Inadequate empirical antimicrobial treatment was more frequent in the colistin group (100% vs. 8%), but there were no differences in the frequency of clinical cure on day 6 of treatment (15% and 17%) or in mortality (29% and 24%).. Colistin appears to be as safe and as effective as other antimicrobials for treatment of sepsis caused by Acinetobacter and Pseudomonas in critically ill patients.

Topics: Acinetobacter; Acinetobacter Infections; Adult; Anti-Bacterial Agents; APACHE; Argentina; Blood Gas Analysis; Cohort Studies; Colistin; Female; Humans; Intensive Care Units; Male; Middle Aged; Prospective Studies; Pseudomonas; Pseudomonas Infections; Treatment Outcome

We performed a limited microbiological study to examine the effect of aerosolized colistin (1 million international units every 8 hours) on the colonization of the respiratory tract with Pseudomonas aeruginosa of five intubated, mechanically ventilated patients in the Intensive Care Unit (ICU). No adverse or side effects of the administered aerosolized colistin were reported. The microbial counts of Pseudomonas aeruginosa prior to the use of aerosolized colistin, as well as during the second, fourth, sixth, and eighth day after the use of the drug were measured. The results of this preliminary study suggest that aerosolized colistin was effective in reducing quickly the microbial counts and eliminating microbial growth of Pseudomonas aeruginosa by the sixth day of use in all studied patients.

Topics: Administration, Inhalation; Anti-Bacterial Agents; Colistin; Humans; Intensive Care Units; Lung; Pseudomonas aeruginosa; Pseudomonas Infections; Respiration, Artificial

To examine the effectiveness of delivery of nebulised colistin by the HaloLite nebuliser compared to the Pari LC Plus in patients with cystic fibrosis.. Randomised crossover trial of 15 patients aged >6 years. Inhalation of one mega unit of colistin in 3 ml diluent, labelled with technetium-99m DTPA, was used to assess lung deposition. The Pari was nebulised to dryness and one button press of the HaloLite was completed. Following a seven day washout period, patients inhaled colistin twice daily for seven days through the first device. Sputum specimens were analysed for colistin levels and pseudomonas load. This procedure was repeated with the alternative device.. Lung uptake of radiolabelled colistin was significantly higher with the Pari. However, lung uptake calculated as a percentage of the amount of drug used was significantly higher for the HaloLite. Time to nebulise was significantly shorter with the HaloLite. Sputum levels of colistin were higher following use of the Pari; this was close to significance.. The manufacturer's recommended dosages for nebulising antibiotics with a HaloLite result in a lower delivery than patients receive when using a Pari nebuliser. The concept of adaptive aerosol delivery has several theoretical advantages but the recommended doses for the HaloLite need to be modified in order to improve effectiveness.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Bacterial Agents; Child; Colistin; Cross-Over Studies; Cystic Fibrosis; Humans; Lung; Nebulizers and Vaporizers; Opportunistic Infections; Pseudomonas Infections; Radiopharmaceuticals; Sputum; Technetium Tc 99m Pentetate

Chronic infection with Pseudomonas aeruginosa is associated with progressive deterioration in lung function in cystic fibrosis (CF) patients. The purpose of this trial was to assess the efficacy and safety of tobramycin nebuliser solution (TNS) and nebulised colistin in CF patients chronically infected with P. aeruginosa. One-hundred and fifteen patients, aged > or = 6 yrs, were randomised to receive either TNS or colistin, twice daily for 4 weeks. The primary end point was an evaluation of the relative change in lung function from baseline, as measured by forced expiratory volume in one second % predicted. Secondary end points included changes in sputum P. aeruginosa density, tobramycin/colistin minimum inhibitory concentrations and safety assessments. TNS produced a mean 6.7% improvement in lung function (p=0.006), whilst there was no significant improvement in the colistin-treated patients (mean change 0.37%). Both nebulised antibiotic regimens produced a significant decrease in the sputum P. aeruginosa density, and there was no development of highly resistant strains over the course of the study. The safety profile for both nebulised antibiotics was good. Tobramycin nebuliser solution significantly improved lung function of patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa, but colistin did not, in this study of 1-month's duration. Both treatments reduced the bacterial load.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosols; Anti-Bacterial Agents; Child; Chronic Disease; Colistin; Cystic Fibrosis; Female; Forced Expiratory Volume; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin

The optimal treatment for the eradication of initial P. aeruginosa infection in CF is still unclear. Recently long-term inhaled tobramycin has been proposed. Here we report the results with brief inhaled and/or systemic anti-pseudomonal treatments. Initial P. aeruginosa colonization was successfully eradicated as demonstrated by negative repetitive throat cultures or sputa and serum antipseudomonal antibodies in 15 of 17 patients for at least two years. Randomized, controlled trials are urgently needed to define the optimal protocol for the eradication of P. aeruginosa. Pseudomonas aeruginosa, infection, treatment, antibodies; inhaled tobramycin

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Adult; Case-Control Studies; Ceftazidime; Child; Child, Preschool; Ciprofloxacin; Colistin; Cystic Fibrosis; Drug Therapy, Combination; Humans; Infant; Injections, Intravenous; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin; Treatment Outcome

The clinical course of cystic fibrosis (CF) is characterised by chronic bronchial infection with Pseudomonas aeruginosa. Therapy with inhaled aminoglycosides was introduced to decrease the rate of infectious exacerbations and to delay pulmonary progression. However, development of resistance to aminoglycosides is frequent. Few investigations are available into the resistance profile under treatment with colistin. Antibiotic resistance to colistin was analysed in 44 adult CF patients treated with inhaled colistin. Resistance to aminoglycosides was observed in 86% of cases (38/44) before therapy and decreased to 43% (19/44) under treatment with colistin. Five patients (11%) developed polymyxin resistance. After cessation of therapy pseudomonas became sensitive to polymyxin within a few months and enabled colistin to be reintroduced. In addition, we performed a pilot study analysing the effect of inhaled colistin on the growth of pseudomonas. The number of Pseudomonas aeruginosa decreased from 16.7 million (CFU) bacteria per ml sputum to 2.9 million under therapy with colistin. There was a more than tenfold increase in bacterial counts after inhaled colistin was stopped. Genotyping revealed no change in the type of pseudomonas strains.. Development of resistance to polymyxin is not rare under long-term treatment with inhaled colistin and requires temporary interruption of therapy. Sputum cultures should therefore be tested regularly for polymyxin resistance in patients treated with inhaled colistin.

Topics: Administration, Inhalation; Adult; Anti-Bacterial Agents; Colistin; Cystic Fibrosis; Drug Resistance, Microbial; Female; Humans; Lung Diseases; Male; Pilot Projects; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections; Sputum

To assess the safety and tolerability of bolus intravenous doses of colistin during acute respiratory exacerbations in adults with cystic fibrosis and chronic Pseudomonas aeruginosa infection.. Twelve patients with acute exacerbations of cystic fibrosis were enrolled in a Phase I open-label study. On day 1, patients received three doses of colistin 2 mega-units (160 mg), reconstituted in 50 mL of NaCl 0.9%, by infusion over 30 minutes three times daily. On days 2, 3, and 4, the same dose of colistin was administered by bolus injection three times a day over five minutes after reconstitution in 20, 15, and 10 mL of NaCl 0.9%, respectively. The injection was given by a nurse or physician using a hand-held syringe. If the latter dose was tolerated, it was continued for the remaining eight days of the study. If any dose was not tolerated, treatment reverted to the previously tolerated concentration, which was continued throughout the remainder of the study.. No serious adverse events occurred during the course of the trial. Patients without total indwelling venous access systems experienced mild to moderate injection pain. There were no clinically significant changes in renal function.. This study indicates that the administration of bolus intravenous colistin as 2 mega-units (160 mg) in 10 mL of NaCl 0.9% three times a day is safe. It is well-tolerated by patients with total indwelling venous access systems.

Topics: Adult; Anti-Bacterial Agents; Colistin; Cystic Fibrosis; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Injections, Intravenous; Male; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections

Sixty nosocomial infections caused by Pseudomonas aeruginosa and Acinetobacter baumannii resistant to aminoglycosides, cephalosporins, quinolones, penicillins, monobactams, and imipenem were treated with colistin (one patient had two infections that are included as two different cases). The infections were pneumonia (33% of patients), urinary tract infection (20%), primary bloodstream infection (15%), central nervous system infection (8%), peritonitis (7%), catheter-related infection (7%), and otitis media (2%). A good outcome occurred for 35 patients (58%), and three patients died within the first 48 hours of treatment. The poorest results were observed in cases of pneumonia: only five (25%) of 20 had a good outcome. A good outcome occurred for four of five patients with central nervous system infections, although no intrathecal treatment was given. The main adverse effect of treatment was renal failure; 27% of patients with initially normal renal function had renal failure, and renal function worsened in 58% of patients with abnormal baseline creatinine levels. Colistin may be a good therapeutic option for the treatment of severe infections caused by multidrug-resistant P. aeruginosa and A. baumannii.

Topics: Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Child; Child, Preschool; Colistin; Creatinine; Cross Infection; Drug Resistance, Multiple; Female; Humans; Injections, Intravenous; Male; Middle Aged; Pseudomonas Infections

Nearly all strains of Pseudomonas aeruginosa are sensitive to colomycin sulphomethate, but studies in the 1970s using large doses demonstrated significant renal and neurotoxic side-effects and it is not now commonly used. In this study colomycin (2 megaunits i.v. t.d.s.) has been used extensively in adult cystic fibrosis (CF) patients and its use reviewed to determine its efficacy and safety profile. Fifty-two CF patients (28 male, 24 female; mean age 26 yrs, range 17-39 yrs) received 135 courses (mean two courses each, range 1-7, median length 14 days) of i.v. colomycin (2,414 patient days in total). It was used in combination with one other i.v. antibiotic in 114 courses (85%) and with two others in 18 (13%). In all cases there was significant improvement in spirometry (pretreatment forced expiratory volume in one second (FEV1) % predicted mean 44.4, range 10-101; post-treatment mean 51.3, range 14-108; p<0.0001). No patient had any neurotoxicity but one developed a skin rash and myositis. There was no change in renal function (urea mean pretreatment 4.1 mmol x L(-1) (sD 1.4), mean post-treatment 43 (2.2), p=NS; creatinine mean pretreatment 77.9 mmol x L(-1) (15.3), mean post-treatment 803 (21.6), p=NS). In the authors' experience intravenous colomycin sulphomethate in moderate doses is an effective and safe antipseudomonal antibiotic which is easy to administer. Other clinicians should consider its use in patients with cystic fibrosis.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Colistin; Cystic Fibrosis; Drug Therapy, Combination; Female; Humans; Injections, Intravenous; Kidney Function Tests; Male; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Sputum; Treatment Outcome

Chronic pulmonary infection with Pseudomonas aeruginosa (PA) develops in most patients with cystic fibrosis (CF) and is associated with a poor prognosis. Much effort has been directed toward treating the chronic infection, but it is almost impossible to eradicate it once established; therefore, prevention is preferable. Since 1989 CF patients at the Danish CF Center in Copenhagen have been treated with an intensive three-step-protocol consisting of colistin inhalations and oral ciprofloxacin at the time of initial PA colonization. This study compares 48 patients treated according to this intensive protocol with 43 historic controls. The study was carried out over 44 months and included 218 patient-years. Only 16% of the treated patients developed chronic PA infection after 3 1/2 years compared with 72% of the control patients (Kaplan Meier estimate, P < 0.005, log rank test). This indicates that aggressive treatment prevented or delayed chronic PA infection in 78% of the patients for 3 1/2 years. Furthermore, aggressive treatment maintained or increased pulmonary function (forced vital capacity and forced expiratory volume in 1 second in percent of predicted values) during the year after inclusion compared with the control group, in which pulmonary function declined (P < 0.01, Mann-Whitney test). Although some of the treated patients eventually developed chronic PA infection, these patients had significantly better pulmonary function at the onset of chronic PA infection compared with control patients (P < 0.001, Mann-Whitney test). When the different steps in the intensive three-step-protocol were analyzed, there was a trend suggesting that 3 months of high-dose treatment with colistin inhalation and oral ciprofloxacin produced the best results in terms of postponement or prevention of chronic PA infection (P < 0.05).

Topics: Adolescent; Adult; Anti-Bacterial Agents; Anti-Infective Agents; Carrier State; Child; Child, Preschool; Chronic Disease; Ciprofloxacin; Colistin; Cystic Fibrosis; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Infant; Lung Diseases; Male; Proportional Hazards Models; Pseudomonas aeruginosa; Pseudomonas Infections; Statistics, Nonparametric; Vital Capacity

Patients with cystic fibrosis have received more intravenous antibiotic courses as median survival has steadily increased. A number of centres have adopted a policy of regular (three monthly) rather than on demand intravenous antipseudomonal antibiotics. More widespread bacterial antibiotic resistance has resulted from this increased antibiotic use. Most Pseudomonas aeruginosa strains remain fully sensitive to colistin but its use has been resisted owing to concerns about neurotoxicity and nephrotoxicity. A study was carried out to assess the safety and efficacy of intravenous colistin in the treatment of acute respiratory exacerbations in adult patients with cystic fibrosis.. Patients with chronic Pseudomonas aeruginosa colonisation who presented with protocol defined respiratory tract exacerbations were randomised to receive treatment for 12 days with either colistin (2 MU tds intravenously) alone or with a second anti-pseudomonal antibiotic. Comparisons of the absolute values of respiratory function tests on days 1, 5, and 12 and of overnight oxygen saturation on days 1 and 12 were the primary outcome measures. Patient's weight, clinical and chest radiographic scores, and peripheral blood markers of inflammation were also documented. The effect of each treatment regimen individually was assessed by the change in clinical measurements from baseline values. Adverse renal effects were monitored by measurement of serum levels of urea and electrolytes, creatinine clearance, and ward urine testing. Neurotoxicity was monitored by direct questioning for symptoms.. Fifty three patients, 18 of whom entered the study twice, were enrolled. The mean forced expiratory volume in one second (FEV1) increased significantly in both groups, mean forced vital capacity (FVC) only with dual therapy. Both groups showed a non-significant increase in overnight oxygen saturation. All patients showed clinical improvement. Thirty seven adverse neurological events (two severe) were reported in 33 patients in the monotherapy group and 37 (none severe) in 36 patients in the dual therapy group. One patient withdrew because of severe weakness and dizziness. All other adverse neurological events were well tolerated and resolved during or shortly after treatment. Significant changes were seen in mean serum urea levels in both groups, but in only four patients to a level above the normal range, and in creatinine clearance in the dual therapy group. At 24 month follow up no long term adverse consequences from intravenous colistin were found in patients who completed the study.. Intravenous colistin is an effective treatment for Pseudomonas aeruginosa associated pulmonary exacerbations in patients with cystic fibrosis. Assessment of the individual effect of each treatment regimen suggests a greater efficacy when colistin is combined with a second antibiotic to which the pseudomonas shows in vitro sensitivity. Changes in renal function should be monitored.

Topics: Acute Disease; Adult; Analysis of Variance; Anti-Bacterial Agents; Colistin; Creatinine; Cystic Fibrosis; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Infusions, Intravenous; Kidney; Male; Pseudomonas Infections; Statistics, Nonparametric; Urea

The objective of this study was to quantify the deposition in the lung of a Colistine aerosol generated using a pneumatic nebuliser (Pari LL(R) equipped with a Pari Master, Pari, Germany) and to compare this with the results obtained with an ultrasonic nebuliser (DP100, DP Medical, France) in four subjects suffering from cystic fibrosis being colonised with Pseudomonas aeruginosa. To quantify the pulmonary deposition of the aerosols we have used an indirect isotopic method which consists in assimilating the kinetics of the molecules studied with a serum albumin tagged with Technetium 99m (Tc99mm) and added to a preparation of Colistine. We have previously verified that the addition of a radioactive tracer does not change the normal distribution or dynamics of the medication within the aerosol and the radioactive counter linked to the tracer reflects the mass of the medicament. The pulmonary deposition was expressed as a percentage of the nebuliser dose. A regional analysis of the deposition (central, peripheral, superior and inferior) was carried out and in central deposition compared to the periphery (C/P) and superior compared to inferior (S/I) were calculated. With the DP100 nebuliser the pulmonary deposition of the aerosol was very reproducible from one patient to another, varying only between 9.5 to 14 percent of the nebuliser dose. With the Pari LL the fraction deposited varied more from one patient to another from 5.6 to 27% of the nebuliser dose. In three of four patients, the pulmonary deposition was superior or equal to that obtained with the ultrasonic nebuliser. The patients whose pulmonary deposition was inferior, using the pneumatic nebuliser, was the youngest in the group and co-ordinately poorly the triggering of the nebuliser with the beginning of inspiration. With the two nebulisers, the pulmonary deposition of Colisitine was very heterogeneous throughout the pulmonary parenchyma. The mean of the ratio C/P and S/I obtained in all four patients was identical (1.35 an 0.86 respectively), indicating a deposition of the aerosol which was predominantly central and inferior but was distributed equally in the peripheral parts of the lung. Pneumatic nebulisers offer a reliable alternative notably for domiciliary treatment for Colistine aerosols in patients suffering from cystic fibrosis. In younger patients who have not yet acquired good motor co-ordination, nebulisers which function continuously or are triggered by inspiration seem to be the pr

Topics: Administration, Inhalation; Adolescent; Adult; Aerosols; Anti-Bacterial Agents; Child; Colistin; Cystic Fibrosis; Equipment Design; Female; Humans; Lung Diseases; Male; Nebulizers and Vaporizers; Pseudomonas Infections; Tissue Distribution

Topics: Adolescent; Aerosols; Bronchial Diseases; Child; Child, Preschool; Chronic Disease; Ciprofloxacin; Colistin; Cystic Fibrosis; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Pseudomonas aeruginosa; Pseudomonas Infections; Sputum; Time Factors

To assess whether chronic pulmonary colonisation with Pseudomonas aeruginosa in cystic fibrosis is preventable, 26 patients who had never received anti-pseudomonas chemotherapy were randomly allocated to groups receiving either no anti-pseudomonas chemotherapy or oral ciprofloxacin and aerosol inhalations of colistin twice daily for 3 weeks, whenever Ps aeruginosa was isolated from routine sputum cultures. During the 27 months of the trial, infection with Ps aeruginosa became chronic in significantly fewer treated than untreated subjects (2 [14%] vs 7 [58%]; p less than 0.05) and there were significantly fewer Ps aeruginosa isolates in routine sputum cultures in the treated group (49/214 [23%] vs 64/158 [41%]; p = 0.0006). Thus, chronic colonisation with Ps aeruginosa can be prevented in cystic fibrosis by early institution of anti-pseudomonas chemotherapy.

Topics: Child; Child, Preschool; Chronic Disease; Ciprofloxacin; Colistin; Cystic Fibrosis; Drug Therapy, Combination; Female; Humans; Infant; Male; Pseudomonas aeruginosa; Pseudomonas Infections; Sputum

In a prospective randomized study to determine whether prevention of colonization of Gram-negative bacteria results in prevention of Gram-negative bacterial infections, 96 intensive care patients were randomly allocated into a control group and a study group. The study group received oral nonabsorbable antimicrobial agents (i.e., tobramycin, amphotericin B, and polymyxin E) in addition to parenteral antibiotics. Colonization with Gram-negative microorganisms in the oropharynx, and respiratory and digestive tracts increased in the control group during their stay, while the study group did not tend to colonize with Gram-negative bacteria. In the control group, 107 nosocomial infections were diagnosed, vs. 42 nosocomial infections in the study group. Nosocomial infections caused by Gram-negative bacteria were significantly less frequent in the study group. Mortality due to an acquired infection was significantly less frequent in the study group. We conclude that colonization, infection, and subsequent mortality by nosocomial Gram-negative bacteria can be prevented by a regime of topically applied nonabsorbable antibiotics.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Anti-Bacterial Agents; Bacteria; Cefotaxime; Child; Colistin; Cross Infection; Digestive System; Drug Therapy, Combination; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Oropharynx; Prospective Studies; Pseudomonas Infections; Random Allocation; Respiratory System; Tobramycin

Forty patients with cystic fibrosis and chronic broncho-pulmonary Pseudomonas aeruginosa infection entered a prospective double-blind placebo-controlled study of colistin inhalation. Active treatment consisted of inhalation of colistin one million units twice daily for three months and was compared to placebo inhalations of isotonic saline. Significantly more patients in the colistin inhalation group completed the study as compared to the placebo group (18 versus 11). Colistin treatment was superior to placebo treatment in terms of a significantly better clinical symptom score, maintenance of pulmonary function and inflammatory parameters. We recommend colistin inhalation therapy for cystic fibrosis patients with chronic P. aeruginosa lung infection as a supplementary treatment to frequent courses of intravenous anti-pseudomonas chemotherapy.

Topics: Administration, Inhalation; Adolescent; Adult; Child; Chronic Disease; Clinical Trials as Topic; Colistin; Cystic Fibrosis; Female; Forced Expiratory Volume; Humans; Lung Diseases; Male; Pseudomonas Infections; Vital Capacity

Topics: Adult; Aerosols; Aged; Bronchitis; Chronic Disease; Colistin; Dyspnea; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Histamine H1 Antagonists; Humans; Kanamycin; Male; Middle Aged; Pseudomonas; Pseudomonas Infections; Respiratory Therapy; Sputum; Ventilators, Mechanical; Virulence

Topics: Adolescent; Adult; Aged; Ampicillin; Carbenicillin; Child; Child, Preschool; Clinical Trials as Topic; Colistin; Escherichia coli Infections; Female; Humans; Injections, Intravenous; Klebsiella Infections; Male; Middle Aged; Nalidixic Acid; Penicillins; Pseudomonas Infections; Sulfonamides; Tetracycline; Urinary Tract Infections; Urine

Experience in treating 81 patients with severe bronchial infection with Pseudomonas aeruginosa is described. For those who were desperately ill high doses of intravenous carbenicillin (18g. or more daily) were successful, even when initial carbenicillin resistance was present. For those who were less desperately ill lower doses of carbenicillin together with high doses of gentamicin (given both intramuscularly and by aerosol) comprised the treatment of choice. Gentamicin alone or colistin gave little or no benefit and cannot be recommended.

Topics: Aerosols; Aged; Bronchial Diseases; Bronchiectasis; Clinical Trials as Topic; Colistin; Gentamicins; Humans; Injections, Intramuscular; Injections, Intravenous; Male; Middle Aged; Penicillins; Pseudomonas aeruginosa; Pseudomonas Infections; Sputum

The emergence of multidrug-resistant Pseudomonas aeruginosa infections has urged the need to find new strategies, such as the use of combinations of antibiotics. Among these, the combination of colistin with other antibiotics has been studied. Here, the action of combinations of colistin and rifampicin on both planktonic and sessile cells of colistin-resistant P. aeruginosa was studied. Dynamic biofilms were formed and treated with such a combination, resulting in an active killing effect of both colistin-resistant and colistin-susceptible P. aeruginosa in biofilms. The results suggest that the action of colistin on the outer membrane facilitates rifampicin penetration, regardless of the colistin-resistant phenotype. Based on these

Topics: Anti-Bacterial Agents; Biofilms; Colistin; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin

Infectious diseases are still the major issue not only due to antibiotic resistance but also causing deaths if not diagnosed at early-stages. Different approaches including nanosized drug delivery systems and theranostics are researched to overcome antibiotic resistance, decrease the side effects of antibiotics, improve the treatment response, and early diagnose. Therefore, in the present study, nanosized, radiolabeled with

Topics: Anti-Bacterial Agents; Colistin; Humans; Liposomes; Precision Medicine; Pseudomonas aeruginosa; Pseudomonas Infections

Several clinical guidelines recommend chronic inhaled therapy for pwCF (people with cystic fibrosis) and chronic Pseudomonas aeruginosa infection of the lungs.. To demonstrate what kind of therapy regimens are used in Germany, we retrospectively analysed chronic inhaled antibiotic therapy within the cohort of the German CF Registry in 2020. For comparison we also analysed the use of inhaled antibiotics in pwCF with intermittent Pseudomonas or without Pseudomonas infection.. A total of 1960 pwCF had chronic P. aeruginosa infection and were retrospectively evaluated. Almost 90% (n = 1751) received at least one inhaled antibiotic. The most commonly used inhaled antibiotic was colistin solution for inhalation (55.2%), followed by aztreonam solution for inhalation (32.6%) and tobramycin solution for Inhalation (30%). Almost 56% of adults and 44% of children alternated two antibiotics for inhalation. In children, alternating colistin + tobramycin was the most often used regimen. In adults, only 23% used colistin + tobramycin; there was a wide range of treatment regimens among adults using two inhaled antibiotics alternately. 2456 pwCF had no Pseudomonas infection, but almost 24% had a chronic inhaled antibiotic therapy, while 56% of 361 pwCF and intermittent chronic Pseudomonas infection had a chronic inhaled antibiotic therapy.. In all three groups the most commonly used inhaled antibiotic was colistin solution for inhalation. Almost 56% of adults and 44% of children with chronic Pseudomonas infection alternated two antibiotics for inhalation. It will be interesting to see how the introduction of the highly effective modulator elexacaftor/tezacaftor/ivacaftor will change the use of inhaled antibiotics.

Topics: Administration, Inhalation; Adult; Anti-Bacterial Agents; Child; Colistin; Cystic Fibrosis; Germany; Humans; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Tobramycin

Pseudomonas aeruginosa frequently becomes resistant to aminoglycosides by the acquisition of aminoglycoside modifying enzyme (AME) genes and the occurrence of mutations in the

Topics: Aminoglycosides; Anti-Bacterial Agents; Ciprofloxacin; Colistin; Drug Resistance, Bacterial; Genomics; Gentamicins; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis; Tobramycin; United States

Topics: Animals; Anti-Bacterial Agents; Colistin; Fosfomycin; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Rats; Sepsis; Tobramycin

Pseudomonas aeruginosa is a Gram-negative bacillus that often causes severe infections during immunosuppression in patients with hematologic malignancies. P. aeruginosa can easily acquire drug resistance, and often develops into multidrug-resistant P. aeruginosa (MDRP). Although many antibiotics are used in combination to treat MDRP infections, colistin and amikacin are less likely to be transferred to the lungs, and inhalation therapy may be used. Herein, we report a Case of pneumonia caused by MDRP after allogeneic hematopoietic stem cell transplantation (HSCT) treated with inhaled colistin and amikacin. This 61-year-old female patient was diagnosed with myelodysplastic syndromes and underwent allogeneic HSCT from an 8/8 HLA-matched unrelated donor after reduced-intensity conditioning. On the day of the stem cell infusion, the patient's sputum culture was found to be positive for MDRP. The patient subsequently developed bacteremia, pneumonia, and lung abscess caused by MDRP, and we administered multidrug antibiotic therapy including colistin and amikacin inhalation therapy. The patient's blood cultures were subsequently turned negative, and the lung abscess disappeared. To our knowledge, this is the first case of MDRP pneumonia after HSCT in which colistin and amikacin inhalation therapy was effective.

Topics: Amikacin; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Hematopoietic Stem Cell Transplantation; Humans; Middle Aged; Pneumonia; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Therapy

Bloodstream infection (BSI) caused by carbapenem-resistant P. aeruginosa (CRPA) has high mortality in hematopoietic stem cell transplant (HSCT) recipients. We performed MIC, checkerboard, time-kill assay, PFGE, PCR, and whole genome sequence and described the clinical outcome through Epi Info comparing the antimicrobial combination in vitro. Mortality was higher in BSI caused by CRPA carrying the lasB virulence gene. The isolates were 97% resistant to meropenem displaying synergistic effect to 57% in combination with colistin. Seventy-three percent of the isolates harbored bla

Topics: Adolescent; Adult; Anti-Bacterial Agents; Brazil; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis; Young Adult

Very limited experimental and clinical data are currently available regarding the cerebrospinal fluid (CSF) penetration of ceftazidime-avibactam in adults. Nevertheless, up to our knowledge, there are no data of ceftazidime-avibactam use in central nervous system infections in pediatric patients. For that, here we describe our experience with the use of ceftazidime-avibactam in addition to intraventricular colistin in a pediatric patient diagnosed with ventriculoperitoneal shunt infection due to multidrug-resistant P. aeruginosa. A 2-year-old boy known to pre-term, delivered at 26 weeks with hydrocephalus that required ventriculoperitoneal shunt which was infected due to P. aeruginosa. He was treated with multiple antipseudomonal agents; however, cultures remained persistently positive. On day 54 of admission, the isolate was reported as multidrug-resistant P. aeruginosa and he was switched to ceftazidime-avibactam and intraventricular colistin. CSF cultures became sterile 3 days after initiation of this antibiotic regimen, and subsequent CSF cultures had no growth. No recurrent episode of central nervous system infections due to P. aeruginosa occurred up to 2 years of follow-up.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Ceftazidime; Central Nervous System Infections; Child, Preschool; Colistin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Humans; Male; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

The aim of this study was to compare the safety and effectiveness of ceftolozane-tazobactam (C-T) to colistin-based regimen for treating infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa.. This was a retrospective, multicentre, observational cohort study of inpatients who received either C-T or intravenous colistin for treating infections caused by MDR P. aeruginosa. The study was conducted in five tertiary care hospitals in Saudi Arabia. The main study outcomes included clinical cure at end of treatment, in-hospital mortality, and acute kidney injury (AKI). Univariate analysis and multivariate logistic regression model were conducted to evaluate the independent effect of C-T on the clinical outcome.. A total of 184 patients were included in the study: 82 patients received C-T, and 102 patients received colistin-based regimen. Clinical cure (77% vs. 57%; P = 0.005; OR, 2.52; 95% CI, 1.32-4.79) was significantly more common in patients who received C-T. After adjusting the difference between the two groups, treatment with C-T is independently associated with clinical cure (adjusted OR, 2.47; 95% CI, 1.16-5.27). In-hospital mortality (39% vs. 49%; P = 0.175; OR, 0.67; 95% CI, 0.37-1.20) was lower in patients who received C-T, but the difference was not significant. AKI (15% vs. 41%; P < 0.001; OR, 0.25; 95% CI, 0.12-0.51) was significantly less common in patients who received C-T.. C-T is associated with a higher rate of clinical cure and lower rate of AKI compared to colistin. Our findings support the preferential use of C-T over colistin-based regimen for treating these infections.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Cephalosporins; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Tazobactam

This study was aimed to evaluate the antibiotic resistance, biofilm formation, and genetic diversity of carbapenem-resistant Pseudomonas aeruginosa (CRPA) strains isolated from four types of nosocomial infections (NIs) including urinary tract infection (UTI), ventilator-associated pneumonia (VAP), surgical site infection (SSI), and bloodstream infection (BSI).. In total, 115 isolates of NIs-causing P. aeruginosa were collected from NIs. Antibiotic susceptibility testing (AST) was performed using disk diffusion method and minimum inhibitory concentrations. Biofilm formation was tested on 96-well polystyrene microtiter plates (MTP). CRPA isolates were genotyped using multiple-locus variable number of tandem repeat analysis (MLVA). The most resistance and susceptibility rates were observed to amikacin (70.6%) and colistin (96.1%), respectively. Colistin and meropenem were the most active antimicrobial agents in VAP, SSI, and BSI. While, colistin and cefepime were the most active in UTIs. In total, 52.2% (n = 60/115) of P. aeruginosa isolates were carbapenem resistant, of which 95.0%, 55.0%, and 5.0% were multidrug-resistant, extensively drug-resistant, and pandrug-resistant, respectively. There was a significant association between resistance to carbapenem and resistance to other antibiotics except for piperacillin/tazobactam. The biofilm production of CRPA isolates was 95.0%, of which 23.3% were strong biofilm producers. Based on MLVA, there were 34 different types of CRPA isolates classified into three main clusters and 5 sub clusters.. The association of CRPA with other antibiotic resistance, the high rates of biofilm production, and the high genetic diversity of the isolates may be a warning of the need for a careful surveillance program.

Topics: Anti-Bacterial Agents; Biofilms; Carbapenems; Colistin; Cross Infection; Drug Resistance, Microbial; Genetic Variation; Humans; Iran; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

Resistant strains of Pseudomonas aeruginosa are common pathogens in the intensive care unit (ICU), limiting available therapeutic options. We aimed to compare ceftolozane/tazobactam (C/T) with colistimethate sodium (CMS) in the treatment of ventilator-associated pneumonia (VAP) due to extensively drug-resistant (XDR) Pseudomonas aeruginosa. A retrospective, observational study was performed at a tertiary care ICU. Clinical and microbiological success rate, 28-day all-cause mortality, and adverse events were compared in patients who received C/T with those treated with systemic CMS. A total of 51 patients were included (18 in the C/T and 33 in the CMS group). Clinical success rates in the C/T and CMS groups were 13 (72.2%) and 10 (30.3%), respectively. On multivariate regression analysis, treatment with C/T was independently associated with clinical success (odds ratio 4.47, 95% CI 1.17-17.08). There was no difference in 28-day all-cause mortality (27.8% and 33.3% in the C/T and CMS group, p = 0.76). Acute kidney injury was more common in patients who received CMS (48.5% vs 11.1%, p = 0.01). In our study, ceftolozane/tazobactam was more efficacious in the treatment of XDR Pseudomonas aeruginosa VAP and showed a better safety profile compared to CMS.

Topics: Anti-Bacterial Agents; Cephalosporins; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Tazobactam

The airways of people with cystic fibrosis (CF) often harbour diverse polymicrobial communities. These airway infections can be impossible to resolve through antibiotic intervention, even though isolates of the individual species present are susceptible to the treatment when tested in vitro. In this work, we investigate how polymicrobial cultures comprised of key CF-associated pathogens respond to challenge with species-specific antimicrobial agents; colistin (targets Pseudomonas aeruginosa), fusidic acid (targets Staphylococcus aureus), and fluconazole (targets Candida albicans). We found that growth in a polymicrobial environment protects the target microorganism (sometimes by several orders of magnitude) from the effect(s) of the antimicrobial agent. This decreased antimicrobial efficacy was found to have both non-heritable (physiological) and heritable (genetic) components. Whole-genome sequencing of the colistin-resistant P. aeruginosa isolates revealed single nucleotide polymorphisms and indels in genes encoding lipopolysaccharide (LPS) biosynthesis and/or pilus biogenesis, indicating that a previously undescribed colistin resistance mechanism was in operation. This was subsequently confirmed through further genetic analyses. Our findings indicate that the polymicrobial nature of the CF airways is likely to have a significant impact on the clinical response to antimicrobial therapy.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Colistin; Cystic Fibrosis; Humans; Pseudomonas aeruginosa; Pseudomonas Infections; Staphylococcus aureus

In a number of chronic respiratory diseases e.g. cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), the production of viscous mucin reduces pulmonary function and represents an effective barrier to diffusion of inhaled therapies e.g. antibiotics. Here, a 2-compartment Transwell model was developed to study impaired diffusion of the antibiotic colistin across an artificial sputum (AS) matrix/medium and to quantify its antimicrobial activity against Pseudomonas aeruginosa NH57388A biofilms (alone and in combination with mucolytic therapy). High-performance liquid chromatography coupled with fluorescence detection (HPLC-FLD) revealed that the presence of AS medium significantly reduced the rate of colistin diffusion (> 85% at 48 h; p < 0.05). Addition of alginate oligosaccharide (OligoG CF-5/20) significantly improved colistin diffusion by 3.7 times through mucin-rich AS medium (at 48 h; p < 0.05). Increased diffusion of colistin with OligoG CF-5/20 was shown (using confocal laser scanning microscopy and COMSTAT image analysis) to be associated with significantly increased bacterial killing (p < 0.05). These data support the use of this model to study drug and small molecule delivery across clinically-relevant diffusion barriers. The findings indicate the significant loss of colistin and reduced effectiveness that occurs with mucin binding, and support the use of mucolytics to improve antimicrobial efficacy and lower antibiotic exposure.

Topics: Alginates; Anti-Bacterial Agents; Biofilms; Colistin; Cystic Fibrosis; Humans; Mucins; Oligosaccharides; Pseudomonas aeruginosa; Pseudomonas Infections

To assess the efficacy of long-term treatment with nebulized colistin in reducing the number of respiratory infections, emergency consultations and hospitalizations in oncological patients.. A retrospective, observational, single-centre study including patients with solid or haematologic malignancies, or pulmonary GVHD after HSTC who received treatment with nebulized colistin for at least six-months to prevent recurrent respiratory infections (July 2010 to June 2017).. Twelve patients were included (median age: 54.4, range: 23-85), 7 with solid malignancies and 5 with haematologic malignancies (2 with pulmonary GVHD). Pseudomonas aeruginosa was the most frequent microorganism in sputum cultures (11/12 patients), all strains were susceptible to colistin. There was a statistically significant reduction (p=0.01) in respiratory infections in the six-month period after starting colistin (median: 1, range: 0-4) compared to the six-month period before (median: 4, range: 1-8). There was also a reduction in emergency consultations (precolistin: median: 1.50, range: 0-3; postcolistin: median: 0, range: 0-3) and hospitalizations (precolistin: median: 1.50, range: 0-3; postcolistin: median: 0, range: 0-3) due to respiratory infections. No colistin-resistant strains were identified.. Long-term treatment with nebulized colistin may be useful to reduce the number of exacerbations in oncological patients with recurrent respiratory infections.

Topics: Administration, Inhalation; Anti-Bacterial Agents; Colistin; Graft vs Host Disease; Hematologic Neoplasms; Humans; Middle Aged; Nebulizers and Vaporizers; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections; Retrospective Studies; Treatment Outcome

Topics: Administration, Inhalation; Anti-Bacterial Agents; Bronchiectasis; Colistin; Fibrosis; Humans; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections

Here, we investigate the impact of phage-antibiotic combinations (PAC) on bacterial killing, resistance development and outer membrane vesicle (OMV) production in multidrug-resistant (MDR) P. aeruginosa.. After screening 10 well-characterized MDR P. aeruginosa strains against three P. aeruginosa phages, representative strains, R10266 and R9316, were selected for synergy testing based on high phage sensitivity and substantial antibiotic resistance patterns, while phage EM was chosen based on host range. To understand the impact of phage-antibiotic combinations (PAC) against MDR P. aeruginosa, time-kill analyses, OMV quantification and phage/antibiotic resistance testing were performed. Phage and meropenem demonstrated synergistic activity against both MDR strains. Triple combination regimens, phage-meropenem-colistin and phage-ciprofloxacin-colistin, resulted in the greatest CFU reduction for strains R9316 (3.50 log. These findings support the potential of phage-antibiotic synergy (PAS) to augment killing of MDR P. aeruginosa. Systematic in vitro and in vivo studies are needed to better understand phage interactions with antipseudomonal antibiotics, to define the role of OMV production in P. aeruginosa PAC therapy and to outline pharmacokinetic and pharmacodynamic parameters conducive to PAS.. This study identifies novel bactericidal phage-antibiotic combinations capable of thwarting resistance development in MDR and XDR P. aeruginosa strains. Furthermore, phage-mediated OMV reduction is identified as a potential mechanism through which PAC potentiates bacterial killing.

Topics: Anti-Bacterial Agents; Bacteriophages; Ciprofloxacin; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Meropenem; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

Pseudomonas aeruginosa is an important nosocomial pathogen with a capacity of resistance to multiple antibiotics and production of various extracellular and cell-associated virulence factors that clearly contribute to its pathogenicity. The objective of this study was to investigate the antibiotic susceptibility, virulence factors, and clonal relationship among clinical isolates of P. aeruginosa. Different clinical specimens from hospitalized patients were investigated for P. aeruginosa. Susceptibility of the isolates was evaluated by disc diffusion and broth microdilution methods, as described by the Clinical and Laboratory Standards Institute (CLSI) guideline. A total of 97 P. aeruginosa isolates were recovered from clinical specimens. The percentage of isolates resistant to antimicrobials was imipenem 25.77%, meropenem 15.46%, gentamicin 16.49%, tobramycin 15.46%, amikacin 16.49%, ciprofloxacin 20.61%, levofloxacin 24.74, ceftazidime 20.61%, piperacillin 15.46%, piperacillin/tazobactam 12.37%, colistin 9.27%, and polymyxin B 11.34%. Of isolates, 87.62% possessed β-hemolytic activity, 78.35% lecithinase, 59.8% elastase, 37.11% DNase, and 28.86% twitching motility. The frequency of virulence genes in isolates was lasB 82.47%, plcH 82.47%, exoA 58.76%, exoS 56.7%, and pilA 10.3%. ERIC-PCR typing clustered P. aeruginosa isolates to 19 common types (CT1-CT19) containing isolates from different hospitals and 43 single types (ST1-ST43). Colistin and polymyxin B were the most effective agents against the majority of P. aeruginosa isolates, emphasizing the effort to maintain their antibacterial activity as last-line therapy. The frequency of some virulence factors and genes was noticeably high, which is alarming. In addition, more effective strategies and surveillance are necessary to confine and prevent the inter-hospital and/or intra-hospital dissemination of P. aeruginosa between therapeutic centers.

Topics: Amikacin; Anti-Bacterial Agents; Ceftazidime; Ciprofloxacin; Colistin; Deoxyribonucleases; Drug Resistance, Bacterial; Genotype; Gentamicins; Humans; Imipenem; Iran; Levofloxacin; Meropenem; Microbial Sensitivity Tests; Pancreatic Elastase; Phospholipases; Piperacillin; Piperacillin, Tazobactam Drug Combination; Polymyxin B; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin; Virulence Factors

Pseudomonas aeruginosa is an adaptable bacterial pathogen that infects a variety of organs, including the respiratory tract, vascular system, urinary tract, and central nervous system, causing significant morbidity and mortality. As the primary goal of this study, we wanted to determine how pigment color production differed between clinical strains of P. aeruginosa, and whether or not that variation was associated with multidrug resistance or the ability to form biofilms. We screened in total 30.1% of yellow, 39.8% green and 30.1% of no pigment-producing P. aeruginosa strains from a total of 143 various clinical isolates. Yellow pigment-producing strains presented significant resistance to antibiotics groups, including β-lactam (91.5%), aminoglycosides (70.5%), and carbapenems (51.9%) compared to green and non-pigmented strains. Notably, 16.3% of yellow pigment-producing strains were resistant to colistin which is used as a last-resort treatment for multidrug-resistant bacteria, whereas only 2.3% of non-pigmented and 1.8% of green pigmented strains were resistant to colistin. Aside from that, yellow pigment-producing strains were frequent producers of enzymes belonging to the lactamase family, including ESBL (55.6%), MBL (55.6%), and AmpC (50%). Compared to the green groups (7.14%) and non-pigmented groups (28.5%), they had a higher frequency of efflux positive groups (64.2%). Notably, when compared to non-pigmented groups, green pigment-producing strains also displayed antibiotic susceptibility behavior similar to yellow pigment-producing strains. The majority of yellow pigment-producing strains outperformed the green and non-pigmented strains in terms of MIC levels when compared to the other two groups of strains. Despite the fact that previous studies have demonstrated a direct correlation between multidrug resistance behaviors and biofilm production, no such statistically significant association between pigment and biofilm formation was found in our investigation. Our research has demonstrated that the correlation of bacterial pigments on their susceptibility to antimicrobial agents. Yellow pigment-producing P. aeruginosa strains posed a significant problem due to the lack of alternative agents against such transformed strains, which may be associated with the development of multidrug resistance.

Topics: Anti-Bacterial Agents; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

Bacteriophage (phage) therapy is an alternative to traditional antibiotic treatments that is particularly important for multidrug-resistant pathogens, such as Pseudomonas aeruginosa. Unfortunately, phage resistance commonly arises during treatment as bacteria evolve to survive phage predation. During

Topics: Animals; Anti-Bacterial Agents; Bacteriophages; Colistin; Humans; Hydrogen Peroxide; Immunity, Innate; Mice; Pseudomonas aeruginosa; Pseudomonas Infections; Pseudomonas Phages

Due to increasing antimicrobial resistance, studies where new treatment options are investigated along with the synergistic effects of natural products with antibiotics have arisen. Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen and infection with multi-drug resistant (MDR) P. aeruginosa poses a critical problem during treatment. Curcumin (CUR) is listed in the literature as one of the promising natural ingredients with its strong antimicrobial activity. In our study, our aim was to investigate the in vitro synergistic effect of CUR with imipenem (IMP) and Colistin (CST) in MDR P. aeruginosa isolates and in vivo activity on Galleria mellonella (G. mellonella) larvae. Three clinical isolates of MDR P. aeruginosa, which were determined to be phenotypically resistant to carbapenems, were used, and KPC and OXA48 resistance genes were determined by PCR method. The synergistic effect of CUR with antibiotics were investigated by the checkerboard method. Larval survival and bacterial load were compared with the in vivo study. In this study, IMP MIC values were significantly reduced (two to eight-fold decrease) in the presence of CUR, and partial synergy was observed. For CST, this value decreased two-fold. Bacterial load was evaluated to investigate the effect of antimicrobials during infection. While the CFUs increased over time in non-treated larvae as compared to the initial inoculum, bacterial load was significantly decreased for the groups treated with CUR, IMP and CST compared to the untreated group (p < 0.05). It was concluded CUR-antibiotic combinations can provide an alternative approach in the treatment of infections with MDR bacteria.

Topics: Animals; Anti-Bacterial Agents; Carbapenems; Colistin; Curcumin; Drug Resistance, Multiple, Bacterial; Larva; Microbial Sensitivity Tests; Moths; Pseudomonas aeruginosa; Pseudomonas Infections

Biofilm formation on endotracheal tubes (ETT) is an important factor in the development of ventilator-associated pneumonia (VAP). This work aimed to investigate the effectiveness of colistin (COL) against the early stages of biofilm formation by

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Biofilms; Ciprofloxacin; Colistin; Humans; Pseudomonas aeruginosa; Pseudomonas Infections; Ventilators, Mechanical

Ceftolozane-tazobactam is an emerging ‎treatment for severe infections caused by multidrug-resistant (MDR) Pseudomonas ‎aeruginosa. However, limited ‎data support its use in bacteremia treatment. This study aimed to assess the effectiveness of the treatment of MDR P. aeruginosa bacteremia using ceftolozane-‎tazobactam-based or colistin-based regimens. ‎ PATIENTS AND METHODS: This retrospective, cohort, multicentre study included adult patients with ‎MDR P. aeruginosa bacteremia treated with either ceftolozane-tazobactam or ‎colistin, between September 2018 and August 2021, at four hospitals in Saudi ‎Arabia. The primary endpoint was the 30-day risk-adjusted mortality. Secondary endpoints included the 14-day risk of mortality, bacterial eradication, and clinical ‎success. Cox proportional hazards ‎regression and relative risk estimation were used for analysis, as appropriate. ‎ RESULTS: In total, 46 patients were included; 17 patients received ceftolozane-‎tazobactam-based regimen, and 29 received a colistin-based regimen. There was no association with the use of ‎ceftolozane-tazobactam compared to colistin and the 30-day risk-adjusted mortality ‎‎(hazard ratio [HR] ‎0.58, 95% confidence interval [CI] 0.16-2.13, P = 0.42). Also, the ‎‎14-day risk of mortality and bacterial eradication were not different between the ‎ceftolozane-tazobactam and colistin regimens, HR 2.1, 95% CI 0.42-10.48; P = 0.36; and ‎relative risk (RR) 0.65; 95% CI 0.28-1.52; P = 0.30; respectively. On the other hand, ‎ceftolozane-tazobactam use was associated with higher clinical success than colistin ‎‎(RR 1.84, 95% CI 1.11-3.06: P = 0.021).‎ CONCLUSION: The risk of mortality of MDR P.aeruginosa bacteremia was ‎similar when treated with ceftolozane-tazobactam-based or colistin-based antimicrobial regimens. A higher clinical success was observed with the ceftolozane-‎tazobactam-based regimen compared to the colistin-based regimen. ‎.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Cephalosporins; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Tazobactam

Topics: Agar; Anti-Bacterial Agents; beta-Lactamases; Clone Cells; Colistin; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

Pseudomonas aeruginosa is a pathogen frequently encountered in healthcare-associated infections and immunocompromised patients. In bacteremia, this pathogen is associated with higher mortality than other Gram-negative pathogens. This increase in mortality was also found globally for multi-resistant compared to susceptible strains. Several factors have been associated with the development of resistance: previous ICU stay, use of carbapenems, and comorbidities were identified in multivariate analysis. In the therapeutic choice, previous antibiotic treatment remains the strongest driver suggesting a potential resistant strain. These risk factors will decide whether multi-resistant strains must be considered in the empiric coverage. For susceptible strains, a single agent can be used, β-lactams are usually the first choice. Associations do not provide any advantage on mortality. Optimization of pharmacokinetic/pharmacodynamic parameters, such as prolonged infusion (for time-dependent antibiotics), increased dosage (for concentration-dependent antibiotics), and therapeutic drug monitoring, also influences the outcome. The increasing number of resistant strains led the clinician to use either recently approved new molecules but also associations. For multi-resistant strains, new molecules such as ceftolozane-tazobactam, ceftazidime-avibactam, and cefiderocol have shown an adequate activity against P. aeruginosa. Older molecules like colistin and fosfomycin are also used in this indication. The complexity of the resistance and consequences on a larger scale of antibiotic prescription will probably lead to more individualized prescriptions.

Topics: Anti-Bacterial Agents; Carbapenems; Colistin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Fosfomycin; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Tazobactam

The Pseudomonas aeruginosa bacterium is a common pathogen of cystic fibrosis (CF) patients due to its ability to evolve resistance to antibiotics during treatments. While P. aeruginosa resistance evolution is well-characterized in monocultures, it is less well-understood in polymicrobial CF infections. Here, we investigated how exposure to ciprofloxacin, colistin, or tobramycin antibiotics, administered at sub-minimum inhibitory concentration (MIC) doses, both alone and in combination, shaped the tolerance evolution of P. aeruginosa (PAO1 lab and clinical CF LESB58 strains) in the absence and presence of a commonly co-occurring species, Stenotrophomonas maltophilia. The increases in antibiotic tolerances were primarily driven by the presence of that antibiotic in the treatment. We observed a reciprocal cross-tolerance between ciprofloxacin and tobramycin, and, when combined, the selected antibiotics increased the MICs for all of the antibiotics. Though the presence of S. maltophilia did not affect the tolerance or the MIC evolution, it drove P. aeruginosa into extinction more frequently in the presence of tobramycin due to its relatively greater innate tobramycin tolerance. In contrast, P. aeruginosa dominated and drove S. maltophilia extinct in most other treatments. Together, our findings suggest that besides driving high-level antibiotic tolerance evolution, sub-MIC antibiotic exposure can alter competitive bacterial interactions, leading to target pathogen extinctions in multispecies communities.

Topics: Anti-Bacterial Agents; Ciprofloxacin; Colistin; Cystic Fibrosis; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Stenotrophomonas maltophilia; Tobramycin

Pseudomonas aeruginosa (P. aeruginosa) has been majorly implicated in the infection of burns, wounds, skin, and respiratory tract. Colistin is considered the last line of defense against P. aeruginosa infections. However, colistin is becoming increasingly invalid in treating patients infected with colistin-resistant (COL-R) P. aeruginosa. As one of the disinfectants used for wound infections, acetic acid (AA) offers good antibacterial and antibiofilm activities against P. aeruginosa. This study investigated the effects of AA on COL-R P. aeruginosa in terms of its antibacterial, antibiofilm, and anti-virulence properties and the corresponding underlying mechanisms.. The antimicrobial susceptibility and growth curve data revealed that 0.078% (v/v) AA exhibited good antibacterial activity against COL-R P. aeruginosa. Subinhibitory concentrations of AA were ineffective in inhibiting biofilm formation, but 4 × and 8 × of the minimum inhibitory concentration (MIC) was effective in removing the preformed biofilms in biofilm-eradication assays. The virulence results illustrated that AA inhibited COL-R P. aeruginosa swimming, swarming, twitching, and pyocyanin and elastase production. The analysis of the potential antibacterial mechanisms of AA on COL-R P. aeruginosa revealed that AA acted by increasing the outer and inner membrane permeability, polarizing the membrane potential, and decreasing the reduction potential in a concentration-dependent manner. The qRT-PCR results revealed that AA may inhibit the virulence of COL-R P. aeruginosa by inhibiting the expression of T3SS-related and QS-related genes.. AA possesses antibacterial, antibiofilm, and anti-virulence properties that ultimately lead to the alteration of the bacterial membrane permeability, membrane potential, and reduction potential. Our findings indicated that AA is presently one of the effective treatment options for infections. A high concentration of AA (> 0.156% v/v) can be used to sterilize biofilm-prone surgical instruments, for hospital disinfection, and for treating the external wound, whereas a low concentration of AA (0.00975-0.039% v/v) may be used as an anti-virulence agent for adjuvant treatment of COL-R P. aeruginosa, thereby further improving the application value of AA in the treatment of infections.

Topics: Acetic Acid; Anti-Bacterial Agents; Biofilms; Colistin; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Quorum Sensing

The multi-drug resistance of Pseudomonas aeruginosa is an overwhelming cause of terminal and persistent lung infections in cystic fibrosis (CF) patients. Antimicrobial synergy has been shown for colistin and ivacaftor, and our study designed a relatively high drug-loading dry powder inhaler formulation containing nanoparticles of ivacaftor and colistin. The ivacaftor-colistin nanosuspensions (Iva-Col-NPs) were prepared by the anti-solvent method with different stabilizers. Based on the aggregation data, the formulation 7 (F7) with DSPG-PEG-OMe as the stabilizer was selected for further studies. The F7 consisted of ivacaftor, colistin and DSPG-PEG-OMe with a mass ratio of 1:1:1. The F7 powder formulation was developed using the ultrasonic spray-freeze-drying method and exhibited a rough surface with relatively high fine particle fraction values of 61.4 ± 3.4% for ivacaftor and 63.3 ± 3.3% for colistin, as well as superior emitted dose of 97.8 ± 0.3% for ivacaftor and 97.6 ± 0.5% for colistin. The F7 showed very significant dissolution improvement for poorly water soluble ivacaftor than the physical mixture. Incorporating two drugs in a single microparticle with synchronized dissolution and superior aerosol performance will maximize the synergy and bioactivity of those two drugs. Minimal cytotoxicity in Calu-3 human lung epithelial cells and enhanced antimicrobial activity against colistin-resistant P. aeruginosa suggested that our formulation has potential to improve the treatment of CF patients with lung infections.

Topics: Administration, Inhalation; Aerosols; Aminophenols; Anti-Bacterial Agents; Cell Line; Colistin; Drug Combinations; Dry Powder Inhalers; Humans; Lung; Nanoparticle Drug Delivery System; Pseudomonas aeruginosa; Pseudomonas Infections; Quinolones

As part of the risk management plan in Europe, a long-term observational study was conducted to monitor the safety of colistimethate sodium dry powder for inhalation (CMS-DPI) compared to other inhaled antibiotics.. A cohort of CMS-DPI patients and a matched cohort were identified from the UK Cystic Fibrosis Registry (UKCFR) from 2014-2018. The primary outcome was a composite endpoint, defined as adverse events (AEs) or new cystic fibrosis (CF) complications. Other outcomes included pulmonary exacerbations and treatment discontinuations.. Of 1466 and 3503 patients in the CMS-DPI and comparator cohorts, respectively, 82.7% and 79.4% had AEs. Among the most common new CF complications were osteopenia, CF-related diabetes, and increased liver enzymes. The adjusted event rate ratio (ERR) for the primary outcome was 1.25 (95% confidence interval [CI]: 1.18-1.33, p<0.001). After excluding new CF complications, there was no difference between cohorts (ERR=1.04, 95% CI: 0.79-1.38, p=0.785). Pulmonary exacerbations were common in CMS-DPI and comparator cohorts (78.0% and 79.9% of patients, respectively), with adjusted ERR of 1.02 (95% CI: 0.95-1.10, p=0.523). Rates of discontinuation were similar in the CMS-DPI and Tobramycin inhalation powder comparator cohorts (37.8% and 39.8% of patients, respectively).. There was no difference in the rate of adverse events between CMS-DPI and comparator cohorts. The safety profile of CMS-DPI is similar to those of other inhaled antibiotics, supporting its long-term safety in people with CF. The UKCFR has developed a successful model for partnership with industry to conduct long-term studies aimed at assessing drug safety.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Bacterial Agents; Child; Colistin; Cystic Fibrosis; Female; Humans; Male; Middle Aged; Pseudomonas Infections; Registries; Respiratory Tract Infections; Symptom Flare Up; United Kingdom

The pharmacokinetics/pharmacodynamics of continuous infusion (CI) beta-lactams for Pseudomonas aeruginosa biofilm infections has not been defined. This study evaluated the efficacy of several dosage regimens of CI ceftazidime, with or without colistin, an antibiotic with a potential antibiofilm effect, against biofilm-embedded P. aeruginosa.. This study demonstrated that, with %T>MIC=100%, CI ceftazidime displayed concentration-dependent antibiofilm activity against P. aeruginosa biofilm, particularly in combination with colistin. These results support the use of high-dosage regimens of CI ceftazidime with colistin against biofilm-associated infections with ceftazidime-susceptible P. aeruginosa.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; Biofilms; Ceftazidime; Colistin; Drug Synergism; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

Colistin is an antibiotic of last resort, but has poor efficacy and resistance is a growing problem. Whilst it is well established that colistin disrupts the bacterial outer membrane (OM) by selectively targeting lipopolysaccharide (LPS), it was unclear how this led to bacterial killing. We discovered that MCR-1 mediated colistin resistance in. Antibiotics are life-saving medicines, but many bacteria now have the ability to resist their effects. For some infections, all frontline antibiotics are now ineffective. To treat infections caused by these highly resistant bacteria, clinicians must use so-called ‘antibiotics of last resort’. These antibiotics include a drug called colistin, which is moderately effective, but often fails to eradicate the infection. One of the challenges to making colistin more effective is that its mechanism is poorly understood. Bacteria have two layers of protection against the outside world: an outer cell membrane and an inner cell membrane. To kill them, colistin must punch holes in both. First, it disrupts the outer membrane by interacting with molecules called lipopolysaccharides. But how it disrupts the inner membrane was unclear. Bacteria have evolved several different mechanisms that make them resistant to the effects of colistin. Sabnis et al. reasoned that understanding how these mechanisms protected bacteria could reveal how the antibiotic works to damage the inner cell membrane. Sabnis et al. examined the effects of colistin on

Topics: Animals; Anti-Bacterial Agents; Cell Membrane; Colistin; Disease Models, Animal; Drug Resistance, Bacterial; Drug Therapy, Combination; Escherichia coli; Escherichia coli Proteins; Female; Humans; Lipopolysaccharides; Membrane Fluidity; Mice, Inbred C57BL; Microbial Viability; Peptides, Cyclic; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections

Nosocomial meningitis caused by Gram-negative bacteria is associated with increasingly common neurosurgical procedures in children, with an increase in incidence recently reported. These infections are associated with an increased risk of mortality, prolonged hospitalisation, and increased costs. In this report, we describe two paediatric cases with central nervous system infections caused by extensively drug-resistant Gram-negative bacteria that were successfully treated with intraventricular colistin. To the best of our knowledge, this is the first comprehensive review and discussion of intraventricular antimicrobial therapy in a paediatric population. Based on our comprehensive review of the relevant literature, it appears that intraventricular administration of colistin may be a promising and effective option in the treatment of central nervous system infections in children who do not respond to other treatment options.

Topics: Acinetobacter Infections; Anti-Bacterial Agents; Child, Preschool; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Humans; Infant; Injections, Intraventricular; Male; Meningitis, Bacterial; Pseudomonas Infections

Comparative "real life" data on the effectiveness and safety of ceftolozane/tazobactam (C/T) versus other regimens (aminoglycosides/colistin/combination), in the treatment of multi-resistant (MDR) and extremely resistant (XDR) Pseudomonas aeruginosa (PA), are needed to establish positions.. Observational, retrospective study of patients with microbiological confirmation of MDR and XDR PA from July 2016 up to December 2018 in a tertiary hospital. Variables: age, sex, comorbidities, risk factors for multidrug resistance, variables related to infection, source of infection, microorganism and type of sample, antibiotic treatment, clinical cure, microbiological cure, recurrence, mortality on admission and 30 days post-discharge. Patients were classified according to received antibiotic treatment, C/T or aminoglycosides/colistin/combination.. A total of 405 patients with PA MDR and XDR infection (73.1% men, mean age 63 ± 15 years) were studied. An 87.1% of PA XDR and a 12.9% MDR were observed. All patients received C/T as targeted therapy and in the aminoglycosides/colistin/combination group were 73.5%. Patients in the C/T group present worse prognostic factors: septic shock (30.0%) and catheterization (90.0%) (p<0.05). There were not statistically significant differences in microbiological cure (p=0.412), recurrence (p=0.880) and clinical cure (p=0.566). There were not statistically significant differences in mortality at admission (p=0.352) or at 30 days after discharge (p=0.231). A 17.2% of the patients with aminoglycosides/colistin/combination had acute kidney injury according to RIFLE criteria and 4.3% with C/T.. The data obtained suggest that there have been no differences in effectiveness (clinical or microbiological cure) in favour of C/T, although, in the period studied, it was used in most cases in multitreated patients with a worse prognosis. Randomized and prospective studies would be needed to establish an adequate positioning.

Topics: Aftercare; Aged; Aminoglycosides; Anti-Bacterial Agents; Cephalosporins; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Patient Discharge; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Tazobactam

Topics: Anti-Bacterial Agents; Chitosan; Colistin; Drug Carriers; Humans; Hyaluronic Acid; Polyelectrolytes; Pseudomonas aeruginosa; Pseudomonas Infections

Pseudomonas aeruginosa cross-infections are related to increased morbidity and mortality in cystic fibrosis (CF).. The aim of the study was to evaluate the incidence of cross-infections with P. aeruginosa in children with CF.. CF patients from whom at least one P. aeruginosa strain had been isolated were included in the study. The strain genotyping was performed using pulse-field gel electrophoresis. The history of contacts between patients was established based on questionnaires.. The study group consisted of 75 patients (aged 1.0-19.2 years) and the material included 170 P. aeruginosa strains. Cross-infections occurred in a group of 26 patients. In this group, the risk of the predicted occurrence of forced expiratory volume in 1 second ≤ 70% was five times greater and the risk of longer cumulative hospitalization time for intravenous antibiotic therapy (>14 days/year) was almost five times greater. In the clonal groups of strains, the multidrug-resistance rate was significantly higher than in other groups. In 2011, all tested strains were susceptible to colistin, whereas in 2012, three strains from the largest clonal group showed high levels of resistance to colistin.. Cross-infections with P. aeruginosa occurred in our group of patients and were associated with poor clinical outcomes. Antimicrobial resistance rate in the strains isolated from such infections was significantly higher, and this included three strains resistant to colistin.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Child; Child, Preschool; Colistin; Cross Infection; Cystic Fibrosis; Drug Resistance, Microbial; Female; Forced Expiratory Volume; Genotype; Humans; Incidence; Infant; Male; Pseudomonas aeruginosa; Pseudomonas Infections; Treatment Outcome; Young Adult

Antibiotic discovery and preclinical testing are needed to combat the

Topics: Animals; Anti-Bacterial Agents; Colistin; Humans; Mice; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; beta-Lactam Resistance; beta-Lactamases; Colistin; Humans; Imipenem; Mutation; Pseudomonas aeruginosa; Pseudomonas Infections

Colistin-resistant Pseudomonas aeruginosa (CRPA), as a health care system threat, is increasing globally. This study aimed was to determine CRPA by high-resolution melting curve (HRM) analysis method. The HRM method was done on standard strains of P. aeruginosa and CRPA strains. Ninefold serial dilutions of known genomic DNA (gDNA) and plasmid DNA (pDNA) concentrations, extracted from P. aeruginosa NCTC13715 and P. aeruginosa NCTC10728 were prepared and tested by melting curve analysis and HRM assay. Data analysis was performed using the Step-One Plus Software v2.3 and hrm Software v3.0.1. The results of the melt curve analysis and HRM showed a very similar melt peak for all positive controls with a melt temperature that ranged from 88·1°C to 88·6°C for the 16srRNA, 90·0°C to 90·05°C for the mcr-1 and 91·2°C to 91·7°C for the pmrA gene. Furthermore, the data indicated that the HRM approach has the sensitivity to detect 10

Topics: Anti-Bacterial Agents; Bacterial Typing Techniques; Colistin; DNA, Bacterial; Humans; Plasmids; Pseudomonas aeruginosa; Pseudomonas Infections; Sensitivity and Specificity; Transition Temperature

Colistin represents the last-line treatment option against many multidrug-resistant Gram-negative pathogens. Several lines of evidence indicate that aminoarabinosylation of the lipid A moiety of lipopolysaccharide (LPS) is an essential step for the development of colistin resistance in Pseudomonas aeruginosa. However, whether it is sufficient to confer resistance in this bacterium remains unclear. The aim of this work was to investigate the specific contribution of lipid A aminoarabinosylation to colistin resistance in P. aeruginosa and evaluate the effect of this resistance mechanism on bacterial fitness. Recombinant strains constitutively expressing the enzymes for lipid A aminoarabinosylation were generated in a small collection of reference and clinical isolates and verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR), lipid A extraction and mass spectrometry. The effect of aminoarabinosylated lipid A on colistin resistance was found to be strain- and culture condition-dependent. Higher levels of resistance were generally obtained in the presence of divalent cations, which appear to be important for aminoarabinosylation-mediated colistin resistance. High colistin resistance was also observed for most strains in human serum and in artificial sputum medium, which should partly mimic growth conditions during infection. The results of growth, biofilm, cell envelope integrity and Galleria mellonella infection assays indicate that lipid A aminoarabinosylation does not cause relevant fitness costs in P. aeruginosa.

Topics: Animals; Anti-Bacterial Agents; Arabinose; Biofilms; Colistin; Disk Diffusion Antimicrobial Tests; Drug Resistance, Multiple, Bacterial; Humans; Lipid A; Moths; Pseudomonas aeruginosa; Pseudomonas Infections

Osteoarticular infections (OIs) caused by fluoroquinolone-resistant Pseudomonas aeruginosa, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, have poor outcomes. We evaluated the outcomes of an optimized strategy of continuous beta-lactam infusion (BL-CI) guided by therapeutic drug monitoring (TDM) for OIs caused by fluoroquinolone-resistant P. aeruginosa.. A prospective observational study of patients with P. aeruginosa OIs in a hospital-based BL-CI program (2016-2018) was carried out. TDM targeting free BL concentrations in plasma (fCss) of at least 3-4 × MIC was performed. We compared failure rates between patients with OIs caused by fluoroquinolone-resistant strains who were treated with BL-CI, with or without colistin, and patients with OIs caused by fluoroquinolone-susceptible strains who were treated with ciprofloxacin.. Fifty-two patients were included in the study, 19 (36.5%) of whom had OIs caused by fluoroquinolone-resistant P. aeruginosa (13 (68.4%) MDR/XDR strains; 11 (57.9%) device-related infections). The median duration of BL-CI was 36 days; ten patients (52.6%) received BL-colistin combinations. Eighty-two samples were utilized in the TDM, and most patients were found to have a median fCss of 3-10 × MIC; 17 dose adjustments were performed and eight patients needed dose decreases, five of which were due to chronic kidney disease or acute kidney injury (AKI). BL-CI was well tolerated, with the most frequent adverse event being AKI. Failure occurred to 4 patients (21.1%), which was similar to the failure rate of patients with OIs caused by fluoroquinolone-susceptible P. aeruginosa treated with ciprofloxacin (5/30 [16.7%]) (p = 0.699). TDM was also used in the initial BL treatment of patients with OIs caused by susceptible strains before those patients were switched to treatment with ciprofloxacin alone (33 patients, 110 samples, 19 dose adjustments).. BL-CI used with/without colistin and supported by TDM may be an alternative and effective treatment option for OIs caused by fluoroquinolone-resistant P. aeruginosa, where limited available therapeutic options exist, especially in the setting of multidrug resistance. Future research should elucidate whether this strategy can produce outcomes similar to those of patients treated for OIs caused by fluoroquinolone-susceptible strains.

Topics: Aged; Anti-Bacterial Agents; beta-Lactams; Bone Diseases, Infectious; Ciprofloxacin; Cohort Studies; Colistin; Drug Monitoring; Drug Resistance, Multiple, Bacterial; Female; Humans; Infusions, Intravenous; Joint Diseases; Male; Microbial Sensitivity Tests; Middle Aged; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections

Carbapenem-resistant Acinetobacter baumannii (CRAB) and Pseudomonas aeruginosa (CRPA), as well as polymyxin-resistant A. baumannii (PMR-AB) and P. aeruginosa (PMR-PA), were used to test different enrichment strategies from spiked stools. Three procedures were compared, namely, direct inoculation on selective plates and plating after a 24-h enrichment step in tryptic soy broth with or without antibiotics. Selective agar plates were used including CHROMagar-Pseudomonas supplemented with meropenem (2 mg/L), and CHROMagar-MDR-Acinetobacter agar and CHROMagar COL-APSE plates. Use of enrichment broths significantly enhanced the recovery of CRAB, CRPA, PMR-AB, and PMR-PA. However, supplementing or not the pre-enrichment broth with antibiotics had no impact. The proposed strategy for screening multidrug-resistant nonfermenters is of low cost, is easy to implement, and might be useful for outbreak containment.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteriological Techniques; Carbapenems; Colistin; Culture Media; Drug Resistance, Multiple, Bacterial; Feces; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Sensitivity and Specificity

Reduced efficacy of antibiotics in bacterial diseases is a global concern in clinical settings. Development of anti-virulence compounds which disarm bacterial virulence is an attractive therapeutic agent for complementary antibiotics usage. One potential target for anti-virulence compounds is quorum sensing (QS), the intercellular communication system in most pathogens, such as Pseudomonas aeruginosa. QS inhibitors (QSIs) can inhibit QS effectively, attenuate QS-mediated virulence, and improve host clearance of infections. While studies focused on developing homoserine-based las QSI, few targeted the quinolone-based pqs QS, which implicated host cytotoxicity and biofilm formation. It is imperative to develop novel anti-pqs-QS therapeutics for combinatorial antibiotic treatment of microbial diseases. We employed a gfp-based transcriptional pqs biosensor to screen a natural compounds library and identify vanillin (4-hydroxy-3-methoxybenzaldehyde), the primary phenolic aldehyde of vanilla bean. The vanillin inhibited pqs expression and its associated phenotypes, namely pyocyanin production and twitching motility in P. aeruginosa. Molecular docking results revealed that vanillin binds to the active site of PqsR, the PQS-binding response regulator. Combinatorial treatment of vanillin with antimicrobial peptide (colistin) inhibited biofilm growth in vitro and improved treatment in the in vivo C. elegans acute infection model. We demonstrated that vanillin could dampen pqs QS and associated virulence, thus providing novel therapeutic strategies against P. aeruginosa infections.

Topics: Animals; Benzaldehydes; Biofilms; Caenorhabditis elegans; Catalytic Domain; Colistin; Drug Therapy, Combination; Gene Expression; Models, Molecular; Molecular Docking Simulation; Pseudomonas aeruginosa; Pseudomonas Infections; Pyocyanine; Quinolones; Quorum Sensing; Virulence

Background Colistin resistance in P. aeruginosa (CRPA) is due to the appearance of superbug strains. As this pathogen gains more transferrable resistance mechanisms and continues to adapt to acquire additional resistance mechanisms during antimicrobial therapy rapidly, we face the growing threat of CRPA in bloodstream infections (BSI). This study designed to evaluate the frequency of CRPA strains producing different β-lactamases by the High-Resolution Melting Curve Analysis (HRMA) method in BSI and to characterize the different types by multilocus sequence typing (MLST).. Sixty-nine (69) P. aeruginosa isolates were collected from blood culture. MIC E-test methods examined the antimicrobial susceptibilities of the bacterial isolates. Detection of resistant strains performed by using HRMA assay.. The strains resistant to amikacin (n = 11; 15.94%) and colistin (n = 10; 14.49%) were the least abundant and the gentamicin (n = 56; 82.6%) and ciprofloxacin (n = 67; 97.10%) resistant strains were the most frequent. Also, 39 isolates (56.52%) considered as multidrug-resistant (MDR), 20 isolates (28.98%) as extensively drug resistant (XDR), and 11 isolates (15.94%) as Pandrug Resistance (PDR). Further, 32 isolates (46.37%) considered as AmpC producer, and 28 isolates (40.57%) were considered an MBL producer. According to HRMA results, the blaSPM gene was detected in 19 isolates (27.53%), blaNDM gene in 11 isolates (15.94%), blaFOX gene in 31 isolates (44.92%), mcr-1 gene in 10 isolates (14.49%), blaACC and blaVIM genes in 27 isolates (39.13%), and blaTEM gene was reported in 20 isolates (28.98%). Furthermore, P. aeruginosa PASGNDM699, ST3340, and ST235 identified in 1.44%, 11.59% and 17.39% isolates, respectively.. CRPA strains play an essential role in the spread of antibiotic resistance in BSI. Likewise, the HRMA method was sensitive and specific for the detection of superbugs. Moreover, MLST analysis of a diverse collection of P. aeruginosa from blood culture suggests that particular strains or clonal complexes are associated with antibiotic resistance profile.

Topics: Anti-Bacterial Agents; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Female; Genetic Variation; Genotype; Humans; Iran; Male; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis; Sequence Analysis

Cystic fibrosis (CF) patients, with Pseudomonas aeruginosa infection, often require repeated aminoglycoside courses for the management of acute pulmonary exacerbations (APEs). Acute kidney injury (AKI) due to aminoglycosides has been reported; little data exist regarding long-term nephrotoxicity with repeated exposure. The objective of this study was to describe the incidence of acute and chronic nephrotoxicity due to cumulative intravenous (IV) aminoglycoside exposure. This is a retrospective, observational study of pediatric and adult CF patients admitted to an academic medical center between January 1, 2006 and October 1, 2018 for APE management. Patients were eligible for inclusion if they received at least five courses of an IV aminoglycoside for at least 7 days each. Cumulative weight-based aminoglycoside dose was reported in milligrams per kilogram. For each admission, baseline and highest serum creatinine were collected to assess the incidence of AKI. The baseline and final estimated glomerular filtration rate (eGFR) were calculated to assess long-term effects on renal function. Sixty-six patients, representing greater than 700 courses, were included in the final analysis. The median cumulative weight-based aminoglycoside dose was 1183 mg/kg of tobramycin or tobramycin equivalent. Twenty percent of courses resulted in AKI; 86% were Stage 1. A repeated measure multivariate model showed colistin, piperacillin/tazobactam, vancomycin, and age were significant AKI risk factors. There was no correlation between cumulative aminoglycoside dose and change in eGFR. AKI from IV aminoglycoside exposure occurred in 20% of courses. Cumulative exposure to IV aminoglycosides in APE management was not correlated with long-term renal dysfunction.

Topics: Acute Kidney Injury; Adolescent; Adult; Age Factors; Anti-Bacterial Agents; Child; Child, Preschool; Colistin; Cystic Fibrosis; Female; Humans; Incidence; Infant; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Pseudomonas Infections; Retrospective Studies; Risk Factors; Tobramycin; Vancomycin; Young Adult

Nebulization of antimicrobial drugs such as tobramycin and colistin is a cornerstone in the treatment of patients with cystic fibrosis (CF) infected with Pseudomonas aeruginosa. However, nebulization has a high treatment burden. The Twincer™ is a dry powder inhaler specifically developed for the inhalation of antibiotics such as colistin. The aim of this study was to compare patient outcomes and experience with colistin dry powder by the Twincer with nebulization of colistin or tobramycin in adult CF patients in a real-life setting.. This was a retrospective study from 01-01-2015 until 01-07-2018. Effectiveness was evaluated by comparing FEV1 decline and exacerbation rate during a mean of 4.1 years of nebulization therapy prior to the initiation of the Twincer against the same values during a mean of 1.7 years of treatment with the Twincer.. Twenty-one patients were evaluated, of whom twelve could be included in the effectiveness analysis, with a total of twenty patient years. Of all patients 71.4% preferred therapy with the Twincer over nebulization. Twincer use resulted in high treatment adherence with an average adherence rate of 92.5%. There was no significant difference in annual decline in FEV1%pred prior to and after start changing from nebulization to the use of the Twincer powder inhaler (median decline -1.56 [-5.57-5.31] and 1.35 [-8.45-6.36]) respectively, p = 0.45 (linear mixed effect model)). No significant difference was found in the number of intravenous or combined total intravenous and oral antibiotic courses during Twincer therapy compared to when using nebulization (1.68 and 2.49 courses during Twincer therapy versus 1.51 and 2.94 courses during nebulization, p = 0.88 and p = 0.63).. Colistin dry powder inhalation with the Twincer is a more patient friendly alternative to nebulization, and we did not observe significant differences in the clinical outcome, regarding lung function and exacerbation rates.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Bacterial Agents; Colistin; Cystic Fibrosis; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Pseudomonas Infections

Topics: Administration, Inhalation; Adult; Anti-Bacterial Agents; Bronchiectasis; Colistin; Cost-Benefit Analysis; Cystic Fibrosis; Humans; Pseudomonas aeruginosa; Pseudomonas Infections

Pseudomonas aeruginosa is a major bacterial pathogen responsible for hospital-acquired infections. Although its epidemiology is considered as non-clonal, certain international high-risk multidrug-resistant clones have been recognized.. From the first report of an intra-hospital outbreak due to an SHV2a-producing P. aeruginosa strain, to describe the emergence of a new ST235-specific lineage harbouring this rare extended-spectrum β-lactamase (ESBL).. Between May and October 2018, four patients hospitalized in the cardiovascular intensive care unit of a French teaching hospital were infected by a multidrug-resistant P. aeruginosa isolate. Serotype and antimicrobial susceptibility were tested; multi-locus sequence type (MLST), core genome MLST, and resistome were determined through whole genome sequencing. A phylogenetic analysis based on single nucleotide polymorphism was performed using available ST235 genomes.. The four strains were susceptible to colistin, ciprofloxacin, ceftazidime-avibactam, and ceftolozane-tazobactam. bla. Among the ST235 P. aeruginosa strains, a sub-lineage sharing a common genetic background and harbouring the bla

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Bacterial Proteins; beta-Lactamases; Ceftazidime; Cephalosporins; Ciprofloxacin; Colistin; Cross Infection; Disease Outbreaks; Drug Combinations; Drug Resistance, Multiple, Bacterial; Female; France; Humans; Microbial Sensitivity Tests; Multilocus Sequence Typing; Polymorphism, Single Nucleotide; Pseudomonas aeruginosa; Pseudomonas Infections; Tazobactam

Respiratory tract infections caused by multidrug-resistant Gram-negative bacteria are serious burdens to the public. Our previous findings indicated that co-loading of colistin and ciprofloxacin via liposomes improved in vitro antimicrobial activities against multidrug resistant Pseudomonas aeruginosa as compared to the monotherapies. The current study aims to investigate the transport behavior of colistin and ciprofloxacin in liposomes using the in vitro Calu-3 cell monolayer, which is a lung epithelial model cultured under the air-interfaced condition. The cell viability results demonstrated that there was no obvious toxicity of cells exposed to single or co-administered drugs at the concentration ≤500 μg/mL. Transport of ciprofloxacin into the cells was easier than that of colistin, which reached a plateau rapidly. Colistin was less trapped in the mucus or adhered to the apical cell membrane, and less transported across the cell monolayer than ciprofloxacin. The deposition of ciprofloxacin on the apical side increased over time (from 1 to 4 h). There was no drug-drug interaction observed during the transport of ciprofloxacin and colistin across the cell monolayer, when they were dosed together in the solution form. The amount of drug transported across the cell monolayer was decreased in both agents when loaded in liposomes. Both drugs were more trapped in the mucus or more adhered to the apical side cell membrane of the cell monolayer when they were in liposomes. This study demonstrated that co-delivery of colistin and ciprofloxacin in a single liposome can reduce transport capacity of both drugs across the lung epithelial cell monolayer and enhance drug retention on the lung epithelial surfaces; therefore, it is a promising approach to treat the respiratory infections caused by multidrug resistant Pseudomonas aeruginosa.

Topics: Anti-Bacterial Agents; Cell Line; Ciprofloxacin; Colistin; Epithelial Cells; Humans; Liposomes; Lung; Pseudomonas aeruginosa; Pseudomonas Infections

A 71-year-old male patient presented with decreased visual acuity, redness, and discharge in his right eye for 5 days. He had undergone evisceration of his left eye several years earlier. Before presentation, he had received chemotherapeutic agents for Kaposi’s sarcoma of the scalp. Slit-lamp examination revealed severe hypopyon and an extensive corneal ulcer with surrounding infiltrate, which extended to the deep stroma. Microbiological evaluation identified the causative agent to be multiple drug-resistant

Topics: Aged; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Eye Infections, Bacterial; Humans; Male; Pseudomonas aeruginosa; Pseudomonas Infections; Sarcoma, Kaposi; Treatment Outcome

Long-term use of nebulized or oral antibiotics is common in the treatment of cystic fibrosis and non-cystic fibrosis bronchiectasis. To date, however, few studies have focused on the use of nebulized antibiotics in COPD patients. The aims of this study are: to establish whether a combination of nebulized colistin plus continuous cyclic azithromycin in severe COPD patients with chronic bronchial infection due to. A retrospective cohort was created for the analysis of patients with severe COPD and chronic bronchial infection due to. We analyzed 32 severe COPD patients who received nebulized colistin for at least three months (median 17 months [IQR 7-24]). All patients but one received combination therapy with continuous cyclic azithromycin (median 24 months [IQR 11-30]). A significant reduction in the number of ECOPD from baseline of 38.3% at two years of follow-up was observed, with a clear decrease in. In patients with severe COPD and chronic bronchial infection due to

Topics: Administration, Inhalation; Aged; Aged, 80 and over; Anti-Bacterial Agents; Azithromycin; Bronchi; Colistin; Disease Progression; Drug Therapy, Combination; Female; Humans; Male; Nebulizers and Vaporizers; Pseudomonas Infections; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; Retrospective Studies; Severity of Illness Index; Sputum; Time Factors; Treatment Outcome

Pulmonary surfactant spreads rapidly over the airway epithelium, a property that could be harnessed to transport drugs into the lungs. For efficient drug delivery, an interaction between pulmonary surfactant and the drug to be administered is likely needed. On the other hand, the interaction should not compromise the activity of surfactant or the drug once delivered in vivo. The antibiotics gentamicin (an aminoglycoside) and polymyxin E represent drugs that could benefit from being delivered directly to the lung, thereby increasing local concentrations and reducing systemic side effects. Our aim was to study how the animal-derived surfactant poractant alfa (Curosurf. In vitro antimicrobial assays and a neonatal near-term rabbit model were used to evaluate the combinations of antibiotics and surfactant against Pseudomonas aeruginosa.. The bactericidal activity of polymyxin E, but not of gentamicin, against P. aeruginosa was partly reduced in vitro in the presence of poractant alfa. In contrast, in the rabbit model of P. aeruginosa pneumonia, polymyxin E administrated together with surfactant was superior in lowering the bacterial load in the lungs compared to polymyxin E alone, without affecting plethysmographically recorded lung compliance.. The results suggest that polymyxin E interacts with poractant alfa, which reduces the antibacterial effect in vitro. However, when polymyxin E mixed with surfactant is used in the in vivo pneumonia model, increased bactericidal effect was observed. This may be due to a more efficient spreading mediated by interactions between polymyxin E and surfactant. These results warrant further studies of surfactant preparations for drug delivery against lung infections.

Topics: Animals; Anti-Bacterial Agents; Biological Products; Colistin; Disease Models, Animal; Drug Carriers; Gentamicins; Phospholipids; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Pulmonary Surfactants; Rabbits

Topics: Aged; Anti-Bacterial Agents; Azabicyclo Compounds; Ceftazidime; Coinfection; Colistin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Enterococcus faecalis; Enterococcus faecium; Eye Neoplasms; Febrile Neutropenia; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Klebsiella Infections; Leukemia, Myeloid, Acute; Male; Melanoma; Meropenem; Middle Aged; Neoplasms, Second Primary; Pseudomonas Infections; Tigecycline

Serious infections such as endocarditis due to extremely drug-resistance gram-negative bacteria are an increasing challenge. Here, we present successful adjunctive use of cefiderocol for a patient with persistently bacteremic healthcare-associated native aortic valve endocarditis due to an extended-spectrum beta-lactamase-positive Pseudomonas aeruginosa susceptible in vitro only to colistin, following failure of conventional therapeutic options.

Topics: Aged; Anti-Bacterial Agents; Aortic Valve; beta-Lactamases; Cefiderocol; Cephalosporins; Colistin; Compassionate Use Trials; Drug Resistance, Multiple, Bacterial; Endocarditis, Bacterial; Female; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Treatment Outcome

Our objective was to evaluate the in vitro activity of ceftolozane-tazobactam against multidrug resistant (MDR) and extensively drug-resistant (XDR) non metallo-β-lactamase producing Pseudomonas aeruginosa clinical isolates at Hospital Universitario Miguel Servet (Zaragoza, Spain) from February 2016 to October 2017.. We evaluated the in vitro activity of ceftolozane-tazobactam and other antipseudomonal antibiotics against 12 MDR and 117 XDR non metallo-β-lactamase producing P. aeruginosa isolates. Ceftolozane-tazobactam minimal inhibitory concentrations (MICs) were determined by MIC gradient diffusion test strip.. Among the 129 MDR/XDR isolates included, 119 (92.2%) were susceptible to ceftolozane-tazobactam, and ten (7.8%) were resistant. MIC50 was 2 mg/L, and MIC90 4 mg/L. Ceftolozane-tazobactam was the second most active antibiotic after colistin, overtaking amikacin.. Ceftolozane-tazobactam is a valuable treatment option for MDR and XDR P. aeruginosa infections in our setting.

Topics: Adult; Aged; Aged, 80 and over; Amikacin; Anti-Bacterial Agents; beta-Lactamases; Cephalosporins; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Spain; Tazobactam

Pseudomonas aeruginosa isolates from Cystic fibrosis (CF) patients are growing slowly, and frequently rendering automated susceptibility testing unsuitable. Colistin is an important antibiotic for treatment of P. aeruginosa infections. Broth microdilution is the only EUCAST endorsed antimicrobial susceptibility test for colistin. The VIZION™ device aids in reading broth microdilution plates and allows safe data transfer to laboratory information systems. In this study, reproducibility between visual MIC readout and readout, employing the VIZION™ device was assessed in susceptibility testing of colistin and beta-lactam antibiotics in P. aeruginosa isolates from CF patients.. Fifty-six unique P. aeruginosa isolates were derived from respiratory secretions of CF patients. Susceptibility testing was performed using commercially available microdilution plates. MIC readout by VIZION™ was compared to visual readout aided by a mirror (reference test).. Pseudomonas aeruginosa isolates displayed significantly slower growth rates compared to quality control isolates. Colistin exact MIC agreement between VIZION™ and visual readout after 24 and 48 h incubation, respectively, was 82% and 95%, essential MIC agreement was 98% and 100%, categorical agreement was 98% and 98% and reliability (weighted kappa) was 0.95 (95% CI = 0.91-0.99) and 0.99 (95% CI = 0.97-1.00). For all five antibiotics, the total number of errors (using VIZION™, in comparison with visual readout) decreased from 15 (5%) to 10 (4%) after 24 and 48 h incubation, respectively.. VIZION™ readout reproducibly determines MIC values in comparison with visual readout after 24 h of incubation. Reproducibility between the VIZION™ and visual readout increases after prolonged incubation of 48 h.

Topics: Anti-Bacterial Agents; beta-Lactams; Colistin; Cystic Fibrosis; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Reproducibility of Results

Ceftolozane/tazobactam is a potential tool for infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa (P. aeruginosa), but its efficacy against some difficult-to-treat infections has not been well defined.. Using an in vitro pharmacodynamic biofilm model, this study evaluated the comparative efficacy of ceftolozane/tazobactam against MDR/extensively drug-resistant (XDR) P. aeruginosa strains, alone and in combination with colistin. Simulated regimens of ceftolozane/tazobactam (2 g/1 g every 8 h), meropenem (2 g every 8 h) and ceftazidime (2 g every 8 h), alone and in combination with colistin (continuous infusion) were evaluated against three colistin-susceptible and ceftazidime-resistant strains: MDR-HUB1, ceftolozane/tazobactam-susceptible and meropenem-susceptible; XDR-HUB2, ceftolozane/tazobactam-susceptible and meropenem-resistant; MDR-HUB3, ceftolozane/tazobactam-resistant and meropenem-susceptible. Antibiotic efficacy was evaluated by decreases in bacterial counts (Δlog CFU/mL) from biofilm-embedded bacteria over 54 h. Resistance emergence was screened.. Among monotherapies, ceftolozane/tazobactam had low killing but no resistance appeared, ceftazidime was ineffective, colistin was initially effective but regrowth and resistance occurred, and meropenem was bactericidal against carbapenem-susceptible strains. Ceftolozane/tazobactam plus colistin was the most effective combination against the meropenem-resistant XDR-HUB2 strain (Δlog CFU/mL 54-0 h = -4.42 vs. -3.54 for meropenem-colistin; P = 0.002), whereas this combination against MDR-HUB1 (-4.36) was less effective than meropenem-colistin (-6.25; P < 0.001). Ceftolozane/tazobactam plus colistin was ineffective against the ceftolozane/tazobactam-resistant strain; meropenem plus colistin was the most bactericidal therapy (-6.37; P < 0.001 vs. others). Combinations of active beta-lactams plus colistin prevented the emergence of colistin-resistant strains.. Combinations of colistin plus ceftolozane/tazobactam and meropenem were the most appropriate treatments for biofilm-related infections caused by XDR and MDR P. aeruginosa strains, respectively. These combinations could be considered as potential treatment options for these difficult to treat infections.

Topics: Anti-Bacterial Agents; beta-Lactamase Inhibitors; Biofilms; Cephalosporins; Colistin; Drug Resistance, Bacterial; Drug Therapy, Combination; Humans; Models, Theoretical; Pseudomonas aeruginosa; Pseudomonas Infections; Tazobactam

Topics: Administration, Inhalation; Administration, Intravenous; Adult; Anti-Bacterial Agents; Azithromycin; Colistin; Cystic Fibrosis; Disease Progression; Female; Forced Expiratory Volume; Humans; Logistic Models; Male; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Tobramycin; Young Adult

Chronic colonisation/infection by Pseudomonas aeruginosa of the bronchiectasis is related to a faster deterioration of lung function, an increase in the number of exacerbations and a higher morbidity and mortality. Nebulised colistin decreases bacteria load. Therefore, a reduction in the number and in the severity of exacerbations and a delay of pulmonary decline is expected. The main objective is to evaluate if the treatment with nebulised colistin, for at least 6 months reduces the number of admissions and visits to the emergency department.. Observational, retrospective and non-interventionist study carried out in an organizational structure with an integrated management. Patients with non-cystic fibrosis bronchiectasis colonised / infected by P. aeruginosa, older than 18 years, were selected. Patients must have received nebulized colistin during at least 6 months. Clinical, microbiological and therapeutic data from the patients were collected from the SERGAS computerized clinical history (IANUS® v.4.20.0503) and the electronic prescription, which were divided into two time periods: 1) 6 months pre-treatment and during the treatment and 2) 12 months pre-treatment and during the treatment, in those who completed 1 year of treatment.. Forty-four patients were included and of these, 29 (65.9%) had a follow-up of 12 months. The use of nebulized colistin decreased significantly the number of visits to the emergency (at 6 months), the frequency and duration of hospitalizations admissions (at 6 and 12 months), the antibiotic consumption (at 6 and 12 months) and the positive cultures. The treatment was well tolerated in almost all patients.. The treatment with nebulised colistin during 6 and 12 months of non-cystic fibrosis bronchiectasis, colonised/infected by P. aeruginosa, seems beneficial for the patient, from the clinical and quality of life point of view, and could reduce the economic cost of the process.

Topics: Administration, Inhalation; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bronchiectasis; Colistin; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Pseudomonas aeruginosa; Pseudomonas Infections; Quality of Life; Retrospective Studies; Treatment Outcome

Extensively drug-resistant (XDR) Pseudomonas aeruginosa (P. aeruginosa) and particularly P. aeruginosa high-risk clones, are of growing concern because treatment options are limited. For years, colistin monotherapy has been the only available treatment, but is well known that is not an optimal treatment. A combination of colistin with another antibiotic could be a possible therapeutic option.. This study aimed to investigate effective antibiotic combinations against 20 XDR P. aeruginosa isolates obtained in a Spanish multicentre study (2015).. Forty-five checkerboards with six antipseudomonal antibiotics (amikacin, aztreonam, ceftazidime, meropenem, colistin, and ceftolozane/tazobactam) were performed to determine whether combinations were synergic or additive by fractional inhibitory concentration indices. On average, 15 different regimens were evaluated in duplicate against the three most prevalent high-risk clones (ST175, ST235, ST111) by time-kill analyses over 24h. The combination showing synergism in the three high-risk clones was validated in all studied XDR isolates.. In time-kill curves, the untreated control failed, as did each study regimen when administered alone. Two combinations were synergistic in the three high-risk clones that were initially studied: amikacin plus ceftazidime and colistin plus meropenem, with the second being the most effective combination. The efficacy of colistin plus meropenem was then tested in all 20 isolates. A synergistic bacterial density reduction for the duration of the study occurred in 80% of the entire XDR collection.. These data suggest that colistin plus meropenem may be a useful combination for the treatment of infections due to XDR P. aeruginosa, including high-risk clones, which warrants evaluation in a clinical trial.

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; Meropenem; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Spain

To determine the influence of local spread of clonal strains and testing of follow-up isolates on categorical (CA) and essential agreement rates (EA) of common colistin (COL) drug susceptibility testing methods with the broth microdilution (BMD) reference method.. COL MICs were determined for 178 bacterial isolates (Enterobacteriaceae, n = 97; Pseudomonas aeruginosa, n = 81) collected within one year from 64 patients by BMD according to ISO standard 20776-1 (reference method), the SensiTest BMD panel (ST), agar dilution (AD), the VITEK 2 instrument, and gradient diffusion (GD) using antibiotic strips of two and Muller-Hinton agar plates of three manufacturers. CA and EA with BMD were calculated for all isolates and compared to the subset of 68 unique isolates.. CA ranges were 79.4% to 94.1% for the unique isolateq panel and 89.9% to 96.1% for all tested isolates. EA ranges were 64.7% to 86.8% and 67.4% to 91.0%, respectively. In both panels, EA for all GD assays was lower than 90%. Both lower and higher EA values ranging from-18.3% (MTS on BD agar) to + 6.3% (AD, Vitek 2) were observed in the full one-year sample. Acquisition of colistin resistance under therapy was observed for 3 patients.. i) Repeat testing and local spread of clonal strains can positively or negatively affect CA and EA, ii) CA is more robust towards local influences than EA, iii) EA of GD and AD methods for COL with the reference BMD method is insufficient.

Topics: Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Biofilms; Colistin; Cystic Fibrosis; Humans; Pseudomonas aeruginosa; Pseudomonas Infections

Pseudomonas aeruginosa is one of the most common pathogens in hospitals. Along with the advent of various drug resistance patterns, rising resistance to colistin, the last alternative against this bacterium, is reported as a major clinical concern all over the world. Initially, Pseudomonas aeruginosa strains were identified by diagnostic tests including phenotypic method, growth at 42°C, Gram staining, culture on Blood Agar, EMB Agar, and biochemical oxidase, and catalase tests. The strains were confirmed using Microgen kit. Then, the resistance pattern of the identified strains was evaluated by Antibiogram. The presence of PmrA and PmrB genes were investigated by PCR method.A total of 60 strains of Pseudomonas aeruginosa were isolated and identified using microscopic, macroscopic and microbiological methods. The lowest resistance was observed against chloramphenicol and colistin antibiotics. Most of the strains harbored the PmrA and PmrB genes. The results of this study indicated an increasing trend in the resistance of the bacterium against different antibiotics. Accordingly, it is necessary to establish an infection control and therapeutic strategy in preventing the spread of such as similar resistant organisms.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Colistin; Drug Resistance, Bacterial; Humans; Iran; Microbial Sensitivity Tests; Polymerase Chain Reaction; Pseudomonas aeruginosa; Pseudomonas Infections; Transcription Factors

The goal was to investigate the mechanisms of colistin resistance and heteroresistance in

Topics: Anti-Bacterial Agents; Bacterial Proteins; China; Colistin; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Gene Expression Regulation, Bacterial; Humans; Lipid A; Microbial Sensitivity Tests; Multilocus Sequence Typing; Mutation; Pseudomonas aeruginosa; Pseudomonas Infections; Repressor Proteins; Transcription Factors

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) infections represent a major therapeutic problem and combination therapy may be the chemotherapeutic option.. Bioluminescent CRPA was developed through sequential subcultures in subinhibitory concentrations of meropenem from an engineered strain of bioluminescent PA Xen5. Then CRPA was injected intraperitoneally to establish an intraperitoneal murine infection model. Treatments of colistin alone or combined with rifampicin or meropenem were started 1 h after infection. In vivo bioluminescence imaging was applied dynamically at 0 h, and 2 and 5 h after treatment. Ex vivo bacterial counts from liver, kidney, spleen, lung and blood samples were also determined 5 h after treatment.. In vivo imaging showed that both low- and high-dose colistin combined with rifampicin resulted in a significant decrease in bioluminescence signals compared with monotherapy of colistin or rifampicin alone, whereas colistin and meropenem combination therapy did not show a greater bactericidal effect compared with monotherapy. Ex vivo bacterial count results also confirmed that combination of both low- and high-dose colistin with rifampicin resulted in significantly reduced colony counts from five kinds of tissue samples. However, only combination of high-dose colistin + meropenem resulted in reduced colony counts merely in lung and blood samples.. Compared with single drugs, colistin and rifampicin combination therapy could exert synergistic effects, which might provide a better alternative when treating CRPA infections in clinical practice. Combination of colistin and meropenem should be considered with caution because it barely shows any synergism in the present in vivo model.

Topics: Animal Structures; Animals; Anti-Bacterial Agents; Bacterial Load; beta-Lactam Resistance; Colistin; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Female; Intraabdominal Infections; Luminescent Measurements; Meropenem; Mice, Inbred BALB C; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Staining and Labeling; Treatment Outcome

Lipid A aminoarabinosylation is invariably associated with colistin resistance in

Topics: Anti-Bacterial Agents; Bacterial Proteins; Colistin; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Humans; Lipid A; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

A new MALDI-TOF MS imipenem hydrolysis assay was developed to optimize detection of carbapenemase-producing strains of Pseudomonas aeruginosa. The method correctly discriminated carbapenemase producers (n=74) from non-producers (n=95) in 99.4% of cases, and successfully detected 100% GES-5 strains (n=5).

Topics: Bacterial Proteins; beta-Lactamases; Cell Membrane; Cell Membrane Permeability; Colistin; Humans; Imipenem; Pseudomonas aeruginosa; Pseudomonas Infections; Sensitivity and Specificity; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

The incidence of infections caused by multidrug-resistant Pseudomonas aeruginosa (MDR-Pa) has become a concern of increasing relevance nowadays. Ceftolozane/tazobactam (C/T) is a novel fifth-generation cephalosporin/β-lactamase inhibitor combination with activity against MDR-Pa.. The clinical records of all patients diagnosed from May 2016 to May 2017 with an infection due to a MDR-Pa treated with C/T were retrospectively reviewed.. A total of 23 patients with 24 episodes of infection due to MDR-Pa were included. The minimum inhibitory concentration (MIC) of C/T against MDR-Pa ranged from 0.75-8μg/mL. In 14 cases (58%) the use of C/T was off-label, including 8 respiratory tract infections (RTIs) and 6 skin and soft-tissue infections, whilst in 10 cases the use was for approved indications, including 7 urinary tract infections and 3 intra-abdominal infections. C/T was the first-line therapy in only three cases with a mean±standard deviation treatment duration of 9.3±4 days, and it was associated with another active drug (aminoglycoside or colistin) in 16 cases. The global clinical cure rate was 88% (21/24 episodes), and the 6-week mortality rate was 22% (5/23 patients) being higher in RTIs (37%). In these infections, three patients received 2/1g every 8h (q8h) and were cured without mortality, whilst three (60%) of five patients receiving 1/0.5g q8h died.. C/T had good clinical responses in different types of infection, including both FDA-accepted and off-label indications. The results support the use of higher doses in RTIs.

Topics: Aged; Anti-Bacterial Agents; Cephalosporins; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections; Retrospective Studies; Tazobactam; Urinary Tract Infections

The emergence of multi-drug resistant bacteria threatens to end the era of antibiotics. Drug resistant bacteria have evolved mechanisms to overcome antibiotics at therapeutic doses and further dose increases are not possible due to systemic toxicity. Here we present a pilot study of ex vivo lung perfusion (EVLP) with high dose antibiotic therapy followed by autotransplantation as a new therapy of last resort for otherwise incurable multidrug resistant lung infections. Severe Pseudomonas aeruginosa pneumonia was induced in the lower left lungs (LLL) of 18 Mini-Lewe pigs. Animals in the control group (n = 6) did not receive colistin. Animals in the conventional treatment group (n = 6) received intravenous application of 2 mg/kg body weight colistin daily. Animals in the EVLP group (n = 6) had their LLL explanted and perfused ex vivo with a perfusion solution containing 200 μg/ml colistin. After two hours of ex vivo treatment, autotransplantation of the LLL was performed. All animals were followed for 4 days following the initiation of treatment. In the control and conventional treatment groups, the infection-related mortality rate after five days was 66.7%. In the EVLP group, there was one infection-related mortality and one procedure-related mortality, for an overall mortality rate of 33.3%. Moreover, the clinical symptoms of infection were less severe in the EVLP group than the other groups. Ex vivo lung perfusion with very high dose antibiotics presents a new therapeutic option of last resort for otherwise incurable multidrug resistant pneumonia without toxic side effects on other organs.

Topics: Animals; Autografts; Colistin; Lung; Lung Transplantation; Perfusion; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Swine

The impact of multidrug-resistant organisms (MDROs), including non-fermentative bacilli (NFBs), is rising and underestimated, especially in intensive care units (ICUs). The growing prevalence of multidrug resistance (MDR) and extensive drug resistance (XDR) is challenging for clinicians, as the treatment options are limited.. The purpose of this study was to analyze the extent of the epidemiological problem of multidrugresistant, extensively drug-resistant and pandrug-resistant (PDR) non-fermentative bacilli isolated from pneumonia and bloodstream infections (BSIs) in patients hospitalized in southern Poland.. This study included 253 NFBs belonging to Acinetobacter sp. (ACI), Pseudomonas sp. (PAR), and Stenotrophomonas sp. (STM). The microorganisms were identified, and susceptibility testing was performed using a semi-automatic system. The different patterns of resistance were defined as MDR, XDR, or PDR strains. Epidemiological typing of A. baumannii from ICUs was performed by repetitive polymerase chain reaction (rep-PCR).. More than half of the strains (57.7%) were isolated within ICUs. ACI-strains came significantly more often from ICU wards. The highest prevalence of ACI and PAR was found in pneumonia, whereas STM dominated in BSIs. ACIs were more frequently resistant than other pathogens to all studied antibiotics except colistin (n = 76; 58.9%), and they belonged to the XDR category. DiversiLab demonstrated the presence of 2 dominant clones in the ACI group, both classified as European Clone 2 (EUII).. Our results indicate serious potential therapeutic problems related to high antibiotic resistance of ACI isolates. The stratification of drug resistance (MDR/XDR/PDR) may become an important tool for the assessment of public health epidemiology and microbiological hazards at the local, national, and international level. It allows clear presentation of the issues concerning the epidemiology of highly resistant bacilli, and the exchange of information between medical staff and local representatives of public health for the implementation of effective measures to reduce drug resistance.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Poland; Prevalence; Pseudomonas; Pseudomonas Infections; Stenotrophomonas

Topics: Acute Disease; Anti-Bacterial Agents; Child; Colistin; Drug Administration Schedule; Humans; Male; Metabolic Clearance Rate; Osteomyelitis; Practice Guidelines as Topic; Pseudomonas aeruginosa; Pseudomonas Infections

Pseudomonas is a group of medically important species that inhabit a wide range of niches, including hospital environments. Controversies have emerged about the possible link between improper use of disinfectants and the emergence of antibiotic resistance in bacteria. The aim of this study was to assess the effect of exposure of antibiotic-susceptible Pseudomonas isolates to sub-inhibitory concentrations of 2 disinfectants-didecyldimonium chloride and sodium hypochlorite-on their antibiotic susceptibility patterns.. This study involved 50 Pseudomonas isolates. The antibiotic susceptibility patterns of the isolates were assessed using broth microdilution method. The minimal inhibitory concentrations (MICs) of each antibiotic were compared before and after exposure to sub-inhibitory concentrations of didecyldimonium chloride and sodium hypochlorite.. After overnight incubation with sub-inhibitory concentrations of sodium hypochlorite, a statistically significant increase was observed in the MICs of colistin (P = .012), ceftazidime (P < .001), amikacin (P < .001), meropenem (P < .001), gentamicin (P < .001), piperacillin-tazobactam (P = .003), and ciprofloxacin (P = .004). In contrast, exposure to sub-inhibitory concentrations of didecyldimonium chloride showed a statistically significant increase in the MICs of amikacin (P < .001), gentamicin (P < .001), meropenem (P = .041), and ciprofloxacin (P = .008).. The use of suboptimal concentrations of sodium hypochlorite and didecyldimonium chloride can lead to the evolution of antibiotic-resistant Pseudomonas strains.

Topics: Amikacin; Anti-Infective Agents; Ceftazidime; Colistin; Disinfectants; Drug Resistance, Bacterial; Hospitals; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Quaternary Ammonium Compounds; Sodium Hypochlorite

A total of 18,656 Enterobacteriaceae and 4,175 Pseudomonas aeruginosa were consecutively collected from 85 US hospitals and tested for susceptibility by broth microdilution methods in a central monitoring laboratory (JMI Laboratories). The antimicrobial susceptibility and frequency of key resistance phenotypes were assessed and stratified by infection type as follows: bloodstream (BSI; 3,434 isolates; 15.0%), pneumonia (6,439; 28.2%), skin and skin structure (SSSI; 4,134; 18.1%), intra-abdominal (IAI; 951; 4.2%), and urinary tract (UTI; 7,873; 34.5%). Ceftazidime-avibactam was active against 99.9% to 100.0% of Enterobacteriaceae and 97.0% (pneumonia) to 99.4% (UTI) of P. aeruginosa isolates. Susceptibility rates were consistently lower for β-lactams, such as ceftazidime (82.3% vs. 87.1-90.8%), piperacillin-tazobactam (87.5% vs. 90.2-95.6%), and meropenem (96.8% vs. 98.4-99.4%) among Enterobacteriaceae from pneumonia compared to other infection types. Susceptibility to gentamicin was also generally lower among isolates from pneumonia, whereas susceptibility to levofloxacin and colistin were lowest among BSI and SSSI isolates, respectively. The occurrence of multidrug-resistance (MDR; 8.2% overall), extensively drug-resistance (XDR; 1.1% overall), and carbapenem-resistant Enterobacteriaceae (CRE; 1.3% overall) phenotypes were markedly higher among isolates from patients with pneumonia compared to other infection types. Among P. aeruginosa, susceptibility rates for ceftazidime, piperacillin-tazobactam, and gentamicin were lowest among isolates from pneumonia, whereas susceptibility to meropenem was similar among isolates from BSI, pneumonia, and IAI (77.3-77.9%), and susceptibility to levofloxacin was markedly lower among UTI isolates (67.1%). The frequencies of P. aeruginosa isolates with MDR and XDR phenotypes were highest among isolates from patients with pneumonia.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Ceftazidime; Colistin; Cross Infection; Drug Combinations; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections; Thienamycins; United States

Topics: Adult; beta-Lactamases; Burns; Colistin; Fatal Outcome; Humans; Male; Middle Aged; Multiple Organ Failure; Pseudomonas Infections; Pseudomonas mendocina; Skin Transplantation; Treatment Outcome

Colistin is a last-resort antibiotic against the critical-status pathogen Pseudomonas aeruginosa. There is still uncertainty regarding how to accurately measure colistin susceptibility in P. aeruginosa. Evaluation of antimicrobial susceptibility testing (AST) methods is largely hampered by the lack of resistant isolates and those around the susceptibility breakpoint. The aim of this study was to generate such strains in a morbidostat device for use in AST method evaluation.. A morbidostat device was used to cultivate susceptible clinical strains into isolates with a wide range of colistin MICs. Subsequently, five commercial AST methods were compared against the gold standard broth microdilution (BMD) method: MICRONAUT-S, SensiTest, Sensititre, Rapid Polymyxin Pseudomonas and Etest.. A total of 131 P. aeruginosa isolates were used for colistin susceptibility test evaluation (100 colistin susceptible and 31 colistin resistant). The 31 colistin-resistant isolates evolved resistance in the morbidostat to different MIC ranges (4-512 mg/L, 100% resistance generation efficacy). The categorical agreement (CA) rates for MICRONAUT-S, SensiTest and Rapid Polymyxin Pseudomonas were 94.7%, 93.9% and 92.4%, respectively. The Sensititre achieved the highest CA score (96.9%), whereas the Etests had the lowest CA score (84%). The very major discrepancy (VMD) rates for all tests were between 3.2% and 67.7%.. The morbidostat device can efficiently provide laboratories with colistin-resistant strains for test evaluation. Although CA rates were high for commercial AST methods except for Etests, none met the ≤1.5% CLSI limit for VMD rates. Performance was generally inferior when using isolates with low-level resistance.

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Clinical Laboratory Techniques; Colistin; Disk Diffusion Antimicrobial Tests; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Pseudomonas; Pseudomonas aeruginosa; Pseudomonas Infections

Biofilm-residing bacteria embedded in an extracellular matrix are protected from diverse physicochemical insults. In addition to the general recalcitrance of biofilm bacteria, high bacterial loads in biofilm-associated infections significantly diminish the efficacy of antimicrobials due to a low per-cell antibiotic concentration. Accordingly, present antimicrobial treatment protocols that have been established to serve the eradication of acute infections fail to clear biofilm-associated chronic infections. In the present study, we applied automated confocal microscopy on

Topics: Animals; Anti-Bacterial Agents; Biofilms; Colistin; Colonic Neoplasms; Colony Count, Microbial; Disease Models, Animal; Drug Administration Schedule; Drug Dosage Calculations; Drug Therapy, Combination; Female; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin; Treatment Outcome

The role of integrons in the transfer of antibiotic resistance is one of the important issues, therefore, this study is aimed to investigate antibiotic resistance pattern and prevalence of class 1 and 2 integrons in P. aeruginosa isolated.. Out of 72 confirmed P. aeruginosa isolates, 50% were from ICU patients. Antibacterial susceptibility pattern showed that isolates were most resistant to ceftazidime (76.4%) and colistin was the most effective antibiotic (100%) and molecular analysis of class I and II integrons showed 55.5% and 29.1% of isolates were positive, respectively and the proportions of MDR isolates were significantly higher among integron-positive isolates with 73.6% compared to negative isolates with 22.9%. Our results showed that there was a correlation among class 1 and 2 integrons with MDR P. aeruginosa isolates. According to the importance of integrons in acquisition and dissemination of antibiotics resistance genes, the performance of antibiotic surveillance programs and investigating the role of integrons is recommended to control the spreading of antibiotics resistance genes.

Topics: Anti-Infective Agents; Ceftazidime; Colistin; Drug Resistance, Multiple, Bacterial; Hospitalization; Humans; Inpatients; Integrons; Iran; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

The use of colistin for the treatment of multiresistant bacteria has led to the emergence of colistin-resistant strains of Gram-negative bacilli. Treatment of infections caused by these pan-drug-resistant bacteria is difficult owing to the paucity of effective antibiotics. We report two cases of ventilator-associated respiratory infection caused by pan-drug-resistant, colistin-resistant Pseudomonas aeruginosa that were successfully treated with ceftolozane-tazobactam.

Topics: Acute-Phase Proteins; Aged; Anti-Bacterial Agents; Cephalosporins; Colistin; Drug Resistance, Bacterial; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Penicillanic Acid; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; Tazobactam

In this study, the prevalence and characteristics of metallo-β-lactamase (MBL)-producing Pseudomonas aeruginosa isolates in South Korea were investigated. Among 215 P. aeruginosa isolates collected from eight hospitals, 77 (35.8%) and 72 (33.5%) were resistant to imipenem and meropenem, respectively. Of the 77 imipenem-resistant isolates, MBL genes were identified in 34 isolates (bla

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Genotype; Humans; Molecular Typing; Prevalence; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Republic of Korea

Intravenous colistimethate sodium (CMS) use in burn center patients is increasing due to the emergence of multidrug-resistant gram-negative bacteria. However, optimal dosing strategies and factors that may contribute to treatment failure are limited. The purpose of this study was to determine factors that may contribute to treatment failure in colistin-treated burn center patients.. This retrospective, observational study included burn center patients that received ≥48h of intravenous CMS between June 1, 2009 and June 30, 2014. Data was collected utilizing the institution's electronic medical record system. Statistical analysis included demographic, univariable, and multivariable analysis to determine factors that may predict clinical failure of burn center patients requiring intravenous CMS.. Eighty-one patients were included in this study, with 55 patients (68%) achieving clinical success. A total daily dose (TDD) of >5mg/kg ideal body weight (IBW) was associated with significantly less clinical failure (odds ratio=0.21; 95% CI, 0.05, 0.91). Additionally, clinical failure was significantly higher in patients with wounds as the primary source of infection, creatinine clearances of 91-120mL/min, and those receiving renal replacement therapy. No difference was observed in nephrotoxicity when comparing TDD >5mg/kg IBW and TDD ≤5mg/kg IBW.. Clinical success was significantly higher with larger intravenous CMS doses in burn center patients. Higher CMS doses were not found to be associated with increased nephrotoxicity within this patient group.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Burn Units; Burns; Colistin; Creatinine; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Outcome Assessment, Health Care; Pseudomonas aeruginosa; Pseudomonas Infections; Renal Replacement Therapy; Retrospective Studies; Treatment Failure

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Bacteriophages; Colistin; Humans; Male; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis

Topics: Aged; Amikacin; Anti-Bacterial Agents; Case-Control Studies; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Immunocompromised Host; Intensive Care Units; Male; Microbial Sensitivity Tests; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Ventilators, Mechanical

Colistin is a last-resort antibiotic commonly used against multidrug-resistant strains of

Topics: Anti-Bacterial Agents; Bacterial Proteins; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Mutation; Pseudomonas aeruginosa; Pseudomonas Infections

Antimicrobial peptides (AMPs) represent a promising therapeutic alternative for the treatment of antibiotic-resistant bacterial infections. The present study investigates the antimicrobial activity of new, rationally-designed derivatives of a short α-helical peptide, RR. From the peptides designed, RR4 and its D-enantiomer, D-RR4, emerged as the most potent analogues with a more than 32-fold improvement in antimicrobial activity observed against multidrug-resistant strains of Pseudomonas aeruginosa and Acinetobacter baumannii. Remarkably, D-RR4 demonstrated potent activity against colistin-resistant strains of P. aeruginosa (isolated from cystic fibrosis patients) indicating a potential therapeutic advantage of this peptide over several AMPs. In contrast to many natural AMPs, D-RR4 retained its activity under challenging physiological conditions (high salts, serum, and acidic pH). Furthermore, D-RR4 was more capable of disrupting P. aeruginosa and A. baumannii biofilms when compared to conventional antibiotics. Of note, D-RR4 was able to bind to lipopolysaccharide to reduce the endotoxin-induced proinflammatory cytokine response in macrophages. Finally, D-RR4 protected Caenorhabditis elegans from lethal infections of P. aeruginosa and A. baumannii and enhanced the activity of colistin in vivo against colistin-resistant P. aeruginosa.

Topics: Acinetobacter baumannii; Animals; Antimicrobial Cationic Peptides; Biofilms; Caenorhabditis elegans; Colistin; Cystic Fibrosis; Drug Design; Drug Resistance, Multiple, Bacterial; Drug Stability; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

To analyze whether the introduction of nebulized colistin in patients with chronic obstructive pulmonary disease (COPD) and infection with. Thirty six patients with COPD and infection with PA treated with nebulized colistin attending a day hospital during a 5-year (January 2010-December 2014) period were prospectively included. Repeated-measures. After the introduction of colistin, the number of admissions decreased from 2.0 to 0.9 per individual year (. Nebulized colistin seems associated with a strong decrease in the number and duration of hospitalizations due to exacerbation in patients with COPD and infection with PA. Clinical trials with a larger number of patients are needed in order to confirm these results.

Topics: Administration, Inhalation; Aged; Anti-Bacterial Agents; Colistin; Disease Progression; Female; Forced Expiratory Volume; Humans; Length of Stay; Lung; Male; Nebulizers and Vaporizers; Patient Admission; Pseudomonas Infections; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Severity of Illness Index; Time Factors; Treatment Outcome; Vital Capacity

Pseudomonas aeruginosa and Acinetobacter spp. are found to be associated with biofilm and metallo-β-lactamase production and are the common causes of serious infections mainly in hospitalized patients. So, the main aims of this study were to determine the rates of biofilm production and metallo beta-lactamase production (MBL) among the strains of Pseudomonas aeruginosa and Acinetobacter spp. isolated from hospitalized patients.. A total of 85 P. aeruginosa isolates and 50 Acinetobacter spp. isolates isolated from different clinical specimens from patients admitted to Shree Birendra Hospital, Kathmandu, Nepal from July 2013 to May 2014 were included in this study. The bacterial isolates were identified with the help of biochemical tests. Modified Kirby-Bauer disc diffusion technique was used for antimicrobial susceptibility testing. Combined disc diffusion technique was used for the detection of MBL production, while Congo red agar method and tube adherence method were used for detection of biofilm production.. Around 16.4% of P. aeruginosa isolates and 22% of the strains of Acinetobacter spp. were metallo β-lactamase producers. Out of 85 P. aeruginosa isolates, 23 (27.05%) were biofilm producers according to tube adherence test while, only 13 (15.29%) were biofilm producers as per Congo red agar method. Similarly, out of 50 Acinetobacter spp. 7 (14%) isolates were biofilm producers on the basis of tube adherence test, while only 5 (10%) were positive for biofilm production by Congo red agar method. Highest rates of susceptibility of P. aeruginosa as well as Acinetobacter spp. were seen toward colistin.. In our study, biofilm production and metallo beta-lactamase production were observed among Pseudomonas aeruginosa and Acinetobacter spp. However, no statistically significant association could be established between biofilm production and metallo beta-lactamase production.

Topics: Acinetobacter; Acinetobacter Infections; Adhesins, Bacterial; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Biofilms; Colistin; Disk Diffusion Antimicrobial Tests; Humans; Nepal; Pseudomonas aeruginosa; Pseudomonas Infections; Tertiary Care Centers

The potential use of liposomes for the pulmonary delivery of colistin has been hindered by their phospholipid membrane permeability resulting in a very low entrapment of colistin in the liposomes. To increase the entrapment capacity of colistin in liposomes, the anionic lipid sodium cholesteryl sulfate (Chol-SO4

Topics: Animals; Anti-Bacterial Agents; Cholesterol Esters; Colistin; Drug Carriers; Drug Compounding; Liposomes; Mice, Inbred Strains; Microscopy, Electron, Transmission; Particle Size; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Static Electricity; Surface Properties; Time Factors; Tissue Distribution

Reports of Pseudomonas aeruginosa with high antimicrobial resistance have steadily emerged, threatening the utility of a mainstay in antipseudomonal therapy. This study evaluated the antimicrobial activities of various combination therapies against P. aeruginosa with high antimicrobial resistance, including multidrug-resistant P. aeruginosa (MDRP) using an in vitro and in vivo study.. We evaluated 24 combination therapies, including colistin, aztreonam, meropenem, ceftazidime, ciprofloxacin, amikacin, rifampicin, arbekacin and piperacillin against 15 MDRP isolates detected at Aichi Medical University Hospital with the break-point checkerboard method. Based on the results of the in vitro study, we evaluated antimicrobial activity against highly antimicrobial-resistant P. aeruginosa with an in vivo murine thigh infection model.. The combination regimens including colistin and aztreonam showed higher antimicrobial activity against the 15 MDRP isolates. In the in vivo study, the high-dose colistin monotherapy (16 mg/kg every 12 h) achieved greater log10 CFU changes than the normal-dose colistin regimen (8 mg/kg every 12 h) against 5 P. aeruginosa isolates, including 2 MDRP isolates (p < 0.05). Aztreonam monotherapy (400 mg every 8 h) yielded bacterial densities similar to untreated control mice for the MDRP isolate evaluated. The combination therapy with a higher dose of colistin had superior antimicrobial activity against 5 P. aeruginosa with colistin (MIC 0.5 μg/ml) and aztreonam (MIC ≥128 μg/ml) than colistin monotherapy.. The data suggest that the combination treatment of colistin and aztreonam could be the most useful for treating highly resistant P. aeruginosa with a higher susceptibility to colistin, including MDRP infections.

Topics: Animals; Anti-Bacterial Agents; Aztreonam; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Mice; Mice, Inbred ICR; Pseudomonas aeruginosa; Pseudomonas Infections

This is the first report to test the loading dosage of colistin against Pseudomonas aeruginosa, including MDRP. Using in vivo murine thigh infection model, in the loading dosage regimen (Day 1:50 mg/kg q12 h, Day 2-3: 25 mg/kg q12 h) group, 5 to 6 log10 CFU/ml reduction compared with control were observed for both strains of P. aeruginosa with colistin MIC 0.5 and 1 μg/mL at 72 h. But, similar reduction was observed for the strains with colistin MIC 0.5 μg/mL only in normal dosage regimen (Day 1-3: 25 mg/kg q12 h) group. For P. aeruginosa with colistin MIC 1 μg/mL, colistin loading dosage regimens showed greater antimicrobial activity than that of without loading dosage group (p < 0.05). These data suggest that the colistin loading regimen would be one of the useful options for P. aeruginosa with antimicrobial resistance infection treatment.

Topics: Animals; Anti-Infective Agents; Colistin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Mice; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Thigh

Topics: Aged; Anti-Bacterial Agents; Azabicyclo Compounds; beta-Lactamase Inhibitors; Ceftazidime; Colistin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Lung Abscess; Male; Meningitis; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Radiography, Thoracic; Tomography, X-Ray Computed; Treatment Outcome

Colistin has a narrow therapeutic window with nephrotoxicity being the major dose-limiting adverse effect. Currently, the optimal doses and therapeutic plasma levels are unknown.. Prospective observational cohort study, including patients infected by colistin-susceptible P. aeruginosa treated with intravenous colistimethate sodium (CMS). Clinical data and colistin plasma levels at steady-state (C. In this series of patients with infections caused by XDR P. aeruginosa infections, C

Topics: Administration, Intravenous; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Biological Availability; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Kidney Diseases; Male; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Risk Factors; Treatment Outcome; Young Adult

Colistin methanesulfonate (CMS) is the only prodrug of colistin available for clinical use for the treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria. Owing to its slow and variable release, an alternative is urgently required to improve effectiveness. Herein we describe a PEGylated colistin prodrug whereby the PEG is attached via a cleavable linker (col-aaPEG) introducing an acetic acid terminated poly (ethylene glycol) methyl ether (aaPEG) onto the Thr residue of colistin. Due to the labile ester containing link, this prodrug is converted back into active colistin in vitro within 24h. Compared to CMS, it showed a similar or better antimicrobial performance against two MDR isolates of Pseudomonas aeruginosa and Acinetobacter baumannii through in vitro disk diffusion, broth dilution and time-kill studies. In a mouse infection model, col-aaPEG displayed acceptable bacterial killing against P. aeruginosa ATCC 27853 and no nephrotoxicity was found after systemic administration, suggesting it to be a potential alternative for CMS.

Topics: Acetic Acid; Acinetobacter baumannii; Animals; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Esters; Kidney; Mice; Microbial Sensitivity Tests; Polyethylene Glycols; Prodrugs; Pseudomonas aeruginosa; Pseudomonas Infections

Tolerance towards antibiotics of Pseudomonas aeruginosa biofilms is recognized as a major cause of therapeutic failure of chronic lung infection in cystic fibrosis (CF) patients. This lung infection is characterized by antibiotic-tolerant biofilms in mucus with zones of O2 depletion mainly due to polymorphonuclear leukocytic activity. In contrast to the main types of bactericidal antibiotics, it has not been possible to establish an association between the bactericidal effects of colistin and the production of detectable levels of OH ˙ on several strains of planktonic P. aeruginosa. Therefore, we propose that production of OH ˙ may not contribute significantly to the bactericidal activity of colistin on P. aeruginosa biofilm. Thus, we investigated the effect of colistin treatment on biofilm of wild-type PAO1, a catalase-deficient mutant (ΔkatA) and a colistin-resistant CF isolate cultured in microtiter plates in normoxic- or anoxic atmosphere with 1 mM nitrate. The killing of bacteria during colistin treatment was measured by CFU counts, and the OH⋅ formation was measured by 3(')-(p-hydroxylphenyl fluorescein) fluorescein (HPF) fluorescence. Validation of the assay was done by hydrogen peroxide treatment. OH⋅ formation was undetectable in aerobic PAO1 biofilms during 3 h of colistin treatment. Interestingly, we demonstrate increased susceptibility of P. aeruginosa biofilms towards colistin during anaerobic conditions. In fact, the maximum enhancement of killing by anaerobic conditions exceeded 2 logs using 4 mg L(-1) of colistin compared to killing at aerobic conditions.

Topics: Aerobiosis; Anaerobiosis; Anti-Bacterial Agents; Biofilms; Colistin; Colony Count, Microbial; Cystic Fibrosis; Fluoresceins; Fluorometry; Humans; Hydroxyl Radical; Microbial Viability; Pseudomonas aeruginosa; Pseudomonas Infections

Emergence of multi-drug resistant (MDR), extensively drug resistant (XDR), and pan-drug resistant (PDR) strains of Pseudomonas aeruginosa pose a significant therapeutic challenge. Managing XDR and PDR Pseudomonas aeruginosa keratitis would be extremely difficult due to paucity of safe and effective topical medications. We aim to describe the clinical features, risk factors, and outcome of XDR and PDR Pseudomonas aeruginosa keratitis.. A retrospective chart review of consecutive cases of XDR and PDR Pseudomonas aeruginosa keratitis were identified from Ocular Microbiology Department. XDR and PDR were defined based on criteria established by Centers for Disease Control and European Centre for Disease Prevention and Control. The following data was collected: age, gender, occupation, symptom duration, systemic and ocular risk factors, infiltrate characteristics, antimicrobial susceptibility, complications, surgical interventions, presenting, and final visual acuity and final outcome. Complete success was defined as resolution of the infiltrate with scar formation on medical treatment alone. Partial success was the resolution following tissue adhesive application. Failure was an inadequate response to medical therapy with progressive increase in infiltrate, corneal melting, and/or perforation necessitating one or more therapeutic penetrating keratoplasties or evisceration.. Fifteen eyes of 13 patients were included. Seven (53.8 %) were male with left eye involvement in nine (60 %) cases. Most common risk factors were bandage contact lens (6, 40 %), topical steroids (5, 33.3 %), previous therapeutic graft (4, 26.6 %), and ocular surface disorder (OSD) following Stevens Johnson Syndrome (SJS) (4, 26.6 %). Of 15 isolates, six (40 %) were sensitive only to imipenem, three (20 %) to colistin, two (13.3 %) to neomycin, one (6.7 %) each to imipenem and colistin, imipenem and ceftazidime, and azithromycin respectively. One isolate was resistant to all antibiotics. Complete success was noted in two (16.67 %), partial success in three (25 %) and failure in seven (58.33 %) eyes. Five (33.3 %) eyes healed on imipenem (three eyes), azithromycin (one eye), and imipenem and colistin (one eye).. XDR and PDR Pseudomonas aeruginosa keratitis are extremely difficult to treat. Globe salvage was possible in all cases; however, more than half required therapeutic grafts. Close monitoring of patients with known ocular and systemic factors is warranted.

Topics: Anti-Bacterial Agents; Ciprofloxacin; Colistin; Corneal Ulcer; Drug Resistance, Multiple, Bacterial; Eye Infections, Bacterial; Female; Humans; Imipenem; Keratoplasty, Penetrating; Male; Microbial Sensitivity Tests; Ofloxacin; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Risk Factors; Visual Acuity

Pseudomonas aeruginosa frequently infects the respiratory tract of cystic fibrosis (CF) patients. Multidrug-resistant phenotypes and high capacity to form stable biofilms are common. Recent studies have described the emergence of colistin-resistant isolates in CF patients treated with long-term inhaled colistin. The use of nanoparticles containing antimicrobials can contribute to overcome drug resistance mechanisms. The aim of this study was to explore antimicrobial activity of nanoencapsulated colistin (SLN-NLC) versus free colistin against P. aeruginosa clinical isolates from CF patients and to investigate their efficacy in biofilm eradication. Susceptibility of planktonic bacteria to antimicrobials was examined by using the broth microdilution method and growth curve assay. Minimal biofilm eradication concentration (MBEC) and biofilm prevention concentration (BPC) were determined to assess antimicrobial susceptibility of sessile bacteria. We used atomic force microscopy (AFM) to visualize treated and untreated biofilms and to determine surface roughness and other relevant parameters. Colistin nanoparticles had the same antimicrobial activity as free drug against planktonic bacteria. However, nanoencapsulated colistin was much more efficient in the eradication of biofilms than free colistin. Thus, these formulations have to be considered as a good alternative therapeutic option to treat P. aeruginosa infections.

Topics: Adult; Anti-Bacterial Agents; Biofilms; Child; Colistin; Cystic Fibrosis; Drug Delivery Systems; Drug Monitoring; Drug Resistance, Bacterial; Female; Humans; Male; Middle Aged; Nanoparticles; Outcome Assessment, Health Care; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory System; Respiratory Tract Infections; Spain

Biofilm growth is a universal survival strategy for bacteria, providing an effective and resilient approach for survival in an otherwise hostile environment. In the context of an infection, a biofilm provides resistance and tolerance to host immune defenses and antibiotics, allowing the biofilm population to survive and thrive under conditions that would destroy their planktonic counterparts. Therefore, the disruption of the biofilm is a key step in eradicating persistent bacterial infections, as seen in many types of chronic disease. In these studies, we used both in vitro minimum biofilm eradication concentration (MBEC) assays and an in vivo model of chronic biofilm infection to demonstrate the biofilm-disrupting effects of an alginate oligomer, OligoG CF-5/20. Biofilm infections were established in mice by tracheal instillation of a mucoid clinical isolate of Pseudomonas aeruginosa embedded in alginate polymer beads. The disruption of the biofilm by OligoG CF-5/20 was observed in a dose-dependent manner over 24 h, with up to a 2.5-log reduction in CFU in the infected mouse lungs. Furthermore, in vitro assays showed that 5% OligoG CF-5/20 significantly reduced the MBEC for colistin from 512 μg/ml to 4 μg/ml after 8 h. These findings support the potential for OligoG CF-5/20 as a biofilm disruption agent which may have clinical value in reducing the microbial burden in chronic biofilm infections.

Topics: Animals; Biofilms; Ciprofloxacin; Colistin; Female; Interleukin-1alpha; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

Multi-drug resistant Pseudomonas aeruginosa causes the type of acute lung injury that is strongly associated with bacteremia, sepsis, and mortality, especially under immunocompromised conditions. Although administration of immunoglobulin solution is an applicable immunotherapy in immunocompromised patients, efficacy of immunoglobulin administration against multi-drug resistant P. aeruginosa pneumonia has not been well evaluated. In this study, we investigated the effectiveness of prophylactic administration of immunoglobulin solution (IVIG) in comparison with that of other types of antimicrobial agents, such as anti-PcrV IgG, piperacillin/tazobactam, or colistin in an immunocompromised mouse model of P. aeruginosa pneumonia. Colistin was the most effective agent for preventing acute lung injury, bacteremia, cytokinemia, and sepsis. Among the four tested antimicrobial agents, after colistin, anti-PcrV IgG and IVIG were the most effective at protecting mice from mortality. Piperacillin/tazobactam did not prevent acute lung injury or bacteremia; rather, it worsened lung histology. The data suggest that using an agent for which a positive result in an in vitro susceptibility test has been obtained may not always prevent acute lung injury in a leukopenic host infected with P. aeruginosa. Clinicians should consider the possibility of discrepancies between in vitro and in vivo tests because the absence of in vitro bactericidal activity in an antimicrobial agent is not always a reliable predictor of its lack of ability to eradicate bacteria in vivo, even in immunocompromised hosts. Based on our findings, the potential protective effects of IVIG against the acute lung injury induced by P. aeruginosa should be reevaluated.

Topics: Animals; Anti-Bacterial Agents; Body Temperature; Colistin; Cytokines; Edema; Immunoglobulin G; Immunoglobulins, Intravenous; Leukopenia; Lung; Male; Mice; Mice, Inbred ICR; Penicillanic Acid; Peroxidase; Piperacillin; Pneumonia, Bacterial; Pre-Exposure Prophylaxis; Protective Agents; Pseudomonas aeruginosa; Pseudomonas Infections; Tazobactam

Drug resistance and tolerance greatly diminish the therapeutic potential of antibiotics against pathogens. Antibiotic tolerance by bacterial biofilms often leads to persistent infections, but its mechanisms are unclear. Here we use a proteomics approach, pulsed stable isotope labelling with amino acids (pulsed-SILAC), to quantify newly expressed proteins in colistin-tolerant subpopulations of Pseudomonas aeruginosa biofilms (colistin is a 'last-resort' antibiotic against multidrug-resistant Gram-negative pathogens). Migration is essential for the formation of colistin-tolerant biofilm subpopulations, with colistin-tolerant cells using type IV pili to migrate onto the top of the colistin-killed biofilm. The colistin-tolerant cells employ quorum sensing (QS) to initiate the formation of new colistin-tolerant subpopulations, highlighting multicellular behaviour in antibiotic tolerance development. The macrolide erythromycin, which has been previously shown to inhibit the motility and QS of P. aeruginosa, boosts biofilm eradication by colistin. Our work provides insights on the mechanisms underlying the formation of antibiotic-tolerant populations in bacterial biofilms and indicates research avenues for designing more efficient treatments against biofilm-associated infections.

Topics: Animals; Anti-Bacterial Agents; Biofilms; Colistin; Drug Resistance, Bacterial; Erythromycin; Humans; Mice; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Quorum Sensing; Staining and Labeling

For antibiotics, extensive animal PKPD studies are often performed to evaluate the PK/PD driver for subsequent use when recommending dosing regimens. The aim of this work was to evaluate a PKPD model, developed based on in vitro time-kill data for colistin, in predicting the relationships between PK/PD indices and the bacterial killing previously observed in mice.. An in silico PKPD model for Pseudomonas aeruginosa exposed to colistin was previously developed based on static in vitro time-kill data. The model was here applied to perform an in silico replication of an in vivo study where the effect of colistin on P. aeruginosa was studied in the thigh infection model. Concentration-time profiles of unbound colistin were predicted and used as input to drive the bacterial killing in the PKPD model. The predicted bacterial count at 24 h was related to each of the PK/PD indices and the results were compared with reported observations in vivo.. The model was found to adequately predict in vivo results from mice; both in terms of which PK/PD index best correlates to effect (fAUC/MIC) as well as the magnitude needed for a 2 log kill. The fAUC/MIC needed to achieve a 2 log reduction in bacterial counts after 24 h was here predicted to be 9 compared with 31 previously reported in vivo.. This study provides further support that PKPD models based on longitudinal data can be a useful tool to make drug development more efficient within the infectious diseases area.

Topics: Animals; Anti-Bacterial Agents; Colistin; Computer Simulation; Disease Models, Animal; Mice; Microbial Sensitivity Tests; Microbial Viability; Pseudomonas aeruginosa; Pseudomonas Infections; Time Factors

The purpose was to evaluate the clinical outcome in multi-drug resistant Pseudomonas aeruginosa (MDR-PA) bacterial keratitis and report the successful use of an alternative antibiotic, topical colistimethate in some of them. The medical records of 12 culture-proven MDR-PA keratitis patients, all exhibiting in vitro resistance by Kirby-Bauer disc diffusion method to ≥ three classes of routinely used topical antibiotics were reviewed. Eight patients were treated with 0.3% ciprofloxacin or ofloxacin, 1 patient with 5% imipenem/cilastatin and 3 patients with 1.6% colistimethate. The outcomes in 8 eyes treated with only fluoroquinolones were evisceration in 4 eyes, therapeutic corneal graft in 1 eye, phthisis bulbi in 1 eye, and no improvement in 2 eyes. The eye treated with imipenem/cilastin required a therapeutic corneal graft. All the three eyes treated with 1.6% colistimethate healed. Colistimethate may prove to be an effective alternative antibiotic in the treatment of MDR-PA keratitis.

Topics: Administration, Topical; Adolescent; Adult; Anti-Bacterial Agents; Child; Colistin; Corneal Ulcer; Drug Resistance, Multiple, Bacterial; Eye Infections, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Visual Acuity

A synthetic antimicrobial peptide was identified as a possible candidate for the development of a new antibacterial drug. The peptide, SET-M33L, showed a MIC90 below 1.5 μM and 3 μM for Pseudomonas aeruginosa and Klebsiella pneumoniae, respectively. In in vivo models of P. aeruginosa infections, the peptide and its pegylated form (SET-M33L-PEG) enabled a survival percentage of 60-80% in sepsis and lung infections when injected twice i.v. at 5 mg/Kg, and completely healed skin infections when administered topically. Plasma clearance showed different kinetics for SET-M33L and SET-M33L-PEG, the latter having greater persistence two hours after injection. Bio-distribution in organs did not show significant differences in uptake of the two peptides. Unlike colistin, SET-M33L did not select resistant mutants in bacterial cultures and also proved non genotoxic and to have much lower in vivo toxicity than antimicrobial peptides already used in clinical practice. The characterizations reported here are part of a preclinical development plan that should bring the molecule to clinical trial in the next few years.

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Colistin; Disease Models, Animal; Drug Resistance, Bacterial; Female; Humans; Klebsiella pneumoniae; Male; Mice; Mice, Inbred BALB C; Pneumonia; Polyethylene Glycols; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis; Skin

Broth microdilution antimicrobial susceptibility testing was performed for ceftazidime-avibactam and comparator agents against 7,062 clinical isolates of Pseudomonas aeruginosa collected from 2012 to 2014 in four geographic regions (Europe, Asia/South Pacific, Latin America, Middle East/Africa) as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance program. The majority of isolates were susceptible to ceftazidime-avibactam, with the proportions susceptible differing marginally across the four regions (MIC90, 8 to 16 μg/ml; 88.7 to 93.2% susceptible), in contrast to lower susceptibilities to the following comparator β-lactam agents: ceftazidime (MIC90, 32 to 64 μg/ml; 71.5 to 80.8% susceptible), meropenem (MIC90, >8 μg/ml; 64.9 to 77.4% susceptible), and piperacillin-tazobactam (MIC90, >128 μg/ml; 62.3 to 71.3% susceptible). Compared to the overall population, susceptibility to ceftazidime-avibactam of isolates that were nonsusceptible to ceftazidime (n = 1,627) was reduced to between 56.8% (Middle East/Africa; MIC90, 64 μg/ml) and 68.9% (Asia/South Pacific; MIC90, 128 μg/ml), but these percentages were higher than susceptibilities to other β-lactam agents (0 to 44% susceptible, depending on region and agent; meropenem MIC90, >8 μg/ml; 26.5 to 43.9% susceptible). For this subset of isolates, susceptibilities to amikacin (MIC90, >32 μg/ml; 53.2 to 80.0% susceptible) and colistin (MIC90, 1 μg/ml; 98.5 to 99.5% susceptible) were comparable to or higher than that of ceftazidime-avibactam. A similar observation was made with isolates that were nonsusceptible to meropenem (n = 1,926), with susceptibility to ceftazidime-avibactam between 67.8% (Middle East/Africa; MIC90, 64 μg/ml) and 74.2% (Europe; MIC90, 32 μg/ml) but again with reduced susceptibility to comparators except for amikacin (MIC90, >32 μg/ml; 56.8 to 78.7% susceptible) and colistin (MIC90, 1 μg/ml; 98.9 to 99.3% susceptible). Of the 8% of isolates not susceptible to ceftazidime-avibactam, the nonsusceptibility of half could be explained by their possession of genes encoding metallo-β-lactamases. The data reported here are consistent with results from other country-specific and regional surveillance studies and show that ceftazidime-avibactam demonstrates in vitro activity against globally collected clinical isolates of P. aeruginosa, including isolates that are resistant to ceftazidime and meropenem.

Topics: Africa; Amikacin; Anti-Bacterial Agents; Asia; Azabicyclo Compounds; beta-Lactams; Ceftazidime; Colistin; Drug Combinations; Humans; Latin America; Meropenem; Microbial Sensitivity Tests; Middle East; Pseudomonas aeruginosa; Pseudomonas Infections; Thienamycins

Multidrug-resistant Pseudomonas aeruginosa has emerged as one of the most important healthcare-associated pathogens. Colistin is regarded as the last-resort antibiotic for multidrug-resistant Gram-negative bacteria, but is associated with high rates of acute kidney injury. The aim of this in vitro study is to search for an alternative treatment to colistin for multidrug-resistant P. aeruginosa infections.. Multidrug and carbapenem-resistant P. aeruginosa isolates were collected between January 2009 and December 2012 at MacKay Memorial Hospital. Minimal inhibitory concentrations (MICs) were determined for various antibiotic combinations. Carbapenemase-producing genes including bla VIM, other β-lactamase genes and porin mutations were screened by PCR and sequencing. The efficacy of carbapenems (imipenem, meropenem, doripenem) with or without rifampicin was correlated with the type of porin mutation (frameshift mutation, premature stop codon mutation) in multidrug-resistant P. aeruginosa isolates without carbapenemase-producing genes.. Of the 71 multidrug-resistant clinical P. aeruginosa isolates, only six harboured the bla VIM gene. Imipenem, meropenem and doripenem were significantly more effective (reduced fold-change of MICs) when combined with rifampicin in bla VIM-negative isolates, especially in isolates with porin frameshift mutation.. Imipenem + rifampicin combination has a low MIC against multidrug-resistant P. aeruginosa, especially in isolates with porin frameshift mutation. The imipenem + rifampicin combination may provide an alternative treatment to colistin for multidrug -resistant P. aeruginosa infections, especially for patients with renal insufficiency.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Doripenem; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Imipenem; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Porins; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Taiwan; Thienamycins

In cystic fibrosis (CF), chronic microbial lung infections are difficult to treat and cause morbidity and increased mortality.. In a multicentre, open-label, exploratory, non-interventional study, inhaled tobramycin (300 mg twice daily) and colistin (1 million I.U. twice daily) were sequentially combined with the aim to investigate the effect on 41 CF patients with chronic P. aeruginosa infections for six months (mean age 24 ± 10.8y).. Six patients had adverse events that were assessed as being related to treatment. Mucus production and coughing both decreased in 39%, whereas FEV1 absolute and relative to baseline increased by 4.9% and 9.1%, respectively (p = 0.004) in 29 patients, who were definitely treated sequentially. Efficacy of the therapy was rated 'excellent' or 'good' by the physicians in 80.5% of the patients.. The results indicate that treatment with inhaled antibiotics, sequentially combined, was very well tolerated by most patients and may have a beneficial effect, even if transitory on lung function and respiratory symptoms.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Bacterial Agents; Chronic Disease; Colistin; Cystic Fibrosis; Drug Administration Schedule; Drug Combinations; Female; Forced Expiratory Volume; Humans; Male; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin; Treatment Outcome

In the last decades, the encapsulation of antibiotics into nanoparticulate carriers has gained increasing attention for the treatment of infectious diseases. Sodium colistimethate-loaded solid lipid nanoparticles (Colist-SLNs) and nanostructured lipid carriers (Colist-NLCs) were designed aiming to treat the pulmonary infection associated to cystic fibrosis patients. The nanoparticles were freeze-dried using trehalose as cryoprotectant. The stability of both nanoparticles was analysed over one year according to the International Conference of Harmonisation (ICH) guidelines by determining the minimum inhibitory concentration (MIC) against clinically isolated Pseudomonas aeruginosa strains and by studying their physico-chemical characteristics. The results showed that Colist-SLNs lost their antimicrobial activity at the third month; on the contrary, the antibacterial activity of Colist-NLCs was maintained throughout the study within an adequate range (MIC ≤16 μg/mL). In addition, Colist-NLCs exhibited suitable physico-chemical properties at 5 °C and 25 °C/60% relative humidity over one year. Altogether, Colist-NLCs proved to have better stability than Colist-SLNs.

Topics: Colistin; Cystic Fibrosis; Drug Stability; Humans; Lipids; Nanoparticles; Pseudomonas aeruginosa; Pseudomonas Infections

In the present study, we challenged the concept that levofloxacin should not be used for the management of ventilator-associated pneumonia (VAP) when minimum inhibitory concentrations (MICs) exceed 2 μg/ml. Multidrug-resistant (MDR) and genetically distinct isolates of Pseudomonas aeruginosa (n = 49) and Acinetobacter baumannii (n = 29) from patients with VAP were exposed over time to levofloxacin, imipenem, colistin and their combinations. Synergy between levofloxacin and imipenem was found in 55.3 % and between levofloxacin and colistin in 90.9 % of isolates of P. aeruginosa within the first 4 h of growth. Synergy with imipenem but not with colistin was dependent of the MIC. Synergy between levofloxacin and imipenem was found in 58.6 % of isolates of A. baumannii after 24 h of growth. Considerable synergy was found between levofloxacin and colistin, reaching 84.8 % of isolates of A.baumannii after 6 h of growth. Synergy was independent from the MIC. These results create hopes that levofloxacin can be used as combination therapy for infections by MDR bacteria.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; Imipenem; Levofloxacin; Microbial Sensitivity Tests; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; Time Factors

Topics: Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Pseudomonas aeruginosa; Pseudomonas Infections

Antibiotic combinations are often used for treating Pseudomonas aeruginosa infections but their efficacy toward intracellular bacteria has not been investigated so far. We have studied combinations of representatives of the main antipseudomonal classes (ciprofloxacin, meropenem, tobramycin, and colistin) against intracellular P. aeruginosa in a model of THP-1 monocytes in comparison with bacteria growing in broth, using the reference strain PAO1 and two clinical isolates (resistant to ciprofloxacin and meropenem, respectively). Interaction between drugs was assessed by checkerboard titration (extracellular model only), by kill curves, and by using the fractional maximal effect (FME) method, which allows studying the effects of combinations when dose-effect relationships are not linear. For drugs used alone, simple sigmoidal functions could be fitted to all concentration-effect relationships (extracellular and intracellular bacteria), with static concentrations close to (ciprofloxacin, colistin, and meropenem) or slightly higher than (tobramycin) the MIC and with maximal efficacy reaching the limit of detection in broth but only a 1 to 1.5 (colistin, meropenem, and tobramycin) to 2 to 3 (ciprofloxacin) log10 CFU decrease intracellularly. Extracellularly, all combinations proved additive by checkerboard titration but synergistic using the FME method and more bactericidal in kill curve assays. Intracellularly, all combinations proved additive only based on both FME and kill curve assays. Thus, although combinations appeared to modestly improve antibiotic activity against intracellular P. aeruginosa, they do not allow eradication of these persistent forms of infections. Combinations including ciprofloxacin were the most active (even against the ciprofloxacin-resistant strain), which is probably related to the fact this drug was the most effective alone intracellularly.

Topics: Anti-Bacterial Agents; Cell Line; Ciprofloxacin; Colistin; Drug Resistance, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; Meropenem; Microbial Sensitivity Tests; Monocytes; Pseudomonas aeruginosa; Pseudomonas Infections; Thienamycins; Tobramycin

Colistin has been increasingly used for the treatment of respiratory infections caused by Gram-negative bacteria. Unfortunately parenteral administration of colistin can cause severe adverse effects. This study aimed to develop an inhaled combination dry powder formulation of colistin and rifapentine for the treatment of respiratory infections. The combination formulation was produced by spray-drying rifapentine particles suspended in an aqueous colistin solution. The combination dry powder had enhanced antimicrobial activities against planktonic cells and biofilm cultures of Pseudomonas aeruginosa, with both minimum inhibitory concentration (MIC) and minimum biofilm inhibitory concentration (MBIC) values (2 and 4 mg/L, respectively) being half that of pure colistin (MIC 4 mg/L and MBIC 8 mg/L) and 1/16th that of pure rifapentine (MIC 32 mg/L and MBIC 64 mg/L). High aerosol performance, as measured via an Aerolizer device, was observed with emitted doses>89% and fine particle fraction (FPF) total>76%. The proportion of submicron particles of rifapentine particles was minimized by the attachment of colistin, which increased the overall particle mass and aerodynamic size distribution. Using the spray-drying method described here, stable particles of amorphous colistin and crystalline rifapentine were distributed homogeneously in each stage of the impinger. Unlike the colistin alone formulation, no deterioration in aerosol performance was found for the combination powder when exposed to a high relative humidity of 75%. In our previous study, surface coating by rifampicin contributed to the moisture protection of colistin. Here, a novel approach with a new mechanism was proposed whereby moisture protection was attributed to the carrier effect of elongated crystalline rifapentine particles, which minimized contact between hygroscopic colistin particles. This inhaled combination antibiotic formulation with enhanced aerosol dispersion efficiency and in vitro efficacy could become a superior treatment for respiratory infections.

Topics: Administration, Inhalation; Anti-Infective Agents; Biofilms; Colistin; Drug Combinations; Drug Synergism; Dry Powder Inhalers; Humans; Microbial Sensitivity Tests; Nanoparticles; Nasal Sprays; Particle Size; Plankton; Powders; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections; Rifampin

In 2010, aztreonam for inhalation solution joined aminoglycosides and colistimethate as a new cystic fibrosis (CF) chronic inhaled antimicrobial therapy. We studied how the introduction of this new inhaled antibiotic class changed the management of US CF patients.. The use of inhaled aminoglycosides, colistimethate, and aztreonam among patients followed in the CF Foundation Patient Registry was analyzed by age group, lung disease stage, and microbiologic status both annually, and at individual visits between 2009 and 2012.. The overall prevalence of inhaled antibiotic use did not change during the period, but the prevalence of annual and any visit treatment with >1 inhaled antibiotic class more than doubled. Adults, those with advanced lung disease, and those with >1 Pseudomonas aeruginosa respiratory culture were more likely to receive >1 antibiotic class.. Inhaled antibiotic management of US CF patients has dramatically changed in association with the introduction of a third inhaled antibiotic class.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosols; Anti-Bacterial Agents; Aztreonam; Child; Colistin; Cystic Fibrosis; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Prevalence; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Tobramycin; Treatment Outcome; Young Adult

Pseudomonas aeruginosa is one of the leading causes of nosocomial infection. The present study tested the in vitro efficacy of ceftazidime or imipenem combined with amikacin, levofloxacin and colistin in P.aeruginosa isolates.. P.aeruginosa strains, isolated from clinical samples, were assessed for antibiotic susceptibility using the disc diffusion method. Antibiotic combination tests were performed using minimum inhibitory concentration (MIC) test strips and the sum of the Fractional Inhibitory Concentration (ΣFIC) index was used to assess synergy.. Out of 60 isolated P.aeruginosa strains, 100% were susceptible to colistin and 26.7% (16 strains) were multidrug resistant. MIC50 and MIC90 values were 2 and 32 µg/ml for imipenem; 1.5 and 24 µg/ml for ceftazidime; 3 and 8 µg/ml for amikacin; 0.38 and 32 µg/ml for levofloxacin; 1 and 1.5 µg/ml for colistin, respectively. Antagonism was not found in any of the antibiotic combinations tested. The amikacin-ceftazidime combination was found to have a synergistic effect in 15% of the strains, but no synergistic effect was detected for other combinations.. In Pseudomonas infection, alternative treatment options using different antibiotic combinations should be tested in vitro and findings should be confirmed by clinical studies.

Topics: Amikacin; Anti-Bacterial Agents; Ceftazidime; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; Imipenem; Levofloxacin; Microbial Sensitivity Tests; Microbial Viability; Pseudomonas aeruginosa; Pseudomonas Infections

In the management of multidrug-resistant infections in critically ill patients with multiorgan dysfunction, consideration must be given to the pharmacokinetics and pharmacodynamics of an antimicrobial agent to optimize dosing. We describe a 25-year-old woman who was undergoing thrice-weekly hemodialysis and developed multidrug-resistant Pseudomonas aeruginosa bacteremia secondary to infected left and right ventricular assist devices. After multiple courses of antibiotics, her blood cultures revealed that the infecting organism was becoming progressively more resistant to antibiotic options. Cefepime 2 g administered over 3 hours/day (in combination with colistimethate) provided adequate drug levels for multidrug-resistant, cefepime-intermediate P. aeruginosa bacteremia in this patient. We present the clinical case of this patient, followed by a discussion of possible therapeutic approaches to be considered, including illustration of the principles of using extended-infusion antimicrobial regimens, and present the patient's resulting clinical course.

Topics: Adult; Anti-Bacterial Agents; Cefepime; Cephalosporins; Colistin; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Heart-Assist Devices; Humans; Infusions, Intravenous; Metabolic Clearance Rate; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Renal Dialysis; Time Factors; Treatment Outcome

Pseudomonas and Burkholderia pose a significant health threat to people with chronic respiratory conditions; the resistance inherent in these bacteria indicates that new antimicrobial strategies are required. Susceptibility of 56 strains of P. aeruginosa and 55 strains of Burkholderia to manuka honey, tobramycin and colistin using microbroth dilution and E strip was determined. MICs of antibiotics with honey were determined to search for synergistic combinations against two representative strains of each genus. All strains exhibited susceptibility to honey ≤10 % (w/v); mean susceptibility of Burkholderia (4.6 % w/v) was lower than P. aeruginosa (7.3 % w/v). Synergistic or additive combinations were found with all four strains tested. Combinations of manuka honey with antibiotics can be used to lower the MIC need to successfully inhibit both P. aeruginosa and B. cepacia. The use of honey as a combination agent may be possible for the management of P. aeruginosa and B. cepacia.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Burkholderia; Burkholderia Infections; Colistin; Cystic Fibrosis; Honey; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin

The shortage of effective antibiotics against carbapenem-resistant Pseudomonas aeruginosa (CRPA) poses a public health threat. Combination treatment may represent a good choice for treating infections caused by CRPA. The aim of this study was to evaluate the in vitro efficacy of fosfomycin in combination with colistin against clinical CRPA isolates. Eighty-seven isolates were collected from three hospitals in China. The checkerboard method and time-kill assay were used to assess the interactions between fosfomycin and colistin. The fosfomycin/colistin combination displayed synergistic and partial synergistic activity against 21.84% and 27.59% of the isolates, respectively. Antagonism was not observed. In combination, the colistin MIC values were ⩽0.5 μg ml(-1) for 91.95% of the isolates. This result differed significantly from those obtained using a single agent treatment (The colistin MIC values were ⩽0.5 μg ml(-1) for only 25.29% of the isolates). In addition, the time-kill assay demonstrated that the fosfomycin/colistin combination treatment exerted bactericidal effects against five isolates and that the regrowth observed after colistin monotherapy was prevented. In summary, the combination of fosfomycin and colistin demonstrated synergistic activity against the CRPA isolates tested in this study. Furthermore, fosfomycin may potentially widen the therapeutic window of colistin, suggesting that this combination could be applied clinically to control infections caused by CRPA.

Topics: Anti-Bacterial Agents; Carbapenems; China; Colistin; Drug Resistance, Bacterial; Drug Synergism; Fosfomycin; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

The prevalence of hospital strains of P. aeruginosa, A. baumannii and K. pneumoniae characterizing by multiple drug resistance to overwhelming majority of antibiotics anew evoked an increased interest to colistin. However, until now there is not enough information concerning pharmacokinetics of colistin to optimize dosage of this pharmaceutical. The study was carried out to analyze pharmacokinetics of both colistin and sodium colistimitate in children with chemically induced neutropenia. To quantitatively detect colistin in blood serum the technique of highly effective fluid chromatography with mass spectrometry was applied. The concentration of colistin was detected in 21 children with chemically induced neutropenia (13 patients with septicemia, 8 children of control group) after intravenous injection of sodium colistimitate. The significant variability of pharmacokinetic parameters of colistin was established both in patients with septicemia and in control group. The technique of highly effective fluid chromatography with mass spectrometry can be applied for therapeutic medicinal monitoring and optimization regimen of dosage.

Topics: Adolescent; Child; Child, Preschool; Colistin; Drug Resistance, Microbial; Female; Humans; Klebsiella pneumoniae; Male; Neutropenia; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis

Topics: Adolescent; Adult; Analysis of Variance; Anti-Bacterial Agents; Chi-Square Distribution; Ciprofloxacin; Cohort Studies; Colistin; Confidence Intervals; Culture Media, Conditioned; Cystic Fibrosis; Female; Follow-Up Studies; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Risk Assessment; Severity of Illness Index; Treatment Outcome; Young Adult

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Colistin; Critical Illness; Drug Resistance, Multiple; Female; Humans; Kidney; Male; Pseudomonas Infections

The impact of physicochemical conditions observed in cystic fibrosis (CF) lung on colistin activity against both planktonic and biofilm P. aeruginosa cells was evaluated. MIC, minimum bactericidal concentration (MBC), and minimum biofilm eradication concentration (MBEC) values were assessed against 12 CF strains both under "CF-like" (anaerobiosis, pH6.4) and "standard" (aerobiosis, pH7.4) conditions. The activity of colistin was significantly higher under "CF-like" conditions compared to "standard" ones, both against planktonic (MIC90: 1 and 4 μg/mL, respectively) and biofilm (MBEC90: 512 and 1.024 μg/mL, respectively) cells, as confirmed by scanning electron microscopy. Improved activity was not related to biofilm matrix amount. It may be necessary to adequately "rethink" the protocols used for in vitro assessment of colistin activity, by considering physicochemical and microbiological features in the CF lung at the site of infection. This could provide a more favorable therapeutic index, rationale for administration of lower doses, probably resulting in reduced toxicity and emergence of resistant clones.

Topics: Anaerobiosis; Anti-Bacterial Agents; Biofilms; Colistin; Culture Media; Cystic Fibrosis; Humans; Hydrogen-Ion Concentration; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Colistin; Critical Illness; Drug Resistance, Multiple; Female; Humans; Kidney; Male; Pseudomonas Infections

Patients suffering from cystic fibrosis (CF) are commonly affected by chronic Pseudomonas aeruginosa biofilm infections. This is the main cause for the high disease severity. In this study, we demonstrate that P. aeruginosa is able to efficiently colonize murine solid tumors after intravenous injection and to form biofilms in this tissue. Biofilm formation was evident by electron microscopy. Such structures could not be observed with transposon mutants, which were defective in biofilm formation. Comparative transcriptional profiling of P. aeruginosa indicated physiological similarity of the bacteria in the murine tumor model and the CF lung. The efficacy of currently available antibiotics for treatment of P. aeruginosa-infected CF lungs, such as ciprofloxacin, colistin, and tobramycin, could be tested in the tumor model. We found that clinically recommended doses of these antibiotics were unable to eliminate wild-type P. aeruginosa PA14 while being effective against biofilm-defective mutants. However, colistin-tobramycin combination therapy significantly reduced the number of P. aeruginosa PA14 cells in tumors at lower concentrations. Hence, we present a versatile experimental system that is providing a platform to test approved and newly developed antibiofilm compounds.

Topics: Animals; Anti-Infective Agents; Biofilms; Cell Line, Tumor; Colistin; Cystic Fibrosis; Disease Models, Animal; Female; Lung Diseases; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin

A 56-year-old woman with systemic lupus erythematosus had bacteremia due to multidrug-resistant Pseudomonas aeruginosa (MDRP). She was initially treated with imipenem-cilastatin, tobramycin, and aztreonam; however, MDRP was still detected intermittently in her plasma. Multidrug-susceptibility tests demonstrated that MDRP was susceptible only to colistin. Therefore, in addition to these antibiotics, the administration of intravenous colistin methanesulfonate, a prodrug formula of colistin, was started at a daily dose of 2.5 mg/kg (as colistin base activity). The initial dose setting was based on the patient's renal function (baseline creatinine clearance=32.7 mL/min). After initiating colistin, the patient's C-reactive protein levels gradually decreased. Blood cultures showed no evidence of MDRP on days 8, 14, and 22 after colistin initiation. However, the patient's renal function went from bad to worse owing to septic shock induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. A few days later, the trough plasma levels of colistin were 7.88 mg/L, which appeared to be higher than expected. After decreasing the colistin dose, the patient's renal function gradually improved. On the final day of colistin treatment, the plasma levels decreased to 0.60 mg/L. MDRP could not be detected in blood culture after colistin treatment. Therefore, we successfully treated a case of bloodstream infection due to MDRP by therapeutic drug monitoring (TDM) of colistin. It is suggested that the monitoring of blood colistin levels by liquid chromatography-tandem mass spectrometry can contribute to safer, more effective antimicrobial therapy of MDRP because TDM facilitates quick decisions on dose adjustments.

Topics: Anti-Bacterial Agents; Bacteremia; Colistin; Drug Monitoring; Drug Resistance, Multiple, Bacterial; Female; Humans; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Treatment Outcome

The revival of polymyxin antibiotics with the advent of multidrug resistant gram-negative bacteria in the recent decade has led to renewed interest in toxicity of this indispensable drug. We report a postoperative case of burst abdomen where colistin was started in view of Pseudomonas organism sensitive to colistin. Subsequently, the patient went into respiratory depression and encephalopathy after starting the treatment. She recovered promptly after stopping the drug.

Topics: Anti-Bacterial Agents; Brain Diseases; Colistin; Female; Humans; Neurotoxicity Syndromes; Pseudomonas; Pseudomonas Infections; Respiratory Insufficiency; Young Adult

We report the emergence and analysis of a cluster of concurrent infections/colonisations with colistin-resistant Klebsiella pneumoniae and OXA-23 carbapenemase-producing Acinetobacter baumannii in patients who had undergone cardiac surgery. We describe the emergence of colistin-resistant K. pneumoniae harbouring blaCTX-M-15, blaSHV-11, blaOXA-1, blaTEM-1 beta-lactamases and aac(6')-Ib-cr fluoroquinolone resistance. Colistin-resistant K. pneumoniae infections (pneumonia, wound infection, urinary tract infections and bacteraemia) occurred in critically ill patients previously treated with colistin for post-surgery infections with carbapenem-resistant Pseudomonas aeruginosa and/or A. baumannii. Although the cause of death could not be directly attributed to a single pathogen, three patients co-infected/colonised with K. pneumoniae, P. aeruginosa and/or A. baumannii died, whilst a fourth patient who had a mono-microbial infection with colistin-resistant K. pneumoniae only survived. The use of mobile intubation equipment in patients that shared the same ward, the clustering of cases over a short period of time, as well as the pulsed-field gel electrophoresis (PFGE) data all suggest cross-contamination between patients, either through equipment or by staff contact transmission. This report presents the 'worst-case scenario' where concurrent infection/colonisation with pathogens exhibiting resistance to different types of last-resort antimicrobials occurred in some of the most debilitated intensive care unit (ICU) patients.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cardiology Service, Hospital; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Romania

This study investigated the exposure-response relationships between unbound colistin in plasma and antibacterial activity in mouse thigh and lung infections.. Dose fractionation studies (subcutaneous colistin sulphate at 1.25-160 mg/kg/day) were conducted in neutropenic mice in which infection (three strains of Pseudomonas aeruginosa and three strains of Acinetobacter baumannii) had been produced by intramuscular thigh injection or aerosol lung delivery. Bacterial burden was measured at 24 h after initiation of colistin treatment. Plasma protein binding was measured by rapid equilibrium dialysis and ultracentrifugation. The inhibitory sigmoid dose-effect model and non-linear least squares regression were employed to determine the relationship between exposure to unbound colistin and efficacy.. Plasma binding of colistin was constant over the concentration range ∼2-50 mg/L. The average ± SD percentage bound for all concentrations was 92.9 ± 3.3% by ultracentrifugation and 90.4 ± 1.1% by equilibrium dialysis. In the thigh model, across all six strains the antibacterial effect of colistin was well correlated with fAUC/MIC (R(2) = 0.82-0.94 for P. aeruginosa and R(2) = 0.84-0.95 for A. baumannii). Target values of fAUC/MIC for 2 log10 kill were 7.4-13.7 for P. aeruginosa and 7.4-17.6 for A. baumannii. In the lung model, for only two strains of P. aeruginosa and one strain of A. baumannii was it possible to achieve 2 log10 kill (fAUC/MIC target values 36.8-105), even at the highest colistin dose tolerated by mice. This dose was not able to achieve bacteriostasis for the other two strains of A. baumannii.. Colistin was substantially less effective in lung infection. The pharmacokinetic/pharmacodynamic target values will assist in the design of optimized dosage regimens.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Load; Colistin; Female; Lung; Mice; Microbial Sensitivity Tests; Plasma; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Soft Tissue Infections; Thigh; Treatment Outcome

We present the case of an extremely low birth weight infant with diffuse gingival noma, initially misdiagnosed as thrush. Multidrug-resistant Pseudomonas aeruginosa strain was cultured and treated with systemic and local colistin with complete healing. Noma neonatorum from multidrug-resistant pathogens may appear in neonatal intensive care units. Old antibiotics may help.Noma (cancrum oris) is a devastating gangrenous disease that leads to destruction of facial tissue with significant morbidity and mortality in children and young adults. Noma has virtually disappeared from Europe and North America, but it is still common among children and young adults in India, Africa, and South America. Noma is a polymicrobial opportunistic infection related to malnutrition and immune dysfunction. In the neonate, a similar but distinct condition, known as "noma neonatorum" was described in 1977, in which gangrenous lesions involve the mucocutaneous junctions of oral, nasal, and anal area, and, occasionally, the eyelids and the scrotum. The neonatal disease has been linked to Pseudomonas aeruginosa, prematurity, and low birth weight. There is no established treatment, and mortality is almost inevitable in the few reported cases. In this study, we present the first European case of noma neonatorum from a multidrug-resistant strain of P aeruginosa.

Topics: Colistin; Diagnostic Errors; Drug Resistance, Multiple, Bacterial; Female; Gingiva; Humans; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Premature; Noma; Pseudomonas aeruginosa; Pseudomonas Infections

In the era of emergence of MDR Pseudomonas aeruginosa, osteoarticular infections (OIs) add more difficulties to its treatment. The role of β-lactams (BLs) is questioned and older drugs need to be reconsidered. The objective of this study was to describe our experience in the management of OIs caused by MDR P. aeruginosa and evaluate different therapeutic options.. This was a retrospective analysis of a prospectively collected cohort (2004-13) of patients with OI caused by MDR P. aeruginosa. We created two groups: (i) Group A (more difficult to treat), prosthetic joint infections (PJIs) and osteoarthritis (OA) managed with device retention; and (ii) Group B (less difficult to treat), OA managed without device retention. Antibiotic treatment was administered according to clinician criteria: monotherapy/combined therapy; and BL used by intermittent bolus (IB)/continuous infusion.. Of 34 patients, 15 (44.1%) had PJI and 19 (55.9%) had OA (8 related to an orthopaedic device). Twenty-three cases (68%) were caused by XDR P. aeruginosa. The initial management included removal of an orthopaedic device in 14 cases, together with antibiotic [alone, 19 (55.9%; 4 colistin, 14 BL-IB and 1 BL continuous infusion); and in combination, 15 (44.1%; 5 BL-IB and 10 BL continuous infusion)]. The overall cure rate was 50% (39% and 63% in Groups A and B, respectively), ranging from 31.6% with monotherapy to 73.3% with combined therapy (P = 0.016), with special interest within Group A (cure rate with combined therapy 71.4%, P = 0.049). After rescue therapy, which included removal of remaining devices, the cure rate reached 85.3%.. We suggest that the BL/colistin combination is an optimized therapy for OI caused by MDR P. aeruginosa, together with an appropriate surgical treatment.

Topics: Aged; Anti-Bacterial Agents; beta-Lactams; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Osteoarthritis; Prospective Studies; Prosthesis-Related Infections; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Treatment Outcome

Exacerbations associated with chronic lung infection with Pseudomonas aeruginosa are a major contributor to morbidity, mortality and premature death in cystic fibrosis. Such exacerbations are treated with antibiotics, which generally lead to an improvement in lung function and reduced sputum P. aeruginosa density. This potentially suggests a role for the latter in the pathogenesis of exacerbations. However, other data suggesting that changes in P. aeruginosa sputum culture status may not reliably predict an improvement in clinical status, and data indicating no significant changes in either total bacterial counts or in P. aeruginosa numbers in sputum samples collected prior to pulmonary exacerbation sheds doubt on this assumption. We used our recently developed lung segmental model of chronic Pseudomonas infection in sheep to investigate the lung microbiota changes associated with chronic P. aeruginosa lung infection and the impact of systemic therapy with colistimethate sodium (CMS).. We collected protected specimen brush (PSB) samples from sheep (n = 8) both prior to and 14 days after establishment of chronic local lung infection with P aeruginosa. Samples were taken from both directly infected lung segments (direct) and segments spatially remote to such sites (remote). Four sheep were treated with daily intravenous injections of CMS between days 7 and 14, and four were treated with a placebo. Necropsy examination at d14 confirmed the presence of chronic local lung infection and lung pathology in every direct lung segment. The predominant orders in lung microbiota communities before infection were Bacillales, Actinomycetales and Clostridiales. While lung microbiota samples were more likely to share similarities with other samples derived from the same lung, considerable within- and between-animal heterogeneity could be appreciated. Pseudomonadales joined the aforementioned list of predominant orders in lung microbiota communities after infection. Whilst treatment with CMS appeared to have little impact on microbial community composition after infection, or the change undergone by communities in reaching that state, when Gram negative organisms (excluding Pseudomonadales) were considered together as a group there was a significant decrease in their relative proportion that was only observed in the sheep treated with CMS. With only one exception the reduction was seen in both direct and remote lung segments. This reduction, coupled with generally increasing or stable levels of Pseudomonadales, meant that the proportion of the latter relative to total Gram negative bacteria increased in all bar one direct and one remote lung segment.. The proportional increase in Pseudomonadales relative to other Gram negative bacteria in the lungs of sheep treated with systemic CMS highlights the potential for such therapies to inadvertently select or create a niche for bacteria seeding from a persistent source of chronic infection.

Topics: Animals; Anti-Bacterial Agents; Bacterial Load; Bronchoalveolar Lavage Fluid; Chronic Disease; Colistin; Disease Models, Animal; Female; Injections, Intravenous; Lung; Male; Microbiota; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections; Sheep, Domestic

Pseudomonas aeruginosa plays an important role in chronic lung infections among patients with cystic fibrosis (CF) through its ability to form antibiotic-resistant biofilms. In P. aeruginosa, biofilm development and the production of several virulence factors are mainly regulated by the rhl and las quorum-sensing (QS) systems, which are controlled by two N-acyl-homoserine lactone signal molecules. In a previous study, we discovered an original QS inhibitor, N-(2-pyrimidyl)butanamide, called C11, based on the structure of C4-homoserine lactone, and found that it is able to significantly inhibit P. aeruginosa biofilm formation. However, recent data indicate that P. aeruginosa grows under anaerobic conditions and forms biofilms in the lungs of CF patients that are denser and more robust than those formed under aerobic conditions. Our confocal microscopy observations of P. aeruginosa biofilms developed under aerobic and anaerobic conditions confirmed that the biofilms formed under these two conditions have radically different architectures. C11 showed significant dose-dependent antibiofilm activity on biofilms grown under both aerobic and anaerobic conditions, with a greater inhibitory effect being seen under conditions of anaerobiosis. Gene expression analyses performed by quantitative reverse transcriptase PCR showed that C11 led to the significant downregulation of rhl QS regulatory genes but also to the downregulation of both las QS regulatory genes and QS system-regulated virulence genes, rhlA and lasB. Furthermore, the activity of C11 in combination with antibiotics against P. aeruginosa biofilms was tested, and synergistic antibiofilm activity between C11 and ciprofloxacin, tobramycin, and colistin was obtained under both aerobic and anaerobic conditions. This study demonstrates that C11 may increase the efficacy of treatments for P. aeruginosa infections by increasing the susceptibility of biofilms to antibiotics and by attenuating the pathogenicity of the bacterium.

Topics: Amides; Anti-Bacterial Agents; Bacterial Adhesion; Biofilms; Ciprofloxacin; Colistin; Cystic Fibrosis; Drug Synergism; Drug Therapy, Combination; Humans; Lung; Microscopy, Confocal; Pseudomonas aeruginosa; Pseudomonas Infections; Pyrimidines; Quorum Sensing; Respiratory Tract Infections; Tobramycin

Topics: Acinetobacter baumannii; Acinetobacter Infections; Amino Acid Substitution; Anti-Bacterial Agents; Colistin; Genes, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Mutation, Missense; Pseudomonas aeruginosa; Pseudomonas Infections; Selection, Genetic

Colistin use has reemerged for the treatment of infections caused by multidrug-resistant Gram-negative bacteria. However, the information on its pharmacokinetics is limited, especially in patients with end-stage renal disease, in which dosage adjustments are contradictory, and evidences the need to investigate the removal of colistin through renal replacement therapies like haemodialysis. This case study showed efficient removal of colistin methanesulphonate and formed colistin during intermittent haemodialysis in a patient infected by polymyxin-only-susceptible Pseudomonas aeruginosa. These results suggest the importance to monitor colistin plasma concentrations in these patients to minimize treatment failure due to suboptimal exposure to antibacterial colistin.

Topics: Aged; Anti-Bacterial Agents; Colistin; Humans; Kidney Failure, Chronic; Male; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections; Renal Dialysis

Topics: Adult; Anti-Bacterial Agents; Carbapenems; Colistin; Doripenem; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Male; Meningoencephalitis; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Surgical Wound Infection; Treatment Outcome

Fosfomycin is active in vitro against extensively drug-resistant (XDR) and pandrug-resistant (PDR) Pseudomonas aeruginosa and Klebsiella pneumoniae carbapenemase-producing strains; however, the in vivo effectiveness against such pathogens is almost unknown. A multicentre, observational, prospective case-series study was performed in 11 ICUs. All consecutive fosfomycin-treated patients suffering from XDR or PDR fosfomycin-susceptible, microbiologically documented infections were recorded. Clinical and microbiological outcomes were assessed. A safety analysis was performed. In total, 68 patients received fosfomycin during the study period, 48 of whom were considered suitable for effectiveness analysis based on predefined criteria. Bacteraemia and ventilator-associated pneumonia were the main infections. Carbapenemase-producing K. pneumoniae and P. aeruginosa were isolated in 41 and 17 cases, respectively. All isolates exhibited an XDR or PDR profile, being fosfomycin-susceptible by definition. Fosfomycin was administered intravenously at a median dose of 24g/day for a median of 14 days, mainly in combination with colistin or tigecycline. Clinical outcome at Day 14 was successful in 54.2% of patients, whilst failure, indeterminate outcome and superinfection were documented in 33.3%, 6.3% and 6.3%, respectively. All-cause mortality at Day 28 was 37.5%. Bacterial eradication was observed in 56.3% of cases. Fosfomycin resistance developed in three cases. The main adverse event was reversible hypokalaemia. In conclusion, fosfomycin could have a place in the armamentarium against XDR and PDR Gram-negative infections in the critically ill. Resistance development during therapy, which has been a matter of concern in previous studies, did not occur frequently. The necessity of combination with other antibiotics requires further investigation.

Topics: Administration, Intravenous; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Fosfomycin; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Minocycline; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Tigecycline; Treatment Outcome

Cystic fibrosis (CF) affects over 9,000 people in the UK and limits life expectancy. CF patients are susceptible to lung infections, most commonly Pseudomonas aeruginosa. Once infection is established, patients require lifetime treatment using nebulised antibiotics. Newer dry powder formulations of antibiotics may reduce treatment burden and improve compliance.. Our objective was to evaluate the cost effectiveness of (i) colistimethate sodium dry powder for inhalation (DPI) and (ii) tobramycin DPI versus nebulised tobramycin for the treatment of chronic P. aeruginosa lung infection in patients with CF from the perspective of the National Health Service (NHS) and Personal Social Services (PSS).. We developed a state transition model based on transitions between three strata of lung function measured in terms of forced expiratory volume in 1 second (FEV1) % predicted. Additional health states representing post-lung transplantation and dead are also modelled. The model structure was informed by systematic reviews of evidence concerning the plausibility of potential relationships between intermediate endpoints and final outcomes. The model assumes that treatment impacts on FEV1 trajectory, which manifest as changes in health-related quality of life. No survival benefit is assumed due to the absence of robust quantifiable evidence. Model parameters were informed by patient-level and aggregate data from two randomised controlled trials together with the best available evidence from the literature. Resource use and costs associated with drug acquisition, the management of exacerbations and reduced nebuliser maintenance were drawn from reference sources and expert opinion. Costs were valued at 2011/2012 prices. Costs and health outcomes were discounted at a rate of 3.5 %. Simple and probabilistic sensitivity analyses were undertaken, including additional analyses of Patient Access Scheme (PAS) price discounts offered by the manufacturers of both DPI products.. Colistimethate sodium DPI is expected to produce fewer quality-adjusted life-years (QALYs) than nebulised tobramycin. Based on its list price, colistimethate sodium DPI is expected to be dominated by nebulised tobramycin. When the PAS is incorporated, the incremental cost-effectiveness ratio (ICER) for colistimethate sodium DPI versus nebulised tobramycin is expected to be approximately £288,600 saved per QALY lost. Based on its current list price, the ICER for tobramycin DPI versus nebulised tobramycin is expected to be approximately £124,000 per QALY gained. When the proposed PAS is included, tobramycin DPI is expected to dominate nebulised tobramycin.. Under their list prices, neither DPI product is likely to represent good value for money for the NHS given current cost-effectiveness thresholds. The PAS discounts have a significant impact upon the economic attractiveness of both DPI products compared against nebulised tobramycin. The clinical effectiveness and cost effectiveness of the DPIs against other nebulised antibiotics, such as aztreonam and inhaled colistimethate sodium, remains unclear.

Topics: Adult; Anti-Bacterial Agents; Colistin; Cost-Benefit Analysis; Cystic Fibrosis; Decision Support Techniques; Dry Powder Inhalers; Humans; Models, Economic; Pneumonia, Bacterial; Probability; Pseudomonas aeruginosa; Pseudomonas Infections; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Survival Analysis; Tobramycin; Young Adult

Increasing evidence suggests that colistin monotherapy is suboptimal at currently recommended doses. We hypothesized that front-loading provides an improved dosing strategy for polymyxin antibiotics to maximize killing and minimize total exposure. Here, we utilized an in vitro pharmacodynamic model to examine the impact of front-loaded colistin regimens against a high bacterial density (10(8) CFU/ml) of Pseudomonas aeruginosa. The pharmacokinetics were simulated for patients with hepatic (half-life [t1/2] of 3.2 h) or renal (t1/2 of 14.8 h) disease. Front-loaded regimens (n=5) demonstrated improvement in bacterial killing, with reduced overall free drug areas under the concentration-time curve (fAUC) compared to those with traditional dosing regimens (n=14) with various dosing frequencies (every 12 h [q12h] and q24h). In the renal failure simulations, front-loaded regimens at lower exposures (fAUC of 143 mg · h/liter) obtained killing activity similar to that of traditional regimens (fAUC of 268 mg · h/liter), with an ∼97% reduction in the area under the viable count curve over 48 h. In hepatic failure simulations, front-loaded regimens yielded rapid initial killing by up to 7 log10 within 2 h, but considerable regrowth occurred for both front-loaded and traditional regimens. No regimen eradicated the high bacterial inoculum of P. aeruginosa. The current study, which utilizes an in vitro pharmacodynamic infection model, demonstrates the potential benefits of front-loading strategies for polymyxins simulating differential pharmacokinetics in patients with hepatic and renal failure at a range of doses. Our findings may have important clinical implications, as front-loading polymyxins as a part of a combination regimen may be a viable strategy for aggressive treatment of high-bacterial-burden infections.

Topics: Anti-Bacterial Agents; Colistin; Humans; In Vitro Techniques; Kidney Diseases; Liver Diseases; Models, Biological; Pseudomonas Infections

Polymyxin B (PMB) and colistin, administered as the prodrug colistin methanesulfonate sodium (CMS), are increasingly used to treat carbapenem-resistant Gram-negative bacteria. Nephrotoxicity is the major dose-limiting adverse effect of both polymyxins. A retrospective cohort study of 132 patients was conducted to evaluate risk factors for acute kidney injury (AKI), classified according to Acute Kidney Injury Network criteria, in patients treated with ≥48h of intravenous PMB or CMS, with particular focus on potential differences between each polymyxin. The overall incidence of AKI was 25.8% (34/132) [20.8% (20/96) and 38.9% (14/36) in patients treated with PMB and CMS, respectively; P=0.06]. In the Cox regression model, doses ≥2million International Units (MIU) of PMB or >9MIU of CMS were the only variable independently associated with AKI [adjusted hazard ratio (aHR)=2.11, 95% confidence interval (CI) 1.01-4.41; P=0.04]. Vancomycin co-administration was strongly associated with AKI, although this was not statistically significant (aHR=2.22, 95% CI 0.98-5.04; P=0.058). There was no statistically significant difference in the incidence of AKI between patients treated with PMB or CMS in the multivariate model (aHR=1.74, 95% CI 0.82-3.69; P=0.15). High dose was the main risk factor for AKI regardless of the polymyxin administered. Vancomycin co-administration likely increases the risk of AKI. Although there was a higher overall incidence of AKI in patients treated with CMS compared with PMB, CMS was not significantly associated with this outcome after adjusting for the above variables.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Acute Kidney Injury; Anti-Bacterial Agents; Cohort Studies; Colistin; Female; Hospital Mortality; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Polymyxin B; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Risk Factors; Vancomycin

The emergence of colistin-resistant Pseudomonas aeruginosa is becoming a serious concern worldwide. We investigated genetic variations involved in the acquisition and loss of colistin resistance in three clinical isogenic P. aeruginosa isolates (GKK-1, GKK-2 and GKK-3) recovered from a single patient and assessed their impacts on colistin resistance.. We applied whole genome sequencing technology to identify single nucleotide polymorphisms and insertions or deletions in two colistin-resistant isolates compared with a susceptible isolate.. Thirty-seven non-synonymous mutations in 33 coding sequences were detected in the colistin-resistant isolates GKK-1 and GKK-3. Only one gene (PA1375) was significantly down-regulated in both colistin-resistant isolates; this gene encodes erythronate-4-phosphate dehydrogenase. Among the eight genes that were up-regulated in the colistin-resistant isolates, three encoded hypothetical proteins (PA1938, PA2928 and PA4541) and five were predicted to be involved in core biological functions, encoding a cell wall-associated hydrolase (PA1199), a response regulator EraR (PA1980), a sensor/response regulator hybrid (PA2583), a glycosyltransferase (PA5447) and an arabinose efflux permease (PA5548). All mutants with allelic replacement of these candidate genes, apart from one (PA1375), exhibited increases in colistin susceptibility, ranging from 2- to 16-fold. Colistin susceptibility decreased in complemented strains compared with the mutants; however, in three cases, resistance did not reach wild-type level.. This study demonstrates genetic differences between P. aeruginosa isogenic isolates and identifies novel determinants that may be associated with the acquisition of colistin resistance. These findings will lay the foundation for a complete understanding of the molecular mechanisms of colistin resistance in P. aeruginosa.

Topics: Anti-Bacterial Agents; Colistin; DNA Mutational Analysis; Drug Resistance, Bacterial; Genome, Bacterial; Humans; Pseudomonas aeruginosa; Pseudomonas Infections; Sequence Analysis, DNA

Topics: Anti-Bacterial Agents; Colistin; Critical Illness; Dose-Response Relationship, Drug; Drug Resistance, Multiple; Humans; Pseudomonas; Pseudomonas Infections; Treatment Outcome

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Cefepime; Cephalosporins; Ciprofloxacin; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Immunocompromised Host; Meropenem; Pseudomonas aeruginosa; Pseudomonas Infections; Thienamycins; Tobramycin; Treatment Failure

The purposes of this study were to establish a rabbit multidrug-resistant Pseudomonas aeruginosa (MDRP) keratitis model, and test the efficacy of levofloxacin, colistin methanesulfate (CL-M), colistin sulfate (CL-S) and polymyxin B (PL-B) against MDRP infection. In a rabbit eye, making a 2-mm circular corneal excision, and MDRP strain #601 or representative P. aeruginosa strain IID1210 were instilled into the corneal concavity. IID1210 was used to confirm this model developed P. aeruginosa keratitis. After MDRP keratitis developed, we treated the eyes with levofloxacin, CL-M, CL-S or PL-B eye drops. The infected eyes were evaluated by clinical score, histopathological examination and viable bacterial count (CFU). Rabbits developed MDRP keratitis reproducibly after instilled the bacteria into the corneal lesion. MDRP produced severe keratitis similarly with IID1210, as shown by slit lamp examination and clinical score. In MDRP keratitis models, clinical scores and viable bacterial counts were significantly lower in levofloxacin- and CL-M-treated groups compared with PBS-treated group, but the magnitudes of reduction were not remarkable. However, clinical scores were dramatically lowered in CL-S- and PL-B-treated groups compared with PBS-treated group. CL-S- and PL-B-treated group were kept corneal translucency and little influx of polymorphonuclear neutrophils in histopathological examination. In addition, both CL-S- and PL-B-treated groups were not detected viable bacteria in infected cornea. Using our MDRP keratitis model, we showed that topical levofloxacin and CL-M are not adequately effective, while CL-S and PL-B are efficacious in controlling MDRP keratitis. Especially, PL-B, which is commercially available eye drop, might be most effective against MDRP.

Topics: Animals; Anti-Bacterial Agents; Colistin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Keratitis; Levofloxacin; Male; Microbial Sensitivity Tests; Polymyxin B; Pseudomonas aeruginosa; Pseudomonas Infections; Rabbits

Topics: Anti-Bacterial Agents; Bronchiectasis; Colistin; Female; Humans; Male; Pseudomonas aeruginosa; Pseudomonas Infections

Colistin combination therapy may be required to treat biofilm-associated infections. We evaluated bacterial killing and emergence of colistin resistance with colistin and doripenem combinations against biofilm-embedded and planktonic multidrug-resistant (MDR) Pseudomonas aeruginosa.. One colistin-susceptible reference strain (PAO1) and two colistin-susceptible MDR clinical isolates (HUB1 and HUB2; both carbapenem resistant) were investigated over 72 h in the CDC biofilm reactor, a dynamic biofilm model. Two colistin regimens (constant concentrations of 1.25 and 3.50 mg/L), one doripenem regimen (Cmax 25 mg/L 8 hourly) and their combination were employed. Microbiological response was examined as log changes and absolute bacterial counts.. For biofilm-embedded bacteria, bactericidal activity was only observed with monotherapy with colistin at 3.50 mg/L. The emergence of colistin resistance occurred with colistin monotherapy against two strains (PAO1 and HUB1), but only with the colistin 3.50 mg/L regimen. Colistin 3.50 mg/L plus doripenem resulted in ∼2-3 log10 cfu/cm(2) initial killing against both clinical isolates and remained synergistic at 72 h. The emergence of colistin resistance was not observed in biofilm-embedded bacteria with either combination. For planktonic bacteria, bactericidal activity was not observed with any monotherapy regimen, although enhanced bacterial killing was observed with doripenem plus colistin 3.50 mg/L against all isolates. Colistin resistance was observed with colistin monotherapy against two isolates, but did not emerge with combination regimens.. Doripenem enhanced killing by colistin of biofilm-embedded cells in both carbapenem-susceptible and -resistant strains, and the combination minimized the emergence of colistin resistance.

Topics: Anti-Bacterial Agents; Biofilms; Carbapenems; Colistin; Colony Count, Microbial; Doripenem; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Microbial Viability; Pseudomonas aeruginosa; Pseudomonas Infections; Time Factors

The aim of this study was to report the utility of topical colistin in multi-drug resistant Pseudomonas aeruginosa bacterial keratitis.. Retrospective interventional case series included 8 patients with culture-proven multi-drug resistant P. aeruginosa (MDR-PA) bacterial keratitis who presented from June 2011 to January 2012 and were treated with colistin 0.19% as monodrug therapy. Clinical/microbiological data were collected from medical records. All patients underwent microbiological corneal scraping. Intensive half-hourly therapy with broad-spectrum antibiotics was changed to colistin 0.19% when antibiotic sensitivity reports were available. The outcome was a "complete success" if resolution of infection occurred with scar formation without any subsequent recurrence up to 2 weeks and "partial success" if it also required a cyanacrylate glue application. The outcome was a "failure" if the patient required a therapeutic graft or if the infection could not be controlled and the eye needed evisceration.. The mean age was 45 ± 16 years; the M:F ratio was 1:1. Seven patients had a history of ocular surgery. The mean size of the infiltrate was 15.41 ± 22.2 mm and was full thickness in 5 patients. Success was achieved in 7 out of 8 patients, and the infiltrate gradually decreased with resolution of infection in a mean duration of 30.5 ± 16 days. Complete and partial success were noted in 4 and 3 patients, respectively. The final visual acuity was 20/60 or better in 4 patients. One patient required a sclerocorneal patch graft. No complications of topical colistin were noticed.. The early use of topical colistin 0.19% was found to be a safe and effective alternative in the management of multi-drug resistant P. aeruginosa bacterial keratitis.

Topics: Administration, Topical; Adolescent; Adult; Aged; Anti-Bacterial Agents; Colistin; Corneal Ulcer; Drug Resistance, Multiple, Bacterial; Eye Infections, Bacterial; Female; Humans; Male; Middle Aged; Ophthalmic Solutions; Pilot Projects; Pseudomonas Infections; Retrospective Studies; Visual Acuity

Infections caused by multidrug resistant (MDR) Pseudomonas aeruginosa are difficult to treat. Antibiotic development is dwindling in recent years. In order to develop new alternate therapies antimicrobial activity of different antibiotic combinations are being studied in vitro and in vivo. Sub-inhibitory concentrations of colistin were tested in combination with ceftazidime or ciprofloxacin by the checkerboard method against 25 MDR strains of P. aeruginosa. Synergy was observed for ceftazidime or ciprofloxacin antibiotic combinations with colistin among 73.3% of MDR3 (R(AMK, GEN, TOB) R(CAZ) R(CIP)) strains and 100% of MDR4 (R(AMK, GEN, TOB) R(CAZ) R(CIP) R(TZP)) strains. 6.6% strains of MDR3 and 14.3% strains of MDR5 (R(AMK, GEN, TOB) R(CAZ) R(CIP) R(TZP) R(IPM)) phenotypes were inhibited by colistin and ceftazidime alone and 6.6% strains of MDR3 phenotypes were inhibited by colistin and ciprofloxacin alone. For the remaining strains, though synergy was not observed, significant reduction in minimum inhibitory concentration was evident. The results of this study are significant as sub-inhibitory concentrations of colistin have an advantage of reducing in vivo toxicity. These findings need further evaluation for clinical use.

Topics: Anti-Bacterial Agents; Ceftazidime; Ciprofloxacin; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Aminoglycosides; Anti-Bacterial Agents; Colistin; Daptomycin; Drug Interactions; Humans; Lipoglycopeptides; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections

Carbapenemase genes are one of the most frequent mechanisms reported in carbapenem-resistant P. aeruginosa; however, description of P. aeruginosa co-harbouring two or more carbapenemases is unusual.. In this study we evaluated the presence of carbapenemase genes and the clonality of P. aeruginosa isolates obtained from a hospital over a 12-year period. A total of 127 isolates of carbapenem-resistant P. aeruginosa recovered from 109 patients feces (four samples), rectal swab (three samples), nasal swab (one sample) and anal abscess (one sample), were evaluated. Minimum inhibitory concentrations of the following antibiotics imipenem, meropenem and polymyxin E were determined by broth microdilution. The molecular profile of isolates was evaluated by pulsed field gel electrophoresis (PFGE). PCR for the following carbapenemase genes blaIMP;blaSPM;blaVIM;blaSIM;blaNDM;blaKPC;blaGES and nucleotide sequencing to confirm the enzyme gene types were performed and compared with the database available on the Internet (BLAST-http://www.ncbi.nlm.nhi.gov/blast/).. All isolates were carbapenem-resistant, their MIC50 and MIC90 were respectively 64 μg/mL and 256 μg/mL to imipenem and 32 μg/mL and 256 μg/mL to meropenem, all isolates except one (MIC = 8 mg/L) were susceptible to polymyxin E. The most frequent carbapenemase genes identified were blaSPM identified in 41 isolates (32%), followed by 10 with blakpc and 5 with blaVIM (3.9%). All belonged to the class SPM-1 and VIM-2. In 2011, one isolate harbouring three carbapenemase genes (SPM-1, VIM-2 and KPC-2) that belonged to a new clone was identified in a hematopoietic stem cell transplanted patient. Then, 19 carbapenem-resistant P. aeruginosa were identified in an outbreak that occurred in the bone marrow transplant unit, all positive for SPM-1 gene, and 9 (47.3%) harbored both SPM-1 and KPC.. Our findings showed that PCR for KPC gene should be performed to evaluate carbapenem resistance in P. aeruginosa and that this agent can harbor more than one carbapenemase gene. Attention should be focused on the possible rapid spread of KPC in P. aeruginosa isolates and for the fact that P. aeruginosa may become a reservoir of this transmissible resistance mechanism.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Colistin; DNA, Bacterial; Electrophoresis, Gel, Pulsed-Field; Genes, Bacterial; Genotype; Hospitals; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Molecular Typing; Polymerase Chain Reaction; Pseudomonas aeruginosa; Pseudomonas Infections; Thienamycins

Discovered in 1949, the antibiotic colistin was initially used for therapeutic purposes. Parenteral use of colistin was gradually abandoned because of its side-effect profile, especially its nephrotoxicity and neurotoxicity. Despite the risk of these potentially serious adverse effects, increasing resistance of Gram-negative bacteria has led to a renaissance of intravenous use of colistin in the last few years. Local administration of colistin is an alternative method to minimise the risk of systemic toxicity. We present a case of extensively drug-resistant Pseudomonas aeruginosa osteomyelitis treated successfully with high-dose colistin- and tobramycin-impregnated bone cement as a drug delivery vehicle. For the first time, local colistin concentrations in drainage and synovial fluid were quantified in order to determine the optimal dose and to minimise serious side effects. Insertion of a bone cement spacer loaded with a high dose of tobramycin and colistin resulted in local colistin levels at the infection site that exceeded the minimum inhibitory concentration (MIC) of colistin against the isolated P. aeruginosa five-fold on Day 4. Thus, the treatment may be expected to exert a prolonged effect. Whereas systemic administration of colistin alone was not sufficient to treat the infection, combined local and parenteral therapy led to eradication of P. aeruginosa in this patient. Plasma colistin levels remained in the therapeutic range, which confirms the systemic safety of the method.

Topics: Anti-Bacterial Agents; Colistin; Drug Carriers; Drug Resistance, Multiple, Bacterial; Humans; Male; Middle Aged; Osteomyelitis; Plasma; Polymethyl Methacrylate; Pseudomonas aeruginosa; Pseudomonas Infections; Synovial Fluid; Tobramycin; Treatment Outcome

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Infective Agents; Colistin; Drug Interactions; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Mutation; Pseudomonas aeruginosa; Pseudomonas Infections

Lung impairment is the most life-threatening factor for cystic fibrosis patients. Indeed, Pseudomonas aeruginosa is the main pathogen in the pulmonary infection of these patients. In this work, we developed sodium colistimethate loaded lipid nanoparticles, namely, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), as a strategy to enhance the antimicrobial therapy against P. aeruginosa in cystic fibrosis patients. The nanoparticles obtained displayed a 200-400 nm size, high drug entrapment (79-94%) and a sustained drug release profile. Moreover, both SLN and NLC presented antimicrobial activity against clinically isolated P. aeruginosa. The integrity of the nanoparticles was not affected by nebulization through a mesh vibrating nebulizer. Moreover, lipid nanoparticles appeared to be less toxic than free sodium colistimethate in cell culture. Finally, an in vivo distribution experiment showed that nanoparticles spread homogenously through the lung and there was no migration of lipid nanoparticles to other organs, such as liver, spleen or kidneys.

Topics: Administration, Inhalation; Animals; Anti-Bacterial Agents; Cell Line; Cell Survival; Colistin; Cystic Fibrosis; Drug Carriers; Drug Delivery Systems; Drug Liberation; Humans; Lipids; Mice; Microbial Sensitivity Tests; Nanoparticles; Particle Size; Pseudomonas aeruginosa; Pseudomonas Infections; Surface Properties; Tissue Distribution

Topics: Anti-Bacterial Agents; Bronchiectasis; Colistin; Female; Humans; Male; Pseudomonas aeruginosa; Pseudomonas Infections

We report a case series of post-operative endophthalmitis due to Pseudomonas aeruginosa. A total of 8 patients operated for cataract, were referred to our facility with acute onset of decreased vision 1-2 days following surgery. All patients had clinical evidence of acute exogenous endophthalmitis with severe anterior chamber exudative reaction. Ocular samples (aqueous aspirate and vitreous tap) for microbiology were taken from all eyes. Microbiology from all revealed P. aeruginosa which was resistant to all antibiotics except colistin. With prompt and accurate microbiological support it was possible to control the infection in all the eyes with the use of colistin intravitreally and intravenously which to the best of our knowledge, has been never reported. Intravitreal injection of colistin could be an option effective in the management of multi-drug-resistant endophthalmitis caused by Gram-negative bacteria.

Topics: Anti-Bacterial Agents; Colistin; Endophthalmitis; Eye Infections, Bacterial; Female; Follow-Up Studies; Humans; Intravitreal Injections; Male; Middle Aged; Phacoemulsification; Pseudomonas aeruginosa; Pseudomonas Infections; Surgical Wound Infection

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Endophthalmitis; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

Most patients with cystic fibrosis (CF) have chronic rhinosinusitis; their sinuses are often colonized with bacteria that can initiate and maintain deleterious pulmonary infections. Theoretically, eradication of the sinus bacteria should reduce the frequency of lung infections and thereby reduce pulmonary morbidity. This article addressed whether bacteria in CF sinuses are eligible for eradication by sinus surgery and postoperative treatment.. A prospective study including 58 CF patients, who had extensive sinus surgery and growth of Pseudomonas aeruginosa, Achromobacter xylosoxidans, and/or Burkholderia multivorans in their sinuses, was initiated. All patients followed a systematic postoperative treatment program of nasal irrigations with saline and colistimethate sodium and systematic endoscopic cleansing. All patients had follow-up examinations including sinus cultures; each side of the nose was cultured separately.. At the 6-month follow-up visit, 49 patients were cultured; 66 of 98 maxillary-ethmoidal complexes (67%) showed no growth of pathogenic bacteria. Some patients were not free from CF pathogenic bacteria at all cultures; however, 20 (41%) patients had no bilateral regrowth (p < 0.01) and 4 patients had no unilateral regrowth at any time during 6 months of follow-up. The eradication of CF pathogens was accomplished in patients from all three lung infection groups: intermittently colonized, chronically infected, and lung transplanted. The patient with the longest follow-up had no bacterial growth for 3 years.. Extensive sinus surgery combined with intensive follow-up can eradicate pathogenic bacteria from CF sinuses.

Topics: Achromobacter denitrificans; Adolescent; Adult; Burkholderia; Burkholderia Infections; Child; Chronic Disease; Colistin; Cystic Fibrosis; Female; Follow-Up Studies; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Nasal Lavage; Paranasal Sinuses; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Rhinitis; Sinusitis; Treatment Outcome; Young Adult

Multidrug-resistant Pseudomonas aeruginosa (MDR-PA) infection creates problems for therapy. Previous studies have found MDR-PA is susceptible to colistin. We studied the in vitro susceptibility of MDR-PA to colistin and determined the minimum inhibitory concentration (MIC). One hundred MDR-PA isolates were obtained from patients at Songklanagarind Hospital, in southern Thailand, during January 2008-March 2011. Antimicrobial susceptibilities to amikacin (AK), ceftazidime (CAZ), ciprofloxacin (CIP), imipenem (IMP) and colistin (CO) were tested by standard disk diffusion method. The antimicrobial susceptibility to colistin and the MIC were determined with the E-test. The MDR-PA isolates were susceptible to ceftazidime, ciprofloxacin, amikacin and imipenem in 1, 5, 11 and 32%, respectively. There were 5 antimicrobial resistance patterns of MDR-PA: AK-CAZ-CIP-IMP (50%), AK-CAZ-CIP (32%), CAZ-CIP-IMP (11%), AK-CAZ-IMP (6%) and AK-CIP-IMP (1%). Colistin had good efficacy against MDR-PA (98% susceptibility rate). The MIC50 and MIC90 for colistin were 1.0 and 1.5 jig/ml, respectively. Only 2 MDR-PA isolates were resistant to colistin with the MICs of 3 and 12 microg/ml, respectively. The majority of MDR-PA isolates remained susceptible to colistin; therefore, colistin is a good option for treatment of MDR-PA.

Topics: Anti-Bacterial Agents; Colistin; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Thailand

Pseudomonas aeruginosa and Acinetobcter spp. are important nosocomial pathogens and carbapenem resistance is an emerging threat. Therapeutic options for infections with these isolates include colistin. This study was conducted to determine the prevalence of carbapenem resistance in P. aeruginosa and Acinetobacter spp. bloodstream isolates, phenotypically characterize the resistance mechanisms and evaluate the in vitro activity of colistin.. Consecutive 145 (95 P.aeruginosa and 50 Acinetobacter spp.) non-repeat isolates were included. Antibiotic susceptibility testing was performed per CLSI guidelines. MIC for carbapenems and colistin was performed using Etest. Isolates showing reduced susceptibility or resistance to the carbapenems were tested for metallo-β-lactamase (MBL) production using imipenem-EDTA combined disk and MBL Etest.. Carbapenem resistance was observed in 40% P. aeruginosa and 66.0% Acinetobacter spp. Carbapenem-resistant (CA-R) isolates were significantly (p <0.05) more frequently resistant to the other antibiotics than carbapenem-susceptible isolates. Approximately half of the CA-R strains were multidrug-resistant, and 3.1-5.5% were resistant to all antibiotics tested. MBL was found in 76.3% and 69.7% of the P. aeruginosa and Acinetobacter spp., respectively. Colistin resistance was observed in three (6.0%) Acinetobacter isolates and eight (8.4%) P. aeruginosa. MIC50 for carbapenems were two to four times higher for MBL-positive compared to MBL-negative isolates, but no difference was seen in MIC for colistin.. Carbapenem resistance was observed to be mediated by MBL in a considerable number of isolates. Colistin is an alternative for infections caused by CA-R isolates; however, MIC testing should be performed whenever clinical use of colistin is considered.

Topics: Acinetobacter; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Colistin; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Administration, Inhalation; Anti-Bacterial Agents; Clinical Trials as Topic; Colistin; Cystic Fibrosis; Drug Monitoring; Drug Therapy, Combination; Dry Powder Inhalers; Humans; Practice Guidelines as Topic; Pseudomonas Infections; Respiratory Function Tests; Respiratory Tract Infections; State Medicine; Tobramycin; United Kingdom

The aim of this study was to evaluate in vitro the efficacy of clinically using colistin methanesulfonate against biofilm-forming multidrug-resistant Pseudomonas aeruginosa (MDRP), with minimum inhibitory concentrations (MICs) of ciprofloxacin, imipenem, and amikacin showing ≥4, 16, and 32 μg/ml, respectively, by disk diffusion susceptibility testing (CLSI document M100-S21). The minimum eradication biofilm concentration (MBEC) of colistin methanesulfonate for strain MDRP-YMD isolated from a patient's urine, which formed a biofilm on plastic pegs attached to a microplate lid, was compared with that of P. aeruginosa ATCC27853 for quality control testing with MICs of ciprofloxacin, imipenem, and amikacin showing ≤1, 4, and 16 μg/ml, respectively. In an uneven biofilm approximately 10 μm thick, as determined with confocal laser scanning microscopy (CLSM), ratios of MBEC to MIC of colistin methanesulfonate against strains MDRP-YMD and ATCC27853 were 10.5 and 8.0, whereas those of minimum bactericidal concentration (MBC) to MIC in planktonic cells were 1.0 and 2.0 μg/ml, respectively. Morphological examination using scanning electron microscopy and CLSM verified that embedded cells in biofilm matrices of the two strains were disrupted and died under the MBEC. Therefore, bactericidal effects of colistin methanesulfonate on biofilm-forming cells of strain MDRP-YMD as well as strain ATCC27853 were significantly decreased compared with those on the planktonic cells.

Topics: Anti-Bacterial Agents; Biofilms; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

Patients with cystic fibrosis (CF) often experience acute pulmonary exacerbations (APE) and may be treated with a wide variety of intravenous antibiotics. The aim of this review is to provide an evidence-based summary of pharmacokinetic/pharmacodynamic (PK/PD), tolerability, and efficacy studies utilizing the intravenous (IV) polymixin antibiotic colistimethate sodium (CMS) in the treatment of APE and to identify areas where further study is warranted. Currently, there is not an international standard on the labeling of CMS products. As a result, this has lead to confusion in the interpretation of the literature with respect to efficacy, tolerance, and optimal dosing strategy. The dosing ranges of IV CMS from the literature are 5.3-12.9 mg/kg/day, maximum 480 mg per day for 60 kg patient (Colomycin® injection-European product) and 8-21.3 mg/kg/day, maximum 800 mg per day for 60 kg patient (Coly-Mycin M® parenteral-US product).The literature supports a CMS dose of 8 mg/kg/day divided every 8 hr (maximum 480 mg/day) for the treatment of APE secondary to Pseudomonas aeruginosa. The maximum recommended CMS dose of 480 mg/day is less than is recommended by the FDA-approved and CFF dosing guidelines but in agreement with UK CF Trust Antibiotic Working Group recommendations. There is debate over the frequency of CMS administration (once daily vs. thrice-daily) and its impact on resistance and clinical efficacy. Further study is needed to determine the tolerability and efficacy of extended-interval dosing of CMS in the treatment of APE.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Colistin; Cystic Fibrosis; Disease Progression; Female; Humans; Male; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Young Adult

Topics: Administration, Intravenous; Aged; Anti-Bacterial Agents; Apnea; Aztreonam; Colistin; Drug Resistance, Multiple, Bacterial; Fatal Outcome; Humans; Male; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Paralysis

Topics: Anti-Bacterial Agents; Colistin; Cystic Fibrosis; Dry Powder Inhalers; Equipment Design; Humans; Nebulizers and Vaporizers; Pseudomonas Infections

Multidrug-resistant (MDR) gram-negative bacteria-related nosocomial infections and ventilator-associated pneumonia (VAP) presents an emerging challenge to clinicians. Older antimicrobial agents such as colistin have become life-saving drugs because of the susceptibility of these pathogens. We report our experience with aerosolized colistin in two preterm and one term neonate with Acinetobacter baumannii and Pseudomonas aeruginosa-related VAP who were unresponsiveness to previous antimicrobial treatment. All pathogens were isolated from tracheal aspirate. We used 5 mg/kg (base activity) aerosolized colistin methanesulfonate sodium in every 12 h as an adjunctive therapy for VAP. VAP was treated by 14, 14, and 16-day courses of aerosolized colistin in these patients, respectively. No adverse effect such as nephrotoxicity or neurotoxicity was observed. We found that aerosolized colistin was tolerable and safe, and it may be an adjunctive treatment option for MDR gram-negative bacterial VAP in neonates. Further studies are needed to determine appropriate doses for aerosolized colistin and its eligibility as an alternative treatment choice in newborns.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Anti-Bacterial Agents; Colistin; Drug Administration Schedule; Drug Resistance, Multiple, Bacterial; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Treatment Outcome

To assess the therapeutic effect and toxicity of intravenous colistin in the treatment of multidrug-resistant (MDR) Gram-negative bacteria in patients with severe burns.. The medical records of 930 patients admitted to the Burn Intensive Care Unit (ICU) at Hallym University Hangang Sacred Heart Hospital, Seoul, South Korea between April 2007 and December 2009 were retrospectively reviewed. Of these, the 104 patients who had received intravenous colistin treatments (104 courses) during this period were enrolled in the study. Changes in creatinine level were analyzed in three groups: all patients receiving colistin (n = 104), patients with undergoing continuous renal replacement therapy (CRRT group; n = 38), and patients not undergoing CRRT (non-CRRT group; n = 66).. Among these patients, the burnt body surface area ranged from 5 to 96% (mean 49.7%). Thirty-five patients (33.7%) suffered inhalation injury, and CRRT was administered to 38 patients. The mean duration of colistin treatment was 14.7 (range 4-71) days. The total dose of colistin was 3,045.7 mg (range 100-13,800). The length of ICU stay was 48.9 (range 7-154) days. Forty patients (38.5%) died. The mean pre-colistin creatinine level of all patients was 1.04 mg/dL, and the mean post-colistin level was 1.34 mg/dL. The mean pre-colistin creatinine level of the CRRT group and non-CRRT group was 1.68 and 0.66 mg/dL, and the mean post-colistin level was 1.68 and 1.14 mg/dL, respectively.. Colistin appears to be a relatively safe and effective treatment for major burn patients with infections caused by MDR Gram-negative bacteria when no other drug is available. Additionally, we found no statistically significant impairment of creatinine levels.

Topics: Acinetobacter; Acinetobacter Infections; Adult; Aged, 80 and over; Anti-Bacterial Agents; Burn Units; Burns; Child; Colistin; Creatinine; Drug Resistance, Multiple, Bacterial; Female; Humans; Length of Stay; Male; Middle Aged; Pseudomonas; Pseudomonas Infections; Renal Replacement Therapy; Republic of Korea; Retrospective Studies; Young Adult

Topics: Amikacin; Anti-Bacterial Agents; Bacterial Load; Colistin; Cystic Fibrosis; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

Adjunctive aerosolized antibiotics (AAA) have been recommended in the setting of Gram-negative ventilator-associated pneumonia (VAP), but little is known about their influence on clinical outcomes.. To assess outcomes associated with AAA for the treatment of Pseudomonas aeruginosa (PA) and Acinetobacter baumannii (AB) VAP.. A retrospective, single-center cohort study at Barnes-Jewish Hospital in St Louis, Missouri. Consecutive subjects treated for bronchoalveolar lavage-confirmed PA or AB VAP between January 1, 2004 and December 31, 2009 were enrolled. Records of subjects treated with AAA were compared to those who did not receive AAAs (NAAA).. Ninety-three patients were evaluated (NAAA n = 74, AAA n = 19, inhaled colistin n = 9, inhaled tobramycin n = 10). Patients receiving AAA were significantly more likely to be infected with multidrug-resistant bacteria (52.6% vs 14.9%, P < .001) and had greater Acute Physiology and Chronic Health Evaluation II scores (21.4 ± 5.7 vs 17.5 ± 5.3, P = .004) compared to patients receiving NAAA. NAAA subjects experienced a shorter time from VAP onset to appropriate intravenous antibiotic initiation (0.5 ± 0.9 d vs 2.6 ± 5.4 d, P = .038), but length of intravenous therapy was similar between groups (12.8 ± 8.5 d vs 17.8 ± 13.3 d, P = .16). The NAAA group demonstrated significantly shorter mechanical ventilation duration (18.9 ± 15.9 d vs 38.4 ± 32.4 days, P < .001), intensive care unit stay (37.5 ± 42.5 d vs 56.3 ± 31.3 d, P = .001), and hospital stay (39.0 ± 42.5 d vs 58.3 ± 33.4 d, P = .001). However, Kaplan-Meier curves for the probability of 30-day survival from VAP onset demonstrated that patients receiving AAA had statistically greater survival (P = .030 by the log rank test).. Patients with PA and AB VAP may experience favorable survival when treated with AAA, despite greater severity of illness and a greater incidence of multidrug-resistant infection. Large randomized trials are needed to further explore this therapy.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Aerosols; Anti-Bacterial Agents; APACHE; Bronchoalveolar Lavage; Colistin; Comorbidity; Female; Humans; Male; Middle Aged; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Statistics, Nonparametric; Survival Rate; Tobramycin; Treatment Outcome

Many Pseudomonas aeruginosa isolates from the airways of patients with cystic fibrosis (CF) are sensitive to antibiotics in susceptibility testing, but eradication of the infection is difficult. The main reason is the biofilm formation in the airways of patients with CF. The pharmacokinetics (PKs) and pharmacodynamics (PDs) of antimicrobials can reliably be used to predict whether antimicrobial regimens will achieve the maximum bactericidal effect against infections. Unfortunately, however, most PK/PD studies of antimicrobials have been done on planktonic cells and very few PK/PD studies have been done on biofilms, partly due to the lack of suitable models in vivo. In the present study, a biofilm lung infection model was developed to provide an objective and quantitative evaluation of the PK/PD profile of antimicrobials. Killing curves were set up to detect the antimicrobial kinetics on planktonic and biofilm P. aeruginosa cells in vivo. Colistin showed concentration-dependent killing, while imipenem showed time-dependent killing on both planktonic and biofilm P. aeruginosa cells in vivo. The parameter best correlated to the elimination of bacteria in lung by colistin was the area under the curve (AUC) versus MIC (AUC/MIC) for planktonic cells or the AUC versus minimal biofilm inhibitory concentration (MBIC; AUC/MBIC) for biofilm cells. The best-correlated parameter for imipenem was the time that the drug concentration was above the MIC for planktonic cells (T(MIC)) or time that the drug concentration was above the MBIC (T(MBIC)) for biofilm cells. However, the AUC/MIC of imipenem showed a better correlation with the efficacy of imipenem for biofilm infections (R(2) = 0.89) than planktonic cell infections (R(2) = 0.38). The postantibiotic effect (PAE) of colistin and imipenem was shorter in biofilm infections than planktonic cell infections in this model.

Topics: Alginates; Animals; Anti-Bacterial Agents; Area Under Curve; Biofilms; Cells, Immobilized; Colistin; Disease Models, Animal; Female; Glucuronic Acid; Hexuronic Acids; Humans; Imipenem; Lung; Microbial Sensitivity Tests; Plankton; Pseudomonas aeruginosa; Pseudomonas Infections

One hundred sixty-nine nonreplicate imipenem-resistant Pseudomonas aeruginosa strains isolated in a large hospital on the coastal region of Croatia were studied. The most active antibiotics were colistin and amikacin. Most of the isolates were multiresistant. The most prevalent serotype was O12, followed by O11. Six strains carried the bla(VIM-2) gene located in a novel class 1 integron composed in its variable part of the bla(VIM-2)-bla(oxa-10)-ΔqacF-aacA4 genes. Metallo-β-lactamase-producing strains belonged to sequence types ST235 and ST111.

Topics: Amikacin; Anti-Bacterial Agents; Base Sequence; beta-Lactamases; Colistin; Croatia; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Humans; Imipenem; Integrons; Microbial Sensitivity Tests; Molecular Sequence Data; Pseudomonas aeruginosa; Pseudomonas Infections; Serotyping

Topics: Administration, Inhalation; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Forecasting; Humans; Nasal Sprays; Pneumonia, Ventilator-Associated; Pseudomonas Infections; Respiratory Tract Infections

The β-barrel assembly machinery (BAM) complex plays a critical role in outer membrane protein (OMP) biogenesis. The outer membrane (OM) of Pseudomonas aeruginosa is centrally involved in mechanisms of antibiotic resistance. This study aimed to identify effects of a synthetic peptide based on conserved sequences in the putative BamA-binding region of BamD, focusing on antibiotic susceptibility and OMP characteristics in P. aeruginosa.. We synthesized a peptide FIRL (Phe-Ile-Arg-Leu-CONH(2)) with a sequence related to that of the BamD protein. We assessed antibiotic susceptibility of P. aeruginosa PAO1 using the chequerboard method and a time-kill assay. Changes in OMPs and in OM permeability were examined using SDS-PAGE, western blot analysis and nitrocefin assays. The combined effects of the peptide and antibiotics were investigated using a mouse pneumonia model.. Although the peptide alone exerted no antimicrobial effect, it reduced the MICs of colistin, levofloxacin, erythromycin, vancomycin and rifampicin for P. aeruginosa PAO1 by 4-fold or more. Time-kill tests revealed bacterial numbers were significantly reduced after 2 h of incubation with the peptide plus colistin or levofloxacin. Moreover, in the presence of the peptide, expression of OprM was reduced by a third, and OM permeability was increased. The combination of the peptide (2.08 mg/kg) and colistin (1.25 mg/kg) significantly reduced P. aeruginosa by more than 1 log cfu/mL in a mouse pneumonia model.. We show, for the first time, that a synthetic peptide based on homologous sequences of BamD can potentiate antibiotic susceptibility of P. aeruginosa.

Topics: Animals; Anti-Bacterial Agents; Bacterial Load; Bacterial Outer Membrane Proteins; Blotting, Western; Colistin; Disease Models, Animal; Drug Therapy, Combination; Electrophoresis, Polyacrylamide Gel; Female; Levofloxacin; Lung; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Ofloxacin; Peptides; Pneumonia, Bacterial; Protein Binding; Pseudomonas aeruginosa; Pseudomonas Infections; Treatment Outcome

Intraventricular colistin, administered as colistin methanesulfonate (CMS), is the last resource for the treatment of central nervous system infections caused by panresistant Gram-negative bacteria. The doses and daily regimens vary considerably and are empirically chosen; the cerebrospinal fluid (CSF) pharmacokinetics of colistin after intraventricular administration of CMS has never been characterized. Nine patients (aged 18 to 73 years) were treated with intraventricular CMS (daily doses of 2.61 to 10.44 mg). Colistin concentrations were measured using a selective high-performance liquid chromatography (HPLC) assay. The population pharmacokinetics analysis was performed with the P-Pharm program. The pharmacokinetics of colistin could be best described by the one-compartment model. The estimated values (means ± standard deviations) of apparent CSF total clearance (CL/Fm, where Fm is the unknown fraction of CMS converted to colistin) and terminal half-life (t(1/2λ)) were 0.033 ± 0.014 liter/h and 7.8 ± 3.2 h, respectively, and the average time to the peak concentration was 3.7 ± 0.9 h. A positive correlation between CL/Fm and the amount of CSF drained (range 40 to 300 ml) was observed. When CMS was administered at doses of ≥5.22 mg/day, measured CSF concentrations of colistin were continuously above the MIC of 2 μg/ml, and measured values of trough concentration (C(trough)) ranged between 2.0 and 9.7 μg/ml. Microbiological cure was observed in 8/9 patients. Intraventricular administration of CMS at doses of ≥5.22 mg per day was appropriate in our patients, but since external CSF efflux is variable and can influence the clearance of colistin and its concentrations in CSF, the daily dose of 10 mg suggested by the Infectious Diseases Society of America may be more prudent.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Central Nervous System Bacterial Infections; Colistin; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Injections, Intraventricular; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections

Nosocomial infections caused by multidrug-resistant (MDR) microorganisms are a common problem around the world, especially in Intensive Care Units. The aim of this study was to investigate the efficacy and safety of colistin therapy in paediatric patients with severe nosocomial infections caused by MDR Gram-negative bacteria. There were 87 episodes in 79 paediatric Intensive Care Unit patients in five different hospitals; each patient was treated intravenously with colistin and evaluated. Of the 79 patients, 54.4% were male and the median age was 30 months. The most commonly isolated microorganism was Acinetobacter baumannii, the most common isolation site was tracheal aspirate fluid and the most common type of infection was ventilator-associated pneumonia. The mean colistin dose in patients without renal failure was 5.4 ± 0.6 mg/kg/day, the mean therapy duration was 17.2 ± 8.4 days and the favourable outcome rate was 83.9%. Serious side effects were seen in four patient episodes (4.6%) during therapy; two patients suffered renal failure and the others had convulsive seizures. Other patients tolerated the drug well. The infection-related mortality rate was 11.5% and the probability of death within the first 9 days of treatment was 10 times higher than after the first 9 days. In conclusion, this study suggests that colistin is effective in the treatment of severe nosocomial infections caused by MDR Gram-negative bacteria and is generally well tolerated by patients, even after relatively long-term use.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Child; Child, Preschool; Colistin; Cross Infection; Drug Administration Schedule; Drug Evaluation; Drug Resistance, Multiple, Bacterial; Female; Humans; Infant; Intensive Care Units, Pediatric; Male; Pseudomonas aeruginosa; Pseudomonas Infections; Renal Insufficiency; Retrospective Studies; Seizures; Time Factors; Treatment Outcome

Squalamine is a steroid extracted from sharks with proven in vitro antibacterial activity. We assessed its efficacy in reducing the lung bacterial load and histological lesions when given via inhalation in a rat model of chronic Pseudomonas aeruginosa pneumonia.. Sprague-Dawley rats were inoculated by tracheal intubation with 150 μL of a solution containing 10(8) cfu/mL of agar bead-embedded P. aeruginosa strain PAO1. MICs of squalamine and colistin for this strain were 2-8 and 0.5-1 mg/L, respectively. Starting the day after infection, the animals were treated twice daily with aerosolized squalamine (3 mg), colistin (160 mg) or 0.9% saline for 6 days. The bacterial load and lung histological lesions were evaluated on the seventh day.. Aerosols of squalamine and colistin resulted in a significant reduction in median (IQR) pulmonary bacterial count compared with saline [10(3) (6 × 10(2)-2 × 10(3)), 10(3) (9 × 10(2)-6 × 10(3)) and 10(5) (9 × 10(4)-2 × 10(5)) cfu/lung, respectively; P < 0.001 for both treated groups versus saline]. The lung weight and the lung histological severity score were significantly lower in both treated groups.. In a model of chronic P. aeruginosa pneumonia, treatment twice daily with a squalamine aerosol for 6 days leads to a significant reduction in the pulmonary bacterial count and pneumonia lesions with an efficacy comparable to that of colistin.

Topics: Administration, Inhalation; Animals; Anti-Bacterial Agents; Bacterial Load; Cholestanols; Chronic Disease; Colistin; Disease Models, Animal; Lung; Male; Microbial Sensitivity Tests; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Rats; Rats, Sprague-Dawley; Treatment Outcome

Topics: Aged; Anti-Bacterial Agents; Cholangitis; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Pseudomonas aeruginosa; Pseudomonas Infections

In view of reports of colistin-induced neurotoxicity in infected patients, the aim of this study was to assess whether the integrity of the blood-brain barrier (BBB) and the brain uptake of colistin are altered in the presence of systemic Pseudomonas aeruginosa infection. Bacteremia was confirmed 8 h after intramuscular administration of P. aeruginosa ATCC 27853 to Swiss Outbred mice, at which time a single subcutaneous dose of colistin sulfate (40 mg/kg of body weight) or an intravenous dose of [(14)C]sucrose (2 μCi) was administered. Despite a substantial elevation in plasma levels of the proinflammatory cytokines tumor necrosis factor alpha, interleukin-1β, and interleukin-6 during bacterial infection, the brain uptake of colistin was similar between infected and noninfected mice with AUC(brain)/AUC(plasma) (where AUC(brain) is the area under the brain concentration-time curve and AUC(plasma) is the area under the plasma concentration-time curve) ratios of 0.023 and 0.024, respectively. Similarly, the brain-to-plasma ratios of [(14)C]sucrose were no different between infected and noninfected mice, consistent with a lack of effect of bacteremia on BBB integrity. To further correlate any relationship between BBB disruption and plasma levels of proinflammatory cytokines, BBB integrity, colistin brain uptake, and plasma proinflammatory cytokines were measured following the administration of Salmonella enterica lipopolysaccharide (LPS), an agent known to induce BBB disruption. Despite LPS inducing a 4-fold increase in colistin brain uptake and a significant (P < 0.05) 1.2-fold increase in [(14)C]sucrose BBB penetration, plasma cytokine levels were lower with LPS treatment relative to those obtained with bacterial infection with P. aeruginosa. This study demonstrates that the brain uptake of colistin is not increased in mice during P. aeruginosa-induced systemic bacteremia despite a significant increase in plasma levels of three proinflammatory cytokines.

Topics: Animals; Bacteremia; Blood-Brain Barrier; Brain; Colistin; Cytokines; Lipopolysaccharides; Male; Mice; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Female; Humans; Male; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Pseudomonas Infections; Tobramycin

The applicability of Etest for synergy testing was evaluated in 100 carbapenem-nonsusceptible Pseudomonas aeruginosa isolates. Combinations of doripenem with amikacin, colistin, or levofloxacin were synergistic or additive against 67%, 31%, and 23% of isolates, respectively. The use of Etest was practical to evaluate the synergy of doripenem with other antipseudomonal agents.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactams; Colistin; Drug Synergism; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Adolescent; Ceftazidime; Colistin; Cystic Fibrosis; Desensitization, Immunologic; Humans; Injections, Intravenous; Male; Pseudomonas Infections

Colistin often remains the only active agent against multidrug-resistant Gram-negative pathogens. The aim of the study was to assess efficacy of nebulized colistin for treating ventilator-associated pneumonia (VAP) caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii.. One hundred and sixty-five patients with VAP caused by P. aeruginosa and A. baumannii were enrolled in a prospective, observational, and comparative study. The sensitive strain group included 122 patients with VAP caused by P. aeruginosa and A. baumannii susceptible to β-lactams, aminoglycosides, or quinolones and treated with intravenous antibiotics for 14 days. The multidrug-resistant strain group included 43 patients with VAP caused by multidrug-resistant P. aeruginosa and A. baumannii and treated with nebulized colistin (5 million international units every 8 h) either in monotherapy (n=28) or combined to a 3-day intravenous aminoglycosides for 7-19 days. The primary endpoint was clinical cure rate. Aerosol was delivered using vibrating plate nebulizer.. After treatment, clinical cure rate was 66% in sensitive strain group and 67% in multidrug-resistant strain group (difference -1%, lower limit of 95% CI for difference -12.6%). Mortality was not different between groups (23 vs. 16%). Among 16 patients with persisting or recurrent P. aeruginosa infection, colistin minimum inhibitory concentration increased in two patients.. Nebulization of high-dose colistin was effective to treat VAP caused by multidrug-resistant P. aeruginosa or A. baumannii. Its therapeutic effect was noninferior to intravenous β-lactams associated with aminoglycosides or quinolones for treating VAP caused by susceptible P. aeruginosa and A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Pneumonia, Ventilator-Associated; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Treatment Outcome

In June 2004 an 8-year-old boy was admitted to a hospital in Thessaloniki, Greece, because of high fever, tachypnea, hypotonia, diarrhea, and tonoclonic convulsions. Phlebovirus infection was diagnosed by IgG seroconversion to Toscana virus. As IgM antibodies were not detected, it is suggested that this was an acute infection caused by a phlebovirus virus distinct from Toscana virus. Complication by a hospital-acquired Pseudomonas aeruginosa pneumonia resulted in 2 months of hospitalization. Slight ataxia was still present on discharge.

Topics: Acyclovir; Anti-Bacterial Agents; Antiviral Agents; Bunyaviridae Infections; Ceftriaxone; Child; Colistin; Cross Infection; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Greece; Humans; Immunoglobulin G; Male; Meningoencephalitis; Phlebovirus; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Treatment Outcome

An experimental study was performed to evaluate the interaction between s-thanatin and colistin both in vitro and in vivo, using two Pseudomonas aeruginosa strains with different patterns of susceptibilities. We evaluated whether selecting for colistin-resistant P. aeruginosa could be prevented in vitro by combining colistin with s-thanatin. The strains were serially exposed in broth to twofold stepwise increasing concentrations of colistin alone or in combination with a fixed concentration [0.25× minimum inhibitory concentration (MIC)] of s-thanatin. We also performed an in vitro synergy study. For in vivo studies, a mouse model of Pseudomonas sepsis has been used. Main outcome measures were lethality and quantitative blood cultures. Exposure to colistin alone gradually selected for Pseudomonas strains with an increased MIC. In vitro studies, s-thanatin showed a positive interaction with colistin, and was able to prevent its resistance. In vivo studies, s-thanatin combined with colistin exhibited the highest efficacy on all main outcome measurements. These results highlight the potential usefulness of this combination and provide a future therapeutic alternative in severe Pseudomonas infections.

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Colistin; Disease Models, Animal; Drug Resistance, Microbial; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis

To compare clinical and microbiologic outcomes in adults without cystic fibrosis who had Pseudomonas aeruginosa bronchial colonization and were receiving inhaled colistin or colistin plus tobramycin with those who were receiving inhaled tobramycin as outpatient treatment.. Prospective, observational cohort study.. Referral pneumology service at a tertiary university care hospital.. Eighty-one Caucasian adults without cystic fibrosis who received 97 courses of inhaled colistin alone, colistin plus tobramycin, or inhaled tobramycin alone as outpatient treatment of P. aeruginosa bronchial colonization between January 2004 and December 2008.. The frequency and duration of hospitalizations for respiratory exacerbations were the primary outcomes compared among treatment groups. Secondary outcomes were emergence of bacterial resistance, antibiotic use during admission, emergence of other opportunistic microorganisms, achievement of sustained P. aeruginosa eradication in the airways, and mortality, as well as safety and changes in respiratory function. No significant differences between colistin and tobramycin were found in the mean number of hospital admissions, duration of hospitalizations, duration of antibiotic treatment, adverse events, mortality, or emergence of other opportunistic microorganisms. Emergence of resistance to colistin was lower than resistance to tobramycin (hazard ratio 0.09, 95% confidence interval [CI] 0.03-0.32). Patients treated with both inhaled antibiotics had fewer days of hospitalization and fewer days of antibiotic use than those treated with tobramycin alone (relative risk [RR] 0.33, 95% CI 0.10-1.12, and RR 0.27, 95% CI 0.08-0.93, respectively).. Results with colistin were similar to those with tobramycin for inhaled treatment of P. aeruginosa colonization in this population; however, combined use of colistin and tobramycin appeared to be associated with fewer days of hospitalization and shorter duration of antibiotic treatment. Prospective, double-blind, placebo-controlled trials of outpatient nebulized antibiotics, especially colistin plus tobramycin, should be performed to ascertain the efficacy of this therapy for treatment of P. aeruginosa colonization in patients without cystic fibrosis.

Topics: Administration, Inhalation; Ambulatory Care; Anti-Bacterial Agents; Bronchitis, Chronic; Colistin; Cystic Fibrosis; Data Interpretation, Statistical; Drug Therapy, Combination; Female; Hospitalization; Humans; Male; Middle Aged; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin; Treatment Outcome

Acquisition of Pseudomonas aeruginosa (Psa) and infection with mucoid strains is associated with repeated pulmonary exacerbations which often require intravenous and long-term nebulised antibiotic treatments, repeated hospitalizations and leads to a more precipitous decline in lung function. Anti-Psa antibiotic therapy early in the course of Psa infection in patients with cystic fibrosis (CF) may result in eradication of Psa and prevention or delay of colonization with the organism. From January 1995 to December 2009 our paediatric CF clinic has followed an early eradication protocol for the first appearance of Psa. In this paper we report on the economic effects after 15 years as reflected in hospitalization and antibiotic usage and cost.. The Psa-eradication protocol includes 2 weeks of IV piperacillin and tobramycin, followed by oral ciprofloxacin for 3 weeks, and nebulised colistimethate for 6 months. The same protocol is used for newly diagnosed CF patients who grow Psa on their first visit or who grow a mucoid strain, multiresistant strain of Psa or whose Psa co-cultured with Burkholderia cepacia complex, and for patients in whom Psa recurs after initial clearance.. 195 Psa eradication courses were completed from 1995 to 2009 with an overall Psa clearance rate of 90%. Patients that only cultured a Psa classic (non-mucoid) strain had a clearance rate was 96.5%. The percentage of children chronically infected with Psa has declined from 44% in 1994 to 15% in 2009.Total days spent in hospital for all reasons declined by 43%; chronic Psa hospital days declined by 75%; IV and nebulised anti-Psa antibiotic costs reduced by 44%.. Results indicate that application of a Pseudomonas eradication protocol as described in this report has economic and resource utilization benefits in addition to clinical benefits.

Topics: Administration, Oral; Adolescent; Anti-Bacterial Agents; Anti-Infective Agents; Burkholderia cepacia complex; Child; Child, Preschool; Ciprofloxacin; Cohort Studies; Colistin; Cystic Fibrosis; Disease-Free Survival; Drug Administration Schedule; Drug Therapy, Combination; Health Care Costs; Health Resources; Humans; Infant; Injections, Intravenous; Nebulizers and Vaporizers; Piperacillin; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin; Treatment Outcome

The in vitro activity of colistin was evaluated against 215 nonduplicated Pseudomonas aeruginosa isolates, including 53 multidrug-resistant isolates, which were collected between 2006 and 2007 from nine tertiary care hospitals in Korea. Colistin-nonsusceptible P. aeruginosa (CNPA) isolates were genotyped using multilocus sequence typing. Sixteen (7.4%) CNPA isolates (minimum inhibitory concentration [MIC], >2 mg/l) were identified, including three resistant isolates. All but one of the MDR P. aeruginosa isolates was susceptible to colistin. Multilocus sequence typing analysis identified 12 sequence types (STs) among 16 CNPA isolates, indicating that colistin nonsusceptibility might arise independently. However, ST244 and ST292, which may be international clones, were found in multiple CNPA isolates. Our data indicate an increase of P. aeruginosa isolates with reduced colistin susceptibility, suggesting the need for continuous surveillance of P. aeruginosa.

Topics: Anti-Bacterial Agents; Bacterial Typing Techniques; Colistin; Drug Resistance, Multiple, Bacterial; Hospitals, Urban; Humans; Microbial Sensitivity Tests; Multilocus Sequence Typing; Pseudomonas aeruginosa; Pseudomonas Infections; Republic of Korea

A 66-year-old male with acute type adult T-cell leukemia that was refractory to chemotherapy underwent unrelated allogeneic bone marrow transplantation after non-myeloablative conditioning with fludarabine, busulfan and total body irradiation. During an episode of neutropenia on day 12 after transplantation, pneumonia and sepsis due to multi-drug resistant Pseudomonas aeruginosa developed. Drug susceptibility tests demonstrated resistance to all kinds of intravenous antibiotics available for P. aeruginosa in Japan. Multi-drug susceptibility tests by the breakpoint-checkerboard plate method were then performed and combination therapy with meropenem hydrate and colistin was started based on the test results. After starting treatment, clinical symptoms and laboratory data immediately improved and engraftment of neutrophils was achieved on day 18. Infections with multi-drug-resistant P. aeruginosa are often critical for patients after hematopoietic stem cell transplantation and are difficult to control. In this paper, we report a case of severe multi-drug-resistant P. aeruginosa infection that was successfully treated by combination therapy selected using the breakpoint-checkerboard plate method.

Topics: Aged; Anti-Bacterial Agents; Bone Marrow Transplantation; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Male; Meropenem; Microbial Sensitivity Tests; Neutropenia; Pseudomonas aeruginosa; Pseudomonas Infections; Thienamycins; Transplantation, Homologous; Treatment Outcome

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

A rise in infections with multidrug-resistant Pseudomonas aeruginosa (MDR-PA) is a significant contributor to increased morbidity and mortality of patients with hematologic malignancies. The aim of this study was to determine the efficacy and safety of colistin (colistimethate sodium) in the treatment of serious infections caused by MDR-PA in these patients.. A matched pair analysis of renal function, toxicities, and outcome of 26 patients receiving colistin and control subjects was done. All patients had clinical signs of sepsis; P. aeruginosa was isolated from blood in 69% of patients in colistin group and 84% in control group. Patients treated with colistin received 3 million units every 8 hours for a median duration of 13 days. Additionally, patients received at least two additional antimicrobial or antifungal drugs.. Resolution of infection was achieved in twenty patients (76.9%) receiving colistin and in 17 (65.4%) control subjects. Mortality rate was 11% in both groups. There was no statistically significant difference in the level of serum creatinine, creatinine clearance, or potassium levels before and after treatment between groups. Only one patient receiving colistin developed de novo renal failure and one displayed transient neurologic toxicity.. Our results suggest that in patients with hematologic malignancies, colistin is effective in treating severe infections caused by MDR-PA while maintaining an acceptable toxicity profile. Prospective randomized studies comparing efficacy and safety of colistin with those of other antipseudomonal drugs are needed.

Topics: Acute Kidney Injury; Adolescent; Adult; Anti-Bacterial Agents; Case-Control Studies; Colistin; Croatia; Drug Resistance, Multiple, Bacterial; Female; Hematologic Neoplasms; Humans; Male; Matched-Pair Analysis; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Treatment Outcome; Young Adult

Wound infections caused by multidrug-resistant bacteria are a major issue in wound care. An occlusive dressing delivering an antimicrobial agent to the wound may be advantageous. The objective of this study was to evaluate an occlusive silk membrane loaded with colistin to establish an effective antimicrobial wound dressing against Gram-negative bacteria in vitro and in vivo.. ST-silk protein membranes (thickness, 100 μm; pore size, <100 nm) were loaded with log-scale colistin dilutions (0.027 to 270 mg/ml) and tested in a modified microbroth dilution assay against Pseudomonas aeruginosa (American Type Culture Collection 27853). A rat burn infection model was used to demonstrate the antimicrobial activity of ST-silk membranes loaded with 270 mg/ml colistin. Finally, a porcine wound infection model was used to study dose response (2.7, 27, and 270 mg/ml colistin loading concentration) in a time-dependent manner (0, 2, 4, and 6 days).. The in vitro study demonstrated a concentration-dependent antimicrobial effect against P. aeruginosa, with complete elimination at the highest loading concentrations (2.7, 27, and 270 mg/ml). All colistin membranes demonstrated lower colony-forming unit counts compared with the corresponding phosphate-buffered saline or carrier controls. The rat burn infection model demonstrated a colony-forming unit reduction of greater than 3 log-scales for the colistin-loaded ST-silk membranes after 3 days. On average, the wounds' colony-forming unit quantity remained at greater than 1000 during the entire follow-up of 6 days, apart from three wounds where complete bacterial clearance was observed.. This study demonstrates that occlusive ST-silk membranes loaded with an antimicrobial agent may be an effective dressing for infected wounds.

Topics: Animals; Anti-Bacterial Agents; Bandages; Burns; Coated Materials, Biocompatible; Colistin; Disease Models, Animal; Membranes, Artificial; Pseudomonas aeruginosa; Pseudomonas Infections; Rats; Rats, Sprague-Dawley; Silk; Stem Cells; Treatment Outcome; Wound Infection

The use of combination antibiotic therapy may be beneficial against rapidly emerging resistance in Pseudomonas aeruginosa. The aim of this study was to systematically investigate in vitro bacterial killing and resistance emergence with colistin alone and in combination with imipenem against multidrug-resistant (MDR) P. aeruginosa. Time-kill studies were conducted over 48 h using 5 clinical isolates and ATCC 27853 at two inocula (~10(6) and ~10(8) CFU/ml); MDR, non-MDR, and colistin-heteroresistant and -resistant strains were included. Nine colistin-imipenem combinations were investigated. Microbiological response was examined by log changes at 6, 24, and 48 h. Colistin combined with imipenem at clinically relevant concentrations increased the levels of killing of MDR and colistin-heteroresistant isolates at both inocula. Substantial improvements in activity with combinations were observed across 48 h with all colistin concentrations at the low inoculum and with colistin at 4× and 16× MIC (or 4 and 32 mg/liter) at the high inoculum. Combinations were additive or synergistic against imipenem-resistant isolates (MICs, 16 and 32 mg/liter) at the 10(6)-CFU inoculum in 9, 11, and 12 of 18 cases (i.e., 9 combinations across 2 isolates) at 6, 24, and 48 h, respectively, and against the same isolates at the 10(8)-CFU inoculum in 11, 7, and 8 cases, respectively. Against a colistin-resistant strain (MIC, 128 mg/liter), combinations were additive or synergistic in 9 and 8 of 9 cases at 24 h at the 10(6)- and 10(8)-CFU inocula, respectively, and in 5 and 7 cases at 48 h. This systematic study provides important information for optimization of colistin-imipenem combinations targeting both colistin-susceptible and colistin-resistant subpopulations.

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Imipenem; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

Combination therapy may be required for multidrug-resistant (MDR) Pseudomonas aeruginosa. The aim of this study was to systematically investigate bacterial killing and emergence of colistin resistance with colistin and doripenem combinations against MDR P. aeruginosa. Studies were conducted in a one-compartment in vitro pharmacokinetic/pharmacodynamic model for 96 h at two inocula (~10(6) and ~10(8) CFU/ml) against a colistin-heteroresistant reference strain (ATCC 27853) and a colistin-resistant MDR clinical isolate (19147 n/m). Four combinations utilizing clinically achievable concentrations were investigated. Microbiological response was examined by log changes and population analysis profiles. Colistin (constant concentrations of 0.5 or 2 mg/liter) plus doripenem (peaks of 2.5 or 25 mg/liter every 8 h; half-life, 1.5 h) substantially increased bacterial killing against both strains at the low inoculum, while combinations containing colistin at 2 mg/liter increased activity against ATCC 27853 at the high inoculum; only colistin at 0.5 mg/liter plus doripenem at 2.5 mg/liter failed to improve activity against 19147 n/m at the high inoculum. Combinations were additive or synergistic against ATCC 27853 in 16 and 11 of 20 cases (4 combinations across 5 sample points) at the 10(6)- and 10(8)-CFU/ml inocula, respectively; the corresponding values for 19147 n/m were 16 and 9. Combinations containing doripenem at 25 mg/liter resulted in eradication of 19147 n/m at the low inoculum and substantial reductions in regrowth (including to below the limit of detection at ∼50 h) at the high inoculum. Emergence of colistin-resistant subpopulations of ATCC 27853 was substantially reduced and delayed with combination therapy. This investigation provides important information for optimization of colistin-doripenem combinations.

Topics: Anti-Bacterial Agents; Carbapenems; Colistin; Colony Count, Microbial; Cystic Fibrosis; Doripenem; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Half-Life; Humans; Models, Biological; Pseudomonas aeruginosa; Pseudomonas Infections

To find out the frequency and susceptibility pattern of multi-drug resistant (MDR) Pseudomonas aeruginosa in clinical specimens.. Cross-sectional observational study.. Department of Microbiology, Army Medical College, National University of Sciences and Technology (NUST), Rawalpindi, from January to September 2010.. Routine clinical specimens were subjected to standard microbiological procedures and the isolates were identified to the species level. The antibiotics susceptibility was determined by Kirby Bauer Disc diffusion method and the results were interpreted according to the Clinical and Laboratory Standards Institute (CLSI) guidelines.. The frequency of MDR Pseudomonas aeruginosa among all the Pseudomonas aeruginosa strains isolated was found to be 22.7%. These isolates were most sensitive to Colistin followed by Piperacillin-Tazobactam and Cefoperazone-Sulbactum.. Increasing fequency of infections due to MDR Pseudomonas aeruginosa is an emerging threat in our set up which an be prevented by prescribing antibiotics judiciously and by adopting proper disinfection measures.

Topics: Anti-Bacterial Agents; Cefoperazone; Colistin; Cross-Sectional Studies; Disk Diffusion Antimicrobial Tests; Drug Resistance, Multiple, Bacterial; Enzyme Inhibitors; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections; Sulbactam

Pseudomonas aeruginosa can develop resistance to polymyxin and other cationic antimicrobial peptides. Previous work has shown that mutations in the PmrAB and PhoPQ regulatory systems can confer low to moderate levels of polymyxin resistance (MICs of 8 to 64 mg/liter) in laboratory and clinical strains of this organism. To explore the role of PhoPQ in high-level clinical polymyxin resistance, P. aeruginosa strains with colistin MICs > 512 mg/liter that had been isolated from cystic fibrosis patients treated with inhaled colistin (polymyxin E) were analyzed. Probable loss-of-function phoQ alleles found in these cystic fibrosis strains conferred resistance to polymyxin. Partial and complete suppressor mutations in phoP were identified in some cystic fibrosis strains with resistance-conferring phoQ mutations, suggesting that additional loci can be involved in polymyxin resistance in P. aeruginosa. Disruption of chromosomal phoQ in the presence of an intact phoP allele stimulated 4-amino-l-arabinose addition to lipid A and induced transcription from the promoter of the pmrH (arnB) operon, consistent with the known role of this lipid A modification in polymyxin resistance. These results indicate that phoQ loss-of-function mutations can contribute to high-level polymyxin resistance in clinical strains of P. aeruginosa.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Colistin; Cystic Fibrosis; Drug Resistance, Bacterial; Female; Humans; Lipid A; Male; Microbial Sensitivity Tests; Mutation; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections

Colistin is used as last treatment option for pneumonia associated with multidrug-resistant (MDR) Pseudomonas spp.. Literature about the best administration mode (inhalation versus parenteral treatment) is lacking.. A retrospective study of 20 intensive care patients with a pneumonia associated with MDR P. aeruginosa receiving colistin sulphomethate sodium (Colistineb®) between 2007 and 2009 was performed. A strain was considered multidrug-resistant if it was resistant to at least 6 of the following antibiotics: piperacillin-tazobactam, ceftazidime, cefepime, meropenem, aztreonam, ciprofloxacin, and amikacin. The administration mode, predicted mortality based on the SAPS3 score, SOFA score at onset of the colistin treatment, clinical and microbiological response, and mortality during the episode of the infection were analysed. The non parametric Kruskal-Wallis and Fisher's Exact test were used for statistical analysis of respectively the predicted mortality/SOFA score and mortality rate.. Six patients received colistin by inhalation only, 5 were treated only parenterally, and 9 by a combination of both administration modes. All patients received concomitant beta-lactam therapy. The mean predicted mortalities were respectively 72%, 68%, and 69% (p = 0.91). SOFA scores at the onset of the treatment were also comparable (p = 0.87). Clinical response was favorable in all patients receiving colistin by inhalation (6/6) and in 40% (2/5) of the patients receiving colistin parenterally (p = 0.06). In the patients with colistin administered both via inhalation and parenterally, clinical response was favorable in 78% of the patients (7/9) (p = 0.27 as compared to the treatment group receiving colistin only parenterally). When all patients with inhalation therapy were compared to the group without inhalation therapy, a favorable clinical response was present in respectively 87% and 40% (p = 0.06). In none of the patients, the Pseudomonas spp. was eradicated from the follow-up cultures.All patients in the parenterally treated group died. None of the patients receiving colistin by inhalation, and 3 of 9 patients of the combination group eventually died (p = 0.002 and p = 0.03 respectively as compared to the group receiving colistin only parenterally).. Aerosolized colistin could be beneficial as adjunctive treatment for the management of pneumonia due to MDR P. aeruginosa.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Humans; Injections, Intravenous; Male; Middle Aged; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Treatment Outcome; Young Adult

There has been an increase in recent years of antimicrobial resistance of Gram negative bacilli (GNB). Carbapenems, the mainstay for the treatment of multidrug resistant GNB infections, are no longer always effective leaving treatment options limited. We present the case of patient with recurrent, complicated urinary tract infections. The current episode was caused by carbapenem-resistant K. pneumoniae and P. aeruginosa and carbapenem-susceptible, but MDR E. cloacae. Resistance to carbapenems of K. pneumoniae was conferred by the production of the class B metallo-beta-lactamase, VIM1. Infection control measures were implemented and following a 2-week course of treatment with colistin, the infection resolved and the patient was discharged. We discuss the changes in the epidemiology, the mechanisms involved and the means of detecting carbapenem resistance in GNB. We would also like to stress the role of infection control measures in limiting patient-to-patient spread of MDR organisms which, are of paramount importance in cases when few treatment options are left available.

Topics: Aged; Anastomosis, Surgical; Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Enterobacter cloacae; Enterobacteriaceae Infections; Humans; Infection Control; Klebsiella Infections; Klebsiella pneumoniae; Male; Nephrolithiasis; Pseudomonas aeruginosa; Pseudomonas Infections; Risk Factors; Treatment Outcome; Urinary Bladder; Urinary Bladder Neoplasms; Urinary Tract Infections

The aim of the present study was to assess the efficacy and safety of colistimethate sodium therapy in multidrug-resistant nosocomial infections caused by Pseudomonas aeruginosa or Acinetobacter baumannii in neonates and children.. Pediatric patients hospitalized at the Uludag University Hospital who had nosocomial infections caused by multidrug-resistant P. aeruginosa or A. baumannii, were enrolled in the study. Colistimethate sodium at a dosage of 50-75 x 10(3) U/kg per day was given i.v. divided into three doses.. Fifteen patients received 17 courses of colistimethate sodium for the following infections: ventilator-associated pneumonia (n= 14), catheter-related sepsis (n= 1) and skin and soft-tissue infection (n= 2). The mean age of patients was 53.2 + 74.7 months (range, 8 days-15 years) and 60% were male. Mortality was 26.6%.. Colistimethate sodium appears to be safe and effective for the treatment of severe infections caused by multidrug-resistant P. aeruginosa or A. baumannii in pediatric patients.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Child; Child, Preschool; Colistin; Cross Infection; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance, Multiple, Bacterial; Female; Follow-Up Studies; Hospitals, University; Humans; Infant; Infant, Newborn; Injections, Intravenous; Intensive Care Units, Neonatal; Intensive Care Units, Pediatric; Male; Microbial Sensitivity Tests; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Statistics, Nonparametric; Treatment Outcome; Turkey

Colistin is increasingly used as last-line therapy against Gram-negative pathogens. The pharmacokinetic (PK)/pharmacodynamic (PD) index that best correlates with the efficacy of colistin remains undefined. The activity of colistin against three strains of Pseudomonas aeruginosa was studied in neutropenic mouse thigh and lung infection models. The PKs of unbound colistin were determined from single-dose PK studies together with extensive plasma protein binding analyses. Dose-fractionation studies were conducted over 24 h with a dose range of 5 to 160 mg/kg of body weight/day. The bacterial burden in the thigh or lung was measured at 24 h after the initiation of treatment. Relationships between antibacterial effect and measures of exposure to unbound (f) colistin (area under the concentration-time curve [fAUC/MIC], maximum concentration of drug in plasma [fC(max)]/MIC, and the time that the concentration in plasma is greater than the MIC [fT > MIC]) were examined by using an inhibitory sigmoid maximum-effect model. Nonlinearity in the PKs of colistin, including its plasma protein binding, was observed. The PK/PD index that correlated best with its efficacy was fAUC/MIC in both the thigh infection model (R(2) = 87%) and the lung infection model (R(2) = 89%). The fAUC/MIC targets required to achieve 1-log and 2-log kill against the three strains were 15.6 to 22.8 and 27.6 to 36.1, respectively, in the thigh infection model, while the corresponding values were 12.2 to 16.7 and 36.9 to 45.9 in the lung infection model. The findings of this in vivo study indicate the importance of achieving adequate time-averaged exposure to colistin. The results will facilitate efforts to define the more rational design of dosage regimens for humans.

Topics: Animals; Anti-Bacterial Agents; Area Under Curve; Colistin; Disease Models, Animal; Female; Humans; Lung; Lung Diseases; Mice; Microbial Sensitivity Tests; Neutropenia; Pseudomonas aeruginosa; Pseudomonas Infections; Specific Pathogen-Free Organisms; Thigh

Topics: Anti-Bacterial Agents; Bacterial Typing Techniques; beta-Lactam Resistance; beta-Lactamases; Brazil; Colistin; Disease Outbreaks; Humans; Molecular Epidemiology; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Administration, Inhalation; Anti-Bacterial Agents; Clinical Trials as Topic; Colistin; Drug Resistance, Bacterial; Humans; Pneumonia, Bacterial; Pseudomonas Infections

Emergence of multidrug-resistant strains in intensive care units has renewed interest in colistin, which often remains the only available antimicrobial agent active against resistant Pseudomonas aeruginosa. The aim of this study is to compare lung tissue deposition and antibacterial efficiency between nebulized and intravenous administration of colistin in piglets with pneumonia caused by P. aeruginosa.. In ventilated piglets, colistimethate was administered 24 h following bronchial inoculation of Pseudomonas aeruginosa (minimum inhibitory concentration of colistin = 2 microg ml(-1)) either by nebulization (8 mg kg(-1) every 12 h, n = 6) or by intravenous infusion (3.2 mg kg(-1) every 8 h, n = 6). All piglets were killed 49 h after inoculation. Colistin peak lung tissue concentrations and lung bacterial burden were assessed on multiple post mortem subpleural lung specimens.. Median colistin peak lung concentration following nebulization was 2.8 microg g(-1) (25-75% interquartile range = 0.8-13.7 microg g(-1)). Colistin was undetected in lung tissue following intravenous infusion. In the aerosol group, peak lung tissue concentrations were significantly greater in lung segments with mild pneumonia (median = 10.0 microg g(-1), 25-75% interquartile range = 1.8-16.1 microg g(-1)) than in lung segments with severe pneumonia (median = 1.2 microg g(-1), 25-75% interquartile range = 0.5-3.3 microg g(-1)) (p < 0.01). After 24 h of treatment, 67% of pulmonary segments had bacterial counts <10(2) cfu g(-1) following nebulization and 28% following intravenous administration (p < 0.001). In control animals, 12% of lung segments had bacterial counts <10(2) cfu g(-1) 49 h following bronchial inoculation.. Nebulized colistin provides rapid and efficient bacterial killing in ventilated piglets with inoculation pneumonia caused by Pseudomonas aeruginosa.

Topics: Administration, Inhalation; Animals; Anti-Bacterial Agents; Colistin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Injections, Intravenous; Nebulizers and Vaporizers; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Swine

Pseudomonas aeruginosa (PsA) is the most common pathogen to cause chronic lung infection in children with cystic fibrosis (CF), and is associated with an increase in both morbidity and mortality. Whilst the non-mucoid strain can be eradicated, it is believed that mucoid PsA is difficult, if not impossible, to eradicate. We hypothesized that with modern and aggressive antibiotic regimes, mucoid PsA can be eradicated in children with CF. We investigated this hypothesis through a retrospective review of respiratory tract cultures of children with CF at The Royal Brompton Hospital, London. Children aged under 16 with a confirmed diagnosis of CF and mucoid PsA on respiratory tract culture during a defined 9-year period were eligible for inclusion. Respiratory tract culture results were followed up for each patient to establish whether children remained infected with mucoid PsA and specifically to identify clearance of infection. Factors which may have been associated with persistence or clearance were also sought. One hundred sixteen children had the minimum dataset, and of these patients 67 (58%) cleared mucoid PsA for more than 1 year. Of the 67 patients who cleared mucoid PsA for more than 1 year, 38 (57%) patients remained clear of mucoid PsA at the last available culture (median 30, range 2-106 clear cultures, and median 55, 12-103 months clear). We conclude that isolation of mucoid PsA does not necessarily equate to lifelong infection. We suggest that trials of eradication of mucoid PsA at first isolation are required.

Topics: Adolescent; Anti-Bacterial Agents; Child; Colistin; Cystic Fibrosis; Female; Gentamicins; Humans; Longitudinal Studies; Male; Nebulizers and Vaporizers; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies

Topics: Aged; Anti-Bacterial Agents; Bronchiectasis; Colistin; Cystic Fibrosis; Drug Evaluation; Female; Humans; Male; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies

Although colistin methanesulfonate (CMS) has been used extensively in critically ill patients infected with multidrug-resistant organisms, the optimum dosing regimen remains to be determined. Herein, we examined the pharmacokinetics of three different dosing regimens of CMS, 3 million units every 8 h (regimen A), 4.5 million units every 12 h (regimen B), 9 million units every 24 h (regimen C) and evaluated the bactericidal activity of serum containing various concentrations of colistin against Pseudomonas aeruginosa with a minimum inhibitory concentration (MIC) of 1 microg/ml. the means +/- SE serum C(max )of colistin for regimens A, B, and C were 3.34+/-0.35, 2.98+/-0.27, and 5.63+/-0.87 microg/ml, respectively. All serum samples containing colistin >4 microg/ml (serum concentration/MIC >4) eliminated P. aeruginosa whereas only 40% of samples containing colistin <4 microg/ml resulted in complete bacterial killing. these findings indicate that the currently used dosing regimens might not provide the most effective therapy with CMS and justify administering larger dosages in longer intervals.

Topics: Aged; Anti-Bacterial Agents; Blood Bactericidal Activity; Colistin; Critical Illness; Dose-Response Relationship, Drug; Female; Humans; Intensive Care Units; Male; Microbial Sensitivity Tests; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections

Both bacteremia and biliary cast syndrome are serious post-transplant complications in liver transplant recipients. In the setting of increasing drug resistance in the current era, management of infections caused by multidrug-resistant (MDR) bacteria has proven challenging. We present a case of a liver transplant recipient who developed biliary cast syndrome and intractable MDR Pseudomonas bacteremia that failed to resolve with conventional antimicrobial therapy and which was finally controlled by a novel combination regimen of colistimethate, doripenem, and tobramycin. Future studies validating the clinical efficacy of this combination strategy are warranted.

Topics: Anti-Bacterial Agents; Bacteremia; Bile Duct Diseases; Carbapenems; Colistin; Doripenem; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Liver Transplantation; Male; Microbial Sensitivity Tests; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin; Treatment Outcome

Inhaled antibiotics are commonly used in the treatment of cystic fibrosis lung disease. A previous study suggested neutrophil elastase activation by colistin in vitro. Here, we investigated direct effects of the commonly used antibiotics colistin and tobramycin on neutrophil elastase activity.. Neutrophil elastase was measured spectrophotometrically. The antibiotics colistin and tobramycin were added in different concentrations with or without the addition of albumin.. Generally, neutrophil elastase activity was lower in the absence of albumin compared to its presence. Both antibiotics, colistin and tobramycin, had inhibitory effects on neutrophil elastase activity except for high concentrations of colistin when albumin was absent.. Our results suggest inhibitory effects of colistin and tobramycin in vitro. There was a clear dependency of neutrophil elastase measurements on the presence of albumin. Clinical studies are needed to investigate potential direct effects of inhaled antibiotics on neutrophil elastase activity in cystic fibrosis airways.

Topics: Administration, Inhalation; Albumins; Anti-Bacterial Agents; Colistin; Cystic Fibrosis; Humans; Leukocyte Elastase; Microbial Sensitivity Tests; Pseudomonas; Pseudomonas Infections; Tobramycin

Data regarding the role of inhaled colistin in critically ill pediatric patients without cystic fibrosis are scarce. Three children (one female), admitted to the intensive care unit (ICU) of a tertiary-care pediatric hospital in Athens, Greece, during 2004-2009 received inhaled colistin as monotherapy for tracheobronchitis (two children), and as adjunctive therapy for necrotizing pneumonia (one child). Colistin susceptible Acinetobacter baumannii and Pseudomonas aeruginosa were isolated from the cases' bronchial secretions specimens. All three children received inhaled colistin at a dosage of 75 mg diluted in 3 ml of normal saline twice daily (1,875,000 IU of colistin daily), for a duration of 25, 32, and 15 days, respectively. All three children recovered from the infections. Also, a gradual reduction, and finally total elimination of the microbial load in bronchial secretions was observed during inhaled colistin treatment in the reported cases. All three cases were discharged from the ICU. No bronchoconstriction or any other type of toxicity of colistin was observed. In conclusion, inhaled colistin was effective and safe for the treatment of two children with tracheobronchitis, and one child with necrotizing pneumonia. Further studies are needed to clarify further the role of inhaled colistin in pediatric critically ill patients without cystic fibrosis.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Albuterol; Anti-Bacterial Agents; Bronchitis; Bronchodilator Agents; Case-Control Studies; Child; Child, Preschool; Colistin; Critical Care; Critical Illness; Cystic Fibrosis; Female; Hospitals, Pediatric; Humans; Infant; Ipratropium; Male; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Tracheitis; Treatment Outcome

Tobramycin and colistin represent 2 standard antimicrobial agents in the treatment of cystic fibrosis (CF) patients who are chronically colonized with Pseudomonas aeruginosa. In this study, we determined the rate of resistance to tobramycin and colistin in 1844 isolates of P. aeruginosa obtained from 22 CF patients under alternate therapy with inhaled tobramycin and colistin. Resistance to tobramycin was observed in 27.5% of isolates. In contrast, all isolates were susceptible to colistin. Molecular typing of selected isolates suggested that only 1 clone occurred over time in each patient. To conclude, resistance to tobramycin in P. aeruginosa isolates from CF patients under antimicrobial therapy may occur while colistin resistance remains uncommon.

Topics: Adult; Anti-Bacterial Agents; Bacterial Typing Techniques; Chronic Disease; Cluster Analysis; Colistin; Cystic Fibrosis; DNA Fingerprinting; Drug Resistance, Bacterial; Female; Genotype; Humans; Male; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin

Cerebrospinal fluid (CSF) shunts significantly improve the quality of life in patients with acute hydrocephalus. However, infections associated with a CSF shunt constitute a severe complication with high morbidity and mortality. We describe a case of CFS shunt infection cured with intrathecal colistin.

Topics: Anti-Bacterial Agents; Cell Membrane; Cerebral Hemorrhage; Cerebral Ventriculitis; Cerebrospinal Fluid Shunts; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Hydrocephalus; Injections, Spinal; Male; Middle Aged; Postoperative Complications; Prosthesis-Related Infections; Pseudomonas aeruginosa; Pseudomonas Infections

Reports of patients with polymyxin-only susceptible gram-negative nosocomial pneumonia treated with inhaled, but without concurrent intravenous, colistin are rare.. Patients admitted in a tertiary 450-bed tertiary care centre during the period 05/01/2005-05/31/2007 and receiving colistin through nebulization, but not systemically, were included in this retrospective case series.. Five patients (three with ventilator-associated pneumonia and two with nosocomial pneumonia) received colistin through nebulization without concomitant intravenous colistin. The isolated pathogens were Acinetobacter baumannii (three cases), Pseudomonas aeruginosa (one case) and the combination of Klebsiella pneumoniae, A. baumannii and P. aeruginosa (one case). They were susceptible only to colistin (three cases) or to colistin and gentamicin (two cases). Intravenous antimicrobial agents given concurrently were piperacillin/tazobactam, meropenem, ceftriaxone and ciprofloxacin; isolated pathogens were resistant to these agents. Four (80%) out of the five patients were cured, survived and were discharged. One patient died. No colistin-related adverse event was observed.. The experience from this case series and other relevant recent reports suggest that treatment of pneumonia due to polymyxin-only susceptible gram-negative bacilli with inhaled colistin (without concurrent systemic administration) deserves further careful investigation.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Treatment Outcome

Topics: Anti-Bacterial Agents; Bacterial Proteins; Colistin; Drug Resistance, Bacterial; Humans; Korea; Methyltransferases; Pseudomonas aeruginosa; Pseudomonas Infections; RNA, Bacterial; RNA, Ribosomal, 16S

Multidrug-resistant Pseudomonas aeruginosa (MDRP) is becoming a serious problem in hospitals, especially in patients on ventilators. Recent data demonstrate that colistin may be effective for these patients, although limited in vitro and in vivo data are available. Our aim was to identify further characteristics of colistin for the therapy of pneumonia caused by MDRP.. The effects of colistin on clinical strains of MDRP were examined by susceptibility test, time-kill assay, lipopolysaccharide (LPS)-blocking assay and a mouse pneumonia model, alone or in combination with other antibiotics. For the pneumonia model, mice were intranasally infected with bacteria and kept in hyperoxic conditions to mimic ventilator-associated pneumonia.. As a single agent, colistin exhibited the strongest activity of the antimicrobial agents tested. In combination, maximum synergy was observed with colistin plus rifampicin. As expected, co-incubation of bacterial culture supernatants with colistin significantly reduced LPS activities with an associated decrease in cellular cytotoxicity. In the pneumonia model, intranasal, but not intravenous, colistin combined with rifampicin produced maximum survival protection. Pharmacokinetic analysis of colistin demonstrated the superiority of intranasal administration, judging from the compartmentalized high concentration and the long half-life in the lungs. Moreover, colistin therapy significantly decreased both production of inflammatory cytokines and LPS activity, even at a dose effecting no change in the bacterial burden in the lung.. These data strongly suggest that colistin may be an important option for combination therapy against critical MDRP infections. For pneumonia especially, intranasal colistin with rifampicin may be beneficial not only for synergistic antibacterial activity, but also for blocking LPS.

Topics: Administration, Intranasal; Animals; Anti-Bacterial Agents; Cell Line; Colistin; Drug Synergism; Drug Therapy, Combination; Female; Half-Life; Humans; Injections, Intravenous; Lipopolysaccharides; Lung; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Microbial Viability; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Survival Analysis

The incidence of multidrug-resistant Pseudomonas aeruginosa (MDRPA) and metallo-beta-lactamase (MBL)-producing P. aeruginosa has increased worldwide. The treatment options are limited for infectious diseases caused by these two organisms. The use of colistin has been of recent interest in cases involving both types. We report the case of a 74-year-old man with acute myeloid leukemia who was successfully treated with intravenous colistin for maxillary sinusitis and orbital cellulites due to MBL-producing MDRPA during neutropenia, and then for pneumonia caused by the bacteria after the recovery of neutrophil counts.

Topics: Aged; Anti-Bacterial Agents; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Leukemia, Myeloid, Acute; Male; Maxillary Sinusitis; Orbital Cellulitis; Pneumonia; Pseudomonas aeruginosa; Pseudomonas Infections; Treatment Outcome

Nosocomial infections by resistant gram-negative microorganisms are important causes of mortality in intensive care unit (ICU)'s. The treatment choices are limited in infections due to Acinetobacter baumannii and Pseudomonas aeruginosa, especially if they are panresistant. In these type of resistant infections, colistin--an old antibiotic--has become a current issue. The aim of this study was to evaluate the efficacy of colistin in 9 cases (6 males, mean age 75.8 +/- 9.4 years), with ventilator associated pneumonia (VAP) caused by panresistant A. baumannii and P. aeruginosa in respiratory ICU. All cases were referred to ICU from other hospitals or clinics. It was detected that 7 of 9 cases were treated with anti-pseudomonal antibiotics before the development of VAP. Panresistant A. baumannii was isolated in 5 cases and P. aeruginosa in 4 cases. VAP by these microorganisms was detected on the 26.6 +/- 12.4th days of invasive mechanical ventilation and the cases were followed up for 54.2 +/- 25.7 days in ICU. During colistin treatment, dermatitis (one case) and nephrotoxicity (one case) were observed as side effects. Microbiological response to colistin was obtained in 6 cases. Three cases died due to non-eradication of panresistant microorganisms and three cases died due to other infections during ICU follow-up. The data presented in this study demonstrates that colistin can be considered as a safe and effective antibiotic in the treatment of panresistant A. baumannii and P. aeruginosa infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Intensive Care Units; Male; Middle Aged; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections

Several guidelines on infection control and treatment of infection exist for cystic fibrosis (CF) caregivers, although the extent of implementation is variable.. Adherence to European Consensus Guidelines for CF was studied by sending surveys to named healthcare professionals in 487 European CF centres/units. Qualitative data analysis was performed.. A total of 177/547 (32%) surveys were returned. Infection control policies were implemented by most (77%) respondents. Separation of patients with Burkholderia cepacia was more common in adults (95%) than children (9%), and was implemented by 53% of respondents for Pseudomonas aeruginosa. Nebulised colistin plus oral ciprofloxacin was the most common (43%) therapy for P. aeruginosa infection. First infections of P. aeruginosa were usually treated with inhaled tobramycin; 41% of repondents did not intervene until lung function deteriorated. Most exacerbations were treated for less than the recommended period.. European Consensus Guidelines are widely adhered to. Areas for improvement include: initiating therapy for exacerbations early, separating infected patients and optimising duration of antibiotic therapy.

Topics: Administration, Inhalation; Adult; Anti-Bacterial Agents; Bacterial Infections; Burkholderia cepacia; Burkholderia Infections; Child; Child, Preschool; Ciprofloxacin; Colistin; Cystic Fibrosis; Europe; Guideline Adherence; Humans; Infection Control; Practice Guidelines as Topic; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections; Surveys and Questionnaires; Tobramycin; Young Adult

The aim of cystic fibrosis (CF) care is to improve both the life expectancy and quality of life of patients. However, rising costs and limited resources of health services must be taken into account. There are many different antibiotic strategies for therapy of Pseudomonas aeruginosa infection in CF patients. In this 5-year retrospective study we found that the cost of treatment of initial infection is considerably lower than the cost of treating chronic P. aeruginosa infections. The percentage distribution of costs of antibiotic treatment in relationship to the administration route was considerably different between outpatients and inpatients. We observed an increase in antibiotic costs with the age of the patient and the decrease in FEV(1)values. The implementation of early eradication treatment, in addition to decreasing the prevalence of patients chronically infected by P. aeruginosa, might also bring about a notable decrease in costs.

Topics: Adult; Anti-Bacterial Agents; Ceftazidime; Child, Preschool; Chronic Disease; Ciprofloxacin; Clavulanic Acids; Colistin; Cost of Illness; Cystic Fibrosis; Humans; Meropenem; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Thienamycins; Ticarcillin; Tobramycin

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Biofilms; Colistin; Humans; Microbial Sensitivity Tests; Microbial Viability; Pseudomonas aeruginosa; Pseudomonas Infections

Adaptive aerosol delivery (AAD) nebuliser devices can reduce treatment times whilst enabling adherence to be monitored using inbuilt data logs. Using one such device, we have monitored nebulised antibiotic adherence in children with Cystic Fibrosis (CF).. In CF children infected with Pseudomonas aeruginosa, downloaded data from an AAD device was used to calculate morning, evening and overall monthly adherence to antibiotic therapy over a year.. Overall monthly adherence to nebulised antibiotic therapy in 28 children was maintained between 60 and 70% over the year. Considerable variation in adherence, both between and within patients, was evident (Mean [SD] coefficient of variation, 37[44]%). Evening adherence (75[37]%) was better than morning adherence (58[34]%: p=0.012). Treatment regimens were changed in 8/28 patients based on adherence data.. Routine adherence monitoring can be implemented in an outpatient setting. Using this type of information it is possible to identify which aspects of treatment can be improved and to work together with families to individualize treatments.

Topics: Administration, Inhalation; Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Colistin; Cystic Fibrosis; Drug Monitoring; Humans; Medication Adherence; Nebulizers and Vaporizers; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies

Colistin is an important cationic antimicrobial peptide (CAMP) in the fight against Pseudomonas aeruginosa infection in cystic fibrosis (CF) lungs. The effects of subinhibitory concentrations of colistin on gene expression in P. aeruginosa were investigated by transcriptome and functional genomic approaches. Analysis revealed altered expression of 30 genes representing a variety of pathways associated with virulence and bacterial colonization in chronic infection. These included response to osmotic stress, motility, and biofilm formation, as well as genes associated with LPS modification and quorum sensing (QS). Most striking was the upregulation of Pseudomonas quinolone signal (PQS) biosynthesis genes, including pqsH, pqsB and pqsE, and the phenazine biosynthesis operon. Induction of this central component of the QS network following exposure to subinhibitory concentrations of colistin may represent a switch to a more robust population, with increased fitness in the competitive environment of the CF lung.

Topics: Anti-Bacterial Agents; Colistin; DNA, Bacterial; Dose-Response Relationship, Drug; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Genes, Bacterial; Humans; Hydroxyquinolines; Oligonucleotide Array Sequence Analysis; Pseudomonas aeruginosa; Pseudomonas Infections; Pyocyanine; Quinolones; Quorum Sensing; Transcriptional Activation

To describe the clinical and microbiological outcomes of patients infected with multidrug-resistant Pseudomonas aeruginosa (MDRP) treated with colistin (colistimethate sodium) and the adverse events observed with this treatment.. Retrospective study of MDRP infections treated with colistin from 1997 to 2006.. 121 episodes were identified. The median daily intravenous dose was 240 mg/day; 28.9% of patients received intravenous and nebulized colistin. Clinical outcome was favorable in ten cases of bacteremia (62.5%, n = 16), 43 cases of bronchial infection (72.9%, n = 59), 13 cases of pneumonia (65%, n = 20), 11 cases of urinary infection (84.6%, n = 13), eight cases of skin and soft tissues (72.7%, n = 11), and in the one case of arthritis and one case of otitis. Eradication was achieved in 31 (34.8%) of the 89 patients with available bacteriologic data. Factors associated with bacteriological failure were smoking, chronic obstructive pulmonary disease (COPD), and previous infection with P. aeruginosa. Nephrotoxicity occurred in ten cases (8.3%), with the associated factors being previous chronic renal insufficiency, diabetes mellitus, and aminoglycoside use. Crude mortality was 16.5%, and related MDRP was 12.4%, and was higher in patients with pneumonia or bacteremia (36.1%) than in other types of infections (8.2%).. Colistin is a safe option for the treatment of MDRP infections, with acceptable clinical outcomes. However, bacteriological eradication is difficult to achieve, especially in COPD patients.

Topics: Administration, Inhalation; Aged; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Injections, Intravenous; Kidney Diseases; Male; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Treatment Outcome

Multidrug resistant Gram-negative rods are emerging as major pathogens and are the cause of difficulty to treat infections. In certain situations colistin is the only active drug.. A retrospective review of the patient's charts admitted at Hôtel-Dieu de France hospital, Beirut, between October 2002 and February 2004 and treated with intravenous colistin.. Fifteen patients were identified; they were suffering from urinary tract infections, cellulitis, osteomyelitis, mediastinitis and intra-abdominal abscess. The microorganisms were resistant to all available antibiotics except colistin. Three strains were also susceptible to aminoglycosides. Pseudomonas aeruginosa was the most frequently isolated pathogen. Colistin was used in monotherapy in 12 patients and combined with amikacin in three patients. At the end of therapy, a 93% rate of favorable clinical outcome was observed. Renal toxicity was encountered among 12 patients. It was severe in only two cases in which creatinine clearance decline surpassed 50% of the baseline value. No neurological toxicity was observed.. Colistin has an important role to play when used for the treatment of infections with multiresistant Gram-negative bacteria. Nephrotoxicity seems much lower than expected and neurotoxicity is minimal.

Topics: Abdominal Abscess; Anti-Bacterial Agents; Colistin; Gram-Negative Bacteria; Humans; Infusions, Intravenous; Kidney; Osteomyelitis; Pseudomonas aeruginosa; Pseudomonas Infections; Pyelonephritis; Retrospective Studies; Urinary Tract Infections

Since 1989, CF-patients intermittently colonized with Pseudomonas aeruginosa have been treated with inhaled colistin and oral ciprofloxacin in the Copenhagen CF-centre. The study evaluates 15 years results of this treatment.. All isolates of P. aeruginosa from CF-patients intermittently colonized with P. aeruginosa from 1989 to 2003 were identified All anti-P. aeruginosa treatments were evaluated for antibiotics used, treatment duration, pseudomonas-free interval and development of chronic infection. All P. aeruginosa isolates were assessed for resistance and for non-mucoid or mucoid phenotype.. 146 CF-patients were included in the study (1106 patient-years). 99 patients had first ever isolate during the study period. Median observation time 7 years (0.1-14.9). 12 patients developed chronic infection. A Kaplan Meyer plot showed protection from chronic infection in up to 80% of patients for up to 15 years. 613 colistin/ciprofloxacin treatments were given. There was no difference in pseudomonas-free interval comparing 3 weeks (5 months) and 3 months (10.4 months) of colistin and ciprofloxacin, but a significant difference compared to no treatment (1.9 months). Patients developing chronic infection had significantly shorter pseudomonas-free interval after treatment of first ever isolate compared to patients remaining intermittently colonized (p<0.003). Treatment failure (P. aeruginosa-positive culture immediately after ended treatment of first ever isolate) was a strong risk factor for development of chronic infection after 3-4 years, OR 5.8. 1093 pseudomonas-isolates were evaluated (86.6% non-mucoid). No colistin-resistance was found. Ciprofloxacin-resistance was found in 4% of isolates.. Treatment of intermittent P. aeruginosa colonization in CF-patients using colistin and ciprofloxacin can protect up to 80% of patients from development of chronic infection for up to 15 years. A positive culture immediately after treatment of first ever isolate is a strong risk factor for development of chronic infection. We found no colistin-resistance and minimal ciprofloxacin-resistance.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Adult; Anti-Bacterial Agents; Child; Child, Preschool; Chronic Disease; Ciprofloxacin; Cohort Studies; Colistin; Cystic Fibrosis; Disease-Free Survival; Female; Humans; Infant; Male; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections; Retrospective Studies; Treatment Outcome; Young Adult

Multidrug-resistant Pseudomonas aeruginosa, especially metallo-beta-lactamase (MBL)-producing P. aeruginosa, is an important pathogen in nosocomial infection and emergence of this pathogen has revived interest in polymyxin B (PMB) and colistin (COL). In this study, we evaluated the efficacies of PMB, COL and other antipseudomonal agents against IMP-type MBL-producing P. aeruginosa both in vitro and in vivo. A total of 75 isolates of bla(IMP)-positive P. aeruginosa obtained from clinical specimens (94.6% of isolates demonstrated resistance to beta-lactam, fluoroquinolone and aminoglycoside agents) were evaluated in the in vitro study. More than 90% of the examined isolates were susceptible to PMB (minimum inhibitory concentration for 50/90% of the isolates (MIC(50)/MIC(90)) 4/4 mg/L), although COL was less potent (MIC(50)/MIC(90) 8/16 mg/L). Cyclophosphamide-treated mice were intraperitoneally inoculated with bla(IMP)-positive P. aeruginosa. Treatment with PMB, but not COL, imipenem/cilastatin or aztreonam, significantly improved the survival rate and decreased the number of bacteria in the blood in a dose-dependent manner. Our results indicate that, among the agents studied, PMB is the most effective agent against bla(IMP)-positive P. aeruginosa.

Topics: Animals; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Colistin; Colony Count, Microbial; Drug Resistance, Bacterial; Male; Mice; Microbial Sensitivity Tests; Polymyxin B; Pseudomonas aeruginosa; Pseudomonas Infections; Reverse Transcriptase Polymerase Chain Reaction; Survival Analysis

Emergence of multi and pan-drug resistant Gram-negative bacteria causing nosocomial infections in intensive care settings has become a challenge for clinicians. The mortality rate of ventilator-associated pneumonia (VAP) is known to increase when the initial microbiological diagnosis and antimicrobial therapy are inappropriate. We present a case of a 18-year-old man, who after being admitted following an accident, had developed VAP due to multi-drug resistant Pseudomonas aeruginosa and Acinetobacter spp. and had a downhill clinical course despite broad-spectrum antibiotic treatment. The strains were found to be Col-S, as the susceptibility was tested. Colistin was instituted, with remarkable recovery. It is imperative to diagnose VAP with multi-drug resistant strains as early as possible; colistin, the 'last resort' antibiotic, if instituted with proper monitoring at the right time, can be life saving.

Topics: Acinetobacter Infections; Adolescent; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Male; Pneumonia, Ventilator-Associated; Pseudomonas Infections; Treatment Outcome

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Amikacin; Brain Ischemia; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Fatal Outcome; Humans; Hydrocephalus; Injections, Spinal; Male; Meningitis, Bacterial; Pseudomonas Infections; Shock, Septic; Surgical Wound Infection; Ventriculostomy

The in vitro activities of various antibiotics, either alone or in combination with colistin methanesulfonate, were assessed using Pseudomonas aeruginosa strains isolated from cystic fibrosis patients.. Except for colistin methanesulfonate, minimum inhibitory concentrations were determined by microbroth dilution technique as described by the Clinical and Laboratory Standards Institute (CLSI); for colistin methanesulfonate, a modified method of the CLSI was used. Minimum bactericidal concentrations were determined as described by the CLSI. The in vitro activities of antibiotics in combination were determined by microbroth checkerboard technique, and results were interpreted by fractional inhibitory concentration index.. According to MIC values, 100, 98, 96 and 84% of the isolates were found susceptible to amikacin, colistin methanesulfonate, meropenem and ceftazidime, respectively. The minimum bactericidal concentrations were generally equal to or twice as high as those of the minimum inhibitory concentrations. With a fractional inhibitory concentration index of < or =0.5 as borderline, synergistic interactions were more frequent with combinations where amikacin was involved than with those with colistin methanesulfonate. No antagonism was observed.. The findings of this study may play a useful role in selecting the appropriate combinations when a single agent is inadequate to treat cystic fibrosis patients with P. aeruginosa infections.

Topics: Anti-Bacterial Agents; Colistin; Cystic Fibrosis; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

Colistin resistant Pseudomonas aeruginosa have rarely been reported in cystic fibrosis (CF) patients.. We performed a 17-year prospective study on colistin susceptibility and compared our findings with clinical variables.. The first outbreak started in 1995 and lasted 5 years. It involved 27 CF patients who had inhaled colistin twice daily for a median of 10 years. Colistin resistant isolates persisted in individual patients for a median of 75 days after colistin was withdrawn. A second outbreak started in 2004. It involved 40 patients, 17 of whom were the same as in the first outbreak. Most resistant isolates belonged to two major clones that had similar genotypes in the two outbreaks. The P. aeruginosa isolates were all non-mucoid and they appeared in a group of chronically infected patients that had been admitted to the same ward for antibiotic treatment and had been followed at the same week-days in the outpatient clinic. Patients were individually isolated to avoid cross-infection and colistin inhalation was avoided in the CF outpatient clinic and in the ward after both outbreaks. Since 2004, no further spread has been observed.. It is important that the colistin resistant clones do not spread to non-infected patients since colistin is an important antibiotic for eradication of initial and intermittent P. aeruginosa colonisation.

Topics: Administration, Inhalation; Adolescent; Adult; Child; Colistin; Cystic Fibrosis; Denmark; Disease Outbreaks; Drug Resistance, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Patient Isolation; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Function Tests

Gram-negative bacilli, including multi-drug-resistant (MDR) Pseudomonas aeruginosa, are responsible for severe intensive care unit (ICU)-acquired infections, mainly pneumonia and bacteremia. The aim of this study was to determine the incidence of MDR strains of Pseudomonas in patients undergoing cardiac surgery, to elucidate the effectiveness of treating these patients with colistin, and to assess the safety of the drug.. A prospective study was conducted among 1,452 patients who underwent surgery for a variety of cardiac lesions over a one-year period, and who spent a portion of the recovery period in the surgical ICU. Their case histories were analyzed to identify infectious complications. Diagnosis of infection was based on clinical data, and the pathogen was tested with respect to its susceptibility to colistin (polymyxin E). The clinical response to the antibiotic was evaluated.. Over the 12-month period, among 115 infected patients, 15 were affected by strains of P. aeruginosa. In 10 patients, this pathogen proved resistant to all potentially active antibiotics except colistin. All of the affected patients were being ventilated mechanically, and eight of them presented with ventilator-associated pneumonia (VAP), whereas one patient suffered a deep incisional surgical site infection and bacteremia and the remaining patient had a superficial infection of a lower-extremity vein graft donor site. The MDR pathogen was introduced to the hospital by three patients transferred from three institutions. All patients were treated with intravenous colistin. In cases of VAP, aerosolized colistin was added. Deterioration of renal function occurred in three patients (30%), all of whom had a history of renal insufficiency. Cure or clinical improvement was observed in seven patients (70%), whereas four patients, including one who improved initially, developed sepsis and died with multiple organ dysfunction syndrome (mortality rate 40%).. The increasing prevalence of MDR P. aeruginosa in ICU patients has rekindled interest in polymyxins, which had been abandoned because of toxic side effects. Colistin retained significant in vitro activity against this virulent organism, had an acceptable safety profile, and should be considered as a treatment option in critically ill patients with infection caused by MDR gram-negative bacilli. Aerosolized colistin may merit further consideration as a therapeutic intervention for patients with refractory pulmonary infections.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cardiac Surgical Procedures; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Intensive Care Units; Male; Middle Aged; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections

Daily nebulized colistin therapy has been used as maintenance therapy for patients with chronic Pseudomonas aeruginosa infection and in treatment protocols aimed at eradicating early P aeruginosa infection. Colistin-induced nephrotoxicity and mild neurotoxic effects have been described but hypersensitivity reactions are rare. However, bronchial constriction has been reported associated with the inhalation of the antibiotic. We report the case of a 63-year-old man who had been diagnosed with bronchiectasis and bronchopleural fistula and who developed severe bronchospasm when using nebulized colistin. A skin prick test (80 mg/mL) with colistin was performed and was negative. An intradermal test was not performed due to its possible irritant effect. As our patient suffered from a tobramycin-resistant P aeruginosa infection, we started a procedure to induce tolerance to 80 mg colistin (8 mg, 16 mg, 24 mg, 32 mg, 40 mg, 80 mg) nebulized in 30-minutes-intervals. No changes in forced expiratory volume in 1 second values were observed and the patient continues on treatment twice daily after the tolerance induction with no new episodes of bronchospasm. We report the first successful procedure to induce tolerance to colistin after escalating doses of inhaled colistin.

Topics: Anti-Bacterial Agents; Bronchial Spasm; Colistin; Drug Administration Schedule; Drug Tolerance; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Pseudomonas Infections; Skin Tests

This study reviewed 56 patients with significant metallo-beta-lactamase (MBL)-producing Pseudomonas aeruginosa infections between May 2002 and March 2004 to identify features associated with mortality. Immunosuppression (p 0.002), bacteraemia (p 0.08) and inadequate antimicrobial therapy (p <0.001) were associated with death. Among those patients treated with adequate therapy, the use of multiple drug treatment regimens (two or three active agents) was associated with a non-significant two-fold increase in survival (p 0.45). Further prospective studies are warranted to determine the optimal treatment of MBL-producing P. aeruginosa infections.

Topics: Aged; Anti-Bacterial Agents; Aztreonam; beta-Lactamases; Canada; Catchment Area, Health; Colistin; Cross Infection; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Survival Rate

The increasing incidence of infections caused by multidrug-resistant Pseudomonas aeruginosa is a worldwide health problem. Because no new antipseudomonal agents are expected to be available in the near future, we evaluated the safety and efficacy of colistin, an old drug with bactericidal activity against this organism. We collected clinical and demographic data on 95 cancer patients diagnosed with infections caused by multidrug-resistant P. aeruginosa between January 2001 and January 2004 and treated with either colistin (colistin group) or at least one active antipseudomonal agent (a beta-lactam antibiotic or a quinolone) (control group). We compared the results obtained for both groups. Thirty-one patients had been treated with colistin and 64 had been treated with an antipseudomonal non-colistin-containing regimen. Compared with the control group, patients in the colistin group had a lower median age (52 and 62 years, respectively; P = 0.012) but were more likely to have had nosocomial infections (87% and 64%, respectively; P = 0.02). Twenty-five patients (81%) in the colistin group and 40 patients (63%) in the control group had an APACHE II score of >15 (P = 0.074). The overall clinical response rates were 52% in the colistin group and 31% in the control group (P = 0.055). Multiple logistic regression analysis showed that those patients treated with colistin were 2.9 times (95% confidence interval, 1.1 to 7.6 times) more likely than those in the control group to experience a clinical response to therapy (P = 0.026). Colistin therapy was at least as effective and as safe a beta-lactam antibiotic or a quinolone in the treatment of infections caused by multidrug-resistant P. aeruginosa and, hence, may be a useful or preferred alternative therapy for this infection in cancer patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Child; Child, Preschool; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Neoplasms; Pseudomonas aeruginosa; Pseudomonas Infections; Regression Analysis; Treatment Outcome

Multidrug-resistant infections present a serious clinical and therapeutical problem. Colistin is an old-used polymyxin with rather poor pharmacokinetic profile and a remarkable nephrotoxicity. However, the emergence of multidrug-resistant bacteria has recently led to the increased use of colistin as a potentially available therapy. This article presents a 75-year-old diabetic woman with an early onset total knee arthroplasty infection by a multidrug-resistant Pseudomonas aeruginosa bacterial isolate that was managed successfully with surgical removal of the knee prosthesis, antibiotic impregnated cement and intravenous administration of colistin for 6 weeks, and second stage revision knee surgery. Two years later, laboratory and imaging studies showed no evidence of recurrence of infection.

Topics: Aged; Anti-Bacterial Agents; Arthroplasty, Replacement, Knee; Bone Cements; Colistin; Comorbidity; Diabetes Mellitus; Drug Resistance, Multiple, Bacterial; Female; Femoral Fractures; Humans; Knee Prosthesis; Prosthesis-Related Infections; Pseudomonas Infections; Reoperation

An experimental study has been performed to compare the in vitro activity and the in vivo efficacy of tachyplesin III, colistin, and imipenem against a multiresistant Pseudomonas aeruginosa strain. In vitro experiments included MIC determination, time-kill, and synergy studies. For in vivo studies, a mouse model of sepsis has been used. The main outcome measures were bacterial lethality, quantitative blood cultures, and plasma levels of lipopolysaccharide, tumor necrosis factor alpha, and interleukin-6. The combination of tachyplesin III or colistin with imipenem showed in vitro synergistic interaction. A significant increase in efficacy was also observed in vivo: combination-treated groups had significantly lower levels of bacteremia than did groups treated with a single agent. Tachyplesin III combined with imipenem exhibited the highest efficacy on all main outcome measurements. These results highlight the potential usefulness of these combinations and provide therapeutic alternatives for serious infections caused by gram-negative bacteria in the coming years.

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Colistin; DNA-Binding Proteins; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Imipenem; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Peptides, Cyclic; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis; Treatment Outcome

To investigate the efficacy of rifampin and colistin in three experimental rat models of Pseudomonas aeruginosa sepsis.. Prospective, randomized, controlled animal study.. Research laboratory in a university hospital.. Adult male Wistar rats.. Adult male Wistar rats were given a) an intraperitoneal injection of 1 mg of P. aeruginosa 10 lipopolysaccharide; b) 2 x 10(10) colony-forming units of P. aeruginosa ATCC 27853; and c) 2 x 10(10) colony-forming units of one clinically multiresistant strain of P. aeruginosa. For each model, all animals were randomized to receive intravenously isotonic sodium chloride solution, 10 mg/kg rifampin, 1 mg/kg colistin, and 10 mg/kg rifampin plus 1 mg/kg colistin.. Lethality, bacterial growth in blood and peritoneum, and endotoxin and tumor necrosis factor-alpha concentrations in plasma were measured. Colistin exerted a strong antimicrobial activity and achieved a significant reduction of plasma endotoxin and tumor necrosis factor-alpha concentration compared with control and rifampin-treated groups. Rifampin exhibited no antimicrobial activity with no substantial impact on endotoxin and tumor necrosis factor-alpha plasma concentrations. The combination of colistin and rifampin resulted in a significant reduction in bacterial count compared with colistin monotherapy, whereas no significant difference was found in positive hem cultures and mortality rates between the two groups.. Colistin and rifampin might have a role in the therapy of multiresistant P. aeruginosa infection.

Topics: Animals; Anti-Bacterial Agents; Cells, Cultured; Colistin; Colony Count, Microbial; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Male; Microbial Sensitivity Tests; Prospective Studies; Pseudomonas Infections; Random Allocation; Rats; Rats, Wistar; Rifampin; Shock, Septic; Survival Analysis

Acinetobacter spp. and Pseudomonas aeruginosa are common pathogens of ventilator-associated pneumonia (VAP). The presentation and outcome of VAP due to Acinetobacter spp. and P. aeruginosa susceptible to carbapenems (Carb-S; imipenem and/or meropenem) and to colistin only (Col-S) were compared in the present retrospective study in three intensive care units. A total of 61 episodes of VAP caused by Acinetobacter spp. or P. aeruginosa were studied, of which 30 isolates were Carb-S and 31 were Col-S. Demographics, worsening of renal function and mortality were not different. The univariate analysis showed that a later onset and a previous episode of VAP, prior antimicrobial therapy for >10 days and previous therapy with carbapenems during the present admission were more frequent in patients with Col-S strains. On multivariate analysis, prior antimicrobial therapy for >10 days and a previous episode of VAP remained significantly associated with Col-S VAP. Approximately 41% of the infections caused by Col-S isolates, but none of those due to Carb-S isolates, had received prior carbapenem therapy. Colistin-susceptible ventilator-associated pneumonia episodes can be effectively treated using colistin without significant renal dysfunction. This susceptibility pattern could be suspected in patients with a previous ventilator-associated pneumonia episode or prior antibiotic therapy for >10 days preceding the present ventilator-associated pneumonia episode.

Topics: Acinetobacter Infections; Analysis of Variance; Anti-Bacterial Agents; Chi-Square Distribution; Colistin; Drug Resistance, Microbial; Female; Humans; Imipenem; Male; Meropenem; Middle Aged; Pneumonia; Pseudomonas aeruginosa; Pseudomonas Infections; Respiration, Artificial; Retrospective Studies; Risk Factors; Thienamycins; Ventilators, Mechanical

Seventy-two isolates of carbapenem-resistant Pseudomonas aeruginosa (CRPA) collected through the Taiwan Surveillance of Antimicrobial Resistance (TSAR) program in 2000 and 2002 were studied for carriage of metallo-beta-lactamase (MBL), integrase genes, and integrons. Epidemiologic relatedness was determined using pulsed-field gel electrophoresis. The prevalence of the MBL genes among CRPA was 36.0% (9 of 25) in TSAR II and 17.0% (8/47) in TSAR III, with prevalence in surveyed hospitals being 19.1% (4/21, TSAR II) and 23.1% (6 of 26, TSAR III). The bla(VIM-3) was detected in 15 of the 17 MBL-positive isolates; the remainder possessed bla(VIM-2). The bla(IMP) was not evident. Class 1 integron was detected in all MBL-positive isolates; amplicon DNA sequences containing the bla(VIM-3) regions were all identical. All MBL-positive isolates remained susceptible to colistin. Molecular typing revealed a predominant strain that comprised 14 of the isolates among the various surveyed hospitals.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Colistin; Electrophoresis, Gel, Pulsed-Field; Humans; Integrases; Integrons; Microbial Sensitivity Tests; Molecular Epidemiology; Population Surveillance; Prevalence; Pseudomonas aeruginosa; Pseudomonas Infections; Taiwan

Our study aimed to determine the efficacy and safety of colistin in the treatment of ventilator-associated pneumonia (VAP) caused by pan-drug-resistant Pseudomonas aeruginosa or Acinetobacter baumanii.. Pairwise, retrospective exposed-unexposed study.. Combined medical and surgical intensive care unit of Habib Bourguiba University Hospital (Sfax, Tunisia).. Sixty patients with VAP caused by pan-drug-resistant A. baumanii or P. aeruginosa matched to 60 controls with VAP caused by A. baumanii or P. aeruginosa susceptible to imipenem. All patients had normal renal function at the onset of antibiotic therapy.. Case patients were treated by colistin intravenously and control patients were treated by imipenem intravenously.. Baseline characteristics were similar between the colistin and imipenem groups. The mean duration of antibiotic therapy for VAP was 9.5+/-3.8 days (range 5-22 days) with colistin and 8.9+/-2.8 days (range 5-20 days) with imipenem (p=0.32). A favorable clinical response to antibiotic therapy for VAP occurred in 45 patients (75%) in the colistin group and in 43 patients (71.7%) in the imipenem group (p=0.68). The time to resolution of infectious parameters after the initiation of antibiotic therapy was not statistically different between the two groups. During the antibiotic course, none of the patients in either group developed renal failure.. We conclude that colistin can be a safe and effective option in the treatments of VAP caused by pan-drug-resistant P. aeruginosa or A. baumanii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Case-Control Studies; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Imipenem; Injections, Intravenous; Intensive Care Units; Male; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Pseudomonas Infections; Retrospective Studies; Time Factors

Topics: Animals; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Gram-Negative Bacterial Infections; Humans; Pseudomonas Infections; Rats; Rifampin; Sepsis; Treatment Failure

Nosocomial outbreaks caused by multidrug-resistant (MDR) Pseudomonas aeruginosa have been associated to fibrocystic patients and isolates harboring metallo-beta-lactamase (MBL) genes. Genotyping is an important tool for interpreting bacterial nosocomial outbreaks and implementing adequate control strategies. The aim of this study was to evaluate whether an outbreak of MDR P. aeruginosa occurring in different hospitals was due to a unique clone or independent isolates. From 2000 to 2003, 108 P. aeruginosa were recovered from colonized/infected inpatients in hospitals of São Luís, Maranhão, Brazil. The susceptibility test was performed with antipseudomonal drugs, and the presence of MBL genes were verified by PCR. Isolates were genotyped by pulsed-field gel electrophoresis (PFGE). The majority of strains was multiresistant including a great number presenting the colistin-only-sensitive (COS) profile. PFGE analysis revealed 54 genotypes, with predominance of three major COS clones (A, C, and E) coexisting at different moments and hospitals. Clone A harbored the bla(SPM) gene. Eight unique genotypes also had the COS profile. Other eight MDR genotypes presented isolates with differences in resistance profiles. Here we detected, for the first time, the coexistence of COS P.aeruginosa genotypes disseminated in several hospitals during long periods, attacking patients under various clinical conditions.

Topics: Anti-Bacterial Agents; Brazil; Colistin; Cross Infection; Disease Outbreaks; Disk Diffusion Antimicrobial Tests; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Genes, Bacterial; Genotype; Hospitals; Humans; Polymerase Chain Reaction; Pseudomonas aeruginosa; Pseudomonas Infections

Considering the increasing use of polymyxins to treat infections due to multidrug resistant Gram-negative in many countries, it is important to evaluate different susceptibility testing methods to this class of antibiotic.. Susceptibility of 109 carbapenem-resistant P. aeruginosa to polymyxins was tested comparing broth microdilution (reference method), disc diffusion, and Etest using the new interpretative breakpoints of Clinical and Laboratory Standards Institute.. Twenty-nine percent of isolates belonged to endemic clone and thus, these strains were excluded of analysis. Among 78 strains evaluated, only one isolate was resistant to polymyxin B by the reference method (MIC: 8.0 microg/mL). Very major and major error rates of 1.2% and 11.5% were detected comparing polymyxin B disc diffusion with the broth microdilution (reference method). Agreement within 1 twofold dilution between Etest and the broth microdilution were 33% for polymyxin B and 79.5% for colistin. One major error and 48.7% minor errors were found comparing polymyxin B Etest with broth microdilution and only 6.4% minor errors with colistin. The concordance between Etest and the broth microdilution (reference method) was respectively 100% for colistin and 90% for polymyxin B.. Resistance to polymyxins seems to be rare among hospital carbapenem-resistant P. aeruginosa isolates over a six-year period. Our results showed, using the new CLSI criteria, that the disc diffusion susceptibility does not report major errors (false-resistant results) for colistin. On the other hand, showed a high frequency of minor errors and 1 very major error for polymyxin B. Etest presented better results for colistin than polymyxin B. Until these results are reproduced with a large number of polymyxins-resistant P. aeruginosa isolates, susceptibility to polymyxins should be confirmed by a reference method.

Topics: Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Bacterial; False Positive Reactions; Humans; Microbial Sensitivity Tests; Polymyxin B; Pseudomonas aeruginosa; Pseudomonas Infections

Multi-drug resistant Pseudomonas aeruginosa has been implicated in a variety of serious therapeutic problems in clinical environments. Among the 968 P. aeruginosa isolates obtained from two hospitals in Daegu, Korea, we acquired 17 isolates that were resistant to all available tested antimicrobial agents, with the exception of colistin (colistin-only sensitive). We characterized the antimicrobial susceptibilities, metallo-beta-lactamases, and epidemiological relatedness among the colistin-only sensitive P. aeruginosa isolates. All colistin-only sensitive isolates were positive in the modified Hodge test and imipenem-EDTA synergy test, thereby indicating the production of metallo-beta-lactamases. 11 isolates from the secondary hospital and six isolates from the tertiary teaching hospital harbored blaVIM-2 and blaIMP-1, respectively. The pulsed-field gel electrophoretic analysis of the SpeI-digested DNA from P. aeruginosa isolates indicated that two different clones of colistin-only sensitive P. aeruginosa originated from each hospital, and had spread within the hospital environment. Overall, colistin-only sensitive P. aeruginosa was detected in Korea for the first time, but no pan-drug resistant bacteria were identified. Nationwide surveillance is required in order to monitor the emergence of colistin-only sensitive or pan-drug resistant bacteria.

Topics: Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Cluster Analysis; Colistin; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Humans; Korea; Microbial Sensitivity Tests; Polymerase Chain Reaction; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Aerosols; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections

Emergence of panresistant gram negative bacilli has lead to the progressive reintroduction of intravenous colistin.. To describe the clinical experience observed with this compound.. A retrospective analysis was performed for all treatments lasting >/= 48 hours. Medical records were analyzed to obtain clinical parameters and microbiological data, evaluate clinical response and evolution until discharge.. 24 treatments lasting >/= 48 hours were applied between June 2005 and September 2006. Intravenous colistin was indicated to treat cases of ventilator-associated (VA) pneumonia (n = 10; 41.7%), abscess or collections (12.5%), bloodstream infections, non-VA pneumonia or urinary tract infections (4.2% each one, respectively). Treatment was initiated on average at 3.2 days (+/- 2.85) from diagnosis of infection. All courses were microbiologically-guided, and involved P. aeruginosa or A. baumannii isolates. Susceptibility was evaluated by E-test in 11 isolates (MIC90 3.6 nicrog/mL, range 0.38 to 4 microg/mL). One isolate was resistant to colistin (9%). A favorable response was observed in 12 treatments (50%) with a relapse in 5 cases (41.7%). Being treated for pneumonia was the only factor associated to failure, (p = 0.04) Eradication was documented in 8 cases (33.3%) and persistence in 11 (45.8%). In 5 cases a microbiological follow-up was not available. Survival at time of discharge was 45.5%. (n = 10) None of the treatment courses was associated with nefrotoxicity.. Intravenous colistin is a safe compound useful to treat various nosocomial infections due to pan-resistant gram negative bacilli. Nonetheless, its clinical efficacy is limited, especially among patients treated for nosocomial pneumonia.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; APACHE; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Treatment Outcome

A case of osteomyelitis caused by multidrug-resistant Pseudomonas aeruginosa is reported in a patient who underwent allogeneic bone marrow transplantation for acute lymphoblastic leukaemia. The patient was successfully treated by prolonged administration of a full dose of colistin and tigecycline, and surgical curettage with the positioning of resorbable calcium sulfate pellets loaded with colistin.

Topics: Adult; Anti-Bacterial Agents; Bone Marrow Transplantation; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Minocycline; Osteomyelitis; Pseudomonas aeruginosa; Pseudomonas Infections; Tigecycline; Transplantation, Homologous

Topics: Administration, Inhalation; Adult; Anti-Bacterial Agents; Colistin; Cystic Fibrosis; Drug Compounding; Fatal Outcome; Female; Humans; Nebulizers and Vaporizers; Prodrugs; Pseudomonas Infections; Respiratory Distress Syndrome

Topics: Adult; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Infusions, Intralesional; Infusions, Intravenous; Injections, Spinal; Meningitis; Pseudomonas aeruginosa; Pseudomonas Infections; Treatment Outcome

A 57-year-old man requiring ventilation after gastric-tube reconstruction (due to oesophageal carcinoma) and a 16-year-old boy with thoracic trauma developed pneumonia caused by Pseudomonas aeruginosa and other pathogens. Their infections persisted during treatment with antibiotics. The antibiotic colistin was added and the clinical condition improved in both patients after 3-4 weeks. Eventually, they both were transferred to a rehabilitation clinic. The use of colistin was abandoned in the 1970s due to alleged nephro- and neurotoxicity. In recent observational studies, the drug appeared to cause fewer toxic side-effects than previously thought. Colistin is only registered for inhaled use for lung infections and for resistant pulmonary infections in patients with cystic fibrosis, but it may also be effective in the treatment of other patients with multidrug-resistant, Gram-negative bacteria.

Topics: Adolescent; Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Humans; Male; Middle Aged; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Treatment Outcome

There is a dearth of information on the pharmacodynamics of "colistin," despite its increasing use as a last line of defense for treatment of infections caused by multidrug-resistant gram-negative organisms. The antimicrobial activities of colistin and colistin methanesulfonate (CMS) were investigated by studying the time-kill kinetics of each against a type culture of Pseudomonas aeruginosa in cation-adjusted Mueller-Hinton broth. The appearance of colistin from CMS spiked at 8.0 and 32 mg/liter was measured by high-performance liquid chromatography, which generated colistin concentration-time profiles. These concentration-time profiles were subsequently mimicked in other incubations, independent of CMS, by incrementally spiking colistin. When the cultures were spiked with CMS at either concentration, there was a substantial delay in the onset of the killing effect which was not evident until the concentrations of colistin generated from the hydrolysis of CMS had reached approximately 0.5 to 1 mg/liter (i.e., approximately 0.5 to 1 times the MIC for colistin). The time course of the killing effect was similar when colistin was added incrementally to achieve the same colistin concentration-time course observed from the hydrolysis of CMS. Given that the killing kinetics of CMS can be accounted for by the appearance of colistin, CMS is an inactive prodrug of colistin with activity against P. aeruginosa. This is the first study to demonstrate the formation of colistin in microbiological media containing CMS and to demonstrate that CMS is an inactive prodrug of colistin. These findings have important implications for susceptibility testing involving "colistin," in particular, for MIC measurement and for microbiological assays and pharmacokinetic and pharmacodynamic studies.

Topics: Anti-Bacterial Agents; Colistin; Culture Media; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Microbial Sensitivity Tests; Prodrugs; Pseudomonas aeruginosa; Pseudomonas Infections; Reference Standards

Nosocomial infections due to MDR P. aeruginosa are an increasing problem. Therapeutical options are few. We describe two haematological patients with severe neutropenia and systemic infection due to MDR P. aeruginosa treated successfully with colistin plus ceftazidime. Severe adverse events were not described.

Topics: Acute Disease; Adrenal Cortex Hormones; Aged; Anemia, Refractory, with Excess of Blasts; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; Ceftazidime; Colistin; Colitis; Disease Susceptibility; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Fatal Outcome; Female; Humans; Infusions, Intravenous; Leukemia, Myeloid; Lymphoma, Non-Hodgkin; Male; Middle Aged; Neoplasms, Second Primary; Peritonitis; Postoperative Complications; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pseudomonas Infections; Radiation Injuries; Spinal Neoplasms; Typhlitis

To report a case of a man who developed temporary hypotension after aerosolized colistin administration.. A 62-year-old Arab male was admitted to the intensive care unit for respiratory failure and septic shock. Simultaneous therapy using intravenous and aerosolized colistin was initiated for the management of multidrug-resistant Pseudomonas aeruginosa. A significant but transient drop in blood pressure occurred when aerosolized colistin was introduced. However, when it was stopped, but intravenous administration was continued, no hypotension was observed. Moreover, the combined use of aerosolized amikacin with intravenous colistin did not significantly affect blood pressure.. It is widely accepted that aerosolization allows safe administration of colistin in the absence of significant systemic adverse effects. However, in our patient, hypotension was observed with aerosolized colistin, but not with the systemic formulation. The lack of adverse effects with administration of aerosolized amikacin in this patient demonstrates the safety of the aerosolization technique. Use of the Naranjo scale indicated a probable relationship between hypotension and aerosolized colistin administration.. This case suggests that hypotension may be induced with administration of aerosolized colistin. Although this effect is rare, clinicians should be aware that hypotension may develop in critically ill patients following aerosolized colistin treatment.

Topics: Administration, Inhalation; Aerosols; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Hypotension; Male; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections

The evaluation of the safety and effectiveness of colistin in association with rifampin and imipenem in 1 diabetic patient with severe diabetic foot infection (DFI) due to multidrug-resistant (MDR) Pseudomonas aeruginosa, complicated by osteomyelitis, is presented in this "Case Report". The patient received colistin after other ineffective antimicrobial treatment when an MDR P aeruginosa strain was isolated by cultural examination, together with a multidisciplinary care approach including surgical debridement and adequate offloading. The efficacy of combination colistin plus rifampin plus imipenem was observed with a checkerboard method and bactericidal activity of the serum. The patient received colistin combination therapy for 6 weeks with cure of the infection and without renal toxicity. These data suggest that colistin, in combination with rifampin and imipenem, is safe and effective, in promoting healing in DFI due to MDR P aeruginosa and suggest the need for controlled clinical studies.

Topics: Aged; Anti-Bacterial Agents; Colistin; Diabetic Foot; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Follow-Up Studies; Humans; Imipenem; Male; Metatarsal Bones; Osteomyelitis; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin

The objective of this study was to determine the efficacy of systemic colistin therapy in the treatment of nosocomial infections caused by multidrug-resistant Acinetobacter baumannii or Pseudomonas aeruginosa and to study related adverse events. We prospectively studied 78 infections caused by multidrug-resistant A. baumannii or P. aeruginosa that were treated with colistin. The sites of infection were pulmonary infection (78.2%), urinary tract infection (7.7%), primary bloodstream infection (11.5%) and meningitis (2.6%). The mean daily dose of colistin was 5.5+/-1.1 MU/day (range 2-9 MU/day) and the mean duration of colistin therapy was 9.3+/-3.8 days (range 5-21 days). A favourable clinical response to colistin occurred in 60 cases (76.9%). Renal failure occurred in only seven cases. We conclude that colistin can be a safe and effective salvage therapeutic option for nosocomial infections caused by multidrug-resistant A. baumannii or P. aeruginosa.

Topics: Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Humans; Intensive Care Units; Prospective Studies; Pseudomonas Infections; Salvage Therapy; Treatment Outcome

Topics: Adolescent; Anti-Bacterial Agents; Brain Diseases; Cerebral Ventricles; Cerebrospinal Fluid Shunts; Colistin; Drug Resistance, Multiple; Humans; Injections, Spinal; Male; Pseudomonas aeruginosa; Pseudomonas Infections; Treatment Outcome

The use of colistin for the treatment of infections caused by multiple-drug-resistant (MDR) gram-negative microorganisms was studied.. The efficacy of colistin for treating infections caused by MDR gram-negative microorganisms and the development of renal toxicity were studied in hospitalized adult patients in Spain. Patients treated between January 2001 and October 2001 were included.. Over the study period, 71 courses of inhaled colistin, 12 courses of i.v. or intramuscular (i.m.) colistin, and 2 courses of intrathecal colistin were administered to 80 patients. All were infected by MDR organisms: 69 (86%) by Acinetobacter baumannii and 11 (14%) by Pseudomonas aeruginosa. In 41 patients (51%), the episodes were caused by A. baumannii strains susceptible exclusively to colistin. The causative organisms were cleared in 92% of the patients from whom posttreatment repeat specimens were obtained. The in-hospital mortality rate was 18% (14 patients). There were no significant changes in mean serum urea or creatinine concentrations in patients receiving i.v. or i.m. therapy.. Colistin was used in 80 patients infected with A. baumannii or P. aeruginosa and appeared to be efficacious and safe.

Topics: Acinetobacter Infections; Colistin; Drug Administration Routes; Drug Administration Schedule; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Inpatients; Length of Stay; Male; Middle Aged; Pseudomonas Infections; Retrospective Studies; Spain; Treatment Outcome

To report 2 cases of multidrug-resistant (MDR) Pseudomonas aeruginosa meningitis and ventriculo-peritoneal shunt (VPS) infection successfully sterilized with intrathecal colistin 10 mg/day after development of nephrotoxicity associated with intravenous administration.. Case 1. A 69-year-old African American woman with a history of subarachnoid hemorrhage and hydrocephalus requiring VPS placement was admitted with VPS infection and meningitis. Cerebrospinal fluid (CSF) cultures revealed MDR P. aeruginosa susceptible only to colistin. Intravenous colistin was initiated but rapidly discontinued due to development of renal dysfunction. Intravenous colistin was the probable cause of the adverse effect. Intrathecal colistin was initiated via an externalized VPS, with subsequent improvement in white blood cell counts in the CSF. Follow-up CSF cultures remained sterile and renal function returned to baseline. Case 2. A 69-year-old white woman with a history of subarachnoid hemorrhage, hydrocephalus, and VPS was transferred from an extended-care facility for management of a VPS infection. CSF cultures revealed MDR P. aeruginosa susceptible only to colistin. Intravenous colistin was initiated but subsequently discontinued due to worsening renal function that, as with the first case, probably correlated with colistin administration and persisted despite dose adjustment. Therapy was changed to intrathecal administration, with subsequent normalization of her CSF white blood cell counts and sterilization of cultures.. The limited availability of antibiotics for treatment of highly resistant or MDR gram-negative organisms has prompted clinicians to reconsider the use of older drugs. Prior reports have suggested that intravenous colistin is a potential alternative for treating highly resistant gram-negative central nervous system infections, specifically Acinetobacter, but its use is limited by nephrotoxicity. Our experience suggests that intrathecal colistin is a potentially curative intervention for the treatment of severe MDR P. aeruginosa meningitis and VPS infections in patients in whom intravenous colistin is not an option.. Intrathecal use of colistin is a potentially safe, effective, and viable treatment option for MDR P. aeruginosa central nervous system infections when intravenous administration is not feasible.

Topics: Aged; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Injections, Spinal; Pseudomonas aeruginosa; Pseudomonas Infections; Ventriculoperitoneal Shunt

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Aerosols; Anti-Bacterial Agents; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Humans; Infusions, Intravenous; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Treatment Outcome

Twenty-one patients with multidrug-resistant (MDR) Acinetobacter baumannii and Pseudomonas aeruginosa pneumonia were treated with nebulized polymyxin E (colistin). Overall clinical and microbiological response rates were 57.1% and 85.7%, respectively. Nebulized colistin may be reasonably efficacious and safe for treatment of MDR pneumonia. Its role in therapy warrants further investigation in comparative studies.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies

We report a case of cystic fibrosis in a 19-year-old woman who suffered from frequent exacerbations of lower respiratory infection due to multidrug-resistant Pseudomonas aeruginosa and who was successfully treated with parenteral colistin. Multidrug-resistant Pseudomonas aeruginosa isolated from sputum had become resistant to all parenteral antibiotics commercially available in Japan. She did not show clinical improvement despite treatment with several different combinations of available antibiotics. We therefore obtained parenteral colistin from a pharmacy outside Japan. She responded well to parenteral colistin without apparent side effects such as serious nephrotoxicity or neurotoxicity. Colistin is therefore an important alternative antibiotic for treating multidrug-resistant Pseudomonas aeruginosa and its use should be considered in severe infection. We hope that parenteral colistin will become available in Japan in the near future.

Topics: Adult; Anti-Bacterial Agents; Bronchitis, Chronic; Colistin; Cystic Fibrosis; Drug Resistance, Multiple, Bacterial; Female; Humans; Injections, Intravenous; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

We studied the effects of increasingly intensive treatment regimens on anti-pseudomonal antibody response and survival in five successive cohorts of a total of 157 Danish cystic fibrosis patients after they had acquired chronic P. aeruginosa lung infection. The time periods were 1971-1975 (N = 21), 1976-1980 (N = 64), 1981-1986 (N = 27), 1987-1993 (N = 26), and 1994-2000 (N = 19). During this 30-year period, we introduced elective 2-week courses of chemotherapy every third month in all chronically infected patients, early aggressive treatment with inhalation of colistin and oral ciprofloxacin for 3 months whenever P. aeruginosa was cultured in sputum from noncolonized patients, and inhalation of recombinant human dornase alfa. There was a significant correlation between the calendar year when chronic P. aeruginosa infection was acquired and the subsequent increase in the level of precipitins (P < 0.00001). The median number of precipitins increased by 5 per year in the oldest calendar year cohort, and 1 per year in the youngest. The median age of onset of chronic P. aeruginosa increased from 9.3 years from 1981-1986 to 13.8 years from 1987-2000. Survival after acquisition of chronic P. aeruginosa lung infection improved with time (P = 0.008). Our study shows that CF patients who are treated intensively have lower antibody responses and longer survival after acquisition of chronic P. aeruginosa lung infection.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antibodies, Bacterial; Child; Ciprofloxacin; Cohort Studies; Colistin; Cystic Fibrosis; Deoxyribonuclease I; Humans; Immunoelectrophoresis, Two-Dimensional; Linear Models; Pseudomonas Infections; Survival Analysis; Time Factors

The aim of the study was to assess the microbiological activity and clinical efficacy of colistin and rifampin combination against multidrug-resistant (MDR) Pseudomonas aeruginosa infections. The antimicrobial activity of the colistin/rifampin combination was evaluated using the checkerboard and time-kill curve methods against different MDR P. aeruginosa strains. The combination of rifampin and colistin resulted fully (1 strain) or partially (5 strains) synergistic for 6/7 strains and minimum inhibitory concentrations (MICs) in combination were reduced to easily obtainable therapeutic levels. The time-kill curves showed that the combination was bactericidal against the strains tested. The clinical efficacy of the combination was tested in four patients with difficult-to treat infections (sepsis or pneumonia) caused by MDR P. aeruginosa. All infections were successfully treated. Our microbiological and clinical observations suggest that the addition of rifampin to colistin may result in a synergistic bactericidal combination that may be useful in patients with infections caused by MDR P. aeruginosa which are difficult to cure.

Topics: Adult; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Female; Humans; Italy; Male; Microbial Sensitivity Tests; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Sampling Studies; Sensitivity and Specificity; Treatment Outcome

An outbreak of a multidrug resistant Pseudomonas aeruginosa including imipenem resistance occurred in the urology intensive care unit at Charles Nicolle Hospital (Tunis). All isolates presented the same antibiotic resistance pattern and were only susceptible to colistin. The epidemic strain was detected in different sites of this unit. Pulsed-field gel electrophoresis after enzymatic restriction using XbaI was performed in order to establish an epidemiologic link between these infections. Genotypic analysis showed two different patterns and the environmental source was identified in both cases. Although the same antibiotype was harbored by all the isolates, two outbreaks occurring in the same period were identified. The strengthening of hygiene measures allowed to stop the outbreak spreading. Since the hospital environment is the major source of Pseudomonas aeruginosa contamination, a continuous surveillance of the patients and the environmental sources is required for the implementation efficient control measures.

Topics: Colistin; Cross Infection; Disease Outbreaks; Drug Resistance, Bacterial; Drug Resistance, Multiple; Electrophoresis, Gel, Pulsed-Field; Genotype; Pseudomonas aeruginosa; Pseudomonas Infections; Urinary Tract Infections

Respiratory infection with Pseudomonas aeruginosa is very common in patients with cystic fibrosis (CF) but antimicrobial resistance rates of CF isolates across the UK are largely unknown.. The susceptibility of 417 CF patient isolates of P aeruginosa from 17 hospitals to six commonly prescribed antibiotics were examined. Isolates were tested by an agar break point dilution method and E-tests according to British Society of Antimicrobial Chemotherapy guidelines. Genotyping of isolates was performed by XbaI DNA macrorestriction and pulsed field gel electrophoresis.. 38% of isolates were susceptible to all of the agents tested; almost half were resistant to gentamicin compared with ceftazidime (39%), piperacillin (32%), ciprofloxacin (30%), tobramycin (10%), and colistin (3%). Approximately 40% were resistant to two or more compounds with ceftazidime in combination with gentamicin, piperacillin or ciprofloxacin being the most common cross resistances. Resistance rates were generally similar to those reported recently from the USA and Germany. A selection of resistant isolates proved to be predominantly genotypically distinct by XbaI DNA macrorestriction but six pairs from three centres had similar genotypes.. The level of resistance to front line antipseudomonal agents, with the exception of colistin, is disturbingly high. The prudent use of antimicrobial drugs and closer monitoring of accumulation of resistant strain populations should be actively considered.

Topics: Adult; Anti-Bacterial Agents; Ceftazidime; Ciprofloxacin; Colistin; Cystic Fibrosis; Drug Resistance, Bacterial; Gentamicins; Humans; Piperacillin; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin

Serious infection due to strains of Pseudomonas aeruginosa that exhibit resistance to all common antipseudomonal antimicrobials increasingly is a serious problem. Colistin was used as salvage therapy for 23 critically ill patients with multidrug-resistant P. aeruginosa infection. Twenty-two patients who had septic shock (n=14) and/or renal failure (n=21) received mechanical ventilatory support at baseline. The most common types of infection were pneumonia (n=18) and intra-abdominal infection (n=5). Colistin was administered for a median of 17 days (range, 7-36 days). Seven patients died during therapy, at a median of 17 days (range, 4-26 days) after initiation of treatment. A favorable clinical response was observed in 14 patients (61%); only 3 patients experienced relapse. Bacteremia was the only significant factor associated with treatment failure (P=.02). One patient manifested diffuse weakness that resolved after temporary cessation of colistin therapy. Colistin provides an important salvage therapeutic option for patients with otherwise untreatable serious P. aeruginosa infection.

Topics: Adult; Aged; Anti-Bacterial Agents; Colistin; Drug Resistance, Microbial; Female; Humans; Infusions, Parenteral; Intensive Care Units; Male; Microbial Sensitivity Tests; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Salvage Therapy; Treatment Outcome

We report on an outbreak of colistin-resistant Pseudomonas aeruginosa (CRPA) that occurred in a United Kingdom pediatric cystic fibrosis (CF) unit and involved six children over a period of 5 years. All CRPA-positive children had received aerosolized colistin therapy before first isolation of resistant organisms (mean duration, 3.1 years). Four of the 6 had also received courses of intravenous colistin in the year before the first isolation of CRPA. No impact of CRPA acquisition on respiratory function, clinical condition, or radiological parameters could be demonstrated. Four of the 6 children carried isolates of CRPA indistinguishable on genotyping. Two of these 4 children were sisters. The other 2 were on the same ward together at time of first isolation, and subsequently shared overlapping admissions with one of the sisters. While there is no conclusive evidence for the route of transmission, the frequency of overlapping in-patient admissions between 3 of these patients is suggestive of patient-to-patient transfer in the nosocomial setting.CF clinicians should be aware that colistin resistance can occur in P. aeruginosa, and some of these strains are capable of spread within CF units.

Topics: Anti-Bacterial Agents; Child; Child, Preschool; Colistin; Cross Infection; Cystic Fibrosis; Disease Outbreaks; Drug Resistance, Microbial; Female; Humans; Pseudomonas aeruginosa; Pseudomonas Infections; Time Factors

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple; Humans; Intensive Care Units; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

Necrotizing external otitis (NEO) is a fulminant Pseudomonas infection of the external auditory canal affecting mainly elderly diabetic patients. Since the early descriptions, many authors have related cases of NEO in non diabetic patients. We report eight cases of NEO in young children. They are less than two years old, they are undernourished and non diabetics. We get a good evolution in spite of our modest therapeutic ways. Emphasis is placed on efficiency of local remedy with colistine.

Topics: Anti-Bacterial Agents; Colistin; Cote d'Ivoire; Female; Humans; Infant; Infant, Newborn; Male; Necrosis; Nutrition Disorders; Otitis Externa; Pseudomonas Infections

The major cause of morbidity and mortality in patients with cystic fibrosis (CF) is respiratory disease (Penketh et al., Thorax 1987; 42: 526-532). Recent studies in the USA have shown that intermittent administration of inhaled tobramycin is beneficial to patients with CF who are chronically infected with Pseudomonas aeruginosa (Ramsey et al., N Engl J Med 1999; 340: 23-30; Ramsey et al., Proceedings of the 12th Annual North American Cystic Fibrosis Conference, 1998, Montreal, Canada; Ramsey et al., Abstract from 23rd European Cystic Fibrosis Conference, 1999, the Hague, Netherlands). In Europe, the use of nebulised colistin in patients chronically infected with P. aeruginosa is widespread. A recently published study compared the efficacy and safety of tobramycin nebuliser solution (TNS) and nebulised colistin in CF patients . One hundred and fifteen patients were randomised to receive either TNS or colistin in a multi-centre open-labelled study that assessed change from baseline in FEV(1) and sputum P. aeruginosa density. TNS produced a mean 6.7% improvement in lung function (P=0.006), whilst there was no significant improvement in the colistin-treated patients. The TNS-treated patients had a significantly greater improvement in lung function than those treated with colistin (P=0.008). The safety profile of both treatments was good. We conclude that patients treated with TNS for 1 month experience improved lung function compared with patients treated with colistin.

Topics: Administration, Inhalation; Anti-Bacterial Agents; Colistin; Cystic Fibrosis; Europe; Humans; Lung Diseases; Nebulizers and Vaporizers; Pseudomonas Infections; Randomized Controlled Trials as Topic; Respiratory Function Tests; Tobramycin; Treatment Outcome

The infection of the airways of cystic fibrosis patients by Pseudomonas aeruginosa is a complex, multistaged process that is associated with a deterioration of lung function. The complexity of the formation of biofilms and their interaction with the immune system means that treatment with antibiotics has been an uncertain science. Tobramycin nebuliser solution (TNS) is a novel formulation of the antibiotic tobramycin developed specifically for inhalation. A recent large trial comparing TNS with inhaled colistin provided an opportunity to define further the effect of antibiotic treatment on microbial infection. In the TNS group, the percentage of patients with a tobramycin minimal inhibitory concentration (MIC) > or = 4 mg l(-1) increased from 38 to 49%, and the percentage of patients with a colistin MIC > or = 4 mg l(-1) remained at 55%. In the colistin group, the percentage of patients with a colistin MIC > or = 4 mg l(-1) remained at 34%, whereas the percentage of patients with a tobramycin MIC > or = 4 mg l(-1) decreased from 27 to 16%. Furthermore, clinical and bacterial response to TNS and colistin was independent of the MIC at baseline. Neither antimicrobial therapy was associated with infection by Burkholderia cepacia or other inherently resistant pathogens. We conclude that conventional measures of antimicrobial resistance may underestimate the effectiveness of tobramycin and colistin when delivered at the high concentrations achieved with the TNS formulation.

Topics: Administration, Inhalation; Anti-Bacterial Agents; Biofilms; Colistin; Cystic Fibrosis; Europe; Humans; Lung Diseases; Microbial Sensitivity Tests; Nebulizers and Vaporizers; Pseudomonas Infections; Randomized Controlled Trials as Topic; Tobramycin

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Child; Ciprofloxacin; Clinical Trials as Topic; Colistin; Cystic Fibrosis; Humans; Pseudomonas Infections; Tobramycin

The in vitro pharmacodynamic properties of colistin and colistin methanesulfonate were investigated by studying the MICs, time-kill kinetics, and postantibiotic effect (PAE) against mucoid and nonmucoid strains of Pseudomonas aeruginosa isolated from patients with cystic fibrosis. Twenty-three clinical strains, including multiresistant strains, and one type strain were selected for MIC determination. Eleven strains were resistant; MICs for these strains were >128 mg/liter. For the susceptible strains, MICs of colistin ranged from 1 to 4 mg/liter, while the MICs of colistin methanesulfonate were significantly higher and ranged from 4 to 16 mg/liter. The time-kill kinetics were investigated with three strains at drug concentrations ranging from 0.5 to 64 times the MIC. Colistin showed extremely rapid killing, resulting in complete elimination at the highest concentrations within 5 min, while colistin methanesulfonate killed more slowly, requiring a concentration of 16 times the MIC to achieve complete killing within 24 h. Colistin exhibited a significant PAE of 2 to 3 h at 16 times the MIC against the three strains after 15 min of exposure. For colistin methanesulfonate, PAEs were shorter at the concentrations tested. Colistin methanesulfonate had lower overall bactericidal and postantibiotic activities than colistin, even when adjusted for differences in MICs. Our data suggest that doses of colistin methanesulfonate higher than the recommended 2 to 3 mg/kg of body weight every 12 h may be required for the effective treatment of P. aeruginosa infections in cystic fibrosis patients.

Topics: Anti-Bacterial Agents; Colistin; Cystic Fibrosis; Humans; Kinetics; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Time Factors

Chronic infection by Pseudomonas aeruginosa (PA) in patients with cystic fibrosis (CF) is preceded by a period of colonization and acute infection. Early aggressive antibiotic treatment of initial colonisation may prevent or at least delay chronic pulmonary infection. We initiated treatment with a combination of IV beta-lactam tobramycin, followed by nebulized colistin when PA was first isolated from patients with CF. Subsequent serial PA isolates obtained from these colonized CF patients were characterized by means of molecular methods to determine whether they were genetically related to the initial strain. Initial colonization was eradicated in all 19 patients. All patients reacquired PA within 3-25 months during the 3 years of follow-up. Fourteen patients acquired a new PA strain with a distinct genotypic profile, suggesting a new source of contamination. Five patients had two PA isolates with identical genotypes, suggesting either previous undetected respiratory tract colonization or a persistent environmental source of contamination.

Topics: Administration, Inhalation; Administration, Oral; Ceftazidime; Child; Child, Preschool; Chronic Disease; Colistin; Colony Count, Microbial; Cystic Fibrosis; DNA, Bacterial; Drug Therapy, Combination; Electrophoresis, Gel, Pulsed-Field; Female; Genotype; Humans; Imipenem; Infant; Male; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Risk Assessment; Tobramycin

Gram-negative bacilli including multidrug-resistant (MDR) Pseudomonas aeruginosa are responsible for a significant proportion of episodes of nosocomial pneumonia. Since the development of new antibiotics with activity against gram-negative organisms has not kept pace with the increase in prevalence of MDR pathogens, there has been renewed interest in antimicrobial agents that had previously been used but had been abandoned because of toxic side effects. This report describes three patients with nosocomial pneumonia or tracheobronchitis due to multiresistant strains of P. aeruginosa for whom aerosolized colistin proved beneficial as supplemental therapy. Aerosolized colistin merits further consideration as a therapeutic intervention for patients with pulmonary infections due to MDR P. aeruginosa.

Topics: Administration, Inhalation; Aged; Anti-Bacterial Agents; Bronchitis; Colistin; Cross Infection; Drug Resistance, Multiple; Humans; Male; Middle Aged; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Tracheitis

Topics: Amikacin; Anti-Bacterial Agents; Antibiotics, Antitubercular; Colistin; Drug Resistance, Multiple; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Middle Aged; Pseudomonas Infections; Rifampin

An 8 year old girl with cystic fibrosis had severe respiratory disease associated with chronic Pseudomonas aeruginosa bronchopulmonary infection. Despite regular courses of intravenous antipseudomonal antibiotics, she continued to deteriorate over 18 months with persistent productive cough, worsening respiratory function, and increasing oxygen dependence. During her 11th admission Streptococcus milleri was isolated from sputum cultures in addition to P aeruginosa. She failed to respond to antipseudomonal antibiotics but improved dramatically with the addition of intravenous benzylpenicillin. Although S milleri is considered a normal mouth commensal and its isolation from sputum of cystic fibrosis patients is of uncertain significance, it was associated with clinically significant infection in this child. S milleri was eradicated with antibiotic treatment and clinical improvement has been maintained.

Topics: Acute Disease; Child; Colistin; Cystic Fibrosis; Drug Therapy, Combination; Female; Floxacillin; Humans; Metronidazole; Penicillin G; Pseudomonas Infections; Sputum; Streptococcal Infections; Streptococcus

Topics: Adult; Aerosols; Anti-Bacterial Agents; Colistin; HIV Infections; HIV-1; Humans; Male; Pseudomonas Infections; Respiratory Tract Infections

Topics: Adolescent; Adult; Bronchial Provocation Tests; Bronchoconstriction; Bronchodilator Agents; Colistin; Cystic Fibrosis; Female; Forced Expiratory Volume; Humans; Male; Nebulizers and Vaporizers; Pseudomonas Infections; Time Factors

Pulmonary exacerbations of cystic fibrosis associated with strains of Pseudomonas aeruginosa that are resistant to multiple antibiotics are becoming increasingly common. The search for treatment alternatives continues and may include the reexamination of older antibiotics. Colistin sulfate is a polypeptide antibiotic with good activity against P. aeruginosa. Although its use was largely discontinued in the early 1970s because of reports of frequent renal and neurologic toxicity, intravenous colistin is often prescribed at our institution for patients with P. aeruginosa resistant to multiple-drug therapy. We prospectively monitored 19 patients during 21 courses of colistin therapy to identify the character and incidence of this agent's toxicity. Only one case of renal toxicity occurred. Six cases of neurotoxicity occurred, which were characterized by perioral paresthesia, ataxia, or both. The rate of intolerable renal adverse effects secondary to colistin therapy was appreciably lower among these patients than that reported previously for other patients. It appears that intravenous colistin can be considered for cystic fibrosis patients with strains of P. aeruginosa that are resistant to more commonly used antibiotics.

Topics: Adolescent; Adult; Ataxia; Child; Child, Preschool; Colistin; Cystic Fibrosis; Drug Monitoring; Female; Humans; Injections, Intravenous; Male; Paresthesia; Prospective Studies; Proteinuria; Pseudomonas aeruginosa; Pseudomonas Infections

We studied the intestinal flora of 23 newborns, whose meconium had yielded a pure culture of Pseudomonas aeruginosa on blood agar medium. Twelve infants had a single serotype of P. aeruginosa in their meconium, 10 had a second serotype and the last infant was carrying three distinct ones. The maximum levels of P. aeruginosa observed during the first week of life were variable among the infants: 1 x 10(3) to 1 x 10(10) CFU/g of stools. The levels diminished progressively afterwards, and after 1 year of age only 1 of the 13 infants examined remained a carrier of P. aeruginosa. In 11 infants a second or a third serotype occurred during the course of the study. The serotypes that appeared secondarily always disappeared before the initial ones. Antibiotics: ampicillin + gentamicin or cefotaxime + netilmicin and colistin which were given to 8 infants had no clear effect on P. aeruginosa levels. Four infants had delayed colonization by Escherichia coli of greater than or equal to 10 days. All 4 had high levels of P. aeruginosa: 1 x 10(7) to 1 x 10(10) CFU/g stool, and antibiotic therapy, rendering it impossible to assess which was the cause of this delay. This colonization by P. aeruginosa did not lead to any clinical trouble.

Topics: Cefotaxime; Colistin; Drug Therapy, Combination; Escherichia coli; Feces; Female; Gentamicins; Humans; Infant, Newborn; Infant, Premature; Infant, Small for Gestational Age; Intestinal Diseases; Male; Meconium; Netilmicin; Pseudomonas aeruginosa; Pseudomonas Infections; Serotyping; Ticarcillin; Time Factors

Topics: Agranulocytosis; Ciprofloxacin; Colistin; Drug Resistance, Microbial; Humans; Microbial Sensitivity Tests; Neutropenia; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Adolescent; Child; Child, Preschool; Colistin; Cystic Fibrosis; Female; Humans; Infant; Male; Pseudomonas Infections; Respiratory Tract Infections

Topics: Administration, Topical; Adult; Anti-Bacterial Agents; Bacterial Infections; Burn Units; Burns; Child; Colistin; Environment, Controlled; Female; Gentamicins; Humans; Male; Methicillin; Penicillin Resistance; Pseudomonas aeruginosa; Pseudomonas Infections; Silver Sulfadiazine; Staphylococcus aureus; United Kingdom; Wound Infection

Topics: Colistin; Drug Therapy, Combination; Humans; Male; Meningitis; Middle Aged; Piperacillin; Pseudomonas Infections

A 38-year-old man acquired a Pseudomonas aeruginosa wound infection after transplant nephrectomy. After an initial response to therapy, Pseudomonas sepsis developed, and he was readmitted to the hospital. Two days after admission, blurred vision developed. Ocular examination revealed a severe vitritis and exudate in the pupillary space on the right side. Endogenous endophthalmitis was suspected, and a diagnostic vitreous aspiration yielded P aeruginosa on culture. The patient was treated with intravitreal, subconjunctival, and topical antibiotics as well as periocular steroids, and was able to achieve useful vision before his death from his systemic illness.

Topics: Adult; Colistin; Combined Modality Therapy; Endophthalmitis; Humans; Kidney Transplantation; Male; Pseudomonas Infections; Surgical Wound Infection

Topics: Carbenicillin; Colistin; Cross Infection; Gentamicins; Hospitals, University; Humans; Nigeria; Penicillin Resistance; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Adult; Aortic Valve; Colistin; Drug Therapy, Combination; Endocarditis, Bacterial; Heart Valve Prosthesis; Humans; Male; Postoperative Complications; Pseudomonas Infections; Rifampin; Tobramycin

Biochemical characteristics and antibiotic susceptibilities of 12 strains of colistin-resistant pseudomonads isolated from clinical specimens are reported. The isolates were short, oxidase-positive, nonfluorescing, gram-negative rods that failed to grow on salmonella-shigella or cetrimide agars, to decarboxylate amino acids, and to reduce nitrates. Most strains peptonized litmus milk and grew at 42 degrees C. Glucose, lactose, maltose, xylose, and fructose were slowly oxidized, whereas sucrose was not. Two homogeneous species were found and tentatively listed as Pseudomonas sp. 1 and Pseudomonas sp. 2, and these were differentiated by gelatin and starch hydrolysis, oxidation of mannitol, and alkalinization of allantoin. The two species were shown to differ from the Center for Disease Control Va group biotype CDC Va-1 in both biochemical characteristics and susceptibility to the aminoglycosides.

Topics: Anti-Bacterial Agents; Carbohydrate Metabolism; Colistin; Drug Resistance, Microbial; Humans; Military Medicine; Oxidation-Reduction; Pseudomonas; Pseudomonas Infections

The bacteriological effect of chemotherapy against Pseudomonas aeruginosa (Ps.ae.) in lungs of patients with cystic fibrosis is reviewed. During a 5-year period 49 children and adults were treated with 190 courses of different antibiotics. The mucoid strains of Ps.ae. disappeared in 72.0% of the courses in which a combination of tobramycin and carbenicillin was employed. Tobramycin given alone had only bacteriological effect in 26.6% of the courses. Colimycin alone or in combination with carbenicillin had no effect. In 18 patients who received subsequent courses of tobramycin and combination of tobramycin and carbenicillin a significant difference in favour of the combination therapy was found, also in cases with many precipitins against Ps.ae. in serum. In 74.5% of the initially successful courses the patients were recolonized with Ps.ae. within 1 month. No nephrotoxic or ototoxic side effects were demonstrated in spite of the high doses of tobramycin (10 mg/kg/24 h) emmployed and the repeated courses.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Carbenicillin; Child; Child, Preschool; Chronic Disease; Colistin; Cystic Fibrosis; Drug Evaluation; Drug Therapy, Combination; Female; Gentamicins; Humans; Infant; Male; Pneumonia; Precipitins; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin

The in vivo antibacterial effectiveness in the rabbit cornea of several commercially available ophthalmic antibiotic preparations was determined against a single strain of Pseudomonas aeruginosa isolated from a human corneal ulcer. Each antibiotic was instilled topically at hourly intervals, and the number of residual viable organisms in the cornea subsequently was ascertained. In vivo measurements correlated well with in vitro data and with generally held clinical impressions. Three antibiotics, gentamicin sulfate, polymyxin B sulfate, and colistin sulfate, suppressed corneal growth of P aeruginosa in commercially available concentrations. Gentamicin was slightly more effective than polymyxin B; both drugs were substantially more effective than colistin. Formulations of gentamicin and polymyxin B containing approximately four times the quantity of drug found in commercial preparations eliminated this P aeruginosa strain from the cornea much more rapidly than did the commercial preparations.

Topics: Administration, Topical; Animals; Anti-Bacterial Agents; Colistin; Gentamicins; Keratitis; Microbial Sensitivity Tests; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections; Rabbits

Distribution of Pseudomonas aeruginosa was observed, both in cancerous hospitalized and ambulatorial patients, through Uroculture or by Screening at the time of admission in Hospital. The data have been statistically evaluated according to the specific sectorial activities. The chemiosensitivity of isolated strains was evaluated for eight antibiotics, selected among the most active ones. Minimal Inhibent Concentration (MIC) and Minimal Bactericidal Concentration (MBC) were also evaluated for Gentamicin and Colistin. The results obtained are relevant to the significance of Pseudomonas aeruginosa infection in neoplastic diseases.

Topics: Colistin; Female; Gentamicins; Hospitals, Special; Humans; Male; Microbial Sensitivity Tests; Neoplasms; Pseudomonas aeruginosa; Pseudomonas Infections; Rome

Topics: Colistin; Humans; Injections, Spinal; Meningitis; Polymyxins; Pseudomonas Infections; Urinary Tract Infections

Two rare species of Pseudomonas were isolated from corneal ulcers in two patients. In the first case P. acidovorans was isolated and suspected as the primary pathogenic microorganism in human disease. In the second case P. stutzeri was isolated from ocular sources, but this is the first report of its role in causing corneal disease. The patient in the second case had a scarred cornea, possibly caused by a previous herpetic infection, and this may have been a predisposing factor to the development of the infection by P. stutzeri. Susceptibility studies of both organisms revealed sensitivity to a wide range of antibiotics but resistance to carbenicillin, a drug currently used in the treatment of infections from P. aeruginosa.

Topics: Abscess; Aged; Anti-Bacterial Agents; Carbenicillin; Colistin; Corneal Ulcer; Edema; Female; Gentamicins; Humans; Intraocular Pressure; Male; Middle Aged; Penicillin Resistance; Pseudomonas; Pseudomonas Infections

Topics: Aged; Bacitracin; Colistin; Female; Humans; Ibuprofen; Phenylpropionates; Pregnancy; Pseudomonas Infections

Opportunistic infections of the external auditory canal or the middle ear due to Pseudomonas aeruginosa occurring in patients with low resistance to infection have a 35 percent mortality rate. Once the process extends into the pneumatized temporal bone, eradication becomes more difficult and the mortality rate increases to 72 percent because of the high incidence of involvement of cranial nerves, adjacent intracranial vessels, and meningitis. Treatment is directed towards the underlying condition, administration of systemic carbenicillin and gentamicin, topical colistin therapy, and judicious surgical debridement. Pseudomonas vaccine may be of help. Fifteen cases are presented. Nine follow the pattern of malignant external otitis and six began as a primary acute otitis media.

Topics: Adult; Aged; Carbenicillin; Colistin; Diabetes Mellitus; Female; Gentamicins; Humans; Infant; Male; Mastoiditis; Middle Aged; Otitis Externa; Otitis Media; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Acute Kidney Injury; Aged; Anti-Bacterial Agents; Burns; Cephalothin; Colistin; Drug Therapy, Combination; Gentamicins; Humans; Male; Middle Aged; Peritonitis; Postoperative Complications; Pseudomonas Infections

Endocarditis of the tricuspid valve due to Pseudomonas aeruginosa in a heroin addict failed to respond to therapy with gentamicin, carbenicillin, and amikacin. Clinical and bacteriologic cure was achieved with oral administration of a trimethoprim-sulfamethoxazole mixture plus parenteral therapy with colistin. In vitro synergism was demonstrated for the three drugs at concentrations achievable in the serum. Therapy for endocarditis due to Pseudomonas continues to be a major problem; however, the successful treatment of this patient warrants consideration for instituting therapy with a trimethoprim-sulfamethoxazole misture plus colistin in individuals with this infection who fail to respond to standard therapeutic regimens for severe infections with Pseudomonas.

Topics: Adult; Colistin; Drug Combinations; Endocarditis, Bacterial; Heart Valve Diseases; Heroin Dependence; Humans; Male; Pseudomonas Infections; Sulfamethoxazole; Tricuspid Valve; Trimethoprim

Fifty organisms of Pseudomonas aeruginosa were injected intralamellarly in both eyes of 60 albino rabbits. Twenty-four hours later, all eyes were graded and stratified into six groups of ten rabbits with equivalent infections. Treatment was begun with gentamicin alone or 0.3% polymyxin B alone, and in combination with acetylcysteine, 0.3M edetate disodium, and 2.500 units/ml of heparin sodium, four times daily. We also compared topical colistin and colistin and topical heparin. After two weeks, those corneas treated with polymyxin B and topical heparin showed a reduction in ulceration, corneal thinning, and descemetocele formation compared to those treated with polymyxin B alone. Based on these studies, heparin was administered topically, four times daily, to three patients with Pseudomonas-induced corneal ulcers in addition to antibiotics. Before treatment all corneas showed evidence of corneal liquefaction and two of the corneas were in imminent danger of perforation. After therapy, no corneas perforated; one patient recovered visual acuity of 6/9 (20/30), one patient recovered visual acuity of 6/6 (20/20) after keratoplasty, and the third has a vascularized leukoma.

Topics: Acetylcysteine; Administration, Topical; Adult; Animals; Colistin; Corneal Ulcer; Drug Therapy, Combination; Edetic Acid; Gentamicins; Heparin; Humans; Male; Middle Aged; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections; Rabbits

The current circumstances associated with Pseudomonas aeruginosa bacteremia are reviewed in 108 episodes to assess the impact of new antimicrobial drugs on this infection. Since 1961, Pseudomonas bacteremia has apparently become more frequent with proportional increases in middle-aged patients. The respiratory tract has become the major source of infection. Clinical features are not characteristic, but infected patients are almost uniformly severely ill before blood stream invasion occurs. The use of gentamicin, carbenicillin and colistin has not changed the outcome of Pseudomonas bacteremia. Although better than no antimicrobial treatment, these drugs cannot be shown to be superior to any other available antibiotics. A reassessment is needed to evaluate the relationship between the in vitro action and the effectiveness of antibiotics in the treatment of Pseudomonas infection and the use of gentamicin, carbenicillin and colistin in these bacteremias. In view of the poor results with antibiotics, investigation into immunologic prophylaxis and therapy is needed. At the present time, control of the patients' underlying disease contributes most towards assuring survival with Pseudomonas bacteremia.

Topics: Anti-Bacterial Agents; Carbenicillin; Chronic Disease; Colistin; Cross Infection; Gentamicins; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Neoplasms; Penicillin Resistance; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis

The susceptibility of clinical isolates of Pseudomonas aeruginosa to six antibiotics was related to the epidemiologic knowledge yielded by serotyping. The agar dilution method for determination of minimal inhibitory concentrations (MICs) and the Habs serotyping system were used. Effectiveness of each agent ranked highest to lowest as follows: tobramycin, colistin, ticarcillin, carbenicillin, gentamicin, and kanamycin. For many isolates, the MICs of gentamicin were close to the peak level in serum. Susceptibility to carbenicillin and to ticarcillin were highly correlated, with MICs of ticarcillin half those of carbenicillin. Similary, susceptibility to gentamicin and to tobramycin were correlated. For susceptible strains, MICs of gentamicin were two to four times greater than those of tobramycin. However, strains resistant to gentamicin were clearly in one of two groups: susceptible to tobramycin or resistant to the drug. Most strains resistant to both gentamicin and tobramycin were serotype 11, whereas those resistant gentamicin and kanamycin only were nonagglutinable.

Topics: Anti-Bacterial Agents; Carbenicillin; Colistin; Gentamicins; Humans; Kanamycin; Microbial Sensitivity Tests; Penicillin Resistance; Pseudomonas aeruginosa; Pseudomonas Infections; Ticarcillin; Tobramycin

The therapeutic potencies of colistin methanesulfonate (CLM) was assessed quantitatively in acute infection of mice with clinically isolated strains of Escherichia coli and Pseudomonas aeruginosa, and effect of different routes of administration was compared. There was no detectable difference in the therapeutic effect of CLM when intramuscular (im) or intravenous (iv) administration was initiated one hour after the infection. On the other hand, a significant difference in ED50 given by im and iv administrations was observed, indicating the superiority of iv administration, when the treatment started 4 to approximately hours after the infection. No difference in the therapeutic effect of polymyxin B (PMB) and tetracycline (TC) administered via either im or iv route was found even in the delayed administration. In contrast to PMB and TC, lower toxicity of CLM was determined when it was administered iv rather than im.

Topics: Acute Disease; Animals; Bacterial Infections; Colistin; Escherichia coli; Escherichia coli Infections; Female; Injections, Intramuscular; Injections, Intravenous; Male; Mesylates; Mice; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections; Tetracycline

Mouse protection tests were carried out with four antibiotics and six strains of Pseudomonas aeruginosa. All strains were susceptible to all four antibiotics by an in vitro test. A heavier bacterial inoculum increased the mean effective dose of gentamicin and tobramycin, but not polymyxin B. Second and third doses of gentamicin in the mouse protection test made little change in the mean effective dose. In the mouse protection tests, tobramycin was the most active antibiotic if the results were analyzed in terms of the therapeutic index or ratio of toxicity to efficacy. Colistimethate was poorly inactive in vivo. Polymyxin B was most active on an absolute basis but also was the most toxic. One strain of Pseudomonas was classified as resistant to gentamicin in vivo although it was susceptible in vitro. Strains of Pseudomonas that were uniformly susceptible to antibiotics in vitro were not uniformly susceptible in the mouse protection test to low doses of antibiotic.

Topics: Animals; Anti-Bacterial Agents; Colistin; Gentamicins; Mice; Microbial Sensitivity Tests; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin

Although the serum bactericidal test is commonly used in the management of infective endocarditis, little has been written about its validity or limitations. We report three cases of gram-negative bacillary endocarditis (Pseudomonas aeruginosa, Vibrio fetus and Serratia marcescens) encountered in 1 year at a Veterans Administration hospital. Serum bactericidal titers were considered necessary to identify inadequate antibiotic regimens or to avoid unnecessary drug toxicity. The limitations of the test, particularly those pertaining to gram-negative infections, are reviewed. Misleading results during treatment with aminoglycoside antibiotics could be due to the tendency of serum to become alkaline on standing. A detailed study of the interaction of the complement-dependent bactericidal system of serum with eight antibiotics is presented. In the context of the serum bactericidal test, the interaction was additive or synergistic in 15 of 16 determinations, indicating the need to include a control study of serum sensitivity of the infecting microorganism in each case.

Topics: Adult; Anti-Bacterial Agents; Bacteria; Blood Bactericidal Activity; Campylobacter fetus; Carbenicillin; Colistin; Endocarditis, Bacterial; Gentamicins; Humans; Hydrogen-Ion Concentration; Male; Microbial Sensitivity Tests; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Serratia marcescens; Tetracycline; Vibrio Infections

Serious complications occurred in 29 of 887 children with puncture wounds of the feet treated over a four-year period at the Dr. Charles A. Janeway Child Health Centre. Osteomyelitis in one of the small bones of the foot was the commonest complication and occurred when a cartilaginous surface (physeal plate or articular cartilage) had been violated. Although systemic signs of osteomyelitis frequently are absent, this infectious process is refractory to medical management. The combined surgical and medical management of this complication is outlined. Management of puncture wounds in the emergency room should include a thorough history concisely recorded, tetanus prophylaxis, and cleansing, debridement, and probing of the wound. Antimicrobial agents are not routinely required but should be reserved for patients presenting late with cellulitis or an established infection. A semisynthetic penicillinase-penicillin appears to be the agent of choice until the results of microbiologic studies are available.

Topics: Adolescent; Cellulitis; Child; Child, Preschool; Colistin; Erythromycin; Female; Foot Injuries; Humans; Klebsiella Infections; Lincomycin; Male; Osteomyelitis; Penicillins; Pseudomonas Infections; Staphylococcal Infections; Streptococcal Infections; Tetracyclines; Wounds, Penetrating

Hospitalized patients with urinary tract infections caused by Pseudomonas aeruginosa or other bacterial pathogens are frequently treated with parenteral antibiotics such as gentamicin. Many of these organisms are shown by Kirby-Bauer disk sensitivity testing to be resistant to tetracycline. One hundred seventy-one such tetracycline-resistant bacterial isolates were studied; 84% were found to be sensitive to achievable urinary concentrations of tetracycline. Two patients with long-standing chronic urinary tract infection with Pseudomonas were treated with tetracycline for a year and a half with excellent results. In a pilot clinical trial, eight of 12 hospitalized patients with urinary tract infection were treated successfully with tetracycline without regard to disk sensitivity data. Institution of tetracycline as soon as the microscopic diagnosis of urinary tract infection is made might be an acceptable empiric approach to the treatment of urinary infection in hospitalized patients who do not show evidence of sepsis.

Topics: Bacteriuria; Carbenicillin; Colistin; Gentamicins; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Nephrectomy; Penicillin Resistance; Proteus mirabilis; Pseudomonas aeruginosa; Pseudomonas Infections; Tetracycline; Urinary Tract Infections

Topics: Aminoglycosides; Anti-Bacterial Agents; Burns; Carbenicillin; Child, Preschool; Colistin; Ecthyma; Female; Follow-Up Studies; gamma-Globulins; Gangrene; Humans; Infant; Male; Penicillin Resistance; Prognosis; Pseudomonas Infections; Serotyping; Skin Manifestations; Sulfadiazine; Wound Infection

Topics: Administration, Topical; Animals; Burns; Colistin; Cross Infection; Disease Models, Animal; Drug Resistance, Microbial; Ecthyma; Enterobacteriaceae; gamma-Globulins; Gentamicins; Humans; Pneumonia; Providencia; Pseudomonas; Pseudomonas Infections; Rats; Sepsis; Simplexvirus; Sulfonamides; Surgical Wound Infection; Thrombophlebitis; Time Factors

Topics: Burns; Carbenicillin; Colistin; Cross Infection; Germany, West; Humans; Patient Care Planning; Penicillin Resistance; Pseudomonas aeruginosa; Pseudomonas Infections; Serotyping; Water Microbiology; Wound Infection

Topics: Animals; Anti-Bacterial Agents; Carbenicillin; Colistin; Drug Combinations; Gentamicins; Male; Mice; Microbial Sensitivity Tests; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Adult; Blood; Carbenicillin; Cephalothin; Colistin; Drug Synergism; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Gentamicins; Heart Valve Prosthesis; Heroin Dependence; Humans; Male; Mesylates; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis; Staphylococcal Infections; Tricuspid Valve

Topics: Animals; Carbenicillin; Colistin; Disease Models, Animal; Drug Therapy, Combination; Gentamicins; Male; Mice; Microbial Sensitivity Tests; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections

To define factors contributing to the adverse prognosis of patients with gram-negative bacillemia and abscess formation, we studied the interaction between polymyxin B, colistin sulfate, gentamicin, or carbenicillin with purulent material. Carbenicillin activity was not significantly altered by incubation with pus. Equal volumes of antibiotic and purulent sediment decreased the effective concentration of polymyxin B, colistin sulfate, or gentamicin from 100 mug/ml to 3 to 6 mug/ml. One milliliter of purulent sediment bound more than 700 mug of gentamicin and 1,500 mug of polymyxin B or colistin sulfate. This effect occurred rapidly, proceeded at 4 and 37 C, was stable for 24 to 48 h, and was altered, but not abolished, by varying the pH of the solution. Antibiotic activity could be removed from pus by high concentrations of protamine sulfate, heparin, sodium chloride, or potassium chloride, suggesting binding rather than inactivation.

Topics: Abscess; Anti-Bacterial Agents; Biological Assay; Carbenicillin; Colistin; Gentamicins; Humans; Polymyxins; Protamines; Pseudomonas aeruginosa; Pseudomonas Infections; Suppuration

Topics: Animals; Colistin; Corneal Ulcer; Disease Models, Animal; Drug Combinations; Gentamicins; Ophthalmic Solutions; Pseudomonas Infections; Rabbits; Sulfates; Wound Healing

Topics: Ampicillin; Anti-Bacterial Agents; Carbenicillin; Cephalothin; Chloramphenicol; Colistin; Dicloxacillin; Escherichia coli Infections; Gentamicins; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature, Diseases; Pseudomonas Infections; Sepsis; Staphylococcal Infections; Streptococcal Infections

Pseudomonas aeruginosa was isolated from the sputum of 63 patients. In 34 the organism was a commensal, in 14 it was causing chronic suppuration, and in 10 had interfered with antibiotics directed against other organisms and was thus indirectly pathogenic. In five patients, all of whom died, the organism could have been acting as an acute pathogen. Attempts should be made to determine the nature of the organism's pathogenicity in a given patient and appropriate therapy withheld or administered accordingly.

Topics: Bronchitis; Carbenicillin; Colistin; Gentamicins; Humans; Lung Diseases; Postoperative Complications; Precipitin Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections; Sputum; Tracheotomy

Intravenous inoculation of 6.2 x 10(10) to 6.7 x 10(10)Pseudomonas aeruginosa organisms into rhesus monkeys 5 days after intratracheal inoculation of 2.0 to 2.5 mg of vincristine sulfate resulted in fatal sepsis in 8 of 10 untreated monkeys. When similarly infected monkeys were treated intramuscularly with 2.5 mg of colistin or 50 mg of carbenicillin per kg per day, all three monkeys in each treatment group survived; one of three monkeys receiving both antibiotics at the above doses died. Six of seven monkeys treated with 1.25 mg of colistin per kg per day and three of seven treated with 25 mg of carbenicillin per kg per day died; four of nine monkeys receiving both antibiotics at these doses died. A combination of the data obtained at both dose levels tested shows that 6 of 10, 3 of 10, and 5 of 12 monkeys, respectively, died after treatment with colistin, carbenicillin, and the colistin-carbenicillin combination. Antibacterial activity of serum from both infected and normal monkeys was not appreciably different when the two antibiotics were given singly or in combination. Under the conditions of this study and with the doses employed, the response of monkeys treated with the antibiotic combination did not differ significantly from that of monkeys treated with a single agent.

Topics: Animals; Carbenicillin; Colistin; Drug Therapy, Combination; Macaca; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Adult; Anti-Bacterial Agents; Colistin; Corneal Ulcer; Cross Infection; Eye Foreign Bodies; Gentamicins; Humans; Male; Middle Aged; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Carbenicillin; Colistin; Ecthyma; Gentamicins; Humans; Leukemia; Leukemia, Lymphoid; Lymphoma; Meningitis; Neutropenia; Pneumonia; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis; Uremia

Topics: Cephalothin; Colistin; Enterococcus faecalis; Escherichia coli Infections; Gentamicins; Humans; Kanamycin; Kidney Failure, Chronic; Kidney Function Tests; Male; Novobiocin; Postoperative Complications; Prostatectomy; Pseudomonas aeruginosa; Pseudomonas Infections; Streptococcal Infections; Urinary Tract Infections; Urologic Diseases

Topics: Adult; Aged; Agranulocytosis; Bacteria; Carbenicillin; Catheterization; Colistin; Diabetes Complications; Drug Combinations; Endocarditis; Female; Gentamicins; Humans; Leukocytosis; Male; Middle Aged; Plasmacytoma; Pregnancy; Prostatic Hyperplasia; Pseudomonas aeruginosa; Pseudomonas Infections; Puerperal Infection; Sepsis; Stevens-Johnson Syndrome; Uremia

Intravenous inoculation of 3.4 x 10(10) to 7.4 x 10(10)Pseudomonas aeruginosa organisms into rhesus monkeys 4 days after intravenous or intratracheal inoculation of 2.0 to 2.5 mg of vincristine sulfate resulted in fatal sepsis in eight of nine monkeys. After intramuscular administration, in two equal doses, of 5 mg of tobramycin, gentamicin, and colistin per kg per day beginning 16 hr after challenge, 4 of 11, 4 of 11, and 3 of 10 monkeys died, respectively. Administration of daily doses of 100 to 400 mg of carbenicillin per kg was followed by death in 5 of 12. Duration of illness in the surviving monkeys in each therapy group was similar. Under the conditions of this study, prior administration of vincristine sulfate resulted in a decrease in leukocytes and enhanced susceptibility to Pseudomonas infection. Using this model for studies of comparative efficacy of antibiotics, we observed comparable results after treatment with tobramycin, gentamicin, colistin, and carbenicillin.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Carbenicillin; Colistin; Gentamicins; Haplorhini; Macaca; Pseudomonas aeruginosa; Pseudomonas Infections; Vincristine

Topics: Animals; Carbenicillin; Colistin; Gentamicins; Glucose; Mice; Neomycin; Penicillin Resistance; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Acute Kidney Injury; Adolescent; Adult; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Colistin; Deafness; Endocarditis, Bacterial; Female; Humans; Kanamycin; Kidney; Kidney Function Tests; Male; Middle Aged; Pseudomonas Infections; Sepsis; Staphylococcal Infections; Streptococcal Infections; Urea; Vancomycin

Topics: Animals; Anti-Bacterial Agents; Carbenicillin; Colistin; Drug Synergism; Gentamicins; Mice; Microbial Sensitivity Tests; Penicillin Resistance; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections; Rabbits

Topics: Acinetobacter; Adolescent; Adult; Alcaligenes; Arm Injuries; Bacillus subtilis; Blast Injuries; Blood; Cephalothin; Chloramphenicol; Colistin; Escherichia coli Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Leg Injuries; Male; Penicillin Resistance; Penicillins; Proteus Infections; Proteus mirabilis; Pseudomonas aeruginosa; Pseudomonas Infections; Serratia marcescens; Streptomycin; Warfare; Wound Infection

Topics: Anti-Bacterial Agents; Child; Child, Preschool; Colistin; Gentamicins; Humans; Infant; Penicillins; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Animals; Anti-Bacterial Agents; Bacteria; Blood Proteins; Colistin; Culture Media; Drug Resistance, Microbial; Escherichia coli Infections; Gentamicins; Hydrogen-Ion Concentration; Kanamycin; Klebsiella Infections; Male; Mice; Mice, Inbred Strains; Microbial Sensitivity Tests; Protein Binding; Pseudomonas aeruginosa; Pseudomonas Infections; Staphylococcal Infections; Staphylococcus; Streptomycin

Topics: Child; Colistin; Endocarditis, Bacterial; Female; Gentamicins; Heart Failure; Heart Valve Prosthesis; Humans; Polymers; Postoperative Complications; Prognosis; Pseudomonas aeruginosa; Pseudomonas Infections; Silicones; Splenomegaly; Tetralogy of Fallot

Topics: Colistin; Femur; gamma-Globulins; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Osteomyelitis; Pseudomonas Infections; Streptomycin

Topics: Adult; Anti-Bacterial Agents; Carbenicillin; Colistin; Drug Synergism; Female; Gentamicins; Humans; In Vitro Techniques; Injections; Male; Meningitis; Middle Aged; Polymyxins; Pseudomonas; Pseudomonas Infections; Species Specificity

Topics: Adult; Anesthesia, Spinal; Bacteriocins; Bacteriophage Typing; Colistin; Female; Humans; Meningitis; Polymyxins; Pregnancy; Pseudomonas Infections; Spinal Puncture

Topics: Adult; Anti-Bacterial Agents; Carbenicillin; Colistin; Corneal Ulcer; Eye Diseases; Female; Gentamicins; Humans; Male; Middle Aged; Penicillin Resistance; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Calcium; Chelating Agents; Colistin; Edetic Acid; Humans; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Animals; Carbenicillin; Colistin; Gentamicins; Humans; Microbial Sensitivity Tests; Penicillins; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Ampicillin; Anti-Bacterial Agents; Carbenicillin; Chloramphenicol; Colistin; Framycetin; Humans; Microbial Sensitivity Tests; Neomycin; Otorhinolaryngologic Diseases; Oxytetracycline; Penicillin Resistance; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections; Streptomycin

Topics: Child; Colistin; Foot Injuries; Humans; Male; Osteomyelitis; Penicillins; Pseudomonas; Pseudomonas Infections; Radiography; Wound Infection

Topics: Child; Colistin; Foot Diseases; Foot Injuries; Gentamicins; Humans; Male; Osteomyelitis; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections; Radiography; Wounds and Injuries

Topics: Adolescent; Adult; Age Factors; Aged; Colistin; Cross Infection; Escherichia coli Infections; Female; Fever; Humans; Kanamycin; Klebsiella Infections; Leukocyte Count; Male; Microbial Sensitivity Tests; Middle Aged; Nitrogen; Penicillins; Proteus Infections; Pseudomonas Infections; Retrospective Studies; Sepsis; Sex Factors; Shock; Uremia

Topics: Adolescent; Carbenicillin; Child; Child, Preschool; Colistin; Cyclophosphamide; Daunorubicin; Humans; Infant; Leukemia, Lymphoid; Penicillins; Prednisone; Pseudomonas Infections; Vincristine

Topics: Adult; Ampicillin; Anti-Bacterial Agents; Antibodies; Carbenicillin; Cell Membrane; Colistin; Complement System Proteins; Drug Antagonism; Drug Synergism; Escherichia coli; Escherichia coli Infections; Gentamicins; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Receptors, Drug; Serum Albumin, Bovine; Streptomycin; Tetracycline

Topics: Carbenicillin; Colistin; Ecthyma; Gentamicins; Humans; Male; Middle Aged; Penicillins; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis

Topics: Administration, Topical; Adolescent; Adult; Aged; Anti-Bacterial Agents; Child; Colistin; Drug Synergism; Drug Therapy, Combination; Eye Diseases; Female; Humans; Male; Middle Aged; Ophthalmic Solutions; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Aged; Ampicillin; Carbenicillin; Colistin; Edrophonium; Humans; Male; Medication Errors; Myasthenia Gravis; Neostigmine; Neuromuscular Depolarizing Agents; Primidone; Pseudomonas Infections; Pyridostigmine Bromide; Respiratory Insufficiency; Urinary Tract Infections

Topics: Colistin; Humans; Pseudomonas Infections

Topics: Colistin; Humans; Kidney; Penicillins; Pseudomonas Infections

Topics: Adolescent; Alanine Transaminase; Ampicillin; Aspartate Aminotransferases; Blood Cell Count; Child; Child, Preschool; Clinical Enzyme Tests; Colistin; Cystic Fibrosis; Drug Synergism; Gentamicins; Humans; Oxacillin; Penicillins; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections; Sputum; Tetracycline

Topics: Anti-Bacterial Agents; Colistin; Drug Synergism; Humans; Oxytetracycline; Polymyxins; Prognosis; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Anti-Bacterial Agents; Carbenicillin; Colistin; Gentamicins; Humans; Penicillins; Polymyxins; Pseudomonas Infections

Topics: Aged; Bacteriological Techniques; Colistin; Enterobacteriaceae Infections; Female; Humans; Injections, Intramuscular; Injections, Intravenous; Male; Middle Aged; Pseudomonas Infections; Urinary Tract Infections

Topics: Adolescent; Adult; Anti-Bacterial Agents; Benzene Derivatives; Bronchopneumonia; Burns; Child; Child, Preschool; Colistin; Gentamicins; Humans; Infant; Injections, Intravenous; Ointments; Penicillins; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis; Sulfonamides; Wound Infection

Topics: Anti-Bacterial Agents; Colistin; Corneal Ulcer; Gentamicins; Humans; Microbial Sensitivity Tests; Penicillins; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Animals; Colistin; Cornea; Corneal Opacity; Corneal Ulcer; Gentamicins; Injections; Polymyxins; Pseudomonas Infections; Rabbits

Topics: Adult; Burns; Burns, Electric; Candidiasis, Cutaneous; Child; Child, Preschool; Colistin; Escherichia coli Infections; Female; Gentamicins; Humans; Male; Patient Isolators; Penicillins; Polymyxins; Proteus Infections; Pseudomonas Infections; Sepsis; Silver Nitrate; Staphylococcal Infections; Streptococcal Infections; Sulfonamides; Toluene

Topics: Anti-Bacterial Agents; Colistin; Cross Infection; Drug Resistance, Microbial; Gentamicins; Humans; Otorhinolaryngologic Diseases; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections; Sterilization

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Air Microbiology; Ampicillin; Ascitic Fluid; Bacteriocins; Benzalkonium Compounds; Catheterization; Cephaloridine; Chloramphenicol; Colistin; Cross Infection; Ethylene Oxide; Filtration; Gentamicins; Humans; Kanamycin; Lysogeny; Middle Aged; Nalidixic Acid; Peritoneal Dialysis; Pseudomonas aeruginosa; Pseudomonas Infections; Renal Dialysis; Sterilization; Streptomycin; Tetracycline; Ultraviolet Rays; Urinary Tract Infections

Topics: Animals; Colistin; Conjunctiva; Contact Lenses; Cornea; Corneal Ulcer; Injections; Photography; Pseudomonas aeruginosa; Pseudomonas Infections; Rabbits; Time Factors; Wound Healing

Topics: Adult; Child; Child, Preschool; Colistin; Drug Synergism; Gentamicins; Humans; Infant; Middle Aged; Penicillin Resistance; Penicillins; Pseudomonas aeruginosa; Pseudomonas Infections; Urinary Calculi; Urinary Tract Infections; Urogenital Abnormalities

Topics: Animals; Bacteria; Colistin; Gentamicins; Mice; Microbial Sensitivity Tests; Microscopy, Electron; Oxytetracycline; Penicillins; Proteus; Proteus Infections; Pseudomonas aeruginosa; Pseudomonas Infections; Shigella; Staphylococcus

Topics: Colistin; Humans; Pseudomonas aeruginosa; Pseudomonas Infections; Urinary Tract Infections

Topics: Adult; Ampicillin; Colistin; Drug Synergism; Female; Humans; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis

Topics: Adolescent; Adult; Aged; Animals; Anti-Bacterial Agents; Bacteria; Child; Child, Preschool; Colistin; Cornea; Corneal Ulcer; Dogs; Drug Resistance, Microbial; Drug Synergism; Edema; Eye Diseases; Female; Humans; Infant; Male; Middle Aged; Ophthalmic Solutions; Panophthalmitis; Pseudomonas; Pseudomonas Infections; Rats; Staphylococcal Infections; Staphylococcus

Topics: Adolescent; Basement Membrane; Colistin; Cytoplasm; Endoplasmic Reticulum; Epithelium; Humans; Kidney; Kidney Diseases; Kidney Glomerulus; Kidney Tubules; Leukemia, Lymphoid; Male; Microscopy, Electron; Plasma Cells; Pseudomonas Infections; Rhinitis; Streptomycin

Topics: Animals; Colistin; Gentamicins; Injections; Keratitis; Neomycin; Ophthalmic Solutions; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections; Rabbits; Tyrothricin

Topics: Animals; Anti-Bacterial Agents; Colistin; Drug Resistance, Microbial; Gentamicins; Guinea Pigs; Hydrogen-Ion Concentration; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Adult; Anti-Bacterial Agents; Colistin; Female; Humans; Meningitis; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections; Time Factors

Topics: Anti-Bacterial Agents; Chloramphenicol; Colistin; Culture Techniques; Drug Resistance, Microbial; Framycetin; Gentamicins; Humans; Immunodiffusion; Indicator Dilution Techniques; Nalidixic Acid; Neomycin; Polymyxins; Pseudomonas; Pseudomonas Infections; Streptomycin; Sulfonamides; Tetracycline

Topics: Adult; Aged; Colistin; Female; Humans; Lung; Male; Middle Aged; Pneumonia; Polymyxins; Pseudomonas Infections

Topics: Colistin; Enterobacteriaceae Infections; Escherichia coli Infections; Humans; Klebsiella Infections; Polymyxins; Pseudomonas Infections

Topics: Cartilage; Child; Chloramphenicol; Colistin; Drug Resistance, Microbial; Foot; Foot Injuries; Humans; Kanamycin; Male; Neomycin; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections; Radiography; Streptomycin; Wound Infection

Topics: Animals; Aqueous Humor; Biological Assay; Blindness; Colistin; Dogs; Eye Diseases; Inflammation; Oxytetracycline; Perfusion; Pseudomonas aeruginosa; Pseudomonas Infections; Staphylococcal Infections; Staphylococcus; Uveitis; Vitreous Body

Topics: Animals; Colistin; Mice; Pseudomonas aeruginosa; Pseudomonas Infections; Pyelonephritis; Sulfates; Sulfonic Acids

Topics: Animals; Colistin; Gentamicins; Kanamycin; Kidney; Mice; Microscopy, Electron; Neomycin; Pseudomonas aeruginosa; Pseudomonas Infections; Spleen; Streptomycin

Topics: Ampicillin; Animals; Colistin; Keratitis; Nalidixic Acid; Penicillins; Proteus; Proteus Infections; Pseudomonas aeruginosa; Pseudomonas Infections; Rabbits

Topics: Ampicillin; Chloramphenicol; Colistin; Cross Infection; Enterobacter; Enterobacteriaceae; Enterobacteriaceae Infections; Epidemiologic Methods; Escherichia coli; Housekeeping, Hospital; Humans; Kanamycin; Methods; Otorhinolaryngologic Diseases; Proteus; Proteus Infections; Pseudomonas aeruginosa; Pseudomonas Infections; Tetracycline

Topics: Acute Disease; Colistin; Humans; Pseudomonas Infections; Urinary Tract Infections

Topics: Ampicillin; Colistin; Communicable Diseases; Humans; Infant, Newborn; Infant, Newborn, Diseases; Meningitis; Oxacillin; Pneumonia; Pseudomonas Infections; Pyoderma; Sepsis

Topics: Colistin; Female; Humans; Kanamycin; Male; Neomycin; Pseudomonas Infections; Respiratory Tract Infections; Streptomycin

Topics: Adolescent; Adult; Antisepsis; Colistin; Conjunctivitis; Corneal Ulcer; Erythromycin; Female; Humans; Infant; Male; Ointments; Ophthalmic Solutions; Preoperative Care; Pseudomonas Infections

Topics: Aged; Biological Assay; Bronchitis; Colistin; Gentamicins; Humans; Injections, Intramuscular; Klebsiella; Male; Middle Aged; Pseudomonas Infections; Respiratory Therapy

Topics: Animals; Anti-Bacterial Agents; Burns; Chloramphenicol; Colistin; Gentamicins; In Vitro Techniques; Mice; Neomycin; Polymyxins; Pseudomonas Infections; Sepsis; Streptomycin; Sulfadiazine; Sulfanilamides

Topics: Adult; Aged; Colistin; Corneal Ulcer; Eye Injuries; Female; Humans; Male; Middle Aged; Polymyxins; Pseudomonas Infections

Topics: Colistin; Cross Infection; Disease Outbreaks; Female; France; Humans; Infant, Newborn; Infant, Premature, Diseases; Male; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Adolescent; Adrenal Cortex Hormones; Colistin; Corneal Ulcer; Female; Humans; Polymyxins; Pseudomonas Infections

Topics: Colistin; Humans; Penicillins; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Bacteriuria; Colistin; Cystitis; Escherichia coli Infections; Humans; Pseudomonas Infections; Pyelonephritis; Sulfonic Acids; Urethritis

Topics: Animals; Burns; Colistin; Gentamicins; In Vitro Techniques; Methicillin; Mice; Penicillinase; Penicillins; Pseudomonas aeruginosa; Pseudomonas Infections; Staphylococcus

Topics: Colistin; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Meningitis; Pseudomonas aeruginosa; Pseudomonas Infections

Five cases of Pseudomonas keratitis have been presented. Suggestions relative to the use of subpalpebral lavage in the management of this infection have been offered.

Topics: Anti-Bacterial Agents; Colistin; Cornea; Drug Therapy, Combination; Eye Infections, Bacterial; Follow-Up Studies; Humans; Instillation, Drug; Keratitis; Polymyxin B; Pseudomonas; Pseudomonas Infections

Topics: Animals; Anti-Infective Agents, Local; Colistin; Dihydrostreptomycin Sulfate; Female; Genital Diseases, Female; Gentamicins; Horse Diseases; Horses; Hydrocortisone; Infertility, Female; Nitrofurantoin; Novobiocin; Oxytetracycline; Penicillin G; Penicillin G Procaine; Penicillins; Polymyxins; Povidone; Pregnancy; Pregnancy, Animal; Pseudomonas Infections

Topics: Animals; Chloramphenicol; Colistin; Kanamycin; Keratitis; Polymyxins; Pseudomonas Infections; Rabbits; Streptomycin; Sulfonamides

Topics: Animals; Anti-Bacterial Agents; Burns; Colistin; Immune Sera; Mice; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis; Wound Infection

Topics: Adult; Ampicillin; Colistin; Hematoma, Subdural; Hepatic Encephalopathy; Humans; Lung Abscess; Male; Methicillin; Middle Aged; Pancreatitis; Penicillin Resistance; Postoperative Complications; Pseudomonas Infections

Topics: Colistin; Creatine; Humans; Pseudomonas Infections; Urinary Tract Infections

Topics: Child; Child, Preschool; Colistin; Humans; Male; Otitis; Pseudomonas Infections; Rhinitis

Topics: Child; Colistin; Female; Humans; Male; Mastoiditis; Pseudomonas Infections; Punctures

Topics: Colistin; Corneal Ulcer; Drug Therapy; Geriatrics; Humans; Pseudomonas aeruginosa; Pseudomonas Infections; Toxicology

Topics: Bacitracin; Child; Colistin; Drug Therapy; Endocarditis; Endocarditis, Bacterial; Enterobacter aerogenes; Escherichia coli Infections; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Infections; Klebsiella; Liver Abscess; Oxacillin; Penicillins; Pseudomonas Infections; Staphylococcal Infections; Streptococcal Infections; Toxicology

Topics: Anticoagulants; Colistin; Diagnosis; Drug Therapy; Enterobacter; Escherichia coli Infections; Heparin; Hydrocortisone; Kanamycin; Klebsiella; Mannitol; Proteus Infections; Pseudomonas Infections; Sepsis; Streptomycin; Urinary Tract Infections; Urology; Vasodilator Agents

Topics: Colistin; Diagnosis; Drainage; Drug Therapy; Geriatrics; Humans; Intestinal Obstruction; Laparotomy; Postoperative Complications; Pseudomonas Infections; Radiography; Urinary Bladder Diseases; Urinary Catheterization; Urinary Tract Infections; Urination Disorders

Topics: Colistin; Drug Therapy; Injections, Intramuscular; Nalidixic Acid; Proteus; Pseudomonas Infections; Toxicology; Urinary Tract Infections

Topics: Adrenal Cortex Hormones; Bacillus; Colistin; Cross Infection; Drug Therapy; gamma-Globulins; Humans; Lung Diseases; Polymyxins; Postoperative Complications; Pseudomonas aeruginosa; Pseudomonas Infections; Resuscitation; Sepsis

Topics: Anti-Bacterial Agents; Chloramphenicol; Colistin; Drug Resistance; Drug Resistance, Microbial; Drug Therapy; Enterobacter; Escherichia coli Infections; Humans; Klebsiella; Nalidixic Acid; Nitrofurantoin; Proteus Infections; Pseudomonas Infections; Pyelonephritis; Statistics as Topic; Sulfonamides; Tetracycline

Colistimethate sodium (Coly-Mycin) was used in the treatment of 17 patients: 13 had urinary tract infections (two of these had positive blood cultures), three had respiratory tract infections, and one patient had both urinary and respiratory tract infections. In nine of the 17 a foreign body-either a carcinoma, a catheter, or a stone-complicated the infection.The dosage used was 1.1-2.3 mg./lb./day with a maximum in one case of 2.4 g. given over an eight-day period. The organisms so treated included Pseudomonas, six; Aerobacter, six and E. coli, two. Both Pseudomonas and Aerobacter were encountered in three cases.On bacteriological grounds, six patients were cured, eight relapsed, and in three the infecting agent was replaced by another organism. The best responses were obtained in those patients with Pseudomonas infection. Side effects included nausea, vomiting, vertigo, paresthesias, and pain at the site of injection.Colistimethate sodium has a place in the treatment of Gram-negative infections excluding Proteus organisms.

Topics: Colistin; Drug Therapy; Enterobacter; Escherichia coli; Escherichia coli Infections; Geriatrics; Humans; Proteus; Pseudomonas Infections; Respiratory Tract Infections; Toxicology; Urinary Tract Infections

Topics: Antibodies; Child; Colistin; Drug Therapy; gamma-Globulins; Humans; Penicillins; Plasmapheresis; Prednisone; Pseudomonas Infections

Topics: Blood; Cerebrospinal Fluid; Colistin; Escherichia coli Infections; Humans; Pseudomonas Infections

Topics: Anemia; Anemia, Aplastic; Blood Cell Count; Bone Marrow Examination; Colistin; Erythromycin; Female; Humans; Neomycin; Prednisone; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic; Pseudomonas Infections; Sepsis; Streptomycin; Testosterone; Tetracycline

Topics: Colistin; Drug Resistance; Drug Resistance, Microbial; Kidney Diseases; Mice; Pathology; Polymyxin B; Polymyxins; Pseudomonas; Pseudomonas Infections; Research; Toxicology

Topics: Anti-Bacterial Agents; Chloramphenicol; Colistin; Cornea; Corneal Transplantation; Debridement; Diathermy; Eye Burns; Eye Injuries; Geriatrics; Humans; Injections, Intra-Arterial; Iontophoresis; Lidocaine; Ophthalmology; Polymyxins; Pseudomonas Infections; Staphylococcal Infections; Streptomycin; Tetracycline; Therapeutic Irrigation; Ulcer

Topics: Anti-Bacterial Agents; Chloramphenicol; Colistin; Drug Resistance; Drug Resistance, Microbial; Kanamycin; Pharmacology; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections; Research; Streptomycin; Tetracycline

Topics: Anti-Bacterial Agents; Bacteriological Techniques; Bacteriuria; Colistin; Enterobacteriaceae; Escherichia coli Infections; Klebsiella; Proteus Infections; Pseudomonas; Pseudomonas Infections; Staphylococcal Infections; Streptococcal Infections; Urinary Tract Infections; Urine

Topics: Acinetobacter; Biomedical Research; Colistin; Enterobacter aerogenes; Escherichia coli Infections; Hydrocortisone; Klebsiella; Neomycin; Otitis Externa; Proteus Infections; Pseudomonas aeruginosa; Pseudomonas Infections; Staphylococcal Infections

Topics: Adolescent; Anti-Bacterial Agents; Antibiotic Prophylaxis; Burns; Child; Chloramphenicol; Colistin; Erythromycin; Escherichia coli Infections; gamma-Globulins; Humans; Immune Sera; Infant; Infant, Newborn; Kanamycin; Novobiocin; Polymyxins; Proteus Infections; Pseudomonas Infections; Salmonella Infections; Sepsis; Serum Albumin; Shigella; Sodium Chloride; Solutions; Staphylococcal Infections; Streptococcal Infections; Tetracycline; Vancomycin

Topics: Amphotericin B; Anti-Bacterial Agents; Chloramphenicol; Colistin; Drug Resistance; Drug Resistance, Microbial; Endocarditis; Endocarditis, Bacterial; Enterobacter aerogenes; Enterobacteriaceae; Erythromycin; Escherichia coli Infections; Kanamycin; Penicillin G; Penicillins; Proteus Infections; Pseudomonas Infections; Ristocetin; Staphylococcal Infections; Streptococcal Infections; Streptomycin; Tetracycline; Vancomycin

Topics: Abscess; Amphotericin B; Brain Abscess; Candidiasis; Carrier State; Child; Chloramphenicol; Colistin; Deoxyribonucleases; DNA; Empyema; Enteritis; Humans; Kanamycin; Meningitis; Methicillin; Penicillins; Peritonitis; Phlebitis; Pneumonia; Pneumothorax; Pseudomonas Infections; Sepsis; Staphylococcal Infections; Sulfadiazine; Troleandomycin

Topics: Colistin; Diagnosis, Differential; Enterobacter; Escherichia coli Infections; Glomerulonephritis; Kanamycin; Prognosis; Proteus Infections; Pseudomonas Infections; Pyelonephritis; Staphylococcal Infections

Topics: Chlortetracycline; Colistin; Esophageal Fistula; Hemothorax; Mediastinitis; Penicillins; Pseudomonas Infections; Streptomycin; Surgical Procedures, Operative; Wounds, Gunshot

Topics: Animals, Newborn; Colistin; Dogs; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Kidney Diseases; Mesylates; Methane; Pseudomonas Infections; Research; Toxicology; Urea

Topics: Colistin; Drug Resistance; Drug Resistance, Microbial; Humans; Kidney Diseases; Polymyxin B; Polymyxins; Pseudomonas Infections; Toxicology

Topics: Anti-Inflammatory Agents; Asthma; Biomedical Research; Bronchitis; Colistin; Heparin; Humans; Injections, Intravenous; Neomycin; Placebos; Pseudomonas Infections; Pulmonary Emphysema; Respiratory Insufficiency; Respiratory Tract Infections

Topics: Abscess; Adolescent; Animals; Child; Colistin; Cornea; Corneal Ulcer; Corynebacterium; Dacryocystitis; Drug Therapy; Geriatrics; Humans; Hydrogen-Ion Concentration; Infant; Ophthalmology; Orbit; Osmosis; Pseudomonas Infections; Rabbits; Research; Staphylococcal Infections; Streptococcal Infections; Ulcer; Uveitis

Topics: Administration, Intravenous; Blood Chemical Analysis; Colistin; Creatine; Creatinine; Humans; Injections, Intramuscular; Injections, Intravenous; Kidney Function Tests; Nitrogen; Pharmacology; Pneumonia; Probenecid; Pseudomonas Infections; Pyelonephritis; Sodium; Urea

Topics: Burns; Colistin; Drug Therapy; Endocarditis; Endocarditis, Bacterial; Humans; Penicillins; Polymyxins; Pseudomonas; Pseudomonas aeruginosa; Pseudomonas Infections; Streptomycin

Topics: Adolescent; Chloramphenicol; Colistin; Cornea; Dexamethasone; Drug Therapy; Iatrogenic Disease; Keratitis; Penicillins; Pseudomonas; Pseudomonas Infections; Recurrence; Toxicology

Topics: Aging; Angiotensins; Bacteremia; Bacteroides; Chloramphenicol; Colistin; Drug Therapy; Enterobacter aerogenes; Escherichia coli Infections; Humans; Iatrogenic Disease; Kanamycin; Metaraminol; Polymyxins; Postoperative Complications; Proteus; Pseudomonas Infections; Sepsis; Sex; Streptomycin; Sympatholytics; Tetracycline; Urinary Tract Infections

Topics: Colistin; Drug Therapy; Escherichia coli Infections; Humans; Meningitis; Pseudomonas aeruginosa; Pseudomonas Infections; Urinary Tract Infections

Topics: Animals; Colistin; Corneal Ulcer; Humans; Lagomorpha; Male; Pseudomonas; Pseudomonas Infections; Rabbits; Sulfanilamide; Sulfanilamides; Sulfonamides

Topics: Bacillus; Colistin; Diagnosis; Drug Therapy; Endocarditis; Endocarditis, Bacterial; Geriatrics; Humans; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Colistin; Enterobacter; Escherichia coli Infections; Klebsiella; Pseudomonas Infections; Urinary Tract Infections

Topics: Colistin; Humans; Pseudomonas Infections; Urinary Tract Infections

Topics: Colistin; Eye, Artificial; Humans; Orbit; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Colistin; Humans; Pseudomonas Infections; Urinary Tract Infections

Topics: Agammaglobulinemia; Anti-Bacterial Agents; Chloramphenicol; Colistin; Diagnosis, Differential; Drug Resistance, Microbial; gamma-Globulins; Humans; Infant; Pseudomonas; Pseudomonas Infections; Sepsis

Topics: Colistin; Enterobacter aerogenes; Enterococcus faecalis; Escherichia coli Infections; Hospitals, General; Humans; Proteus Infections; Pseudomonas aeruginosa; Pseudomonas Infections; Staphylococcal Infections; Streptococcal Infections; Urinary Tract Infections

Topics: Colistin; Humans; Injections; Injections, Intramuscular; Keratoconjunctivitis; Neomycin; Ophthalmic Solutions; Penicillins; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections; Streptomycin

Topics: Colistin; Humans; Kidney Function Tests; Male; Pharmacology; Pseudomonas Infections; Pyelonephritis; Radioisotopes; Radionuclide Imaging; Staphylococcal Infections; Urography; Vasopressins

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Chloramphenicol; Colistin; Humans; Neomycin; Nitrofurantoin; Penicillins; Pseudomonas Infections; Pyelonephritis; Streptomycin; Sulfamethizole; Sulfathiazoles; Tetracycline

Topics: Alcoholism; Colistin; Cross Infection; Cystoscopy; Humans; Lung Abscess; Nephritis; Nephritis, Interstitial; Pseudomonas aeruginosa; Pseudomonas Infections; Streptomycin; Urinary Catheterization

Topics: Bacitracin; Child; Chloramphenicol; Colistin; Escherichia coli Infections; Gastroenteritis; Humans; Infant; Infant, Newborn; Kanamycin; Neomycin; Nitrofurantoin; Polymyxins; Proteus Infections; Pseudomonas Infections

Topics: Acid-Base Equilibrium; Colistin; Hydrocortisone; Neomycin; Otitis Externa; Pseudomonas Infections; Staphylococcal Infections

Topics: Animals; Colistin; Corneal Ulcer; In Vitro Techniques; Lagomorpha; Pharmacology; Pseudomonas; Pseudomonas Infections; Rabbits; Research; Sulfanilamide; Sulfanilamides; Sulfonamides

Chapman, George B. (Cornell University Medical College, New York, N.Y.). Cytological aspects of antimicrobial antibiosis. II. Cytological changes associated with the exposure of Pseudomonas aeruginosa and Bacillus megaterium to colistin sulfate. J. Bacteriol. 84:180-185. 1962-Broth cultures of Pseudomonas aeruginosa and Bacillus megaterium were exposed to the antibiotic colistin sulfate. Control (unexposed) and exposed cells were fixed, dehydrated, and embedded in methacrylate. Ultrathin sections were examined in an RCA EMU2-D electron microscope. Two conspicuous cytological changes were noted in P. aeruginosa. The nuclear material was no longer demonstrable in its normal sites, leaving an empty space, and the cytoplasm lost its granularity, becoming homogeneous. In B. megaterium, the latter change was also noted. The nuclear material, however, although no longer demonstrable, did not leave an empty space. Rather, it seemed that cytoplasmic material had engulfed and masked nuclear areas. Cells which showed these changes were nonviable.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antibiosis; Bacillus megaterium; Colistin; Pseudomonas; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Colistin; Humans; Mesylates; Methane; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Anti-Bacterial Agents; Colistin; Humans; Laboratories; Pseudomonas Infections

Topics: Colistin; Keratitis; Pseudomonas; Pseudomonas Infections

Topics: Anti-Bacterial Agents; Bacterial Infections; Colistin; Humans; Infections; Pseudomonas Infections

Topics: Anti-Bacterial Agents; Bacillus; Cartilage Diseases; Colistin; Ear Auricle; Ear, External; Gram-Positive Bacteria; Humans; Otitis Externa; Pseudomonas Infections

Topics: Anti-Bacterial Agents; Colistin; Eye Infections; Humans; Pseudomonas Infections

Topics: Anti-Bacterial Agents; Child; Colistin; Humans; Infant; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Anti-Bacterial Agents; Colistin; Conjunctiva; Cornea; Corneal Diseases; Disease; Keratitis; Pseudomonas Infections

Topics: Anti-Bacterial Agents; Colistin; Eye Diseases; Humans; Pseudomonas Infections