colistin and Pneumonia--Bacterial

Antimicrobial resistance (AMR) is a global health issue, which needs to be tackled without further delay. The World Health Organization(WHO) has classified three gram-negative bacteria, Pseudomonas aeruginosa, Klebsiella pneumonia and Acinetobacter baumannii, as the principal responsible for AMR, mainly causing difficult to treat nosocomial lung and wound infections. In this regard, the need for colistin and amikacin, the re-emerged antibiotics of choice for resistant gram-negative infections, will be examined as well as their associated toxicity. Thus, current but ineffective clinical strategies designed to prevent toxicity related to colistin and amikacin will be reported, highlighting the importance of lipid-based drug delivery systems (LBDDSs), such as liposomes, solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), as efficient delivery strategies for reducing antibiotic toxicity. This review reveals that colistin- and amikacin-NLCs are promising carriers with greater potential than liposomes and SLNs to safely tackle AMR, especially for lung and wound infections.

Topics: Acinetobacter baumannii; Amikacin; Anti-Bacterial Agents; Colistin; Drug Delivery Systems; Drug Resistance, Multiple, Bacterial; Humans; Liposomes; Lung; Microbial Sensitivity Tests; Pneumonia, Bacterial; Pseudomonas aeruginosa; Wound Infection

Multidrug-resistant pneumonia is a common cause of hospital-related morbidity and mortality across the world. The high prevalence of multidrug-resistant pneumonia due to resistant gram-negative pathogens has led to a re-introduction of colistin. The adverse events associated with intravenous colistin can be alleviated by administering the drug nasally (i.e., inhalation) or in a combination including both inhalation and intravenous presentations of the drug. A review study compared the impact of these administration methods on clinical, morbidity, and mortality-related outcomes in patients with multiple-drug resistant pneumonia. However, the publication of newer cohort trials, warrants an update of the state of the evidence. To compare the clinical, morbidity, and mortality outcomes in patients with multidrug-resistant pneumonia receiving either intravenous colistin or combined drug presentations (ie, inhaled and intravenous)..  A systematic search of the academic literature was performed according to the PRISMA guidelines across five databases (Web of Science, EMBASE, CENTRAL, Scopus, and MEDLINE). We conducted a random-effect meta-analysis to compare outcomes such as rate of clinical cure, microbiological eradication, nephrotoxicity, and overall mortality in patients with multidrug-resistant pneumonia receiving either intravenous colistin, inhaled colistin, or a combination of those administration routes..  From 963 studies, we found 16 eligible studies with 1651 patients (61.6 ± 7.7 years) with multidrug-resistant pneumonia who had received either intravenous, inhaled colistin or a combined inhaled/intravenous administration. Our meta-analysis revealed higher rates of clinical cure (OR, 1.61) and microbiological eradication (1.37) in patients receiving combined intravenous/inhaled colistin than in those receiving intravenous colistin alone. Additional analyses revealed higher rates of nephrotoxicity (1.30) and mortality (1.44) in patients receiving intravenous colistin than in those receiving combined intravenous/inhaled colistin..  We provide evidence showing improved clinical, morbidity, and mortality outcomes in patients with multidrug-resistant pneumonia receiving inhaled colistin or combined inhaled/intravenous colistin than those receiving intravenous colistin alone. These findings should help clinicians stratify the risks associated with different colistin administration routes to manage multidrug-resistant pneumonia.

Topics: Administration, Inhalation; Administration, Intravenous; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Pneumonia, Bacterial

Klebsiella pneumoniae producing KPC-type carbapenemase causes severe nosocomial infection at a high mortality rate. Nosocomial pneumonia in particular is associated with high mortality, likely due to the unfavorable pulmonary pharmacokinetics of the antibiotics used against this agent. Therefore, early and accurate microbiological identification and susceptibility evaluation are crucial in order to optimize antibiotic therapy. We report a case of ventilator-associated pneumonia caused by colistin-resistant K. pneumoniae producing KPC-type carbapenemase treated using a carbapenem-sparing therapy and tailored according to the serum procalcitonin concentration in order to limit the duration of antibiotic therapy.

Topics: Adult; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Calcitonin; Calcitonin Gene-Related Peptide; Colistin; Cross Infection; Drug Resistance, Bacterial; Drug Therapy, Combination; Equipment Contamination; Fosfomycin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Minocycline; Pneumonia, Bacterial; Protein Precursors; Tigecycline; Treatment Outcome; Ventilators, Mechanical

We sought to evaluate the effectiveness of the antibiotic treatment administered for infections caused by carbapenemase-producing Enterobacteriaceae. The PubMed and Scopus databases were systematically searched. Articles reporting the clinical outcomes of patients infected with carbapenemase-producing Enterobacteriaceae according to the antibiotic treatment administered were eligible. Twenty nonrandomized studies comprising 692 patients who received definitive treatment were included. Almost all studies reported on Klebsiella spp. In 8 studies, the majority of infections were bacteremia, while pneumonia and urinary tract infections were the most common infections in 12 studies. In 10 studies, the majority of patients were critically ill. There are methodological issues, including clinical heterogeneity, that preclude the synthesis of the available evidence using statistical analyses, including meta-analysis. From the descriptive point of view, among patients who received combination treatment, mortality was up to 50% for the tigecycline-gentamicin combination, up to 64% for tigecycline-colistin, and up to 67% for carbapenem-colistin. Among the monotherapy-treated patients, mortality was up to 57% for colistin and up to 80% for tigecycline. Certain regimens were administered to a small number of patients in certain studies. Three studies reporting on 194 critically ill patients with bacteremia showed individually significantly lower mortality in the combination arm than in the monotherapy arm. In the other studies, no significant difference in mortality was recorded between the compared groups. Combination antibiotic treatment may be considered the optimal option for severely ill patients with severe infections. However, well-designed randomized studies of specific patient populations are needed to further clarify this issue.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; Carbapenems; Colistin; Critical Illness; Drug Therapy, Combination; Enterobacteriaceae; Humans; Minocycline; Pneumonia, Bacterial; Survival Analysis; Tigecycline; Urinary Tract Infections

The administration of antibiotics by the inhaled route is a widely recognized treatment in patients with cystic fibrosis (CF) and bronchiectasis. Tobramycin solution for inhalation (TOBI) has been available for many years and is licensed in the USA and Europe. While strong data support the use of aerosolized antibiotics for the treatment of respiratory infections in patients with CF or bronchiectasis, only a few clinical studies have examined the role of aerosolized antibiotics in the treatment of pneumonia, including ventilator-associated pneumonia (VAP) in these patients. During the last decade increasing interest has been directed towards alternative treatments to the systemic administration of antimicrobial agents for the treatment of patients with hospital-acquired pneumonia or VAP due to multidrug-resistant (MDR) Gram-negative bacteria. Recent publications demonstrate the clinical benefits from administering inhaled aminoglycosides or polymyxins in patients with hospital-acquired pneumonia or VAP. In addition to antibiotics, antifungals, and antivirals have been administered by inhalation to specific groups of critically ill patients. However, randomized controlled trials dealing with the administration of anti-infective agents via the respiratory tract are necessary in order to validate the efficacy, safety, advantages, and disadvantages of this therapeutic approach for the treatment of nosocomial pneumonia.

Topics: Administration, Inhalation; Aerosols; Anti-Bacterial Agents; Colistin; Cross Infection; Humans; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; 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

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

A 55-year old man developed a hemorrhagic pneumonia, likely due to infection with Kytococcus sedentarius during neutropenia following induction chemotherapy for acute myeloid leukemia. Severe mucosal barrier injury and the selective pressure of broad-spectrum antibiotics probably made it possible for this normally harmless commensal to penetrate the gut, spread through the blood stream, and invade the lungs.

Topics: Actinomycetales; Actinomycetales Infections; Acyclovir; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; Bacterial Translocation; Cefepime; Cephalosporins; Clostridium Infections; Colistin; Cytarabine; Daunorubicin; Drug Therapy, Combination; Etoposide; Fatal Outcome; Hemoptysis; Humans; Hydroxyurea; Immunocompromised Host; Intestinal Mucosa; Leukemia, Myeloid, Acute; Male; Metronidazole; Middle Aged; Neutropenia; Pneumonia, Bacterial; Superinfection; Teicoplanin; Trimethoprim, Sulfamethoxazole Drug Combination

Although investigations are limited, adjunctive aerosolized antibiotics have been advised in the setting of gram-negative ventilator-associated pneumonia (VAP). This study aimed to compare the efficiency of inhaled colistin with inhaled fosfomycin/tobramycin in treating VAP due to extensively drug-resistant (XDR) Acinetobacter baumannii.. This single center open-label randomized controlled trial included 60 patients who developed XDR A. bumannii VAP. Eligible participants were randomly assigned to two groups (no. 30). Regardless of the assignment, all participants received meropenem (2 g as a 3-h extended infusion every 8 h) plus intravenous colistin (a loading dose of 9 million IU and then 4.5 million IU every 12 h). The control group was given inhaled colistin (1 million IU every 8 h), and the case group received inhaled tobramycin/fosfomycin (300 mg every 12 h/80 mg every 12 h) as adjunctive therapy. The primary outcome was treatment duration, and the secondary outcomes were Clinical Pulmonary Infection Score (CPIS) trend and mortality rate in the groups. The decision to stop treatment was made by the treating physician.. The mean treatment duration was 13.73 ± 3.22 days in the colistin group and 10.85 ± 2.84 days in the tobramycin/fosfomycin group; the mean treatment duration in the latter group was lower significantly (P = 0.001). CPIS was decreased in the groups significantly (P < 0.001), but the mean changes of CPIS were significantly different between the groups, and in the inhaled tobramycin/fosfomycin group, a greater reduction (P = 0.005) was observed. Two (6.67%) patients in the control group and three (10%) patients in the case group died.. The use of inhaled tobramycin/fosfomycin in cases with XDR A. bumannii VAP was associated with a shorter treatment duration in this open-label trial.

Topics: Administration, Inhalation; Anti-Bacterial Agents; Colistin; Fosfomycin; Humans; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Tobramycin; Treatment Outcome

An urgent need exists for antibiotics to treat infections caused by carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (ABC). Sulbactam-durlobactam is a β-lactam-β-lactamase inhibitor combination with activity against Acinetobacter, including multidrug-resistant strains. In a phase 3, pathogen-specific, randomised controlled trial, we compared the efficacy and safety of sulbactam-durlobactam versus colistin, both in combination with imipenem-cilastatin as background therapy, in patients with serious infections caused by carbapenem-resistant ABC.. The ATTACK trial was done at 59 clinical sites in 16 countries. Adults aged 18 years or older with ABC-confirmed hospital-acquired bacterial pneumonia, ventilator-associated bacterial pneumonia, ventilated pneumonia, or bloodstream infections were randomised 1:1 using a block size of four to sulbactam-durlobactam (1·0 g of each drug in combination over 3 h every 6 h) or colistin (2·5 mg/kg over 30 min every 12 h) for 7-14 days. All patients received imipenem-cilastatin (1·0 g of each drug in combination over 1 h every 6 h) as background therapy. The primary efficacy endpoint was 28-day all-cause mortality in patients with laboratory-confirmed carbapenem-resistant ABC (the carbapenem-resistant ABC microbiologically modified intention-to-treat population). Non-inferiority was concluded if the upper bound of the 95% CI for the treatment difference was less than +20%. The primary safety endpoint was incidence of nephrotoxicity assessed using modified Risk, Injury, Failure, Loss, End-stage renal disease criteria measured by creatinine level or glomerular filtration rate through day 42. This trial is registered at ClinicalTrials.gov, NCT03894046.. Between Sep 5, 2019, and July 26, 2021, 181 patients were randomly assigned to sulbactam-durlobactam or colistin (176 hospital-acquired bacterial pneumonia, ventilator-associated bacterial pneumonia, or ventilated pneumonia; and five bloodstream infections); 125 patients with laboratory-confirmed carbapenem-resistant ABC isolates were included in the primary efficacy analysis. 28-day all-cause mortality was 12 (19%) of 63 in the sulbactam-durlobactam group and 20 (32%) of 62 in the colistin group, a difference of -13·2% (95% CI -30·0 to 3·5), which met criteria for non-inferiority. Incidence of nephrotoxicity was significantly (p<0·001) lower with sulbactam-durlobactam than colistin (12 [13%] of 91 vs 32 [38%] of 85). Serious adverse events were reported in 36 (40%) of 91 patients in the sulbactam-durlobactam group and 42 (49%) of 86 patients in the colistin group. Treatment-related adverse events leading to study drug discontinuation were reported in ten (11%) of 91 patients in the sulbactam-durlobactam group and 14 (16%) of 86 patients in the colistin group.. Our data show that sulbactam-durlobactam was non-inferior to colistin, both agents given in combination with imipenem-cilastatin, for the primary endpoint of 28-day all-cause mortality. Sulbactam-durlobactam was well tolerated and could be an effective intervention to reduce mortality from serious infections caused by carbapenem-resistant ABC, including multidrug-resistant strains.. Entasis Therapeutics and Zai Lab.

Topics: Acinetobacter baumannii; Adult; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Cilastatin, Imipenem Drug Combination; Colistin; Humans; Microbial Sensitivity Tests; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Sepsis

In vitro models showing synergism between polymyxins and carbapenems support combination treatment for carbapenem-resistant Gram-negative (CRGN) infections. We tested the association between the presence of in vitro synergism and clinical outcomes in patients treated with colistin plus meropenem.. This was a secondary analysis of AIDA, a randomized controlled trial comparing colistin with colistin-meropenem for severe CRGN infections. We tested in vitro synergism using a checkerboard assay. Based on the fractional inhibitory concentration (ΣFIC) index for each colistin-meropenem combination, we categorized results as synergistic, antagonistic or additive/indifferent. The primary outcome was clinical failure at 14 days. Secondary outcomes were 14- and 28-day mortality and microbiological failure.. The sample included 171 patients with infections caused by carbapenem-resistant Acinetobacter baumannii (n = 131), Enterobacteriaceae (n = 37) and Pseudomonas aeuruginosa (n = 3). In vitro testing showed synergism for 73 isolates, antagonism for 20 and additivism/indifference for 78. In patients who received any colistin plus meropenem, clinical failure at 14 days was 59/78 (75.6%) in the additivism/indifference group (reference category), 54/73 (74.0%) in the synergism group (adjusted odds ratio (aOR) 0.76, 95% CI 0.31-1.83), and 11/20 (55%) in the antagonism group (aOR 0.77, 95% CI 0.22-2.73). There was no significant difference between groups for any secondary outcome. Comparing the synergism group to patients treated with colistin monotherapy, synergism was not protective against 14-day clinical failure (aOR 0.52, 95% CI 0.26-1.04) or 14-day mortality (aOR1.09, 95% CI 0.60-1.96).. In vitro synergism between colistin and meropenem via checkerboard method did not translate into clinical benefit.

Topics: Aged; Aged, 80 and over; Carbapenems; Colistin; Cross Infection; Drug Resistance, Bacterial; Drug Synergism; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Bacterial; Treatment Outcome

Topics: Anti-Bacterial Agents; Bacteremia; Carbapenem-Resistant Enterobacteriaceae; Colistin; Creatinine; Drug Resistance, Bacterial; Enterobacteriaceae Infections; Healthcare-Associated Pneumonia; Humans; Intention to Treat Analysis; Kaplan-Meier Estimate; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Sample Size; Sisomicin

Efficacy of colistin and ampicillin-sulbactam have not been compared in treatment of ventilator-associated pneumonia due to A. baumannii. Efficacy of colistin and ampicillin-sulbactam in combination with meropenem were compared in treatment of ventilator-associated pneumonia due to carbapenem-resistant A. baumannii.. 47 patients with ventilator-associated pneumonia due to carbapenem-resistant A. baumannii were randomized to receive meropenem/colistin or meropenem/ampicillin-sulbactam for 14 days. Clinical and microbiological responses and 28-day mortality were considered as outcomes.. Clinical response (75 vs 69.6%; p = 0.75) and microbial eradication (87.50 vs 91.3%; p = 0.59) were comparable between meropenem/colistin and meropenem/ampicillin-sulbactam groups, respectively.. In this study, clinical and microbiological response were comparable between the meropenem/colistin and meropenem/ampicillin-sulbactam groups.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Ampicillin; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Combinations; Drug Resistance, Bacterial; Female; Humans; Male; Meropenem; Middle Aged; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Sulbactam

We tested 76 extensively drug-resistant (XDR) Acinetobacter baumannii isolates by the checkerboard method using only wells containing serum-achievable concentrations (SACs) of drugs. Checkerboard results were correlated by time-kill assay and clinical outcomes. Minocycline-colistin was the best combination in vitro, as it inhibited growth in one or more SAC wells in all isolates. Patients who received a combination that inhibited growth in one or more SAC wells demonstrated better microbiological clearance than those who did not (88% versus 30%; P = 0.025). The checkerboard platform may have clinical utility for XDR A. baumannii infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Bacterial; Drug Synergism; Drug Therapy, Combination; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Bacterial; Respiratory Tract Infections; Treatment Outcome

Cases of ventilator-associated pneumonia (VAP) due to multidrug-resistant (MDR) Acinetobacter baumannii and Pseudomonas aeruginosa are common in hospitalized patients at Siriraj Hospital, Bangkok, Thailand. Parenteral colistimethate sodium (CMS) has been used for therapy of VAP caused by MDR A. baumannii and P. aeruginosa at Siriraj Hospital over the past few years, with modest favourable outcomes. Objectives To determine whether nebulized CMS as adjunctive therapy of Gram-negative VAP was safe and beneficial.. This was a randomized controlled study in 100 adults who developed Gram-negative VAP (clinical trial registration number: NCT00920270). All patients received systemic antibiotics according to the decisions of their responsible physicians. The patients were randomized to receive an additional 4 mL of nebulized sterile normal saline (NSS) (n = 49) or nebulized CMS equivalent to 75 mg of colistin base in 4 mL of NSS (n = 51) every 12 h until systemic antibiotic therapy of VAP was ended.. The baseline characteristics of the patients and conventional therapy of VAP in both groups were comparable. Most of the cases of VAP were caused by MDR A. baumannii and/or P. aeruginosa. All isolates of Gram-negative bacteria were susceptible to colistin. Favourable clinical outcome was 51.0% in the CMS group and 53.1% in the control group (P = 0.84). Patients in the CMS group had significantly more favourable microbiological outcome when compared with patients in the control group (60.9% versus 38.2%, P = 0.03). Bronchospasm was observed in 7.8% of patients in the CMS group and in 2.0% of patients in the control group (P = 0.36). Renal impairment was observed in 25.5% of patients in the CMS group and in 22.4% of patients in the NSS group (P = 0.82).. Nebulized CMS as adjunctive therapy of Gram-negative VAP seems to be safe. However, a beneficial effect on clinical outcomes of adjunctive nebulized CMS for therapy of Gram-negative VAP was not ascertained.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Cross Infection; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Treatment Outcome

To determine the effect of oral decontamination with either chlorhexidine (CHX, 2%) or the combination chlorhexidine-colistin (CHX-COL, 2%-2%) on the frequency and the time to onset of ventilator-associated pneumonia in Intensive Care patients.. Double blind, placebo-controlled, multicentre, randomised trial.. Consecutive ICU patients needing at least 48 h of mechanical ventilation were enrolled in a randomized trial with 3 arms: CHX, CHX-COL, and placebo (PLAC). The trial medication was administered in the oral cavity every 6 h. Oropharyngeal swabs were obtained daily and analysed quantitatively for Gram-positive and Gram-negative microorganisms. Endotracheal colonisation was monitored twice weekly. Ventilator-associated pneumonia was diagnosed on the basis of a combination of clinical, radiological and microbiological criteria.. Of 385 patients included, 130 received PLAC, 127 CHX and 128 CHX-COL. Baseline characteristics in the three groups were comparable. The daily risk of ventilator-associated pneumonia was reduced in both treatment groups compared to PLAC: 65% (HR= 0.352; 95% CI: 0.160-0.791; p = 0.012) for CHX and 55% (HR= 0.454; 95%/ CI: 0.224-0.925; p = 0.030) for CHX-COL. CHX-COL provided a significant reduction in oropharyngeal colonisation with both Gram-negative and Gram-positive microorganisms, whereas CHX significantly affected only colonisation with Gram-positive microorganisms. There were no differences in the duration of mechanical ventilation, ICU-stay or ICU-survival.. Oral decontamination of the oropharyngeal cavity with chlorhexidine or the combination chlorhexidine-colistin reduced the incidence and the time to onset ofventilator-associated pneumonia.

Topics: Administration, Topical; Adult; Anti-Bacterial Agents; Anti-Infective Agents, Local; Chlorhexidine; Colistin; Critical Care; Double-Blind Method; Drug Combinations; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Length of Stay; Male; Middle Aged; Mouth; Oropharynx; Placebos; Pneumonia, Bacterial; Time Factors; Trachea; Ventilators, Mechanical

To compare the safety and efficacy of ampicillin/sulbactam (Amp/Sulb) and colistin (COL) in the treatment of multidrug resistant Acinetobacter baumannii ventilator-associated pneumonia (VAP).. A prospective cohort study in adult critically ill patients with VAP. Patients were randomly assigned to receive Amp/Sulb (9 g every 8h) or COL (3 MIU every 8h) intravenously. Dosage was adjusted according to creatinine clearance.. A total of 28 patients were enrolled (15 COL, 13 Amp/Sulb). Resolution of symptoms and signs occurred in 60% (9/15) of the COL group and 61.5% (9/13) of the Amp/Sulb group, improvement in 13.3% (2/15) vs. 15.3% (1/13) and failure in 26.6% (4/15) vs. 23% (3/13), respectively. The difference was not statistically significant. Bacteriologic success was achieved in 66.6% (10/15) vs. 61.5% (8/13) in the COL and Amp/Sulb groups, respectively (p<0.2). Mortality rates (14 days and 28 days) were 15.3% and 30% for the Amp/Sulb and 20% and 33% for the COL group, respectively. Adverse events were 39.6% (including 33% nephrotoxicity) for the COL group and 30.7% (15.3% nephrotoxicity) for the Amp/Sulb group (p=NS).. Colistin and high-dose ampicillin/sulbactam were comparably safe and effective treatments for critically ill patients with MDR A. baumannii VAP.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Ampicillin; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Sulbactam

Ventilator-associated pneumonia (VAP) is the most frequently occurring nosocomial infection associated with increased morbidity and mortality. Although oral decontamination with antibiotics reduces incidences of VAP, it is not recommended because of potential selection of antibiotic-resistant pathogens. We hypothesized that oral decontamination with either chlorhexidine (CHX, 2%) or CHX/colistin (CHX/COL, 2%/2%) would reduce and postpone development of VAP, and oral and endotracheal colonization.. To determine the effect of oral decontamination with CHX or CHX/COL on VAP incidence and time to development of VAP.. Consecutive patients needing mechanical ventilation for 48 h or more were enrolled in a randomized, double-blind, placebo-controlled trial with three arms: CHX, CHX/COL, and placebo (PLAC). Trial medication was applied every 6 h into the buccal cavity. Oropharyngeal swabs were obtained daily and quantitatively analyzed for gram-positive and gram-negative microorganisms. Endotracheal colonization was monitored twice weekly.. Of 385 patients included, 130 received PLAC, 127 CHX and 128 CHX/COL. Baseline characteristics were comparable. The daily risk of VAP was reduced in both treatment groups compared with PLAC: 65% (hazard ratio [HR]=0.352; 95% confidence interval [CI], 0.160, 0. 791; p=0.012) for CHX and 55% (HR=0.454; 95% CI, 0.224, 0. 925; p=0.030) for CHX/COL. CHX/COL provided significant reduction in oropharyngeal colonization with both gram-negative and gram-positive microorganisms, whereas CHX mostly affected gram-positive microorganisms. Endotracheal colonization was reduced for CHX/COL patients and to a lesser extent for CHX patients. No differences in duration of mechanical ventilation, intensive care unit stay, or intensive care unit survival could be demonstrated.. Topical oral decontamination with CHX or CHX/COL reduces the incidence of VAP.

Topics: Administration, Topical; Adult; Anti-Bacterial Agents; Anti-Infective Agents, Local; Chlorhexidine; Colistin; Critical Care; Double-Blind Method; Drug Combinations; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Length of Stay; Male; Middle Aged; Mouth; Oropharynx; Placebos; Pneumonia, Bacterial; Time Factors; Trachea; Ventilators, Mechanical

A randomized, double-blind, placebo-controlled trial of selective decontamination of the oropharynx and gastrointestinal tract was conducted on 61 intubated patients in a medical-surgical intensive care unit (ICU) to determine the impact on nosocomial pneumonia, other infections, and emergence of colonization or infection with antibiotic-resistant bacteria. Over 8 months, 30 patients received an oral paste and solution containing polymyxin, gentamicin, and nystatin; 31 patients received a placebo paste and solution. At study entry, patients in both groups were seriously ill (mean acute physiologic score, 27.2), frequently had pulmonary infiltrates (73.8%), and were likely to be receiving systemic antibiotics (86.9%). There were no differences between study patients and control patients in these characteristics or in frequency of any nosocomial infection (50% vs. 55%), nosocomial pneumonia (27% vs. 26%), febrile days (2.3 vs. 2.0), duration of antibiotic therapy (14.0 vs. 13.4), or mortality rates (37% vs. 48%). There was no difference in infections caused by antibiotic-resistant gram-negative bacilli, although a trend towards more frequent infection with gentamicin-resistant enterococci was found for study patients. Selective decontamination did not appear to be effective in our very ill medical-surgical ICU patients, although the number of patients in our trial was sufficient to detect only a 50% or greater reduction in pneumonia rates.

Topics: Colistin; Cross Infection; Decontamination; Double-Blind Method; Drug Resistance, Microbial; Female; Gentamicins; Humans; Intensive Care Units; Male; Middle Aged; Nystatin; Pneumonia, Bacterial; Prospective Studies

The importance or necessity of a loading dose when prescribing intravenous colistin has not been well established in clinical practice, and approximate one-third to half of patients with carbapenem-resistant gram-negative bacteria (CRGNB) infection did not receive the administration of a loading dose. The aim of this study is to investigate the efficacy and risk of acute kidney injury when prescribing intravenous colistin for critically ill patients with nosocomial pneumonia caused by CRGNB.. This was a multicenter, retrospective study that recruited ICU-admitted patients who had CRGNB-associated nosocomial pneumonia and were treated with intravenous colistin. Then, we classified the patients into colistin loading dose (N = 85) and nonloading dose groups (N = 127). After propensity-score matching for important covariates, we compared the mortality rate, clinical outcome and microbiological eradication rates between the groups (N = 67).. The loading group had higher percentages of patients with favorable clinical outcomes (55.2% and 35.8%, p = 0.037) and microbiological eradication rates (50% and 27.3%, p = 0.042) at day 14 than the nonloading group. The mortality rates at days 7, 14 and 28 and overall in-hospital mortality were not different between the two groups, but the Kaplan-Meier analysis showed that the loading group had a longer survival time than the nonloading group. Furthermore, the loading group had a shorter length of hospital stay than the nonloading group (52 and 60, p = 0.037). Regarding nephrotoxicity, there was no significant difference in the risk of developing acute kidney injury between the groups.. The administration of a loading dose is recommended when prescribing intravenous colistin for critically ill patients with nosocomial pneumonia caused by CRGNB.

Topics: Anti-Bacterial Agents; Carbapenems; Colistin; Critical Illness; Gram-Negative Bacteria; Humans; Pneumonia, Bacterial; Retrospective Studies

To investigate the association between adjunctive nebulized colistin and treatment outcomes in critically ill patients with nosocomial carbapenem-resistant Gram-negative bacterial (CR-GNB) pneumonia.. This retrospective, multi-centre, cohort study included individuals admitted to the intensive care unit with nosocomial pneumonia caused by colistin-susceptible CR-GNB. Enrolled patients were divided into groups with/without nebulized colistin as adjunct to at least one effective intravenous antibiotic. Propensity score matching was performed in the original cohort (model 1) and a time-window bias-adjusted cohort (model 2). The association between adjunctive nebulized colistin and treatment outcomes was analysed.. In total, 181 and 326 patients treated with and without nebulized colistin, respectively, were enrolled for analysis. The day 14 clinical failure rate and mortality rate were 41.4% (75/181) versus 46% (150/326), and 14.9% (27/181) versus 21.8% (71/326), respectively. In the propensity score-matching analysis, patients with nebulized colistin had lower day 14 clinical failure rates (model 1: 41% (68/166) versus 54.2% (90/166), p 0.016; model 2: 35.3% (41/116) versus 56.9% (66/116), p 0.001). On multivariate analysis, nebulized colistin was an independent factor associated with fewer day 14 clinical failures (model 1: adjusted odds ratio (aOR) 0.59, 95% CI 0.37-0.92; model 2: aOR 0.37, 95% CI 0.21-0.65). Nebulized colistin was not associated independently with a lower 14-day mortality rate in the time-dependent analysis in both models 1 and 2.. Adjunctive nebulized colistin was associated with lower day 14 clinical failure rate, but not lower 14-day mortality rate, in critically ill patients with nosocomial pneumonia caused by colistin-susceptible CR-GNB.

Topics: Anti-Bacterial Agents; Carbapenems; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacterial Infections; Healthcare-Associated Pneumonia; Humans; Pneumonia, Bacterial; Retrospective Studies; Treatment Outcome

Stenotrophomonas maltophilia-induced pulmonary haemorrhage is considered a fatal infection among haematological patients. The outcome can be explained by the patients' immunity status and late diagnosis and treatment.. We present the rare case of successful outcome in a 61-year-old female who developed alveolar haemorrhage and acute respiratory distress syndrome 8 days after a chemotherapy session for her acute lymphoblastic leukaemia, in the context of secondary bone marrow aplasia. Stenotrophomonas maltophilia was isolated in sputum culture. The patient benefitted from early empirical treatment with colistin followed by trimethoprim/sulfamethoxazole, according to the antibiogram. Despite a severe initial clinical presentation in need of mechanical ventilation, neuromuscular blocking agents infusion, and ventilation in prone position, the patient had a favourable outcome and was discharged from intensive care after 26 days.. Stenotrophomonas maltophilia severe pneumonia complicated with pulmonary haemorrhage is not always fatal in haematological patients. Empirical treatment of multidrug-resistant Stenotrophomonas maltophilia in an immunocompromised haematological patient presenting with hemoptysis should be taken into consideration.

Topics: Anti-Bacterial Agents; Colistin; Drug-Related Side Effects and Adverse Reactions; Female; Gram-Negative Bacterial Infections; Hemorrhage; Humans; Immunocompromised Host; Middle Aged; Pneumonia, Bacterial; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pulmonary Alveoli; Respiratory Distress Syndrome; Sputum; Stenotrophomonas maltophilia; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Recently, paradoxical combinations of colistin with anti-Gram-positive bacterial agents were introduced as a treatment alternative for multidrug-resistant Acinetobacter baumannii (MDRAB) infection. We assessed the therapeutic efficacy of the colistin-linezolid combination regimen in vitro and in a murine model of Acinetobacter baumannii pneumonia. A multidrug-resistant clinical strain (MDRAB31) and an extensively drug-resistant clinical strain (XDRAB78) were used in this study. The survival rates of mice and bacterial counts in lung tissue were used to assess the effects of colistin-linezolid combination. The survival rates of colistin-linezolid combination groups significantly increased compared with colistin groups for MDRAB31 (72% versus 32%, P = 0.03) and for XDRAB78 (92% versus 68%, P = 0.031). The colistin-linezolid combination groups significantly reduced the bacterial counts in lung tissue compared with colistin groups for MDRAB31 and for XDRAB78 (P < 0.05). The colistin-linezolid combination had a bactericidal and synergistic effect compared with colistin alone in time-kill assay and in murine model of pneumonia. Our data demonstrated the synergistic effect of colistin-linezolid combination regimen as a treatment alternative for the severe pulmonary infection caused by MDRAB and XDRAB.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Antitubercular Agents; Colistin; Disease Models, Animal; Drug Synergism; Extensively Drug-Resistant Tuberculosis; Female; Linezolid; Lung; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Pneumonia, Bacterial; Time Factors; Tuberculosis, Multidrug-Resistant

To assess the pharmacokinetics of formed colistin in plasma and the safety of two different high doses of colistimethate sodium administered via nebulization in critically ill surgical patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP).. Formed colistin plasma concentrations were measured in critically ill surgical patients with pneumonia treated with two different doses of nebulized colistimethate sodium (3 MIU/8 h versus 5 MIU/8 h). Adverse events possibly related to nebulized colistimethate sodium were recorded.. Twenty-seven patients (15 in the 3 MIU/8 h group and 12 in the 5 MIU/8 h group) were included. Colistin plasma concentrations were unquantifiable (<0.1 mg/L) in eight (53.3%) patients in the 3 MIU/8 h group and in seven patients (58.3%) in the 5 MIU/8 h group. Median (IQR) quantifiable colistin plasma concentrations before nebulization and at 1, 4 and 8 h were 0.17 (0.12-0.33), 0.20 (0.11-0.24), 0.17 (0.12-0.23) and 0.17 (0.11-0.32) mg/L, respectively, in the 3 MIU/8 h group and 0.20 (0.11-0.35), 0.24 (0.12-0.44), 0.24 (0.10-0.49) and 0.23 (0.11-0.44) mg/L, respectively, in the 5 MIU/8 h group, with no differences between the two groups at any time. Renal impairment during nebulized treatment was observed in three patients in each group, but was unlikely to be related to colistimethate sodium treatment. Nebulized colistimethate sodium therapy was well tolerated and no bronchospasms or neurotoxicity events were observed.. In this limited observational case series of critically ill patients with HAP or VAP treated with high doses of nebulized colistimethate sodium, systemic exposure was minimal and the treatment was well tolerated.

Topics: Administration, Inhalation; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Critical Illness; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Prospective Studies

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

We describe a case of one patient with cystic fibrosis who developed a pan-resistant Burkholderia cepacia complex rapidly progressive bacteraemic pneunonia, following bilateral lung transplantation. The patient was treated with a targeted combination antibiotic therapy (meropenem plus ceftazidime/avibactam plus high doses of nebulized colistimethate sodium). Evolution of the disease was complicated by multiple organ system dysfunction. Finally, clinical improvement and microbiological cure was achieved.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Burkholderia cepacia complex; Burkholderia Infections; Colistin; Cystic Fibrosis; Drug Resistance, Multiple, Bacterial; Humans; Lung Transplantation; Male; Pneumonia, Bacterial; Treatment Outcome; X-Rays

Topics: Anti-Bacterial Agents; Colistin; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Humans; Pneumonia, Bacterial; Retrospective Studies; Saudi Arabia; Treatment Outcome

A 60-year-old woman received meropenem/colistin treatment for bilateral pneumonia caused by a ST15 carbapenemase producing Klebsiella pneumoniae. The patient recovered but re-infection with the same (ST15), but now colistin-resistant K. pneumoniae, occurred. The molecular mechanism of the emerged colistin resistance was identified as mgrB gene modification by insertion element (IS) IS903B.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Bacterial; Recurrence

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

Background Gram negative pathogens are increasingly resistant to commonly used first line antibiotics and colistin is in most cases the only medicine available. There is very limited information available comparing the effectiveness and costs of low versus high dose colistin with studies showing efficacy with both doses and with variable levels of adverse effects. The absence of a definite dosing strategy makes a model to compare low dose and high dose colistin invaluable in making decisions regarding the appropriate use of colistin. Objective This study was designed to evaluate the cost effectiveness of low versus high dose colistin in the treatment of Pneumonia caused by colistin-only sensitive gram negative bacteria from the perspective of a tertiary care hospital in Saudi Arabia. Setting 300-bed tertiary care hospital in Saudi Arabia. Method A retrospective review was conducted to compare the costs and outcomes of treatment of pneumonia with low versus high dose colistin. The model followed an average patient from initiation of treatment until clinical cure or failure. Main outcome measures The main outcomes were cure, nephrotoxicity, total direct costs per episode, cost per additional cure and cost per nephrotoxicity avoided. Results There was no significant difference between high and low dose colistin with regards to clinical cure (30% vs. 21%; p = 0.292). Significantly more patients experienced nephrotoxicity with high versus low dose colistin (30% vs. 8%; p = 0.004). With low dose colistin the incremental costs per nephrotoxicity avoided was SAR-3056.28. One-way sensitivity analyses did not change the overall results. Conclusion Low dose was not inferior to high dose colistin in terms of clinical cure and had a lower incidence of nephrotoxicity resulting in significant cost avoidance.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Clinical Decision-Making; Colistin; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Healthcare-Associated Pneumonia; Humans; Male; Middle Aged; Pneumonia, Bacterial; Retrospective Studies; Saudi Arabia; Treatment Outcome

Amidst the ever-rising threat of antibiotics resistance, colistin, a decade-old antibiotic with lingering toxicity concern, is increasingly prescribed to treat many drug-resistant, gram-negative bacteria. With the aim of improving the safety profile while preserving the antimicrobial activity of colistin, a nanoformulation is herein developed through coacervate complexation with polyanionic peptides. Upon controlled mixing of cationic colistin with polyglutamic acids, formation of liquid coacervates was demonstrated. Subsequent stabilization by DSPE-PEG and homogenization through micro-fluidization of the liquid coacervates yielded nanoparticles 8 nm in diameter. In vitro assessment showed that the colistin antimicrobial activity against multiple drug-resistant bacterial strains was retained and, in some cases, enhanced following the nanoparticle assembly. In vivo administration in mice demonstrated improved safety of the colistin nanoparticle, which has a maximal tolerated dose of 12.5 mg/kg compared to 10 mg/kg of free colistin. Upon administration over a 7-day period, colistin nanoparticles also exhibited reduced hepatotoxicity as compared to free colistin. In mouse models of Klebsiella pneumoniae bacteremia and Acinetobacter baumannii pneumonia, treatment with colistin nanoparticles showed equivalent efficacy to free colistin. These results demonstrate coacervation-induced nanoparticle assembly as a promising approach towards improving colistin treatments against bacterial infections. STATEMENT OF SIGNIFICANCE: Improving the safety of colistin while retaining its antimicrobial activity has been a highly sought-after objective toward enhancing antibacterial treatments. Herein, we demonstrate formation of stabilized colistin nanocomplexes in the presence of anionic polypeptides and DSPE-PEG stabilizer. The nanocomplexes retain colistin's antimicrobial activity while demonstrating improved safety upon in vivo administration. The supramolecular nanoparticle assembly of colistin presents a unique approach towards designing antimicrobial nanoparticles.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Bacteremia; Colistin; Klebsiella Infections; Klebsiella pneumoniae; Mice; Mice, Inbred BALB C; Nanoparticles; Pneumonia, Bacterial

To determine the impact of using colistin for multidrug-resistant organisms in neonates.. This retrospective study was conducted at the Shifa International Hospital, Islamabad, Pakistan, and comprised microbiological data of babies from January 2010 to October 2012.The data was reviewed to identify the babies infected with multidrug-resistant organisms and who had received colistin therapy. SPSS 16 was used for data analysis.. Of the 30 neonates, 24(80%) were males and 6(20%) were females. Besides, 16(53.3%) neonates were preterm babies (< 37 weeks gestation). Two or more risk factors for multidrug-resistant organisms were present in 13(44%) babies. Mechanical ventilation was found in 26(87%) neonates and prior prolonged use of antibiotics in 7(23%). The commonest pathogen isolated was Acinetobacter, in 22(73%) cases. All isolates were susceptible to colistin but pan-resistant to multiple antibiotics, including cephalosporins, amikacin, meropenem and piperacillin/tazobactam. Colistin therapy was used for bacteraemia in 2(7%) cases, clinical sepsis 18(60%), pneumonia 2(7%) and tracheitis 8(26.7%). Moreover, 15(50%) neonates received both intravenous and aerosolised colistin while 9(30%) received aerosolised therapy alone.. Colistin therapy was well tolerated in neonates for the treatment of multidrug-resistant organisms.

Topics: Acinetobacter Infections; Administration, Inhalation; Administration, Intravenous; Anti-Bacterial Agents; Asphyxia Neonatorum; Bacteremia; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Infant, Newborn; Infant, Premature; Male; Neonatal Sepsis; Pneumonia, Bacterial; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Retrospective Studies; Tracheitis

In the present study 60 samples were collected from lower respiratory tract of patients suffering from Ventilator Associated Pneumonia (VAP) admitted in surgical and medical Intensive Care Units (ICUs) of Khyber Teaching Hospital, Peshawar, Pakistan. Recovered pathogens were characterized and their susceptibility pattern against commonly used antibacterial agents investigated. Most frequent bacterial pathogen found was methicillin- resistant Staphylococcus aureus (MRSA) (40%) followed by members of Enterobacteriaceae (22%; of which Escherichia coli (50%), Klebsiella pneumonia (30%), Enterobacter cloacae (10%) and Citrobacter freundii (10%), Pseudomonas aeruginosa 20% and Acinetobacter baumannii 18%. Majority of the specimens yielded polymicrobial growth (85.75% polymicrobial growth compared to 14.25% specimens yielding monomicrobial growth). The susceptibility pattern showed that A. baumannii was the most resistant bacterial pathogen. Based on the results of susceptibility pattern obtained in the present study, combination of linezolid with meropenem and colistin has been found to be the best combination option for empirical therapy for VAP pathogens in this region.

Topics: Adult; Anti-Bacterial Agents; Bacteria; Case-Control Studies; Colistin; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Humans; Intensive Care Units; Linezolid; Male; Meropenem; Microbial Sensitivity Tests; Pakistan; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Sputum; Trachea

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

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; beta-Lactamase Inhibitors; Cathelicidins; Cell Membrane; Colistin; Daptomycin; Drug Resistance, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; Methicillin-Resistant Staphylococcus aureus; Mice, Inbred BALB C; Microbial Sensitivity Tests; Penicillanic Acid; Pneumonia, Bacterial; Tazobactam

Aerosolized colistin methanesulfonate (CMS) has been used for the treatment of extensively drug-resistant Acinetobacter baumannii (XDRAB) pneumonia and eradication of XDRAB colonization in the respiratory tract. The aims of this study were to compare the efficacy, adverse effects, clinical outcomes, and microbiological eradication of the cases of XDRAB pneumonia or colonization.. We retrospectively reviewed the medical records of patients who received aerosolized CMS for the treatment of pneumonia and airway colonization due to XDRAB.. Clinical data from 118 patients were studied. The mean age of 57 patients in the pneumonia group was 79.4 years, and that of 61 patients in the colonization group was 80.0 years. Patients with XDRAB pneumonia were more likely to be ventilator-dependent than colonized patients (46.5% vs. 21.3%; p = 0.005), receive steroid therapy (49.1% vs. 31.1%; p = 0.046), and be admitted to an intensive care unit (ICU) at the time of aerosolized CMS treatment (56.1% vs. 32.8%; p = 0.011). The in-hospital mortality rate was higher in the pneumonia group than the colonization group (50.9% vs. 33.3%; p = 0.05). Microbiological eradication of XDRAB in airway samples was achieved in 75% (89 of 118) patients. In pneumonia patients, XDRAB eradication was associated with resolution or improvement of presenting symptoms and signs of infection by the end of treatment relative to the noneradicated group (57.8% vs. 25%; p = 0.044), but had no influence on 30-day mortality. In colonized patients, no difference in clinical outcomes was noted between the eradicated and noneradicated groups.. Aerosolized CMS therapy has acceptable efficacy for XDRAB pneumonia, but no proven efficacy for XDRAB airway colonization.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Hospital Mortality; Humans; Intensive Care Units; Male; Pneumonia, Bacterial; Retrospective Studies; Treatment Outcome

The Gram-negative bacillus Stenotrophomonas maltophilia (SM) is an emerging MDR opportunistic pathogen. Recent studies identify a potentially relevant activity of azithromycin against Gram-negative bacteria overlooked in standard bacteriological testing. We investigated azithromycin activity against SM in testing conditions incorporating mammalian tissue culture medium and host defence factors.. MIC testing, chequerboard assays, time-kill assays and fluorescence microscopy were performed for azithromycin, the cationic peptide antibiotic colistin and the human defence peptide cathelicidin LL-37 alone or in combination in cation-adjusted Mueller-Hinton broth or mammalian tissue culture media. Azithromycin sensitization of SM to host immune clearance was tested in a human neutrophil killing assay and a murine pneumonia model.. We observed potent bactericidal activity of azithromycin against SM in mammalian tissue culture medium absent in bacteriological medium. Colistin and LL-37 strongly potentiated azithromycin killing of SM by increasing drug entry. Additionally, azithromycin sensitized SM to neutrophil killing and increased SM clearance in the murine pneumonia model.. Despite lack of activity in standard MIC testing, azithromycin synergizes with cationic peptide antibiotics to kill SM in medium mimicking tissue fluid conditions. Azithromycin, alone or in combination with colistin, merits further exploration in therapy of drug-resistant SM infections.

Topics: Animals; Anti-Infective Agents; Antimicrobial Cationic Peptides; Azithromycin; Cathelicidins; Colistin; Disease Models, Animal; Drug Synergism; Gram-Negative Bacterial Infections; Humans; Mice; Microbial Sensitivity Tests; Neutrophils; Pneumonia, Bacterial; Stenotrophomonas maltophilia; Treatment Outcome

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

Tigecycline has in vitro activity against multidrug-resistant and extensively drug-resistant Acinetobacter baumannii (MDR/XDRAB), and may constitute an alternative therapy for treating pneumonia caused by MDR/XDRAB. The aim of this study was to compare the efficacy of tigecycline-based therapy with colistin-based therapy in patients with MDR/XDRAB pneumonia. Between January 2009 and December 2010, patients in the intensive care unit who were diagnosed with MDR/XDRAB pneumonia and treated with either tigecycline or colistin mono-/combination therapy were reviewed. A total of 70 patients were included in our analysis. Among them, 30 patients received tigecycline-based therapy, and 40 patients received colistin-based therapy. Baseline characteristics were similar in the two groups. Clinical success rate was 47% in the tigecycline group and 48% in the colistin group (P = 0.95). There were no differences between the groups with regard to other clinical outcomes, with the exception that nephrotoxicity was observed only in the colistin group (0% vs. 20%; P = 0.009). Clinical and microbiological success rates were numerically higher, and mortality rates were numerically lower in combination therapy group than in the monotherapy group. Multivariate analysis indicated that monotherapy was independently associated with increased clinical failure (aOR, 3.96; 95% CI, 1.03-15.26; P = 0.046). Our results suggest that tigecycline-based therapy was tolerable and the clinical outcome was comparable to that of colistin-based therapy for patients with MDR/XDRAB pneumonia. In addition, combination therapy may be more useful than monotherapy in treatment of MDR/XDRAB pneumonia.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Minocycline; Pneumonia, Bacterial; Retrospective Studies; Tigecycline; Treatment Outcome

Currently, in vitro synergy with colistin has not translated into improved clinical outcomes. This study aimed to compare colistin combination therapy to colistin monotherapy in critically ill patients with multi-drug resistant gram-negative (MDR-GN) pneumonia. This was a retrospective analysis of critically ill adult patients receiving intravenous colistin for MDR-GN pneumonia comparing colistin combination therapy to colistin monotherapy with a primary endpoint of clinical cure. Combination therapy was defined by administration of another antibiotic to which the MDR-GN pathogen was reported as susceptible or intermediate. Ninety patients were included for evaluation (41 combination therapy and 49 monotherapy). Baseline characteristics were similar between groups. No difference in clinical cure was observed between combination therapy and monotherapy in univariate analysis, nor when adjusted for APACHE II score and time to appropriate antibiotic therapy (57.1 vs. 63.4 %, adjusted OR 1.15, p = 0.78). Microbiological cure was significantly higher for combination therapy (87 vs. 35.5 %, p < 0.001). Colistin combination therapy was associated with a significant improvement in microbiological cure, without improvement in clinical cure. Based on the in vitro synergy and improvement in microbiological clearance, colistin combination therapy should be prescribed for MDR-GN pneumonia. Further research is warranted to determine if in vitro synergy with colistin translates into improved clinical outcomes.

Topics: Administration, Intravenous; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Pneumonia, Bacterial; Retrospective Studies; Treatment Outcome; Young Adult

In this study, we sought to evaluate the pharmacokinetics of colistin after intravenous administration of colistimethate sodium (CMS) in the critically ill neonates with Gram-negative bacterial infections. A single intravenous dose of CMS [approximately 150,000 IU/kg, equivalent to 5 mg/kg colistin base activity (CBA)] was administered to 7 critically ill neonates. Mean (±SD) maximum plasma colistin concentration and area under the time-concentration curve from 0 to infinity were 3.0 ± 0.7 µg/mL and 25.3 ± 10.4 µg·h/mL, respectively. Time to maximum concentration, half-life, apparent volume of distribution and clearance were 1.3 ± 0.9 hours, 9.0 ± 6.5 hours, 7.7 ± 9.3 L/kg and 0.6 ± 0.3 L/h/kg, respectively. After a dose regimen of 5 mg/kg CBA every 24 hours, the average concentration expected at steady state is 1.1 ± 0.4 µg/mL. In critically ill neonates, a single intravenous dose of 5 mg CBA/kg (approximately 150,000 IU/kg of CMS) resulted in suboptimal plasma concentrations of colistin. According to our pharmacokinetics data, the dosage of CMS currently used in critically ill neonates is insufficient.

Topics: Administration, Intravenous; Anti-Bacterial Agents; Bacteremia; Colistin; Critical Illness; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Pneumonia, Bacterial; Prospective Studies

The ratio of the area under the free (unbound) concentration-time curve to minimum inhibitory concentration (fAUC/MIC) was proposed to be the pharmacokinetic/pharmacodynamic index most strongly linked to the antibacterial effect of colistin against Acinetobacter baumannii. A retrospective study of patients who received colistin to treat pneumonia caused by extensively drug-resistant (XDR) A. baumannii over a 4-year period was performed to assess the impact of the colistin MIC on mortality. A total of 227 patients were included in the analysis. The 7-day and 14-day mortality rates of patients with XDR A. baumannii pneumonia receiving colistin therapy were 15.0% and 23.8%, respectively. In the multivariate analysis, Acute Physiology and Chronic Health Evaluation (APACHE) II score, days from index culture to first dose of colistin, underlying tumour and septic shock at presentation were independent predictors of mortality in patients with XDR A. baumannii pneumonia receiving colistin therapy. In the univariate analysis, the colistin dose based on ideal body weight (IBW) correlated with patient outcome. Therefore, the use of IBW appeared to be more appropriate to calculate the colistin dosage. In addition, these results highlight the clinical significance of colistin MIC in patients with XDR A. baumannii pneumonia receiving colistin therapy. Although MICs were in the 'susceptible' range, patients infected with isolates with high colistin MICs showed a poorer clinical response rate than patients infected with isolates with low colistin MICs. Further clinical studies are needed to evaluate the roles of colistin MIC for predicting mortality in XDR A. baumannii pneumonia with a high colistin MIC.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Colistin; Decision Support Techniques; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Pneumonia, Bacterial; Prognosis; Retrospective Studies; Survival Analysis; Young Adult

Emerging resistance to colistin in clinical Acinetobacter baumannii isolates is of growing concern. Since current treatment options for these strains are extremely limited, we investigated the in vitro activities of various antimicrobial combinations against colistin-resistant A. baumannii Nine clinical isolates (8 from bacteremia cases and 1 from a pneumonia case) of colistin-resistant A. baumannii were collected in Asan Medical Center, Seoul, South Korea, between January 2010 and December 2012. To screen for potential synergistic effects, multiple combinations of two antimicrobials among 12 commercially available agents were tested using the multiple-combination bactericidal test (MCBT). Checkerboard tests were performed to validate these results. Among the 9 colistin-resistant strains, 6 were pandrug resistant and 3 were extensively drug resistant. With MCBT, the most effective combinations were colistin-rifampin and colistin-teicoplanin; both combinations showed synergistic effect against 8 of 9 strains. Colistin-aztreonam, colistin-meropenem, and colistin-vancomycin combinations showed synergy against seven strains. Colistin was the most common constituent of antimicrobial combinations that were active against colistin-resistant A. baumannii Checkerboard tests were then conducted in colistin-based combinations. Notably, colistin-rifampin showed synergism against all nine strains (100%). Both colistin-vancomycin and colistin-teicoplanin showed either synergy or partial synergy. Colistin combined with another β-lactam agent (aztreonam, ceftazidime, or meropenem) showed a relatively moderate effect. Colistin combined with ampicillin-sulbactam, tigecycline, amikacin, azithromycin, or trimethoprim-sulfamethoxazole demonstrated limited synergism. Using MCBT and checkerboard tests, we found that only colistin-based combinations, particularly those with rifampin, glycopeptides, or β-lactams, may confer therapeutic benefits against colistin-resistant A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Aztreonam; Bacteremia; Ceftazidime; Colistin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Meropenem; Microbial Sensitivity Tests; Pneumonia, Bacterial; Retrospective Studies; Rifampin; Teicoplanin; Thienamycins; Vancomycin

Colistimethate sodium (CMS) is increasingly used to treat multidrug-resistant Gram-negative bacilli infections. However, the incidence of CMS-associated nephrotoxicity has not been evaluated in patients with carbapenem-resistant Acinetobacter baumannii (CRAB) pneumonia. This retrospective study included 120 patients with CRAB pneumonia treated with intravenous CMS for ≥72 h. The objective of the study was to determine risk factors for CMS-induced nephrotoxicity and 30-day mortality in patients with CRAB pneumonia. Of the 120 patients with CRAB pneumonia, 61 (51%) developed nephrotoxicity. Multivariate analysis showed that dose per ideal body weight (IBW) [odds ratio (OR)=1.28, 95% confidence interval (CI) 1.01-1.62; P=0.04], Charlson co-morbidity index (OR=1.31, 95% CI 1.06-1.60; P=0.01) and septic shock (OR=3.16, 95% CI 1.32-7.60; P=0.01) were associated with CMS-associated nephrotoxicity. Thirty-day mortality was 33% (39/120). Multivariate analysis showed that higher daily doses of CMS per IBW [hazard ratio (HR)=0.81, 95% CI 0.67-0.98; P=0.03] and longer duration of CMS therapy (HR=0.86, 95% CI 0.79-0.95; P=0.002) were associated with increased survival. Septic shock (HR=3.91, 95% CI 1.95-7.83; P<0.001) and corticosteroid use (HR=3.49, 95% CI 1.67-7.28; P=0.001) were associated with decreased survival in patients with CRAB pneumonia. Higher daily doses of CMS per IBW, Charlson comorbidity index and septic shock were significant risk factors for CMS-associated nephrotoxicity. However, CMS-associated nephrotoxicity does not appear to have an impact on mortality.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Intravenous; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactam Resistance; Colistin; Female; Humans; Incidence; Male; Middle Aged; Pneumonia, Bacterial; Renal Insufficiency; Retrospective Studies; Treatment Outcome

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

An increase in the antibiotic resistance among members of the Enterobacteriaceae family has been observed worldwide. Multidrug-resistant Gram-negative rods are increasingly reported. The treatment of infections caused by Escherichia coli and other Enterobacteriaceae has become an important clinical problem associated with reduced therapeutic possibilities. Antimicrobial carbapenems are considered the last line of defense against multidrug-resistant Gram-negative bacteria. Unfortunately, an increase of carbapenem resistance due to the production of Klebsiella pneumoniae carbapenemase (KPC) enzymes has been observed. In this study we describe the ability of E. coli to produce carbapenemase enzymes based on the results of the combination disc assay with boronic acid performed according to guidelines established by the European Community on Antimicrobial Susceptibility Testing (EUCAST) and the biochemical Carba NP test. Moreover, we evaluated the presence of genes responsible for the production of carbapenemases (bla KPC, bla VIM, bla IMP, bla OXA-48) and genes encoding other β-lactamases (bla SHV, bla TEM, bla CTX-M) among E. coli isolate. The tested isolate of E. coli that possessed the bla KPC-3 and bla TEM-34 genes was identified. The tested strain exhibited susceptibility to colistin (0.38 μg/mL) and tigecycline (1 μg/mL). This is the first detection of bla KPC-3 in an E. coli ST479 in Poland.

Topics: Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Escherichia coli; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Pneumonia, Bacterial; Tigecycline

Topics: Anti-Bacterial Agents; Colistin; Humans; Microbiota; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated

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

Use of colistin has re-emerged for the treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria, but information on its pharmacokinetics and pharmacodynamics is limited, especially in critically ill patients. Recent data from pharmacokinetic/pharmacodynamic (PK/PD) population studies have suggested that this population could benefit from administration of higher than standard doses of colistimethate sodium (CMS), but the relationship between administration of incremental doses of CMS and corresponding PK/PD parameters as well as its efficacy and toxicity have not yet been investigated in a clinical setting. The objective was to study the PK/PD differences of CMS and colistin between three different CMS dosage regimens in the same critically ill patient. A critically ill patient with nosocomial pneumonia caused by a MDR Acinetobacter baumannii received incremental doses of CMS. During administration of the different CMS dosage regimens, CMS and colistin plasma concentrations were determined and PK/PD indexes were calculated. With administration of the highest CMS dose once daily (720 mg every 24h), the peak plasma concentration of CMS and colistin increased to 40.51 mg/L and 1.81 mg/L, respectively, and the AUC0-24/MIC of colistin was 184.41. This dosage regimen was efficacious, and no nephrotoxicity or neurotoxicity was observed. In conclusion, a higher and extended-interval CMS dosage made it possible to increase the exposure of CMS and colistin in a critically ill patient infected by a MDR A. baumannii and allowed a clinical and microbiological optimal response to be achieved without evidence of toxicity.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Colistin; Critical Illness; Cross Infection; Drug Resistance, Multiple, Bacterial; Humans; Male; Microbial Sensitivity Tests; Plasma; Pneumonia, Bacterial

Polymyxins have recently again become important because of multidrug-resistant (MDR) gram-negative pathogens. The aim of this study was to evaluate the clinical and microbiological efficacy and toxicity of different dosages of colistin in patients infected with MDR microorganisms that were sensitive only to colistin. The study was conducted in the 1,200-bed Ankara Numune Training and Research Hospital. Patients with normal renal function who received colistin for 48 h or more were retrospectively evaluated. Clinical response was defined as resolution of fever and clinical and laboratory findings. Microbiological response was defined as bacteriological eradication from the infection site. Nephrotoxicity was defined as at least two consecutive serum creatinine measurements with an increase of 0.5 mg/dl from baseline at least 24 h apart after 2 or more days of colistin therapy. Twenty-four patients were included in the study: total clinical response was obtained in 17 of 24 (70.8 %) patients and microbiological response in 15 of 24 (62.5 %) patients. Patients were grouped according to colistin dosage of 3 × 1 million units (MU) versus 3 × 2 MU. Clinical response rates were 69.2 % and 72.7 %, respectively (p = 0.65). Microbiological response rate was similar (p = 0.62). Nephrotoxicity was revealed in 1 of 13 patients (7.7 %) for the 3 × 1 MU group and 2 of 11 patients (18.2 %) in the 3 × 2 MU group (p = 0.57). The nephrotoxicity rate was greater with higher dosages of colistin, but the difference was not statistically significant. Renal function of patients receiving higher dosages of colistin should be more closely monitored.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Pneumonia, Bacterial; Treatment Outcome; Urinary Tract Infections; Young Adult

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Anti-Bacterial Agents; Child; Colistin; Drug Resistance, Multiple, Bacterial; Germany; Humans; Infusions, Intravenous; Intensive Care Units, Pediatric; Male; Pneumonia, Bacterial; Religion and Medicine; Russia; Seizures, Febrile; Water Microbiology

This study investigates the clinical and epidemiological features of Chryseobacterium indologenes infections and antimicrobial susceptibilities of C indologenes.. With 215 C indologenes isolates between January 1, 2004 and September 30, 2011, at a medical center, we analyzed the relationship between the prevalence of C indologenes infections and total prescription of colistin and tigecycline, clinical manifestation, antibiotic susceptibility, and outcomes.. Colistin and tigecycline were introduced into clinical use at this medical center since August 2006. The increasing numbers of patients with C indologenes pneumonia and bacteremia correlated to increased consumption of colistin (p = 0.018) or tigecycline (p = 0.049). Among patients with bacteremia and pneumonia, the in-hospital mortality rate was 63.6% and 35.2% (p = 0.015), respectively. Administration of appropriate antibiotics showed significant benefit in 14-day survival in patients with C indologenes bloodstream infection (p = 0.040). In bacteremic patients, old cardiovascular accident (p = 0.036) and cancer (p = 0.014) were the most common comorbidity. The most common co-infection pathogen in patients with C indologenes pneumonia was Acinetobacter baumannii (36/91, 39.6%), followed by Pseudomonas aeruginosa (23/91, 25.3%), carbapenem-resistant A baumannii (22/91, 24.2%), and Klebseilla pneumoniae (13/91, 14.3%). Antimicrobial susceptibility testing of the 215 isolates showed that trimethoprim-sulfamethoxazole was the most active agent (susceptibility rate: 87.4%), followed by cefoperazone-sulbactam (48.0%).. The present study showed a trend of increasing prevalence of C indologenes infection after introduction of colistin and tigecycline usage. The bacteremia group had higher mortality rate than the pneumonia group. Increasing resistance to piperacillin-tazobactam, ceftazidime, cefepime, and newer fluoroquinolone were noticed in our analysis. Trimethoprim-sulfamethoxazole was a potential antimicrobial agent in vitro for C indologenes. To avoid collateral damage, we emphasize the importance of antibiotic stewardship program.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Chryseobacterium; Colistin; Drug Prescriptions; Drug Resistance, Bacterial; Female; Flavobacteriaceae Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Bacterial; Prevalence; Survival Analysis; Tigecycline

The identification of the optimal agent for administration via the respiratory tract when treating pneumonia caused by carbapenem-resistant Acinetobacter baumannii (CRAB).. A murine model of acute CRAB pneumonia was established by intratracheal (i.t.) inoculation with 2.5 × 10⁷ colony-forming units (CFU) of A. baumannii strain Ab396 plus 10% porcine mucin. After 4h the infected BALB/c mice were treated intratracheally with 25μl of either 0.85% saline (control group), colistimethate sodium (CMS) (166 666 U/kg, CMS group), imipenem/cilastatin (30/30 mg/kg, imipenem group), or meropenem (20mg/kg, meropenem group), every 8h. The therapeutic efficacy of these agents was examined.. A. baumannii strain Ab396 was susceptible to CMS only. However, meropenem treatment did give a significantly superior survival rate (100%) compared to treatment with imipenem (50%), CMS (33%), or saline (0%) (p<0.001 vs. the control and CMS groups, p=0.006 vs. the imipenem group, by log-rank test). Furthermore, compared to the other groups, the meropenem group demonstrated significantly more favorable results in terms of tissue penetration of the antibiotic, bacterial clearance, normalization of the wet lung-to-body weight ratio, and down-regulation of pro-inflammatory cytokine levels in the lungs.. Administration of meropenem via the respiratory tract proved to have the best therapeutic efficacy among the antibiotics tested when treating advanced murine CRAB pneumonia.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Acute Disease; Animals; Anti-Bacterial Agents; Carbapenems; Cilastatin; Cilastatin, Imipenem Drug Combination; Colistin; Cytokines; Disease Models, Animal; Drug Combinations; Drug Resistance, Bacterial; Female; Imipenem; Meropenem; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Pneumonia, Bacterial; Stem Cells; Thienamycins

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

Extremely drug-resistant (XDR; i.e. resistant to all antibiotics except colistin or tigecycline) Acinetobacter baumannii has emerged as one of the most common and highly antibiotic-resistant causes of infection. Diabetes is a risk factor for acquisition of and worse outcomes from A. baumannii infection. We sought to develop diabetic mouse models of A. baumannii bacteraemia and pneumonia and validate these models by comparing the efficacy of antibiotic treatment in these models with the established neutropenic mouse models.. Diabetic or neutropenic mice were infected via intravenous inoculation or inhalation in an aerosol chamber with an XDR A. baumannii. Treatment with colistin started 24 h after infection and continued daily for 7 days. Survival served as the primary endpoint while tissue bacterial burden and histopathological examination served as secondary endpoints.. Lethal infection was achieved for the neutropenic and diabetic mice when infected intravenously or via inhalation. Neutropenic mice were more susceptible to infection than diabetic mice in the pneumonia model and equally susceptible in the bacteraemia model. Both models of bacteraemia were sensitive enough to detect virulence differences among different clinical strains of A. baumannii. In the pneumonia model, colistin treatment was effective in improving survival, reducing lung bacterial burden and histologically resolving the infection compared with placebo only in diabetic mice.. We developed novel models of A. baumannii bacteraemia and pneumonia in diabetic mice. These models can be used to study mechanisms of infection, develop immunotherapeutic strategies and evaluate drug efficacies against highly lethal A. baumannii infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacteremia; Bacterial Load; Colistin; Diabetes Complications; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Histocytochemistry; Humans; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; Pneumonia, Bacterial; Survival Analysis; Treatment Outcome

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

In this study we aimed to assess the safety and efficacy of high-dose IV colistin (COL) and aerosolized COL for the treatment of Acinetobacter baumannii ventilator-associated pneumonia (VAP). Critically ill adult patients who received IV COL for multidrug-resistant A. baumannii VAP were evaluated retrospectively. A total of 45 patients were evaluated [15 patients with high-dose COL (2.5 mg/kg every 6 h), 20 patients with normal dose (2.5 mg/kg every 12 h), and 10 patients with low dose, determined according to creatine clearance]. Aerosolized COL was used in 29 patients treated with parenteral COL and 16 patients received only parenteral COL. The clinical response rates on the fifth day were 50, 30, and 27 % with the normal, low, and high doses, respectively. However, the clinical response rates at the end of the therapy had declined to 30, 30, and 7 % with the normal, low, and high doses, respectively. The bacteriological clearance rates at the end of the therapy were 65, 75, and 64 %, with the normal, low, and high doses, respectively. With the aerosolized COL, the clinical response rates on the fifth day and at the end of the therapy were 35 and 14 %, whereas these rates were 44 and 38 % without the aerosolized COL. Bacteriological clearance rates with and without the aerosolized COL were 76 and 69 %, respectively. The nephrotoxicity rate was 40 % for the high-dose COL, whereas it was 35 % for the normal dose, and 20 % for the low-dose COL. In conclusion, higher doses of COL and aerosolized COL had no advantages over lower doses in alleviating multidrug-resistant A. baumannii VAP. Moreover, the higher doses and the aerosolized COL increased the nephrotoxicity risk and seemed not to be safe.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Administration, Intravenous; Adult; Aerosols; Aged; Anti-Bacterial Agents; Chi-Square Distribution; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Kidney Diseases; Male; Middle Aged; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Retrospective Studies; Statistics, Nonparametric; Turkey

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

Due to increasing drug resistance, available antimicrobial options are limited in the treatment of Acinetobacter baumannii infections. Particularly in cases caused by extensively drug-resistant (XDR) A. baumannii, combination regimens must also be taken into consideration. In this study, the efficacies of tigecycline, colistin and tigecycline/colistin combination on bacterial counts in lung tissue were investigated in a rat pneumonia model. One A. baumannii strain resistant to all antimicrobial agents except tigecycline and colistin was selected for the study. In vivo studies revealed a >3 log reduction in bacterial counts in the tigecycline, colistin and combination groups at 24 h and 48 h compared with the control group. No significant differences were determined between colistin, tigecycline and combination groups (P>0.05). On the other hand, differences between treatment groups and the control group were statistically significant (P=0.01). A greater reduction in bacterial counts was observed at 48 h compared with 24 h in the tigecycline group than in the colistin group (P=0.038 and P=0.139, respectively); the most significant decrease between 24 h and 48 h was observed in the combination group (P=0.014). Despite detection of in vitro synergistic activity in this study, no statistically significant differences were found between colistin, tigecycline and combination treatments in terms of efficacy on bacterial counts in lung tissue. In the treatment of infections with a high mortality rate such as pneumonia caused by XDR A. baumannii, combining tigecycline with colistin during the first 48 h and continuing treatment with one of these agents seems a rational approach.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Load; Colistin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Lung; Minocycline; Pneumonia, Bacterial; Rats; Rats, Wistar; Tigecycline; Time Factors; Treatment Outcome

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

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

The objectives of this study were to assess the determinants of empirical antibiotic choice, prescription patterns and outcomes in patients with hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) in Europe. We performed a prospective, observational cohort study in 27 intensive care units (ICUs) from nine European countries. 100 consecutive patients on mechanical ventilation for HAP, on mechanical ventilation>48 h or with VAP were enrolled per ICU. Admission category, sickness severity and Acinetobacter spp. prevalence>10% in pneumonia episodes determined antibiotic empirical choice. Trauma patients were more often prescribed non-anti-Pseudomonas cephalosporins (OR 2.68, 95% CI 1.50-4.78). Surgical patients received less aminoglycosides (OR 0.26, 95% CI 0.14-0.49). A significant correlation (p<0.01) was found between Simplified Acute Physiology Score II score and carbapenem prescription. Basal Acinetobacter spp. prevalence>10% dramatically increased the prescription of carbapenems (OR 3.5, 95% CI 2.0-6.1) and colistin (OR 115.7, 95% CI 6.9-1,930.9). Appropriate empirical antibiotics decreased ICU length of stay by 6 days (26.3±19.8 days versus 32.8±29.4 days; p=0.04). The antibiotics that were prescribed most were carbapenems, piperacillin/tazobactam and quinolones. Median (interquartile range) duration of antibiotic therapy was 9 (6-12) days. Anti-methicillin-resistant Staphylococcus aureus agents were prescribed in 38.4% of VAP episodes. Admission category, sickness severity and basal Acinetobacter prevalence>10% in pneumonia episodes were the major determinants of antibiotic choice at the bedside. Across Europe, carbapenems were the antibiotic most prescribed for HAP/VAP.

Topics: Acinetobacter Infections; Adult; Aged; Aminoglycosides; Anti-Bacterial Agents; Carbapenems; Colistin; Cross Infection; Europe; Female; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Piperacillin; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Quinolones; Respiration, Artificial; Severity of Illness Index; Treatment Outcome

To analyze the efficacy of nebulized colistin in the microbiological eradication and clinical improvement of patients with pulmonary infection by multi-resistant Acinetobacter baumannii (MAB).. A retrospective study.. Intensive Care Unit of a Tertiary hospital.. Hospitalized patients on invasive mechanical ventilation with positive MAB cultures of the airway.. All received treatment with colistin (CL). Nosocomial pneumonia (NP) or Tracheobronchitis (TB) was determined according to routine criteria and colonization (CO) was determined in the case of a positive culture in the absence of infection criteria. Three groups of patients were defined: those treated with nebulized CL, those treated with IV CL and those treated with IV CL plus nebulized CL.. Baseline characteristics. Microbiological eradication and clinical recovery were evaluated according to routine criteria.. 83 patients were studied, 54 of whom were treated, with the following diagnoses: 15 (27.8%) with NP, 16 (29.6%) with TB and 23 patients (42.6%) with CO. Nebulized CL was used in 36 patients (66.7%): 66.7% of which for CO, 33.3% in treatment for TB and in no case of NP. In 61.1% of the patients, IV CL was used: 22.2% of which for CO, 38.9% for TB and 38.9% in NP. The combination of IV CL and nebulized CL was used in 15 patients (27.8%): 5 patients (33.3%) CO, 2 patients (13.3%) TB and 8 patients (53.3%) NP. Microbiological eradication was achieved in 32 patients (59.3%), with the following distribution: 8 (47.1%) with IV CL, 15 (83.3%) with nebulized CL and 9 patients (69.2%) with a combination of IV CL and nebulized CL. Clinical recovery was achieved in 42 patients (77.8%): 12 (80%) with IV CL, 18 (94.7%) with nebulized CL and 12 (85.7%) with a combination of nebulized and IV CL. These differences were not significant. In the group of patients with infection due to TB and NP (31 patients, 57.4%), microbiological eradication was achieved in 5 patients (100%) treated with nebulized CL and in 6 of the 9 patients (42.9%) treated with IV CL, the difference being significant (P<.05). Clinical recovery in this group was 100% (6 patients) treated with nebulized CL and 75% (9 of the 12 patients) in the IV CL group. This difference was not significant.. Our study suggests that treatment with colistin in patients with pulmonary infection with multi-resistant Acinetobacter baumannii could be more efficient if it were to be administrated solely nebulized or in combination with IV colistin rather than administered solely intravenously.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Adult; Aged; Bronchitis; Colistin; Critical Illness; Cross Infection; Dose-Response Relationship, Drug; Drug Evaluation; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Injections, Intravenous; Male; Middle Aged; Nebulizers and Vaporizers; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Retrospective Studies; Tracheitis; Tracheotomy

Topics: Administration, Inhalation; Aerosols; Anti-Bacterial Agents; Colistin; Gram-Negative Bacterial Infections; Humans; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Statistics as Topic; Treatment Outcome

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

Ventilator-associated pneumonia (VAP) as a result of multidrug-resistant Gram-negative bacteria has contributed to the revival of the use of intravenous (i.v.) colistin. However, the additional administration of inhaled colistin for VAP is controversial. We performed a retrospective cohort study of patients with microbiologically documented VAP who received i.v. colistin with or without inhaled colistin. Seventy-eight patients with VAP received i.v. plus inhaled colistin, whereas 43 patients received i.v. colistin alone. The mean +/- SD daily dosage of i.v. colistin was 7.0 +/- 2.4 and 6.4 +/- 2.3 million international units (IU), respectively (p 0.13); the average daily dosage of inhaled colistin was 2.1 +/- 0.9 million IU. The outcome of infection was cure for 62/78 (79.5%) patients who received i.v. plus inhaled colistin vs. 26/43 (60.5%) patients who received i.v. colistin alone (p 0.025); all-cause in-hospital mortality was 31/78 (39.7%) vs. 19/43 (44.2%), respectively (p 0.63); all-cause intensive care unit (ICU) mortality was 28/78 (35.9%) vs. 17/43 (39.5%), respectively (p 0.92). The use of inhaled colistin was independently associated with the cure of VAP in a multivariable analysis (OR 2.53, 95% CI 1.11-5.76). Independent predictors of mortality were a higher APACHE II score (OR 1.12, 95% CI 1.04-1.20), presence of malignancy (OR 4.11, 95% CI 1.18-14.23) and lower daily dosage of i.v. colistin (OR 0.81, 95% CI 0.68-0.96). The outcome of VAP was better in patients who received inhaled colistin with i.v. colistin than those who received i.v. colistin alone. There was no difference in all-cause in-hospital and ICU mortality between the two groups. Randomized controlled trials are needed to evaluate further the role of inhaled colistin in VAP.

Topics: Administration, Inhalation; Adult; Aged; Anti-Bacterial Agents; Cohort Studies; Colistin; Female; Humans; Injections, Intravenous; Male; Middle Aged; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Retrospective Studies; Survival Analysis; Treatment Outcome

There are currently no defined optimal therapies available for multidrug-resistant (MDR) Acinetobacter baumannii infections. We evaluated the efficacy of rifampin, imipenem, sulbactam, colistin, and their combinations against MDR A. baumannii in experimental pneumonia and meningitis models. The bactericidal in vitro activities of rifampin, imipenem, sulbactam, colistin, and their combinations were tested using time-kill curves. Murine pneumonia and rabbit meningitis models were evaluated using the A. baummnnii strain Ab1327 (with MICs for rifampin, imipenem, sulbactam, and colistin of 4, 32, 32, and 0.5 mg/liter, respectively). Mice were treated with the four antimicrobials and their combinations. For the meningitis model, the efficacies of colistin, rifampin and its combinations with imipenem, sulbactam, or colistin, and of imipenem plus sulbactam were assayed. In the pneumonia model, compared to the control group, (i) rifampin alone, (ii) rifampin along with imipenem, sulbactam, or colistin, (iii) colistin, or (iv) imipenem plus sulbactam significantly reduced lung bacterial concentrations (10.6 +/- 0.27 [controls] versus 3.05 +/- 1.91, 2.07 +/- 1.82, 2.41 +/- 1.37, 3.4 +/- 3.07, 6.82 +/- 3.4, and 4.22 +/- 2.72 log(10) CFU/g, respectively [means +/- standard deviations]), increased sterile blood cultures (0% versus 78.6%, 100%, 93.3%, 93.8%, 73.3%, and 50%), and improved survival (0% versus 71.4%, 60%, 46.7%, 43.8%, 40%, and 85.7%). In the meningitis model rifampin alone or rifampin plus colistin reduced cerebrospinal fluid bacterial counts (-2.6 and -4.4 log(10) CFU/ml). Rifampin in monotherapy or with imipenem, sulbactam, or colistin showed efficacy against MDR A. baumannii in experimental models of pneumonia and meningitis. Imipenem or sulbactam may be appropriate for combined treatment when using rifampin.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Imipenem; Meningitis, Bacterial; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Pneumonia, Bacterial; Rabbits; Rifampin; Sulbactam; Treatment Outcome

The emergence of highly resistant gram-negative pathogens in hospitals around the world has placed emphasis on colistin, a seemingly ancient drug. Respiratory failure from colistin was reported in the years following its release; however, there are no recent reports of colistin-induced respiratory failure. We report a case of intravenous colistin- and, later, inhalational colistin-induced respiratory failure.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Adult; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Infusions, Intravenous; Pneumonia, Bacterial; Respiratory Insufficiency

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

Lung transplantation (LTX) requires continual systemic immunosuppression, which can result in infections that may compromise recipient survival. A recent outbreak of Acinetobacter baumannii at our institution resulted in infections experienced in both LTX recipients and nontransplant patients. A retrospective review was conducted of patients who had A. baumannii recovered from blood, other normally sterile body fluids, and/or respiratory secretions and who had clinical follow-up extending to 1 year postinfection. A. baumannii was considered "multidrug-resistant" when its growth was not inhibited by minimum inhibitory concentrations of multiple antibiotics. Despite the resistance profile, patients were treated with a combination of antibiotics, which included tigecycline, colistimethate, and when susceptible, imipenem. Once infection was diagnosed, immunosuppression was reduced in all LTX recipients. Six LTX recipients became infected with A. baumannii and were contrasted to infections identified in 14 non-LTX, nonimmunosuppressed patients. A. baumannii was persistently recovered in 4 of 6 LTX recipients (66.7%) compared with only 1 of 14 (7.1%) non-LTX patients (χ(2) = 9.9, p = 0.005). LTX recipients received antibiotic therapy for an average of 76 ± 18.4 days compared with 16.0 ± 6.8 days for the non-LTX patients (p = 0.025, Mann-Whitney U test). All 4 of the 6 (66.7%) LTX recipients died as a consequence of their infection compared with 1 of 14 (7.1%) of the non-LTX patients (χ(2) = 9.9, p = 0.005). Despite receiving more antibiotic therapy, LTX recipients who were infected with multidrug-resistant A. baumannii were less likely to clear their infection and experienced greater mortality compared with non-LTX patients.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Humans; Imipenem; Immunosuppressive Agents; Lung Transplantation; Minocycline; Pneumonia, Bacterial; Radiography; Retrospective Studies; Tigecycline

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

Enterobacter cloacae is an important nosocomial pathogen responsible for various infections. Little is known about the synergistic effects of imipenem and colistin against multidrug-resistant E. cloacae. Therefore, we investigated the in vitro effects of imipenem and colistin against a clinical isolate of multidrug-resistant E. cloacae.. A strain of E. cloacae, designed Ent 831, was isolated from the sputum of a woman who developed severe pneumonia in a medical intensive care unit. Minimal inhibitory concentrations (MICs) of imipenem and colistin were determined by the agar dilution method. The synergistic effects were investigated using the time-kill method.. MICs of imipenem and colistin for E. cloacae strain Ent 831 were 0.5 microg/mL and 1.0 microg/mL, respectively. Using a standard inoculum (5 x 10(5)) CFU/mL), synergism was shown with a concentration of two times the MICs of imipenem and colistin. Furthermore, four times the MIC of imipenem completely inhibited bacterial growth for more than 48 hours, but four times the MICs of colistin resulted in re-growth after 4 hours. There was no synergism between imipenem and colistin at two times the MICs against a high concentration inoculum (6.24 x 10(6)) CFU/mL). Nevertheless, imipenem, with or without colistin, at a concentration of four times MICs could inhibit the growth of bacteria for more than 48 hours.. High-dose imipenem, alone or in combination with colistin, is effective against multidrug-resistant E. cloacae. Colistin alone, even at a high dose, is not effective. However, in vitro susceptibility to antimicrobial compounds does not always correlate with clinical success. Thus further testing of these antibiotic combinations in animal models is needed in order to predict their suitability for clinical use.

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Enterobacter cloacae; Female; Gram-Positive Bacterial Infections; Humans; Imipenem; Microbial Sensitivity Tests; Microbial Viability; Middle Aged; Pneumonia, Bacterial; Sputum; Time Factors

The spread of antimicrobial resistance among members of the Enterobacteriaceae is a significant clinical threat. We report the treatment of pan-resistant Klebsiella pneumoniae bacteraemia with combination tigecycline and colistin in a 49-year-old male and review available therapeutic options. Despite a poor prognosis, the patient recovered, but remains colonized with the pan-resistant isolate.

Topics: Animals; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Bacterial; Tigecycline

To report a case of recurrent Stenotrophomonas maltophilia ventilator-associated pneumonia (VAP) that was successfully treated with doxycycline and aerosolized colistin.. A 28-year-old male was admitted with a severe head injury and required mechanical ventilation. The patient developed S. maltophilia VAP on hospital day 17, which was cured after 7 days of treatment with high-dose intravenous trimethoprim/sulfamethoxazole (TMP/SMX). However, on day 34, the patient developed recurrent S. maltophilia VAP that did not respond clinically or demonstrate eradication on follow-up culture after 10 days of TMP/SMX. At that time, TMP/SMX was discontinued and treatment was initiated with intravenous doxycycline and aerosolized colistin. The VAP episode was cured after 14 days of treatment with doxycycline/aerosolized colistin.. S. maltophilia is an emerging cause of VAP in some centers. This organism is associated with high mortality rates and has few treatment options because it is intrinsically resistant to most drug classes. Recent data suggest that doxycycline and aerosolized colistin each are effective in treatment of other multidrug-resistant organisms, such as Pseudomonas aeruginosa and Acinetobacter baumannii. However, this is the first report describing the use of this antibiotic regimen for S. maltophilia. High-dose TMP/SMX is considered to be the drug of choice primarily based on excellent in vitro activity. Few data exist on how to treat patients who fail therapy with TMP/SMX or cannot receive that drug because of resistance, allergy, or adverse events. Thus, it is important to report alternative methods for treating this infection.. The positive clinical response to doxycycline and aerosolized colistin seen in the patient described here suggests that this combination may be an alternative treatment in patients who fail initial treatment or cannot receive standard therapies.

Topics: Administration, Inhalation; Adult; Aerosols; Anti-Bacterial Agents; Anti-Infective Agents; Colistin; Doxycycline; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Gram-Negative Bacterial Infections; Humans; Injections, Intravenous; Male; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Stenotrophomonas maltophilia; Trimethoprim, Sulfamethoxazole Drug Combination

We report a case of hypersensitivity pneumonitis, possibly due to aerosolized colistin therapy for severe multi-resistant Gram-negative pneumonia. Microbiological eradication was achieved with colistin therapy, which was stopped after 12 days in view of rising eosinophilia and possible lung fibrosis. The eosinophil count started to normalize 3 days after stopping colistin therapy and the patient was eventually weaned to minimal ventilatory support.

Topics: Administration, Inhalation; Aged; Alveolitis, Extrinsic Allergic; Anti-Bacterial Agents; Colistin; Female; Humans; Pneumonia, Bacterial; Treatment Outcome

We sought to evaluate the safety and feasibility of inhaled aminoglycosides or colistin in cancer patients with ventilator-associated pneumonia (VAP) due to Gram-negative bacteria (GNB). A retrospective case-matched study was obtained after obtaining IRB approval in patients at the intensive care unit at our NCI-designated comprehensive cancer center between 1999 and 2005. Sixteen patients with GNB-VAP who received inhaled aminoglycosides or colistin were compared with 16 patients who had received these antibiotics intravenously alone. Eligible patients were required to have received at least six doses of inhaled therapy, or 3 or more days of intravenous therapy. Clinical Pulmonary Infection Scores were used to assess pneumonia severity. Standard ATS criteria were used to define VAP. Patients treated with inhaled antibiotics were less likely to have received corticosteroids (13% vs 50%; P < 0.02) and had a higher median baseline creatinine level (0.85 vs 0.6 mg/dL; P < 0.02) than patients treated intravenously. Pseudomonas aeruginosa (69%) was the most common cause of VAP. There were no serious adverse events associated with inhaled antibiotics. Patients who received these antibiotics intravenously developed renal dysfunction (31%); none of the patients treated with inhaled antibiotics developed nephrotoxicity (P < or = 0.04). Patients treated with inhaled antibiotics were more likely to have complete resolution of clinical (81% vs 31% in the intravenous antibiotic group; P < 0.01) and microbiologic infection (77% vs 8% in the intravenous antibiotic group: P < 0.0006). In a multivariate analysis adjusted for corticosteroid use, inhaled antibiotic therapy was predictive of complete clinical resolution (odds ratio [OR], 6.3; 95% confidence interval [CI], 1.1, 37.6; P < 0.04) and eradication of causative organisms (OR 36.7; 95% CI, 3.3, 412.2; P < 0.003). In critically ill cancer patients with Gram-negative VAP, inhaled aminoglycosides were tolerated without serious toxicity and may lead to improved outcome.

Topics: Administration, Inhalation; Adult; Aged; Aminoglycosides; Anti-Bacterial Agents; Case-Control Studies; Colistin; Critical Illness; Drug Resistance; Female; Gram-Negative Bacterial Infections; Humans; Immunologic Factors; Male; Middle Aged; Neoplasms; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Retrospective Studies; Severity of Illness Index; Steroids; Treatment Outcome

Acinetobacter baumannii is an important cause of nosocomial infection with increasing carbapenem resistance. The aim of this study was to compare the efficacy of colistin+rifampicin and imipenem+rifampicin combinations with that of several other antibiotic regimens against carbapenem-resistant A. baumannii pneumonia using an immunosuppressed mouse model. Three different A. baumannii strains with diverse resistance mechanisms (OXA-51-, IMP-1- and VIM-2-type beta-lactamases) were used. Among the monotherapy regimens, only rifampicin significantly reduced the bacterial load in lungs 24 h after infection with the OXA-51-producing strain. Addition of rifampicin to either imipenem or colistin yielded synergistic results after 48 h. Rifampicin was bactericidal against the IMP-1-producing strain, and only the imipenem+rifampicin combination yielded synergistic effects. In contrast, rifampicin alone was not effective against the VIM-2-producing strain, but the imipenem+rifampicin combination was bacteriostatic even at 24 h post-infection. Tigecycline and amikacin were not effective against any of the three strains. Rifampicin-based combinations were effective against A. baumannii bacteraemia and improved survival regardless of the strain type. Contrary to the similar minimum inhibitory concentration results, the antibacterial effects of rifampicin were quite different according to the strains; a tailored antibiotic strategy must be considered in treatment. Addition of rifampicin to either imipenem or colistin would be effective.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Carbapenems; Colistin; Disease Models, Animal; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Humans; Imipenem; Immunosuppression Therapy; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Neutropenia; Pneumonia, Bacterial; Rifampin; Treatment Outcome

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

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

: To study the efficacy of intratracheal colistin sulfate therapy in a murine model of acute pneumonia caused by a clinical CRAB strain, Ab396. Colistin therapy has currently achieved a favorable outcome in patients with carbapenem-resistant Acinetobacter baumannii (CRAB) infections, but parenteral colistin may have limited therapeutic efficacy for CRAB pneumonia.. : A controlled, in vivo experimental study.. : Research laboratory of a medical center.. : Female BALB/c mice.. : The minimal inhibitory concentrations of antibiotics were measured. Acute pneumonia was established by intratracheal inoculation with an inoculum size of 2.5 x 10 colony-forming units Ab396 plus 10% porcine mucin into the lungs of mice, verified by histopathological examinations, and then treated with or without antibiotics. Mice received intratracheal saline treatment as a control group, intraperitoneal administration (IP) imipenem/cilastatin plus sulbactam (IP IS group, 80/80 mg/kg and 40 mg/kg every 8 hrs, n = 30), IP colistin sulfate (IP CS group, 150,000 U/kg every 8 hrs, n = 30), and intratracheal colistin sulfate (intratracheal CS group, 75,000 U/kg every 8 hrs, n = 30) at 2 hrs after intratracheal inoculation of Ab396.. : The minimal inhibitory concentrations of colistin sulfate, imipenem/cilastatin, or sulbactam for Ab396 were 2 microg/mL, 128 microg/mL, or 32 microg/mL, respectively. Compared with the mice in the control, IP IS, and IP CS groups, those in intratracheal CS group had a significantly favorable outcome at 72 hrs after infection (survival rate = 0%, 10%, 0% and 100%, respectively; all p < .001, log-rank test). Furthermore, intratracheal therapy decreased significantly the bacterial loads in the lungs and normalized the wet lung/body weight ratios in mice with acute pneumonia.. : The intratracheal colistin sulfate therapy led to more favorable outcomes than therapies by IP colistin sulfate or imipenem/cilastatin plus sulbactam in mice with early CRAB pneumonia.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Carbapenems; Colistin; Disease Models, Animal; Drug Resistance, Bacterial; Female; Mice; Mice, Inbred BALB C; Pneumonia, Bacterial; Time Factors; Trachea

Ventilator-associated pneumonia (VAP) remains the leading cause of death in patients with intensive care unit (ICU) acquired infections associated with an attributable mortality around 30%. Increasing antimicrobial resistance in patients with VAP challenges intensivists to search for alternative therapeutic options. There is scarcity of data in the literature concerning the administration of aerosolized colistin in critically ill patients with VAP due to multidrug-resistant (MDR) Gram-negative pathogens.. To assess the safety and effectiveness of aerosolized colistin as an adjunctive to the intravenous antimicrobial therapy for the treatment of VAP due to MDR Gram-negative pathogens, we prospectively examined all patients, who received inhaled colistin.. Sixty critically ill patients with a mean APACHE II score 16.7, received aerosolized colistin for the treatment of VAP due to MDR pathogens [Acinetobacter baumannii (37/60 cases), Pseudomonas aeruginosa (12/60 cases) and Klebsiella pneumoniae strains (11/60 cases)]. Half of the isolated pathogens were susceptible only to colistin. Mean (+/-SD) daily dosage of aerosolized colistin was 2.2 (+/-0.7) million international units (IU). All patients received 2946 inhalations of colistin and the mean duration of administration was 16.4 days. Fifty-seven patients received concomitant intravenous treatment with colistin or other antimicrobial agents. Bacteriological and clinical response of VAP was observed in 50/60 (83.3%) patients. No adverse effects related to inhaled colistin were recorded. All cause hospital mortality was 25% while mortality attributable to VAP was 16.7%.. Aerosolized colistin may be considered as adjunctive to intravenous treatment in patients with VAP due to MDR Gram-negative bacteria susceptible to colistin in critically ill patients. Although colistin is safe and effective, the best route of administration remains unclear. In addition, controlled comparative studies are needed to establish its effectiveness and safety.

Topics: Administration, Inhalation; Adult; Aerosols; Aged; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple; Female; Gram-Negative Bacterial Infections; Humans; Intensive Care Units; Male; Middle Aged; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Prospective Studies; Treatment Outcome

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: 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

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Colistin; Combined Modality Therapy; Cross Infection; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Pneumonia, Bacterial; Respiration, Artificial; Rifampin

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

Topics: Administration, Topical; Anti-Bacterial Agents; Anti-Infective Agents, Local; Chlorhexidine; Colistin; Drug Combinations; Humans; Intubation, Intratracheal; Ointments; Oropharynx; Pneumonia, Bacterial; Respiration, Artificial; Risk Factors; Ventilators, Mechanical

Topics: Acinetobacter Infections; Anti-Bacterial Agents; Biomedical Research; Colistin; Critical Care; Databases, Bibliographic; Decision Making; Drug Resistance, Multiple, Bacterial; Humans; Information Storage and Retrieval; Pneumonia, Bacterial

The clinical and economic consequences of the emergence of multidrug-resistant Gram-negative bacteria in the intensive care unit (ICU) setting, combined with the high mortality rate among patients with nosocomial pneumonia, have stimulated a search for alternative therapeutic options to treat such infections. The use of adjunctive therapy with aerosolized colistin represents one of these. There is extensive experience with use of aerosolized colistin by patients with cystic fibrosis, but there is a lack of data regarding the use of aerosolized colistin in patients without cystic fibrosis.. We conducted the present study to assess the safety and effectiveness of aerosolized colistin as an adjunct to intravenous antimicrobial therapy for treatment of Gram-negative nosocomial pneumonia. We retrospectively reviewed the medical records of patients hospitalized in a 450-bed tertiary care hospital during the period from October 2000 to January 2004, and who received aerosolized colistin as adjunctive therapy for multidrug-resistant pneumonia.. Eight patients received aerosolized colistin. All patients had been admitted to the ICU, with mean Acute Physiological and Chronic Health Evaluation II scores on the day of ICU admission and on day 1 of aerosolized colistin administration of 14.6 and 17.1, respectively. Six of the eight patients had ventilator-associated pneumonia. The responsible pathogens were Acinetobacter baumannii (in seven out of eight cases) and Pseudomonas aeruginosa (in one out of eight cases) strains. Half of the isolated pathogens were sensitive only to colistin. The daily dose of aerosolized colistin ranged from 1.5 to 6 million IU (divided into three or four doses), and the mean duration of administration was 10.5 days. Seven out of eight patients received concomitant intravenous treatment with colistin or other antimicrobial agents. The pneumonia was observed to respond to treatment in seven out of eight patients (four were cured and three improved [they were transferred to another facility]). One patient deteriorated and died from septic shock and multiple organ failure. Aerosolized colistin was well tolerated by all patients; no bronchoconstriction or chest tightness was reported.. Aerosolized colistin may be a beneficial adjunctive treatment in the management of nosocomial pneumonia (ventilator associated or not) due to multidrug-resistant Gram-negative bacteria.

Topics: Aerosols; Anti-Bacterial Agents; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Humans; Intensive Care Units; Male; Middle Aged; Pneumonia, Bacterial; Treatment Outcome

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

Topics: Aerosols; Anti-Bacterial Agents; Chemistry, Pharmaceutical; Colistin; Drug Administration Routes; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacterial Infections; Humans; Pneumonia, Bacterial

Successful therapy of carbapenem-resistant Acinetobacter baumannii strains has been reported with colistin, but recently we argued against its use as monotherapy because of the poor results obtained in a mouse pneumonia model. Our aim was to identify antibiotic combinations that were valid therapeutic alternatives in the same model.. We used two carbapenem-resistant A. baumannii strains (D and E; MICs of imipenem, 8 and 512 mg/L, respectively). MICs of tobramycin, rifampicin and colistin for both strains were 8, 8 and 0.5 mg/L, respectively.. In infections caused by strain D, lung bacterial counts (log(10) cfu/g, mean +/- s.d.) were: controls (10.86+/-0.25), imipenem (5.99+/-0.59, P < 0.05 versus controls), and colistin (10.43 +/- 1.09); imipenem + tobramycin was the most active combination (5.46+/-0.62, P < 0.05 versus controls). In infections caused by strain E, results were: controls (10.82+/-0.33), rifampicin (5.62+/-0.26, P < 0.05 versus controls), colistin (8.38+/-1.22, P < 0.05 versus controls), and imipenem (11.01+/-0.2); rifampicin + imipenem (3.79+/-0.99) and rifampicin + tobramycin (3.96+/-0.30) were the most active combinations (P < 0.05); results with rifampicin + colistin (5.59+/-1.17) were similar to those with rifampicin alone.. Our data indicate that imipenem can still be the best alternative for carbapenem-resistant A. baumannii infections with moderate levels of imipenem resistance, preferably combined with aminoglycosides. For strains highly resistant to imipenem, a combination of rifampicin with imipenem, tobramycin or colistin may be useful, if resistance to rifampicin is only moderate.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; beta-Lactams; Carbapenems; Colistin; Disease Models, Animal; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Humans; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Pneumonia, Bacterial; Rifampin; Tobramycin

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Cross Infection; Humans; Pneumonia, Bacterial; Respiration, Artificial

The treatment of life-threatening infections due to carbapenem-resistant Acinetobacter baumannii has become a serious challenge for physicians worldwide. Often, only colistin shows in general good in vitro activity against these carbapenem-resistant strains, but its antibacterial efficacy in comparison with the antibiotics most used in clinical practice is not well known. We studied the efficacy of colistin versus those of imipenem, sulbactam, tobramycin, and rifampin in an experimental pneumonia model with immunocompetent mice. We used three strains of A. baumannii corresponding to the main clones (A, D, and E) involved in the outbreaks of our hospital, with different grades of resistance to imipenem (imipenem MICs of 1, 8, and 512 microg/ml, respectively) and to the other antibiotics. The MIC of colistin was 0.5 microg/ml for the three strains. Reduction of log(10) CFU/g in lung bacterial counts, clearance of bacteremia, and survival versus results with controls were used as parameters of efficacy. Imipenem and sulbactam (Deltalung counts: -5.38 and -4.64 log(10) CFU/ml) showed the highest level of bactericidal efficacy in infections by susceptible and even intermediate strains. Tobramycin and rifampin (-4.16 and -5.15 log(10) CFU/ml) provided good results against intermediate or moderately resistant strains, in agreement with killing curves and pharmacodynamics. On the contrary, colistin showed the weakest antibacterial effect among the antibiotics tested, both in killing curves and in the in vivo model (-2.39 log(10) CFU/ml; P < 0.05). We conclude that colistin did not appear as a good option for treatment of patients with pneumonia due to carbapenem-resistant A. baumannii strains. Other alternatives, including combinations with rifampin, may offer better therapeutic profiles and thus should be studied.

Topics: Acinetobacter; Acinetobacter Infections; Aminoglycosides; Animals; Anti-Bacterial Agents; Colistin; Drug Resistance, Microbial; Female; Lung; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Pneumonia, Bacterial; Rifampin; Survival Analysis

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

Patients requiring long-term ventilation are at high risk of lower airway infections, generally of endogenous development. Patients on long-term ventilation, in particular via a tracheostomy, may develop tracheobronchitis or pneumonia of exogenous pathogenesis, ie, caused by microorganisms not carried in the oropharynx. The frequency of exogenous colonization or infection has previously been reported to be as high as 33%. A prospective observational cohort study of 2 years was undertaken to evaluate the efficacy of topical antibiotics in the prevention of exogenous colonization or infection of the lower airways. The antibiotic combination of polymyxin E and tobramycin in a 2% paste was applied four times a day on the tracheostoma.. A total of 23 children (median age, 4.1 months; range, 0 to 215 months) were enrolled in the study from September 1, 1996, until August 30, 1998. Surveillance samples of the oropharynx were obtained before tracheostomy and thereafter twice weekly. Diagnostic samples of the lower airways were taken once weekly and on clinical indication.. Fourteen children (61%) had a total of 16 episodes of tracheal colonization or infection with 20 potentially pathogenic microorganisms. Only one child had tracheobronchitis with Streptococcus pneumoniae and Haemophilus influenzae during the 2-year study. Of the 16 colonization episodes, 12 (75%) were of primary endogenous pathogenesis, ie, caused by microorganisms present in the oropharynx at the time of tracheostomy. Community microorganisms including S pneumoniae, H influenzae, Moraxella (Branhamella) catarrhalis, and Staphylococcus aureus were the predominating bacteria. Three patients acquired nosocomial bacteria Pseudomonas aeruginosa and Hafnia alvei in the oropharynx, subsequently followed by secondary colonization of the lower airways. There was one failure of the prophylaxis: one patient (4%) had exogenous colonization with Pseudomonas pickettii.. Topical antibiotics applied to the tracheostoma were found to be effective in reducing the exogenous route of colonization of the lower respiratory tract, compared with clinical experience and the literature. This promising technique requires further evaluation in randomized trials.

Topics: Administration, Topical; Adolescent; Antibiotic Prophylaxis; Bacteriological Techniques; Child; Child, Preschool; Cohort Studies; Colistin; Cross Infection; Drug Therapy, Combination; Female; Humans; Infant; Infant, Newborn; Male; Oropharynx; Pilot Projects; Pneumonia, Bacterial; Prospective Studies; Tobramycin; Tracheostomy; Treatment Outcome

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