colistin and Respiratory-Tract-Infections

To evaluate whether intravenous plus inhaled combination (IV/INHCC) compared to intravenous monotherapy (IVCM) was associated with patient outcomes and identify factors influencing study outcomes.. PubMed and Scopus were searched till November 2016. Studies were included if they evaluated adult patients with lower respiratory tract infections due to MDR/XDR Gram-negative bacteria and reported comparative mortality data (adjusted and unadjusted) for patients receiving IV/INHCC versus IVCM. Random effects meta-analyses were performed.. Thirteen studies (11 retrospective, 2 prospective) were included. The overall quality of data was low to very low and characterized by the lack of adjusted data. The majority of the studies were designed to evaluate the outcome of the meta-analysis. Both IV and inhaled colistin were administered at variable doses. There was no difference in mortality between IV/INHCC and IVCM when all studies were combined (13 studies, 1115 patients, risk ratio 0.94, 95% confidence interval 0.81-1.08). Only the analysis that included studies with low-dose IV colistin showed significant difference in favor of IV/INHCC versus IVCM (0.65, 0.45-0.94).. Overall, low quality data suggest that IV/INHCC did not lower mortality in patients with MDR Gram negative infections unless low IV colistin dose was administered.

Topics: Administration, Inhalation; Administration, Intravenous; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Pneumonia, Ventilator-Associated; Prospective Studies; Respiratory Tract Infections; Retrospective Studies; Treatment Outcome

Inhaled antibiotics have been used to treat chronic airway infections since the 1940s. The earliest experience with inhaled antibiotics involved aerosolizing antibiotics designed for parenteral administration. These formulations caused significant bronchial irritation due to added preservatives and nonphysiologic chemical composition. A major therapeutic advance took place in 1997, when tobramycin designed for inhalation was approved by the U.S. Food and Drug Administration (FDA) for use in patients with cystic fibrosis (CF) with chronic Pseudomonas aeruginosa infection. Attracted by the clinical benefits observed in CF and the availability of dry powder antibiotic formulations, there has been a growing interest in the use of inhaled antibiotics in other lower respiratory tract infections, such as non-CF bronchiectasis, ventilator-associated pneumonia, chronic obstructive pulmonary disease, mycobacterial disease, and in the post-lung transplant setting over the past decade. Antibiotics currently marketed for inhalation include nebulized and dry powder forms of tobramycin and colistin and nebulized aztreonam. Although both the U.S. Food and Drug Administration and European Medicines Agency have approved their use in CF, they have not been approved in other disease areas due to lack of supportive clinical trial evidence. Injectable formulations of gentamicin, tobramycin, amikacin, ceftazidime, and amphotericin are currently nebulized "off-label" to manage non-CF bronchiectasis, drug-resistant nontuberculous mycobacterial infections, ventilator-associated pneumonia, and post-transplant airway infections. Future inhaled antibiotic trials must focus on disease areas outside of CF with sample sizes large enough to evaluate clinically important endpoints such as exacerbations. Extrapolating from CF, the impact of eradicating organisms such as P. aeruginosa in non-CF bronchiectasis should also be evaluated.

Topics: Administration, Inhalation; Amikacin; Amphotericin B; Anti-Bacterial Agents; Aztreonam; Ceftazidime; Colistin; Cystic Fibrosis; Gentamicins; Humans; Nebulizers and Vaporizers; Respiratory Tract Infections; Tobramycin

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

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

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

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

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

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

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

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

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

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

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

To assess the effectiveness of selective digestive decontamination (SDD) on the control of nosocomial infection (NI) in critically ill pediatric patients.. A prospective, randomized, non-blinded and controlled clinical microbiology study.. The pediatric intensive care unit (PICU) of a tertiary level pediatric university hospital. CRITERIA FOR INCLUSION: Patients 1 month to 14 years old, who underwent some kind of manipulation or instrumentation (mechanical ventilation, vascular cannulation, monitoring of intracranial pressure, thoracic or abdominal drainage, bladder catheterization, peritoneal dialysis, etc.) and/or presented a neurological coma requiring a stay in the PICU of 3 or more days.. Over a period of 2 years, 244 patients met the inclusion criteria; 18 patients were withdrawn because of protocol violation. The treatment group comprised 116 patients and the control group, 110 patients.. The treatment group received a triple therapy of colimycin, tobramycin and nystatin administered orally or via nasogastric tube every 6 hours. All patients with mechanical ventilation or immune-depression received decontamination treatment of the oropharyngeal cavity with hexitidine (Oraldine 0.5 mg/ml) every 6-8 hours in accordance with the PICU's conventional protocol.. Up to 10 types of nosocomial infection were diagnosed following criteria of the Centers for Disease Control (CDC). The severity and manipulation of the patients on admission was assessed using the therapeutic intervention scoring system (TISS) and multi-organ system failure scores (MOSF).. UNIVARIANT ANALYSIS: SDD did not significantly reduce the incidence of NI, antibiotic use, the length of stay, or mortality; although a small percentage of respiratory and urinary tract infections was detected, catheter-related bacteremia was the most common infection. MULTIVARIANT ANALYSIS: Controlling the risk factors for each child through log regression showed that SDD acted as a protective factor for more than 90% of the sample with respect to the appearance of respiratory and urinary tract infections, reducing the risk of such infections to 1/5 and 1/3, respectively.. SDD was effective in controlling respiratory and urinary tract infections in children admitted to the PICU, but it did not reduce the incidence of other types of nosocomial infection.

Topics: Adolescent; Antibiotic Prophylaxis; Child; Child, Preschool; Colistin; Cross Infection; Digestive System; Drug Therapy, Combination; Female; Hexetidine; Humans; Infant; Intensive Care Units, Pediatric; Male; Multiple Organ Failure; Multivariate Analysis; Nystatin; Prospective Studies; Regression Analysis; Respiratory Tract Infections; Severity of Illness Index; Tobramycin; Urinary Tract Infections

The influence of topical antimicrobial prophylaxis (TAP) on colonization of oropharynx and trachea was studied in patients receiving and not receiving prophylaxis. Twenty-two patients in Intensive Care Unit (ICU) I (Group 1) received TAP (tobramycin, colistin, and amphotericine B in oropharynx and stomach). Simultaneous to Group 1, 21 patients (Group 2) not receiving TAP were studied in ICU I. A control group of patients admitted to another, identical, ICU (ICU II), where no TAP was administered, were studied simultaneously (Group 3a, n = 23). A second control group (Group 3b, n = 31), was formed by collecting data from patients admitted to ICU I in Period II. Patients receiving TAP were less frequently colonized than patients not receiving prophylaxis. Moreover, of the patients not receiving TAP, those staying in the ICU where TAP was administered (Group 2) were less frequently colonized than patients in another ICU (Group 3). Of the patients not colonized on admission, those staying in the ICU where TAP was administered remained free of colonization for a longer time. In the ICU where no TAP was administered, more patients were colonized simultaneously and cross-acquisition occurred more frequently. TAP significantly influenced colonization of oropharynx and trachea in patients receiving and not receiving prophylaxis within the same ICU as compared with patients not receiving prophylaxis in another identical ICU.

Topics: Administration, Topical; Aged; Amphotericin B; Colistin; Colony Count, Microbial; Cross Infection; Drug Therapy, Combination; Enterobacteriaceae; Female; Humans; Intensive Care Units; Male; Middle Aged; Oropharynx; Prospective Studies; Pseudomonadaceae; Respiratory Tract Infections; Tobramycin; Trachea

The objective of this study was to assess the effect of a novel regimen of antibiotic prophylaxis on the incidence of lower respiratory tract infection in patients requiring prolonged (at least five days) mechanical ventilation. The design was a controlled, prospective, randomized trial, with blinded comparison of the groups regarding the incidence of respiratory tract infection in an intensive care unit of a university hospital. After determination of the APACHE II score for severity of disease, 88 patients were randomly divided in three groups. Twenty-four of these patients did not complete five days of mechanical ventilation, and eight were withdrawn for other reasons. Fifty-six patients (18 in group 1, 21 in group 2, 17 in group 3) completed the study. Patients in both control groups 1 and 2 did not receive antibiotic prophylaxis, but the two groups differed in the antibiotic policy in case of infection. Patients in group 3 received antibiotic prophylaxis consisting of norfloxacin, polymyxin E, and amphotericin B, applied topically in oropharynx and stomach from time of ICU admission until extubation, and intravenous cefotaxime 500 mg three times a day during the first five days of admission. In both control groups, about 90 percent of the patients acquired microbial colonization of oropharynx or stomach. In group 3, only 12 percent and 24 percent of the patients acquired colonization of oropharynx and stomach, respectively (p less than 0.001). This resulted in a reduction of the incidence of lower respiratory tract infection (78 percent in group 1, 62 percent in group 2, 6 percent in group 3 [p = 0.0001]). The regimen of antibiotic prophylaxis studied prevented respiratory tract infection in mechanically ventilated patients. Antibiotic prophylaxis should be considered in all patients expected to require prolonged mechanical ventilation.

Topics: Administration, Topical; Amphotericin B; Bacteria; Cefotaxime; Colistin; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Infusions, Intravenous; Intensive Care Units; Male; Middle Aged; Norfloxacin; Oropharynx; Prospective Studies; Respiration, Artificial; Respiratory Tract Infections; Severity of Illness Index; Stomach

A comparative, prospective study was made of the incidence of infection in the lower airway (purulent tracheobronchitis and pneumonia) in long-term patients who were mechanically ventilated due to respiratory failure of noninfectious origin. Twenty-eight patients were randomly allocated into a study group (A, n = 13) in which a nonabsorbable paste containing 2% tobramycin, 2% amphotericin B, and 2% polymyxin E was administered locally to decontaminate the oropharynx, and a control group (B, n = 15) in which a paste without antibiotics was also applied to the oropharynx. We studied the effectiveness of the prophylactic technique in decontaminating the oropharynx and trachea of organisms potentially pathogenic for the respiratory system. Decontamination was successful in ten of 13 patients in group A vs. one of 15 patients in group B (p less than .001). The results demonstrated a lower rate of infection in the lower respiratory tract in the study group (three patients with tracheobronchitis and no pneumonias) than in the control group (three patients with tracheobronchitis and 11 with pneumonia), the difference between both being highly significant (p less than .001). Two (15%) patients in group B developed sepsis of pulmonary origin. None of the patients on prophylactic treatment developed this complication. Although the overall mortality was similar in both groups (group A, 30% vs. group B, 33%), we believe that infection contributed to a great extent to the death of two of five patients in group B. We conclude that nosocomial pneumonia, which is a frequent complication in critically ill patients on mechanical ventilation, could be prevented by local application of nonabsorbable antibiotics to the oropharynx.

Topics: Administration, Topical; Adolescent; Adult; Aged; Amphotericin B; Child; Colistin; Cross Infection; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Oropharynx; Prospective Studies; Respiration, Artificial; Respiratory Tract Infections; Tobramycin

Compared to parenteral administration of colistin, its direct pulmonary administration can maximize lung drug deposition while reducing systemic adverse side effects and derived nephrotoxicity. Current pulmonary administration of colistin is carried out by the aerosolization of a prodrug, colistin methanesulfonate (CMS), which must be hydrolized to colistin in the lung to produce its bactericidal effect. However, this conversion is slow relative to the rate of absorption of CMS, and thus only 1.4 % (w/w) of the CMS dose is converted to colistin in the lungs of patients receiving inhaled CMS. We synthesized several aerosolizable nanoparticle carriers loaded with colistin using different techniques and selected particles with sufficient drug loading and adequate aerodynamic behavior to efficiently deliver colistin to the entire lung. Specifically, we carried out (i) the encapsulation of colistin by single emulsion-solvent evaporation with immiscible solvents using polylactic-co-glycolic (PLGA) nanoparticles; (ii) its encapsulation using nanoprecipitation with miscible solvents using poly(lactide-co-glycolide)-block-poly(ethylene glycol) as encapsulating matrix; (iii) colistin nanoprecipitation using the antisolvent precipitation method and its subsequent encapsulation within PLGA nanoparticles; and (iv) colistin encapsulation within PLGA-based microparticles using electrospraying. Nanoprecipitation of pure colistin using antisolvent precipitation showed the highest drug loading (55.0 ± 4.8 wt%) and spontaneously formed aggregates with adequate aerodynamic diameter (between 3 and 5 μm) to potentially reach the entire lung. These nanoparticles were able to completely eradicate Pseudomonas aeruginosa in an in vitro lung biofilm model at 10 µg/mL (MBC). This formulation could be a promising alternative for the treatment of pulmonary infections improving lung deposition and, therefore, the efficacy of aerosolized antibiotics.

Topics: Anti-Bacterial Agents; Bacterial Infections; Colistin; Drug Carriers; Humans; Nanoparticles; Particle Size; Respiratory Tract Infections; Solvents

We investigated the therapeutic capacity of the isolated Klebsiella bacteriophage NK20 against pandrug-resistant strains. Moreover, we assessed the impact of resistance development on the overall therapeutic outcome both in vitro and in vivo.. The pandrug-resistant K. pneumoniae Kp20 is used as a host strain for the isolation of bacteriophages using sewage samples. Spot assay was then used to compare the spectra of the isolated phages, while kinetic and genomic analysis of the phage with the broadest spectrum was assessed. Antibacterial potential of the phage was assessed using turbidimetric assay and MIC with and without colistin. Finally, the therapeutic efficacy was evaluated in vivo using a rat respiratory infection model.. The isolated lytic bacteriophage (NK20) showed a relatively broad spectrum and an acceptable genomic profile. In vitro antibacterial assay revealed bacterial resistance development after 12 h. Colistin inhibited bacterial regrowth and reduced pandrug-resistant strains' colistin MICs. Despite the isolation of resistant clones, intranasal administration of NK20 significantly (p < 0.05) reduced the bacterial load in both the pulmonary and blood compartments and rescued 100 % of challenged rats. Histological and immunological analysis of treated animals' lung tissue revealed less inflammation and lower TNF-α and caspase-3 expression.. NK20 is a promising candidate that rescued rats from untreatable, pan-drug-resistant K. pneumoniae Kp20. Moreover, it steers the evolution of resistant mutants with higher sensitivity to colistin and less virulence, opening the door for using phages as sensitizing and anti-virulence entities rather than direct killer.

Topics: Animals; Anti-Bacterial Agents; Bacteriophages; Colistin; Genomics; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Rats; Respiratory Tract Infections

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

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

Systemic colistin is often utilized for management of drug resistant lower respiratory tract infections (LRTI). Nebulized administration of colistin allows direct instillation of active agent to maximize concentrations and limit systemic toxicities. Current literature supports efficacy of nebulized colistin as adjunctive treatment for LRTI. However, there is a paucity of data surrounding safety of this administration technique.. The electronic medical record (EMR) was queried to identify patients treated with nebulized colistin between January 1, 2016 and December 31, 2018. The data collected from the EMR and hospital adverse drug reaction (ADR) reporting systems included: demographics, dose, serum creatinine (SCr), concomitant nephrotoxins, infecting pathogen, treatment-emergent ADRs, and drug toxicities. The primary outcome was prevalence of renal, neurologic, or respiratory ADRs secondary to nebulized colistin.. Thirty-two patients were administered nebulized colistin during the study period. Approximately 19% of patients had baseline chronic kidney disease. Cultures were positive in 29 patients of which 11 organisms were resistant to all tested antimicrobials. Three patients experienced acute kidney injury (AKI), 1 patient experienced a neurologic reaction, and 1 patient experienced a respiratory reaction, though none were considered treatment-related.. The results of our study signify localized administration of colistin results in a low incidence of systemic adverse events. Nebulized colistin is a safe adjunct for managing LRTI.

Topics: Anti-Bacterial Agents; Colistin; Creatinine; Drug Resistance, Multiple, Bacterial; Humans; Kidney; Respiratory Tract Infections

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

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

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

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

Topics: Anti-Bacterial Agents; Colistin; Guidelines as Topic; Humans; Microbial Sensitivity Tests; Polymyxin B; Polymyxins; Respiratory Tract Infections; United States; Urinary Tract Infections

The aim of this study was to design and characterize dry powder inhaler formulations of ciprofloxacin and colistin co-loaded liposomes prepared by the ultrasonic spray-freeze-drying (USFD) technique. Liposomal formulations and powder production parameters were optimized to achieve optimal characteristics and in-vitro performance such as encapsulation efficiency (EE), particle size, particle distribution index (PDI), fine particle fraction (FPF), emitted dose (ED) and in vitro antibacterial activity. The formulation (F6) with the mannitol (5% w/v) as the internal lyoprotectant and sucrose (5%, w/v), mannitol (10%, w/v) and leucine (5%, w/w) as the external lyoprotectants/aerosolization enhancers showed an optimal rehydrated EE values of ciprofloxacin and colistin (44.9 ± 0.9% and 47.0 ± 0.6%, respectively) as well as satisfactory aerosol performance (FPF: 45.8 ± 2.2% and 43.6 ± 1.6%, respectively; ED: 97.0 ± 0.5% and 95.0 ± 0.6%, respectively). For the blank liposomes, there was almost no inhibitory effect on the cell proliferation in human lung epithelial A549 cells, showing that the lipid materials used in the liposome formulation is safe for use in pulmonary drug delivery. The cytotoxicity study demonstrated that the optimized liposomal formulation (F6) was not cytotoxic at least at the drug concentrations of colistin 5 μg/mL and ciprofloxacin 20 μg/mL. Colistin (2 mg/L) monotherapy showed no antibacterial effect against P. aeruginosa H131300444 and H133880624. Ciprofloxacin (8 mg/L) monotherapy showed moderate bacterial killing for both clinical isolates; however, regrowth was observed in 6 h for P. aeruginosa H133880624. The liposomal formulation displayed superior antibacterial activity against clinical isolates of Pseudomonas aeruginosa H131300444 and P. aeruginosa H133880624 compared to each antibiotic per se. These results demonstrate that the liposomal powder formulation prepared by USFD could potentially be a pulmonary delivery system for antibiotic combination to treat multi-drug resistant Gram-negative lung infections.

Topics: A549 Cells; Administration, Inhalation; Anti-Bacterial Agents; Ciprofloxacin; Colistin; Drug Combinations; Drug Resistance, Bacterial; Drug Resistance, Multiple; Drug Synergism; Gram-Negative Bacterial Infections; Humans; Liposomes; Powders; Pseudomonas aeruginosa; Respiratory Tract Infections

Colistimethate sodium (colistin) is used to treat multidrug-resistant gram negative infections. We describe the profile and outcomes of patients given colistin in a tertiary level government hospital in Manila, Philippines.. We performed a retrospective study of adult patients given intravenous colistin between January 2015 to June 2018 in the Philippine General Hospital. We defined clinical success as a composite of hemodynamic stability, quick Sequential Organ Failure Assessment (qSOFA) score, and microbiological cure.. 250 patients were included, half (49.2%) were admitted in the ICU. Median age was 55 years. There was an increase in qSOFA, APACHE II score, and septic shock from baseline to 24 h prior to colistin use. Most patients had pneumonia (90.8%) with extensively drug-resistant Acinetobacter baumannii as the most common isolate (78.8%). Colistin was given in combination with meropenem (96.4%) for a median of 12 days. Nephrotoxicity was seen in 30.8%, with renal replacement therapy needed in 6%. Clinical success was seen in 61.2% of patients and overall mortality was 41.6%.. Colistin was frequently used in combination with a carbapenem for treatment of XDR-related respiratory infections. Nephrotoxicity was a common adverse effect. Clinical success was modest and overall mortality was high.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Intravenous; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Gram-Negative Bacterial Infections; Hospitalization; Humans; Male; Meropenem; Middle Aged; Organ Dysfunction Scores; Philippines; Respiratory Tract Infections; Retrospective Studies; Tertiary Care Centers; Treatment Outcome; Young Adult

The aim of this study was to assess colistin use in a country endemic for multidrug-resistant Gram-negative bacteria (MDR-GNB).. Colistin prescription patterns were evaluated in 22 Italian centres. Factors associated with use of colistin in combination with other anti-MDR-GNB agents were also assessed.. A total of 221 adults receiving colistin were included in the study. Their median age was 64 years (interquartile range 52-73 years) and 134 (61%) were male. Colistin was mostly administered intravenously (203/221; 92%) and mainly for targeted therapy (168/221; 76%). The most frequent indications for colistin therapy were bloodstream infection and lower respiratory tract infection. Intravenous colistin was administered in combination with at least another anti-MDR-GNB agent in 80% of cases (163/203). A loading dose of 9 MU of colistimethate was administered in 79% of patients receiving i.v. colistin and adequate maintenance doses in 85%. In multivariable analysis, empirical therapy [odds ratio (OR) = 3.25, 95% confidence interval (CI) 1.24-8.53;P = 0.017] and targeted therapy for carbapenem-resistant Enterobacterales infection (OR = 4.76, 95% CI 1.69-13.43; P = 0.003) were associated with use of colistin in combination with other agents, whilst chronic renal failure (OR = 0.39, 95% CI 0.17-0.88; P =  0.024) was associated with use of colistin monotherapy.. Colistin remains an important option for severe MDR-GNB infections when other treatments are not available. Despite inherent difficulties in optimising its use owing to peculiar pharmacokinetic/pharmacodynamic characteristics, colistin was mostly used appropriately in a country endemic for MDR-GNB.

Topics: Administration, Intravenous; Aged; Anti-Bacterial Agents; Colistin; Cross-Sectional Studies; Drug Prescriptions; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Endemic Diseases; Female; Gram-Negative Bacterial Infections; Humans; Italy; Male; Middle Aged; Respiratory Tract Infections; Sepsis

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

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

Multi-drug resistant Acinetobacter baumannii has emerged as important nosocomial pathogen associated with various infections including lower respiratory tract. Limited therapeutic options contribute to increased morbidity and mortality. Acinetobacter baumannii has the ability to persist in the environment for prolonged periods. Breach in infection control practices increases the chances of cross transmission between patients and inter/intraspecies transmission of resistance elements. The present prospective work was conducted among patients with lower respiratory tract infections (LRTI) in the intensive care unit (ICU) to study the etiology with special reference to Acinetobacter baumannii and the role of immediate patient environment in the ICU as possible source of infection. Acinetobacter baumannii were characterized for antimicrobial susceptibility, mechanism of carbapenem resistance and virulence determinants. Molecular typing of the clinical and environmental isolates was undertaken to study the probable modes of transmission.. Appropriate respiratory samples from 107 patients with LRTI admitted to ICU during September 2016 to March 2017 were studied for likely bacterial pathogens. Environmental samples (n = 71) were also screened. All the samples were processed using conventional microbiological methods. Consecutive Acinetobacter spp. isolated from clinical and environmental (health care workers and environment from ICU) samples were included in the study. Antimicrobial susceptibility was performed as per CLSI guidelines. Carbapenem resistance, mediated by carbapenemase genes (bla. Carbapenem resistant Acinetobacter baumannii (CRAB) is an important cause of LRTI in the ICU. PFGE suggests spread of carbapenem resistant isolates via cross transmission among patients and the environment. The detection of bla

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Biofilms; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Gene Transfer, Horizontal; Genes, Bacterial; Genotype; Hospitals; Humans; India; Intensive Care Units; Microbial Sensitivity Tests; Microbiological Techniques; Molecular Typing; Phenotype; Prevalence; Prospective Studies; Respiratory Tract Infections; Species Specificity; Virulence

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Colistin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Klebsiella pneumoniae; Lung; Mice; Microbial Sensitivity Tests; Respiratory Tract Infections

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

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

Polymyxins are one of the last-line antibiotics for multidrug-resistant Acinetobacter baumannii. Reports have demonstrated the emergence of colistin heteroresistance in A. baumannii, which can complicate assessment of minimum inhibitory concentrations and promote resistance to colistin. We aimed to determine the presence of colistin heteroresistance in A. baumannii isolates and correlate the results with clinical and microbiological outcomes via a retrospective study of 24 adult patients: 12 blood and 12 invasive respiratory cultures positive for colistin-susceptible A. baumannii between 1 January 2013 and 31 July 2015. Heteroresistance testing was performed by plating a 100-μL bacterial cell suspension on Mueller-Hinton agar plates containing 0, 1, 2, and 4 μg/mL colistin, and assessing for growth at 24 and 48 h. Colistin heteroresistance was exhibited in 83% of isolates. Median age was 56 [43-65] years, 10 (42%) patients resided at a facility prior to admission, 5 (21%) had a chronic tracheostomy, 18 (75%) were in the intensive care unit at the time of culture collection, and median infection-related length of stay was 12 [7-15] days. Clinical and microbiological cures were achieved in 75% of patients. Overall infection-related mortality was 21%. Our study demonstrated a high rate of colistin heteroresistance in clinical isolates of colistin-susceptible A. baumannii, although this was not associated with suboptimal clinical outcomes due to the use of aggressive colistin dosing and combination therapy. Further studies are needed to establish the association between in vitro colistin heteroresistance and clinical and microbiological outcomes.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Cohort Studies; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Respiratory Tract Infections; Retrospective Studies

Identification of risks of mortality for carbapenem-resistant Acinetobacter baumannii (CRAB), with early implementation of an appropriate therapy, is crucial for the patients' outcome. The aim of this study was to survey mortality risk factors in 182 patients with CRAB bacteremia in a medical center in Taiwan.. A total of 182 isolates of CRAB bacteremia were collected from 2009 to 2012 in Mackay Memorial Hospital, Taipei, Taiwan These isolates were identified by using the genotypic method. Risk of attributable mortality analysis was carried out with a Cox proportional hazards model.. The 182 CRAB isolates belonged to 38 different pulsotypes. The attributable mortality rate of the 182 patients was 58.24%. The risk factors for attributable mortality included intensive care unit stay [hazard ratio (HR): 2.27; p = 0.011], an Acute Physiology and Chronic Health Evaluation II score of >20 (HR: 2.19; p < 0.001), respiratory tract as the origin of bacteremia (HR: 3.40; p < 0.001), and previous use of ceftriaxone (HR: 2.51; p = 0.011). The appropriateness of antimicrobial therapy was 18.87% (20/106) in the mortality group versus 88.16% (67/76) in the survivor group (p < 0.001). The sensitivity of CRAB to colistin was 100% and to tigecycline was 40.11%.. The risk factors for mortality for CRAB included intensive care unit stay, a high Acute Physiology and Chronic Health Evaluation II score, respiratory tract as the origin of bacteremia, and previous use of ceftriaxone. Early implementation of an antimicrobial agent that had the highest in vitro activity against CRAB in patients at risk of CRAB bacteremia and high mortality may improve their outcome.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; APACHE; Bacteremia; Carbapenems; Colistin; Drug Resistance, Bacterial; Female; Humans; Intensive Care Units; Male; Microbial Sensitivity Tests; Minocycline; Respiratory Tract Infections; Retrospective Studies; Risk Factors; Tigecycline

Colistin is often the only effective antibiotic against the respiratory infections caused by multidrug-resistant Gram-negative bacteria. However, colistin-resistant multidrug-resistant isolates have been increasingly reported and combination therapy is preferred to combat resistance. In this study, five combination formulations containing colistin (COL) and rifampicin (RIF) were prepared by spray drying. The lowest minimum inhibitory concentration (MIC) value against Pseudomonas aeruginosa PAO1 was measured for the formulation of COL/RIF = 4:1 with relatively high emitted doses (over 80%) and satisfactory fine particle fractions (over 60%). Data from X-ray photoelectron spectroscopy (XPS) and nano-time-of-flight secondary ion mass spectrometry (ToF-SIMS) showed the surfaces of particles were mainly covered by rifampicin even for the formulation with a mass ratio of COL/RIF = 4:1. Because colistin is hygroscopic and rifampicin is hydrophobic, moisture absorption of combination formulations was significantly lower than the pure colistin formulation in the dynamic vapour sorption results. To investigate the dissolution characteristics, four dissolution test methods (diffusion Franz cell, modified Franz cell, flow-through and beaker methods) were employed and compared. The modified Franz cell method was selected to test the dissolution behaviour of aerosolised powder formulations to eliminate the effect of membrane on dissolution. The results showed that surface enrichment of hydrophobic rifampicin neither affected aerosolisation nor retarded dissolution rate of colistin in the combination formulations. For the first time, advanced surface characterisation techniques of XPS and ToF-SIMS have shown their capability to understand the effect of surface composition on the aerosolisation and dissolution of combination powders.

Topics: Administration, Inhalation; Aerosols; Anti-Bacterial Agents; Colistin; Dry Powder Inhalers; Microbial Sensitivity Tests; Particle Size; Pseudomonas aeruginosa; Respiratory Tract Infections; Rifampin; Solubility; Surface Properties

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

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

Colistin is increasingly used as a last option for the treatment of severe infections due to Gram-negative bacteria in critically ill patients requiring intermittent hemodialysis (HD) for acute renal failure. Our objective was to characterize the pharmacokinetics (PK) of colistin and its prodrug colistin methanesulfonate (CMS) in this population and to suggest dosing regimen recommendations. Eight intensive care unit (ICU) patients who were under intermittent HD and who were treated by CMS (Colimycine) were included. Blood samples were collected between two consecutive HD sessions. CMS and colistin concentrations were measured by a specific chromatographic assay and were analyzed using a PK population approach (Monolix software). Monte Carlo simulations were conducted to predict the probability of target attainment (PTA). CMS nonrenal clearance was increased in ICU-HD patients. Compared with that of ICU patients included in the same clinical trial but with preserved renal function, colistin exposure was increased by 3-fold in ICU-HD patients. This is probably because a greater fraction of the CMS converted into colistin. To maintain colistin plasma concentrations high enough (>3 mg/liter) for high PTA values (area under the concentration-time curve for the free, unbound fraction of a drug [fAUC]/MIC of >10 and fAUC/MIC of >50 for systemic and lung infections, respectively), at least for MICs lower than 1.5 mg/liter (nonpulmonary infection) or 0.5 mg/liter (pulmonary infection), the dosing regimen of CMS should be 1.5 million international units (MIU) twice daily on non-HD days. HD should be conducted at the end of a dosing interval, and a supplemental dose of 1.5 MIU should be administered after the HD session (i.e., total of 4.5 MIU for HD days). This study has confirmed and complemented previously published data and suggests an a priori clear and easy to follow dosing strategy for CMS in ICU-HD patients.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Critical Illness; Drug Administration Schedule; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Lung; Male; Microbial Sensitivity Tests; Middle Aged; Renal Dialysis; Respiratory Tract Infections

Nephrotoxicity is the main adverse effect of colistin and polymyxin B (PMB). It is not clear whether these two antibiotics are associated with different nephrotoxicity rates. We compared the incidences of renal failure (RF) in patients treated with colistimethate sodium (CMS) or PMB for ≥48 h. A multicenter prospective cohort study was performed that included patients aged ≥18 years. The primary outcome was renal failure (RF) according to Risk, Injury, Failure, Loss, and End-stage renal disease (RIFLE) criteria. Multivariate analysis with a Cox regression model was performed. A total of 491 patients were included: 81 in the CMS group and 410 in the PMB group. The mean daily doses in milligrams per kilogram of body weight were 4.2 ± 1.3 and 2.4 ± 0.73 of colistin base activity and PMB, respectively. The overall incidence of RF was 16.9% (83 patients): 38.3% and 12.7% in the CMS and PMB groups, respectively (P< 0.001). In multivariate analysis, CMS therapy was an independent risk factor for RF (hazard ratio, 3.35; 95% confidence interval, 2.05 to 5.48;P< 0.001) along with intensive care unit admission, higher weight, older age, and bloodstream and intraabdominal infections. CMS was also independently associated with a higher risk of RF in various subgroup analyses. The incidence of RF was higher in the CMS group regardless of the patient baseline creatinine clearance. The development of RF during therapy was not associated with 30-day mortality in multivariate analysis. CMS was associated with significantly higher rates of RF than those of PMB. Further studies are required to confirm our findings in other patient populations.

Topics: Acute Kidney Injury; Adult; Age Factors; Aged; Aged, 80 and over; Anti-Bacterial Agents; Body Weight; Colistin; Drug Administration Schedule; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Intensive Care Units; Intraabdominal Infections; Kidney Failure, Chronic; Male; Middle Aged; Multivariate Analysis; Polymyxin B; Prospective Studies; Respiratory Tract Infections; Risk Factors; Survival Analysis

At the Shaare Zedek Medical Center, we have been using colistimethate sodium (CMS) for empiric as well as pathogen-directed treatment. We present our 10-year experience.. We conducted a retrospective case-series analysis of patients admitted from 1 January 2004 through 1 May 2014 who received at least one dose of CMS. Patient characteristics analysed for all admission for which patients received CMS, included: age, number of re-admissions, admission ward, renal function, disposition and microbiology results. Overall trend in defined daily dose (DDD) for CMS and resistant isolates was analysed.. A total of 5603 admissions met inclusion criteria. Patients' mean (±SD) age was 80 ± 14 years, 1162 (48%) of the admissions were from a healthcare facility and 4367 (78%) of the admissions were to general Internal Medicine wards. The median number of hospital admissions per patient was 5, median admission and discharge creatinine (mg/dl) were 1.05 and 1.01, respectively; 2.3% of admissions required first-time dialysis. The discharge rate from the hospital was 58.4%. Excluding intrinsically CMS-resistant gram-negative organisms, bloodstream and urine isolates were 98% and 100% susceptible, respectively. CMS use (DDDs) increased during the study (p for trend = 0.04) without significant increase in incidence of multidrug-resistant organisms.. Colistimethate sodium use at our institution has increased during this 10-year period. Nevertheless, there is no increasing trend in CMS-resistant organisms, 58% of the patients were discharged alive, and we did not observe significant nephrotoxicity in patients prescribed CMS. CMS should be reserved for microbiologically confirmed extensively drug-resistant gram-negative infections.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Colistin; Community-Acquired Infections; Cross Infection; Drug Resistance, Bacterial; Female; Gram-Negative Bacterial Infections; Hospitalization; Humans; Male; Microbial Sensitivity Tests; Respiratory Tract Infections; Retrospective Studies; Urinary Tract Infections

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

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

Selective decontamination of the digestive tract (SDD) and selective oropharyngeal decontamination (SOD) have been shown to improve intensive care unit (ICU) patients' outcomes. The aim of this study was to determine the effects of long-term use of SDD and SOD on colistin and tobramycin resistance among gram-negative bacteria.. We performed a post hoc analysis of two consecutive multicentre cluster-randomised trials with crossover of interventions. SDD and SOD were alternately but continuously used during 7 years in five Dutch ICUs participating in two consecutive cluster-randomised trials. In both trials, to measure colistin and tobramycin resistance among gram-negative bacteria, rectal and respiratory samples were obtained monthly from all patients present in the ICU.. The prevalence of tobramycin resistance in respiratory and rectal samples decreased significantly during long-term use of SOD and SDD. (rectal samples risk ratio (RR) 0.35 (0.23 to 0.53); respiratory samples RR 0.48 (0.32 to 0.73), SDD compared to standard care). Colistin resistance in rectal and respiratory samples did not change (rectal samples RR 0.63 (0.29 to 1.38); respiratory samples RR 1.26 (0.35 to 4.57), SDD compared to standard care).. In this study, in a setting with low antimicrobial resistance rates, the prevalence of resistance against colistin and tobramycin among gram-negative isolates did not increase during a mean of 7 years of SDD or SOD use.

Topics: Anti-Bacterial Agents; Colistin; Decontamination; Drug Resistance, Bacterial; Gastrointestinal Tract; Gram-Negative Bacteria; Humans; Intensive Care Units; Oropharynx; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Tobramycin

Recent studies suggested that high doses of colistin are necessary in the treatment of serious infections. However, few studies have evaluated such treatment. The objective of this study was to evaluate the effectiveness and nephrotoxicity of high-dose colistin in critically ill patients with respiratory infections associated with carbapenem-resistant Acinetobacter baumannii (CRAB).. This was a retrospective cohort study of critically ill cancer patients who received high-dose intravenous colistin for treatment of CRAB-related respiratory infections. Patients received colistimethate sodium 9 million IU/day or an equivalent dose, adjusted for renal function. Treatment effectiveness was evaluated by determining the microbiological clearance, recurrent and new CRAB-related infections, and mortality in the intensive care unit (ICU). Nephrotoxicity was defined according to the RIFLE (risk, injury, failure, loss, and end-stage kidney disease) criteria.. A total of 89 patients met the inclusion criteria. Microbiological clearance was observed in 51 (66.2%) subjects who had at least 2 follow-up cultures (n = 77). In patients who achieved microbiological clearance, recurrent and new CRAB-related infections occurred in 3 (5.9%) and 9 (17.6%) subjects, respectively. Fifty-seven patients (64%) died in the ICU. Thirty-five (39.3%) subjects developed nephrotoxicity according to the RIFLE criteria, which was classified as risk in 4 (11.4%) subjects, injury in 8 (22.8%) subjects, and failure in 21 (60%) subjects.. In critically ill cancer patients, high-dose colistin was associated with microbiological clearance in about two-thirds of the subjects with CRAB-related respiratory infections but mortality was high. A significant portion of patients developed nephrotoxicity while receiving colistin therapy.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Carbapenems; Colistin; Critical Illness; Drug Resistance, Bacterial; Female; Humans; Intensive Care Units; Male; Middle Aged; Neoplasms; Respiratory Tract Infections; Retrospective Studies; Treatment Outcome

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

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

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

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

For many respiratory infections caused by multidrug-resistant Gram-negative bacteria, colistin is the only effective antibiotic despite its nephrotoxicity. A novel inhaled combination formulation of colistin with a synergistic antimicrobial component of rifampicin was prepared via co-spray drying, aiming to deliver the drug directly to the respiratory tract and minimize drug resistance and adverse effects. Synergistic antibacterial activity against Acinetobacter baumannii was demonstrated for the combination formulation with high emitted doses (96%) and fine particle fraction total (FPFtotal; 92%). Storage of the spray-dried colistin alone formulation in the elevated relative humidity (RH) of 75% resulted in a substantial deterioration in the aerosolization performance because the amorphous colistin powders absorbed significant amount of water up to 30% by weight. In contrast, the FPFtotal values of the combination formulation stored at various RH were unchanged, which was similar to the aerosolization behavior of the spray-dried rifampicin-alone formulation. Advanced surface chemistry measurements by XPS and ToF-SIMS demonstrated a dominance of rifampicin on the combination particle surfaces, which contributed to the moisture protection at the elevated RH. This study shows a novel inhalable powder formulation of antibiotic combination with the combined beneficial properties of synergistic antibacterial activity, high aerosolization efficiency, and moisture protection.

Topics: Acinetobacter baumannii; Administration, Inhalation; Aerosols; Anti-Bacterial Agents; Colistin; Drug Combinations; Drug Synergism; Humans; Humidity; Mass Spectrometry; Microbial Sensitivity Tests; Particle Size; Photoelectron Spectroscopy; Powders; Respiratory Tract Infections; Rifampin

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

Nosocomial infections and their rational antibiotic treatment represent a major challenge for the healthcare nowadays. In this context, gramnegative bacteria including Pseudomonas aeruginosa, Acinetobacter baumanii and Enterobacteriaceae spp. are etiologically important and characterized by a significant level of antibiotic resistance. To examine dynamics of the respiratory tract colonization by hospital flora, tracheal aspirates obtained at three time points from 69 children with severe craniocerebral trauma during their stay in ICU were analysed. Colonization was observed on the 4th day of the ICU stay with predomination of K. pneumoniae (45%) and A. baumanii (27-37%). P. aeruginosa was detected after the 8th day of the ICU stay with the isolation rate of 33%. Substantial proportions of P. aeruginosa (61%), A. baumanii (78%) and K. pneumoniae (25%) were resistant to carbapenems. In 65 carbapemen resistant isolates, the presence of carbapenemases was examined using PCRs. OXA-48 carbapenemase was detected in 11 out of 14 (78%) K. pneumoniae isolates. Among the A. baumanii isolates, 30/31 (97%) carried OXA-40 and 1/31 (3%) had OXA-23 carbapenemases. None of the examined A. baumanii and K. pneumoniae isolates produced metallo-betalactamases (MBL). In contrast, all 20 carbapenem resistant P. aeruginosa isolates produced a MBL, and in 12 out of 20 (60%) of theme VIM-2 was detected. Thus, gramnegative nosocomial microflora rapidly colonizes ICU patients and has a high level of resistance to antibiotics, including carbapenems.

Topics: Acinetobacter baumannii; Aminoglycosides; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; beta-Lactams; Child; Colistin; Craniocerebral Trauma; Cross Infection; Drug Monitoring; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Gene Expression; Humans; Intensive Care Units, Pediatric; Klebsiella pneumoniae; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Respiratory Tract Infections; Trachea; Trauma Severity Indices

Following a bloodstream infection in June 2011 with Ralstonia mannitolilytica in a premature infant treated with a humidifying respiratory therapy device, an investigation was initiated at the Hadassah Medical Centres in Jerusalem. The device delivers a warmed and humidified mixture of air and oxygen to patients by nasal cannula. The investigation revealed colonisation with R. mannitolilytica of two of 15 patients and contamination of components of five of six devices deployed in the premature units of the Hadassah hospitals. Ten isolates from the investigation were highly related and indistinguishable from isolates described in an outbreak in 2005 in the United States (US). Measures successful in containing the US outbreak were not included in user instructions provided to our hospitals by the distributor of the device.

Topics: Anti-Bacterial Agents; Colistin; Disease Outbreaks; Disinfection; Drug Resistance, Bacterial; Equipment Contamination; Gram-Negative Bacterial Infections; Humans; Humidity; Infant, Newborn; Infant, Premature; Israel; Oxygen Inhalation Therapy; Ralstonia pickettii; Respiratory Tract Infections

In many respiratory infections caused by multi-drug-resistant Gram-negative bacteria, colistin is often the last-line drug for treatment despite its nephrotoxicity when administered parenterally. Inhalation therapy of colistin has great potential to improve the efficacy while reducing adverse effects. In this study, inhalable powder formulations of colistin (sulphate) were produced via spray drying. The colistin powders were found to have intact antimicrobial activity against Acinetobacter baumannii measured by broth micro-dilution. Both the raw material and spray-dried formulations were amorphous and absorbed significant amount of water up to 30% (w/w) at relative humidity (RH) of at least 70%. The spray-dried formulations were physically stable in the amorphous form at 60% RH and 25°C, having a high aerosol efficiency (emitted dose >86% and fine particle fraction total >83%) which remained unchanged after a 3-month storage. Storage at an elevated RH of 75% resulted in the aerosolisation performance significantly decreased, and at RH 90%, the formulation particles fused together (but without re-crystallisation). Although spray drying has been extensively used for generating inhalable drug particles, this is the first report that colistin powder can be physically stable in the amorphous form at ambient conditions, indicating that spray-drying approach is suitable for producing inhalable colistin powder formulation.

Topics: Acinetobacter baumannii; Administration, Inhalation; Aerosols; Chemistry, Pharmaceutical; Colistin; Drug Stability; Drug Storage; Dry Powder Inhalers; Humidity; Particle Size; Powders; Respiratory Tract Infections

Topics: Administration, Inhalation; Adult; Anti-Bacterial Agents; Bronchoalveolar Lavage Fluid; Colistin; Cystic Fibrosis; Humans; Lung Transplantation; Respiratory Tract Infections; Retrospective Studies; Treatment Outcome; Young Adult

Colistin methanesulfonate (CMS), the inactive prodrug of colistin, is administered by inhalation for the management of respiratory infections. However, limited pharmacokinetic data are available for CMS and colistin following pulmonary delivery. This study investigates the pharmacokinetics of CMS and colistin following intravenous (i.v.) and intratracheal (i.t.) administration in rats and determines the targeting advantage after direct delivery into the lungs. In addition to plasma, bronchoalveolar lavage (BAL) fluid was collected to quantify drug concentrations in lung epithelial lining fluid (ELF). The resulting data were analyzed using a population modeling approach in S-ADAPT. A three-compartment model described the disposition of both compounds in plasma following i.v. administration. The estimated mean clearance from the central compartment was 0.122 liters/h for CMS and 0.0657 liters/h for colistin. Conversion of CMS to colistin from all three compartments was required to fit the plasma data. The fraction of the i.v. dose converted to colistin in the systemic circulation was 0.0255. Two BAL fluid compartments were required to reflect drug kinetics in the ELF after i.t. dosing. A slow conversion of CMS (mean conversion time [MCTCMS] = 3.48 h) in the lungs contributed to high and sustained concentrations of colistin in ELF. The fraction of the CMS dose converted to colistin in ELF (fm,ELF = 0.226) was higher than the corresponding fractional conversion in plasma after i.v. administration. In conclusion, pulmonary administration of CMS achieves high and sustained exposures of colistin in lungs for targeting respiratory infections.

Topics: Animals; Anti-Bacterial Agents; Colistin; Lung; Male; Rats; Rats, Sprague-Dawley; Respiratory Tract Infections

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

Repeated isolation of multidrug-resistant Acinetobacter baumannii (MDRAB) from respiratory secretions poses a great challenge for infection control. We conducted a retrospective case-control study to evaluate the efficacy and adverse effect of inhaled colistin methanesulfonate (CMS) in the eradication of MDRAB from the respiratory tract. Patients who were admitted to Taipei Veterans General Hospital between February 2009 and June 2010, had at least two sets of monomicrobial culture of MDRAB from respiratory secretions, and remained in hospital for at least 14 days after the first isolation of MDRAB (index day) were included. Patients who received intravenous CMS were excluded. Patients who received CMS inhalation for ≥ 3 days were selected as cases whereas the controls were matched for age and Acute Physiology and Chronic Health Evaluation II score. Thirty-nine cases and controls were identified. The duration of CMS inhalation was 10.9 ± 3.6 days. The use of inhaled CMS was the only independent factor associated with the eradication of MDRAB within 14 days after the index day (OR 266.33; 95% CI 11.26-6302.18, p <0.001), and shortened the duration of MDRAB recovery from the respiratory tract by 13.3 ± 1.45 days. The adverse effects were similar for both groups. The increase of colistin minimal inhibitory concentrations in the last isolate compared with the index isolate from the same patient did not differ between the two groups. In conclusion, our study demonstrated that inhaled CMS enhanced the eradication of MDRAB from the respiratory tract without significant clinical adverse effect or impact on colistin resistance.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Aged; Aged, 80 and over; Anti-Bacterial Agents; APACHE; Case-Control Studies; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Respiratory Tract Infections; Retrospective Studies; Statistics, Nonparametric; Taiwan

This study describes and analyzes Acinetobacter baumannii antibiotic susceptibly profile in Aleppo, Syria, thus providing vital information for guiding treatment of A baumannii infections. Two hundred sixty nonrepetitive A baumannii isolates were studied over 3.5 years. Resistance rates are at the higher end of globally reported levels. Newer cephalosporins and β-lactamase-resistant agents are becoming practically ineffective. Better activity is limited to carbapenems and colistin, which elicited the highest susceptibility levels.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Anti-Bacterial Agents; Carbapenems; Child; Child, Preschool; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Infant; Microbial Sensitivity Tests; Prevalence; Respiratory Tract Infections; Retrospective Studies; Syria; Urinary Tract Infections; Young Adult

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

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

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

Antibiotic inhalation has become widely accepted as a standard treatment for cystic fibrosis (CF) airway infection. We assessed the prevalence and context of inhaled antibiotic use in the North American CF population. Our working hypothesis was that a shift from acute to chronic use of inhaled antibiotics has coincided with increased prevalence of use among CF patients.. Descriptive statistics were collected for 30,833 patients enrolled in the Epidemiologic Study of CF (ESCF) during 1996 through 2005. A multivariate analysis was performed on data from a subgroup of 18,021 patients enrolled in ESCF during 2003 through 2005.. The prevalence of inhaled antibiotic use in the North American CF population increased during 1996 through 2005 due to increased chronic use, while acute use to treat pulmonary exacerbations decreased. In 2005, 50% of CF patients used inhaled tobramycin and 9% used inhaled colistin chronically; most of the latter used both agents concurrently. Airway obstruction severity and airway infection status were predictors of inhaled antibiotic use.. Increased chronic use and decreased acute use of inhaled antibiotics presumably reflect a shift toward more proactive management of airway infections in the North American CF population. The effects of these usage patterns on long-term clinical outcomes and emergence of antibiotic-resistant Pseudomonas aeruginosa strains warrant further study.

Topics: Administration, Inhalation; Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Colistin; Cystic Fibrosis; Drug Utilization; Female; Humans; Male; Respiratory Tract Infections; Tobramycin

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

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

Topics: Anti-Bacterial Agents; Chronic Disease; Colistin; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Respiratory Tract Infections

Nonantimicrobial effects of antibiotics may contribute to their activity in the treatment of infective airway disease. The aim of this study was to identify antibiotics used for the treatment of infection in cystic fibrosis that may alter the activity of human neutrophil elastase (HNE) and Pseudomonas aeruginosa elastase (PE). The effect of antibiotics on the activity of purified HNE and PE, and HNE in sputum was assessed using colourimetric and fluorescent substrate assays by kinetic measurements, and by examining the interaction of HNE with inhibitors. Ceftazidime, tobramycin, and gentamycin slightly inhibited purified HNE activity whereas erythromycin and colistin significantly stimulated purified HNE and PE (395 and 557%, respectively). However, only colistin increased HNE activity in sputum (+102%) and was therefore studied in more detail. This increase in activity was not due an interference with the specific inhibition of HNE by alpha1-antitrypsin but colistin was found to reverse the inhibitory effects of small molecular weight molecules like heparin. Colistin increases the activity of human neutrophil elastase and Pseudomonas aeruginosa elastase, two proteases that contribute to the pathogenesis of cystic fibrosis airway disease.

Topics: Adolescent; Adult; alpha 1-Antitrypsin; Amino Acid Chloromethyl Ketones; Anti-Bacterial Agents; Anticoagulants; Bacterial Proteins; Ceftazidime; Child; Colistin; Cystic Fibrosis; Enzyme Activation; Erythromycin; Female; Gentamicins; Heparin; Humans; In Vitro Techniques; Leukocyte Elastase; Male; Metalloendopeptidases; Respiratory Tract Infections; Serine Proteinase Inhibitors; Sputum; Tobramycin

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

We report the results of a prophylactic regime designed to prevent endogenous colonization and infection of the lower airways by Gram-negative bacilli. The 27 study patients spent an average of 30 days (range 11 to 84) in the respiratory ICU, during which time they were on mechanical ventilation. Within 3 days of application of 2% polymyxin E and tobramycin in an adhesive paste to the buccal mucosa, the oral cavity of each patient was free of Gram-negative bacilli, and subsequently, no patient developed tracheal aspirates containing Gram-negative bacilli, and no study patient developed nosocomial pneumonia.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Colistin; Drug Therapy, Combination; Female; Gram-Negative Bacteria; Humans; Male; Middle Aged; Pneumonia; Prospective Studies; Respiration, Artificial; Respiratory System; Respiratory Tract Infections; Tobramycin

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

Topics: Administration, Oral; Adolescent; Adult; Anti-Bacterial Agents; Child; Colistin; Cystic Fibrosis; Gentamicins; Humans; Infusions, Parenteral; Outpatient Clinics, Hospital; Pseudomonas aeruginosa; Respiratory Function Tests; Respiratory Tract Infections; Staphylococcus

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

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

Topics: Colistin; Culture Media; Elasticity; Respiratory Tract Infections; Serratia marcescens; Sputum

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Cephaloridine; Chloramphenicol; Colistin; Erythromycin; Escherichia coli; Female; Gentamicins; Humans; Kanamycin; Lincomycin; Male; Meningitis; Microbial Sensitivity Tests; Middle Aged; Novobiocin; Penicillins; Radiography; Respiratory Tract Infections; Sepsis; Staphylococcus; Streptococcus; Streptomycin; Sulfonamides; Tetracycline; Urinary Tract Infections

Topics: Anti-Bacterial Agents; Colistin; Cross Infection; Disease Outbreaks; Humans; Intensive Care Units; Klebsiella; Klebsiella Infections; Meningitis; Neurosurgery; Respiratory Tract Infections; Sputum; Urinary Tract Infections

High doses of colistin were used in the treatment of severely ill patients with refractory klebsiella chest and urinary tract infections. At the same time renal function was monitored to determine possible nephrotoxicity. In all patients it produced acute renal failure and in some acute tubular necrosis. Though renal failure contributed to the final cause of death in some cases, in the majority death was due to the primary neurological illness.

Topics: Acute Kidney Injury; Adult; Aged; Colistin; Creatinine; Female; Humans; Kidney; Kidney Function Tests; Klebsiella Infections; Male; Metabolic Clearance Rate; Middle Aged; Respiratory Tract Infections; Urea; Urinary Tract Infections

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

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

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

Topics: Colistin; Drug Therapy; Humans; Penicillins; Respiratory Tract Infections

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

Topics: Bronchitis; Colistin; Humans; Penicillins; Respiratory Tract Infections