Intravenous polymyxin B for the treatment of nosocomial pneumonia caused by multidrug-resistant Pseudomonas aeruginosa (original) (raw)
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Polymyxin B versus other antimicrobials for the treatment of Pseudomonas aeruginosa bacteraemia
Journal of Antimicrobial Chemotherapy, 2011
To compare the efficacy of intravenous polymyxin B with other antimicrobials in the treatment of nosocomial Pseudomonas aeruginosa bacteraemia, assessing many potential confounding factors, including optimal dosage regimens of drugs. Methods: A retrospective cohort study was performed. Patients ≥18 years of age and who received appropriate therapy for ≥48 h for P. aeruginosa bacteraemia were analysed. Clinical covariates were assessed and compared between patients treated with polymyxin B and other drugs (comparators). Data were retrieved from medical records. Renal toxicity was also assessed. A Cox regression model was performed including variables with a P ≤0.20 in the comparison between both groups. Results: A total of 133 patients were included: 45 (33.8%) treated with polymyxin B and 88 (66.2%) with comparators. Most comparators (83.0%) were b-lactams. The overall in-hospital mortality was 41.4% (55/133): 66.7% (30/45) and 28.4% (25/88) in polymyxin B and comparator groups, respectively (P≤ 0.001). The final multivariate model showed that treatment with polymyxin B was independently associated with in-hospital mortality (adjusted hazard ratio 1.91, 95% confidence interval 1.05-3.45), after adjustment for Pitt bacteraemia score, and the presence of mechanical ventilation and primary bloodstream infection. Patients treated with polymyxin B presented a higher rate of ≥100% increase in creatinine level from baseline than comparators [11/45 (24.4%) versus 4/88 (4.5%); P ¼ 0.002], although this was not subjected to multivariate analysis. Conclusions: Intravenous polymyxin B therapy was inferior to other drugs in the treatment of P. aeruginosa bacteraemia, as indicated by the higher rate of in-hospital mortality.
Antimicrobial Agents and Chemotherapy, 2015
There is no clinical evidence supporting the use of polymyxin B in combination with another antimicrobial for infections caused by extensively drug-resistantAcinetobacter baumanniiorPseudomonas aeruginosaisolates. We developed a cohort study of patients in two intensive care units from teaching hospitals to evaluate treatment with intravenous polymyxin B for ≥48 h for severeA. baumanniiorP. aeruginosainfections. Covariates potentially associated with 30-day mortality were evaluated in a Cox proportional hazards model. A total of 101 patients were included; 33 (32.7%) were treated with polymyxin B in combination with an antimicrobial lackingin vitroactivity and 68 (67.3%) with polymyxin B in monotherapy. The overall 30-day mortality was 59.4% (60 patients), comprising 42.4% (14 of 33) and 67.6% (46 of 68) in combination and monotherapy groups, respectively (P= 0.03). The mortality rates were 18.5/1,000 patient days and 36.4/1,000 patient days in the combination and monotherapy groups...
European Journal of Clinical Microbiology & Infectious Diseases, 2005
Multidrug-resistant strains of Pseudomonas aeruginosa have become increasingly problematic in certain hospitals. For a 3-month period in 2001, all unique patient isolates were collected from 15 hospitals in Brooklyn, New York, USA. Of 691 isolates, only 70% were susceptible to imipenem and 56% to ciprofloxacin. These susceptibility rates were lower than those found in a prior surveillance study in 1999 (76% and 71% susceptible to imipenem and ciprofloxacin, respectively; p<0.001). The rate of imipenem resistance was associated with fluoroquinolone usage at each hospital (p=0.04). All isolates were susceptible to polymyxin B and 95% to amikacin. Among 195 imipenem-resistant isolates, 47 unique ribotypes were found. However, four ribotypes accounted for >50% of isolates and were shared by most hospitals. Time-kill studies with 13 unique multiresistant strains revealed that polymyxin B was bactericidal against all strains at 4 mg/l, but only against 3 of 13 (23%) strains at 2 mg/l. Using 2 mg/l, significant bacterial regrowth was evident for 5 of 13 (38%) strains. The addition of azithromycin to polymyxin B (2 mg/l) produced a mean decrease of 1 log cfu/ml greater than polymyxin alone and allowed bacterial regrowth in only 2 of 13 (15%) strains. Multiresistant P. aeruginosa is highly endemic to this city, with a few strains having spread among most hospitals. Polymyxin B remains active against all isolates and produces concentration-dependent killing in vitro. Azithromycin appears to enhance the in vitro activity of polymyxin B. The clinical utility of this combination remains to be established.
International Journal of Antimicrobial Agents, 2011
The emergence of multidrug-resistant (MDR) strains has made it difficult to treat infections caused by Pseudomonas aeruginosa. In order to develop new alternative therapies for the treatment of MDR P. aeruginosa infections, the antimicrobial activities of different antibiotic combinations have been studied in vitro and in vivo. In this study, the in vitro antimicrobial activities of six different combinations of polymyxins and -lactams against 34 clinical isolates of P. aeruginosa were evaluated. For the combinations tested by the checkerboard method, an indifferent effect was observed for all strains. However, 27 strains (19 MDR) showed reductions in their minimal inhibitory concentration (MIC) for at least one of the antibiotics in the combinations evaluated. Combination with polymyxins resulted in reductions of the -lactam MICs, with a change in the resistance category to susceptible in eight MDR strains. These results from the in vitro evaluation suggest that combinations of polymyxins and -lactams may significantly reduce the MICs of the antibiotics tested. These combinations require further evaluation for use in medical practice.
Infection, 2012
Purpose This study was designed to compare the efficacy of polymyxin B with other antimicrobials in the treatment of ventilator-associated pneumonia (VAP) and tracheobronchitis (VAT) by Pseudomonas aeruginosa or Acinetobacter baumannii. Methods A prospective cohort study was performed. Patients [18 years of age with the diagnosis of VAP or VAT who received appropriate therapy for [48 h were analyzed. The primary outcome was 30-day mortality. Clinical covariates were assessed and compared between the groups. Results A total of 67 episodes were analyzed: 45 (67 %) treated with polymyxin B and 22 (33 %) with comparators. The crude 30-day mortality was 53 % (24 of 45) in the polymyxin B group and 27 % (6 of 22) in the comparator group (P = 0.08). Multivariable analysis using Cox regression models indicated that polymyxin B treatment was independently associated with increased mortality. Conclusions Polymyxin B treatment in the currently recommended dosage may be inferior to other drugs in the treatment of VAP and VAT caused by organisms tested as susceptible in vitro to this agent.
The Journal of Critical Care Medicine
Introduction Critically ill patients in intensive care units are at high risk of dying not only from the severity of their illness but also from secondary causes such as hospital-acquired infections. USA national medical record-data show that approximately 10% of patients on mechanical ventilation in an intensive care unit developed ventilator-associated pneumonia. Polymyxin B has been used intravenously in the treatment of multi-drug resistant gram-negative infections, either as a monotherapy or with other potentially effective antibiotics, and the recent international guidelines have emphasised the use of nebulised polymyxin B together with intravenous polymyxin B to gain the optimum clinical outcome in ventilator-associated pneumonia cases caused by multi-drug resistant gram-negative infections. Methods One hundred and seventy-eight patients with ventilator-associated pneumonia due to multi-drug resistant K. pneumoniae were identified during the study period. Following the inclus...
Pharmacodynamics of Polymyxin B against Pseudomonas aeruginosa
Antimicrobial Agents and Chemotherapy, 2005
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Aerosolized Polymyxin-E For The Treatment Of Multidrug Resistant Respiratory Tract Infections
Background: Bacterial Pneumonia caused by multidrug resistant gram negative organisms were successfully treated with nebulized colistimethate sodium. The mainstay of therapy deals with early and vigorous antibiotic treatment to prevent further deterioration. An important consideration is to identify the causative organism and recognize the resistance pattern so as to optimize antimicrobials. Intravenous administration of antibiotics do not provide sufficient concentration of the drug to the lung tissues for underlying infection to be treated. Nebulizing certain antibiotics, accomplishing therapeutic concentration at the lung tissues provide promising effect in eradicating the pathogenic organism. Materials and methods: In order to trace the efficacy of nebulization, a retrospective observational study was done with 53 inpatients including three neonates who required colistimethate nebulization. Medical records were accessed using pharmacy databases based on patient who received colistin 1 MIU. We excluded those patients whose dose was adjusted on the basis of renal impairment or administered intrathecally. Results: The most common organisms causing pneumonia were Klebsiella pneumoniae 42 (32.5%), Acinetobacter baumannii 35 (27.1%) and Pseudomonas aeruginosa 32 (24.8%). 82.8% Acinetobacter baumannii, 69% Klebsiella pneumoniae, 28.5% Escherichia coli, and 28.1% Pseudomonas aeruginosa were resistant tocarbapenems, requiring Polymyxin therapy. Nebulized colistin was considered as a therapeutic option after failure of available broad spectrum antibiotic or the documentation of Carbapenemase producing multidrug resistant pathogen. About 14/22 (63.6%) of Multi Drug Sensitive (MDS) organism and 26/37 of Extensive Drug Resistant (XDR) organism had cure at day 7 of nebulization with Polymyxin E. Conclusion: Most of the XDR organisms like Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii required more than 7 days of nebulization or an add-on with another anbtibiotic. We conclude that nebulization with higher dose of Polymyxin E is an effective therapy for multidrug resistant gram negative organisms.
1975
Surgical Intensive Care Unit (RSICU) were included in a prospective study of the effects of a polymyxin (2.5 mg/kg body wt/day in six divided doses) or a placebo aerosol sprayed into the posterior pharynx and tracheal tube (if present), during 11 alternating 2-mo treatment cycles. The incidence of upper airway colonization in the RSICU with Pseudomonas aeruginosa was 1.6% during the polymyxin treatment cycles (total 374 patients) and 9.7% during the placebo cycles (370 patients) (xi = 23.2, P < 0.01). 3 patients in the RSICU acquired Pseudomonas pneumonia, as defined by independent "blinded" assessors, during the polymyxin cycles while 17 acquired a Pseudomonas pneumonia during the placebo cycles (x' = 10.2, P < 0.01). The overall mortality was similar in both placebo and polymyxintreated groups (12.2 vs. 12.0%). Systemic antibiotic usage was similar in the different cycles; 49% of patients in the placebo and 53% in the polymyxin-treated groups received systemic antibiotics while in the RSICU.