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Polymyxin B nephrotoxicity and efficacy against nosocomial infections caused by multiresistant gram-negative bacteria
John P Ouderkirk1, Jill A Nord, Glenn S Turett
1Section of Infectious Diseases, Department of Medicine, Saint Vincent's Hospital--Manhattan, New York, New York 10011, USA.
Abstract:
Reported rates of nephrotoxicity associated with the systemic use of polymyxins have varied widely. The emergence of infections due to multiresistant gram-negative bacteria has necessitated the use of systemic polymyxin B once again for the treatment of such infections. We retrospectively investigated the rate of nephrotoxicity in patients receiving polymyxin B parenterally for the treatment of infections caused by multiresistant gram-negative bacteria from October 1999 to September 2000. Demographic and clinical information was obtained for 60 patients. Outcome measures of interest were renal toxicity and clinical and microbiologic efficacy. Renal failure developed in 14% of the patients, all of whom had normal baseline renal function. Development of renal failure was independent of the daily and cumulative doses of polymyxin B and the length of treatment but was significantly associated with older age (76 versus 59 years, P = 0.02). The overall mortality was 20%, but it increased to 57% in those who developed renal failure. The organism was cleared in 88% of the patients from whom repeat specimens were obtained. The use of polymyxin B to treat multiresistant gram-negative infections was highly effective and associated with a lower rate of nephrotoxicity than previously described.
Insights
Systemic polymyxin B effectively treats multiresistant gram-negative infections. While 14% of patients experienced nephrotoxicity, it was linked to older age, not drug dosage, suggesting a safer profile than previously reported.
Area of Science:
- Infectious Diseases
- Nephrology
- Pharmacology
Background:
- Polymyxins, including polymyxin B, are crucial for treating infections caused by multidrug-resistant gram-negative bacteria.
- Previous studies reported variable rates of nephrotoxicity with systemic polymyxin use.
- The re-emergence of multidrug-resistant infections necessitates a clear understanding of polymyxin B's safety profile.
Purpose of the Study:
- To retrospectively investigate the incidence of nephrotoxicity in patients receiving parenteral polymyxin B.
- To evaluate the clinical and microbiologic efficacy of polymyxin B in treating infections caused by multidrug-resistant gram-negative bacteria.
- To identify factors associated with the development of renal toxicity.
Main Methods:
- Retrospective analysis of 60 patients treated with parenteral polymyxin B from October 1999 to September 2000.
- Collection of demographic and clinical data, including baseline renal function, daily and cumulative drug doses, and treatment duration.
- Assessment of renal toxicity, clinical outcomes, microbiologic clearance, and mortality.
Main Results:
- Nephrotoxicity, defined as renal failure, occurred in 14% of patients, all with normal baseline renal function.
- Development of renal failure was significantly associated with older age (76 vs. 59 years; P = 0.02) and independent of drug dosage or treatment duration.
- Overall mortality was 20%, increasing to 57% in patients who developed renal failure. Microbiologic clearance was achieved in 88% of patients.
Conclusions:
- Systemic polymyxin B is highly effective for treating multidrug-resistant gram-negative bacterial infections.
- The observed rate of nephrotoxicity (14%) is lower than previously described in the literature.
- Older age is a significant risk factor for polymyxin B-induced nephrotoxicity, while dosage and duration do not appear to be.
- Polymyxin B remains a valuable therapeutic option for challenging infections, with careful patient selection advised.