Incidence and predictors of acute kidney injury associated with intravenous polymyxin B therapy
Introduction
Polymyxins comprise a drug class originally developed in the 1940s that fell out of favor in the 1980s, in large part due to nephrotoxicity.1 Recent emergence of multidrug-resistant (MDR) gram-negative organisms has necessitated their increased use as they are often the only, or one of a few options, to which these organisms are susceptible.2 Polymyxins are available as colistin (polymyxin E) and polymyxin B. Both forms have the same mechanism of action, antimicrobial activity and spectra, but differ somewhat in their amino acid structural components, potency, and pharmacokinetics.3
Several studies have examined the nephrotoxicity of colistin since its re-establishment as a common treatment option for MDR gram-negative infections. Three of these use the RIFLE (Risk, Injury, Failure, Loss, and End-stage kidney disease) criteria, a well-validated tool for classifying renal dysfunction and acute kidney injury (AKI), in an attempt to standardize definitions of nephrotoxicity and allow for comparison.4, 5, 6, 7, 8 These studies found rates of AKI with colistin to be 43–54%.6, 7, 8 To our knowledge, no studies have examined the rates of nephrotoxicity associated with polymyxin B using the RIFLE criteria. Current literature published on this topic report nephrotoxicity rates of 4–55% with polymyxin B, however various definitions of nephrotoxicity were used.9, 10, 11, 12, 13, 14, 15
While many institutions use colistin, there are also institutions utilizing polymyxin B. We sought to describe the incidence of AKI as defined by the RIFLE criteria, as well as identify predictors of its development in patients receiving intravenous polymyxin B.
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Study design, setting, patient population
A retrospective cohort study was performed at New York-Presbyterian Hospital, a 2000+ bed tertiary care medical center in New York City comprised of two main campuses, Columbia University Medical Center and Weill Cornell Medical Center. Patients ≥ 18 years old who received intravenous polymyxin B therapy for at least 3 days from January to December 2010 were included. They were identified as having received intravenous polymyxin B from pharmacy dispensing records. Patients were excluded if they
Results
A total of 73 patients met the inclusion and exclusion criteria and were included in the analysis. The mean age of the cohort was 58 years and the majority (55%) were men. The median Charlson Comorbidity Index was 3 (IQR 1–4) with the most common underlying illnesses being pulmonary disease (38%), diabetes mellitus (33%), and cardiovascular disease (30%). The cohort also included solid organ transplant recipients (15%), patients with malignancies (14%), and HIV-infected patients (4%). Almost
Discussion
To our knowledge this is the first study to report the incidence and predictors of polymyxin B nephrotoxicity utilizing the definitions of acute renal failure outlined by the RIFLE criteria. A summary of published studies reporting on the incidence of nephrotoxicity in patients receiving polymyxin B since publication of this standardized classification system in 2004 are summarized in Table 4. It is well known that the polymyxins are associated with nephrotoxicity but interpretation of previous
Acknowledgments
The authors wish to acknowledge Jimmy Duong, MPH for his assistance with the statistical analysis. His assistance was provided through the Irving Institute for Clinical and Translational Research supported by Grant Number UL1 RR024156 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research, and its contents are solely the responsibility of the authors and do not necessarily represent the official view of
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At time of research, affiliation: Department of Pharmacy, New York-Presbyterian Hospital, 622 W 168th St, New York, NY 10032.