Incidence and predictors of acute kidney injury associated with intravenous polymyxin B therapy

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Summary

Background

Increases in multidrug-resistance among gram-negative organisms have necessitated the use of polymyxins. To date, the incidence of acute kidney injury (AKI) associated with polymyxin B has not been evaluated using RIFLE criteria.

Methods

Adult patients who received polymyxin B were retrospectively evaluated to determine the incidence of AKI during polymyxin B therapy using RIFLE criteria. Predictors of AKI were identified by comparing characteristics of patients with and without AKI.

Results

A total of 73 patients were included. The incidence of AKI was 60%. Ten (14%) patients discontinued therapy due to nephrotoxicity. Median duration of polymyxin B was 11 days with a median cumulative dose of 18 mg/kg. Concomitant nephrotoxins were received in 69 (95%). Patients with AKI had a higher median cumulative dose (1578 mg vs. 800 mg; p = 0.02), a higher body mass index (BMI) (27.2 vs. 24.5 kg/m2; p = 0.03), and were more likely to receive vancomycin (82% vs. 55%; p = 0.03) compared to those without AKI. After controlling for polymyxin B duration, independent predictors of AKI were higher BMI and concomitant vancomycin.

Conclusions

The incidence of AKI during polymyxin B therapy was 60%. Further studies are needed to define dosing parameters that maximize efficacy and minimize nephrotoxicity.

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.

Section snippets

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.

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