The identification and characterization of acute kidney injury (AKI) associated with systemic polymyxins in the management of severe gram-negative infections
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Background The global rise in antibiotic resistance has led to an increased need for effective antimicrobial treatments. Polymyxins have re-emerged in recent years due to their strong antimicrobial activity against resistant gram-negative pathogens. However, there is concern of renal toxicity associated with the use of polymyxins. This study aims to assess the frequency of occurrence of acute kidney injury (AKI) in the context of incident use of intravenous (IV) polymyxin E (sodium colistimethate; CMS) or IV polymyxin B (PMB), and subsequent mortality, healthcare resource utilization and total hospitalization costs associated with AKI, separately for patients receiving CMS or PMB. Methods A retrospective cross-sectional database analysis using Premier was conducted from January 1, 2012 and September 30, 2015. Patients were included if they were ≥18 years of age with incident treatment of CMS or PMB for ≥3 consecutive days (defined as the index admission). Patients with polymyxin use in the previous six months were excluded. Patients with cystic fibrosis or who received both CMS and PMB during the same admission were excluded. The last admission included was on August 31, 2015, allowing for a 30-day follow-up period. Outcome variables included frequency of AKI occurrence, mortality, healthcare utilization and total hospitalization costs during the index admission, and hospital re-admissions occurring within a 30-day period following discharge for the index admission. Descriptive statistics were used to summarize patient characteristics. Bivariate statistics were used to compare healthcare utilization, costs and readmissions in patients who did and did not experience AKI during the index admission. A multivariable logistic regression was conducted to determine the association between AKI during the index admission and mortality. All analyses were stratified by type of polymyxin (CMS or PMB). Results A total of 4,886 patients with incident use of a polymyxin were included; 4,103 patients received CMS and 783 received PMB. The frequency of occurrence of AKI was 31% in the CMS cohort and 27% in the PMB cohort. In the multivariable analysis, the presence of AKI during the index admission was associated with significantly higher mortality in both the CMS cohort (OR 2.26; 95% Confidence Interval (CI) 1.92 to 2.66; p<0.001) and the PMB cohort (OR 2.73; 95% CI 1.81 to 4.12; p<0.001). In both cohorts, patients who experienced AKI had longer hospital stays, more transfers to the ICU, and more days spent in the ICU compared to those who did not experience AKI (p<0.001 for each outcome). The presence of AKI during the index admission was significantly associated with 30-day readmission in the CMS cohort (p<0.001), but not in the PMB cohort (p=0.86). Mean total hospitalization costs for patients in the CMS cohort who experienced AKI were $42,653 higher than for patients who did not experience AKI (95% CI $34,566 to $50,749; p<0.001). Mean total hospitalization costs for patients in the PMB cohort who experienced AKI were $32,978 higher than for patients that did not experience AKI (95% CI $13,926 to $52,030; p<0.001). Conclusions In both CMS and PMB cohorts, frequency of AKI occurrence, mortality, healthcare utilization, and mean total hospitalization costs were significantly higher in patients who experienced AKI during incident use of polymyxin.
- Pharmaceutics