Coadministration of Minocycline with Colistin in Critically Ill Patients Is Associated with Reduced Frequency of Acute Renal Failure: A Retrospective Cohort Analysis.
Antimicrob Agents Chemother. 2017 Oct 16;:
Authors: Lodise TP, Fan W, Griffith DC, Dudley MN, Sulham KA
Nonclinical studies have suggested oxidative damage, caspase-mediated apoptosis, and inducible nitric oxide synthase levels may be involved in the pathogenesis of colistin (CST)-associated acute renal failure. Synergistic antibacterial activity of minocycline (MIN) with polymyxins has been demonstrated in vitro, and MIN inhibits caspase 1, caspase 3, and inducible nitric oxide synthase, leading to the hypothesis that coadministration of CST with MIN (CST-MIN) may reduce incidence of acute renal failure. A multicenter retrospective cohort study was conducted using the Premier Research database to examine the impact of CST-MIN on acute renal failure. Inclusion criteria were: age ≥18 years, intensive care unit admission at CST initiation, primary International Classification of Diseases (ICD)-9 diagnosis of pneumonia or sepsis, non-dialysis at hospital admission, and discharge between January 2010 and December 2015. ICD-9 code 584.XX or ICD-10 code N17 was used to define acute renal failure. Baseline comparisons, 1:8 propensity score matching, and confirmatory logistic regression analyses were conducted. In total, 4,817 patients received CST and met inclusion criteria; 93 received CST-MIN. Unadjusted frequency of acute renal failure was significantly lower in patients receiving CST-MIN versus CST (11.8% vs. 23.7%, P = 0.007). Similar results were seen in propensity score matching (12.0% vs. 22.3%, P = 0.031) and logistic regression analyses (odds ratio 0.403, P = 0.006). Mortality and 30-day readmission rates were similar between groups. Acute renal failure rate was not impacted by prevalence of baseline renal disease. CST-MIN in critically ill patients may reduce CST-associated acute renal failure. Further evaluation in prospective clinical studies is warranted.
PMID: 29038261 [PubMed - as supplied by publisher]