A Retrospective Cohort Analysis Shows that Coadministration of Minocycline with Colistin in Critically Ill Patients Is Associated with Reduced Frequency of Acute Renal Failure

作者：Lodise Thomas P.^*; Fan Weihong; Griffith David C.; Dudley Michael N.; Sulham Katherine A.^*

来源：Antimicrobial Agents and Chemotherapy, 2018, 62(1): e01165-17.

DOI：10.1128/AAC.01165-17

• multidrug resistance
• acute renal failure
• nephrotoxicity
• minocycline
• colistin

Nonclinical studies have suggested that oxidative damage, caspase-mediated apoptosis, and inducible nitric oxide synthase levels may be involved in the pathogenesis of colistin (CST)-associated acute renal failure. MIN inhibits caspase 1, caspase 3, and inducible nitric oxide synthase, leading to the hypothesis that coad-ministration of CST with MIN (CST-MIN) may reduce the incidence of acute renal failure as well as produce additive or synergistic antimicrobial effects. 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 as follows: age of >= 18 years, intensive care unit admission at CST initiation, primary International Classification of Diseases 9 (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 than CST (11.8% versus 23.7%, P = 0.007). Similar results were seen in propensity score matching (12.0% versus 22.3%, P = 0.031) and logistic regression analyses (odds ratio of 0.403, P = 0.006). Mortalities and 30-day readmission rates were similar between groups. The 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 of this combination in prospective clinical studies is warranted.

• 出版日期2018-1