Association Between Colistin Dose and Microbiologic Outcomes in Patients With Multidrug-Resistant Gram-Negative Bacteremia

Background. Colistin is increasingly used for the treatment of multidrug-resistant gram-negative infections. However, colistin dosing varies greatly and the optimal regimen is unknown. The purpose of this study was to determine if colistin dosing correlates with patient outcomes. Methods. This retro...

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Bibliographic Details
Published in:	Clinical infectious diseases Vol. 56; no. 3; pp. 398 - 404
Main Authors:	Vicari, Giulia, Bauer, Seth R., Neuner, Elizabeth A., Lam, Simon W.
Format:	Journal Article
Language:	English
Published:	Oxford Oxford University Press 01-02-2013
Subjects:	Anti-Bacterial Agents - administration & dosage Anti-Bacterial Agents - adverse effects Antibacterial agents Antibiotics. Antiinfectious agents. Antiparasitic agents Antimicrobials ARTICLES AND COMMENTARIES Bacteremia Bacteremia - drug therapy Bacteremia - microbiology Bacterial diseases Bacterial infections Bacterial sepsis Biological and medical sciences Blood Clinical outcomes Colistin Colistin - administration & dosage Colistin - adverse effects Dosage Dose-Response Relationship, Drug Drug dosages Drug resistance Drug Resistance, Multiple, Bacterial - drug effects Female Gram-negative bacteria Gram-Negative Bacteria - isolation & purification Gram-Negative Bacterial Infections - drug therapy Gram-Negative Bacterial Infections - microbiology Health outcomes Human bacterial diseases Humans Infection Infections Infectious diseases Injections, Intravenous Intravenous administration Male Medical sciences Microbiology Middle Aged Mortality Nephrotoxicity Patients Pharmacology. Drug treatments Renal function Retrospective Studies Sepsis Treatment Outcome Human Prognosis Colistin Cyclic peptides Bacteremia Infection Antibiotic Polypeptide Multiple resistance Bacteriosis Antibacterial agent Dose Gram negative bacteria
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Summary:	Background. Colistin is increasingly used for the treatment of multidrug-resistant gram-negative infections. However, colistin dosing varies greatly and the optimal regimen is unknown. The purpose of this study was to determine if colistin dosing correlates with patient outcomes. Methods. This retrospective study included patients with gram-negative bacteremia treated with intravenous colistin for at least 72 hours. The primary objective was to determine if colistin dose (mg of colistin base activity/kg/day) independently predicts day-7 microbiological success. Secondary objectives included evaluation for an association between colistin dose and 7-day mortality, 28-day mortality, and the development of acute kidney insufficiency (AKI). Results. Seventy-six patients were included in the analysis, with 52 patients (68%) achieving 7-day microbiological success. The median colistin dose was significantly higher in patients who achieved microbiological success (2.9 vs 1.5 mg/kg/day; P = .011). After adjusting for baseline severity of illness and concomitant tigecyline use, higher colistin dose independently correlated with microbiological success (adjusted odds ratio per 1 mg/kg/day = 1.74; 95% confidence interval, 1.11–2.71; P = .015). The median colistin dose was also significantly higher among survivors at day 7 (2.7 vs 1.5 mg/kg/day; P = .007). However, no difference was observed in colistin dose when comparing survivors and nonsurvivors at day 28. A significantly higher colistin dose was given to patients who developed AKI during therapy (3.8 vs 1.6 mg/kg/day; P < .001). Conclusions. Higher colistin dose independently predicted microbiological success, which may partially explain the similar association with 7-day mortality. However, higher colistin doses may also precipitate worsening renal function.
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ISSN:	1058-4838 1537-6591
DOI:	10.1093/cid/cis909