title: Colistin combination therapy improves microbiologic cure in critically ill patients with multi-drug resistant gram-negative pneumonia.
abstract: Currently, in vitro synergy with colistin has not translated into improved clinical outcomes. This study aimed to compare colistin combination therapy to colistin monotherapy in critically ill patients with multi-drug resistant gram-negative (MDR-GN) pneumonia. This was a retrospective analysis of critically ill adult patients receiving intravenous colistin for MDR-GN pneumonia comparing colistin combination therapy to colistin monotherapy with a primary endpoint of clinical cure. Combination therapy was defined by administration of another antibiotic to which the MDR-GN pathogen was reported as susceptible or intermediate. Ninety patients were included for evaluation (41 combination therapy and 49 monotherapy). Baseline characteristics were similar between groups. No difference in clinical cure was observed between combination therapy and monotherapy in univariate analysis, nor when adjusted for APACHE II score and time to appropriate antibiotic therapy (57.1 vs. 63.4 %, adjusted OR 1.15, p = 0.78). Microbiological cure was significantly higher for combination therapy (87 vs. 35.5 %, p < 0.001). Colistin combination therapy was associated with a significant improvement in microbiological cure, without improvement in clinical cure. Based on the in vitro synergy and improvement in microbiological clearance, colistin combination therapy should be prescribed for MDR-GN pneumonia. Further research is warranted to determine if in vitro synergy with colistin translates into improved clinical outcomes.
authors.affiliation: Department of Pharmacy, Franciscan Healthcare - Munster, Munster, IN, USA.
authors.forename: N L
authors.initials: NL
authors.lastname: Parchem
authors.affiliation: Department of Pharmacy, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Bauer
authors.affiliation: Department of Surgery, Beth Israel Deaconess Medical Center / Harvard Medical School, Boston, MA, USA.
authors.forename: C H
authors.initials: CH
authors.lastname: Cook
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.|Clinical Epidemiology, The Ohio State University, Columbus, OH, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Mangino
authors.affiliation: Johns Hopkins Medical Center, Baltimore, MD, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Jones
authors.affiliation: Center for Biostatistics, The Ohio State University, Columbus, OH, USA.
authors.forename: K
authors.initials: K
authors.lastname: Porter
authors.affiliation: Department of Pharmacy, The Ohio State University Wexner Medical Center, Columbus, OH, USA. claire.murphy@osumc.edu.
authors.forename: C V
authors.initials: CV
authors.lastname: Murphy
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D003091:Colistin / Q000627:therapeutic use*; D016638:Critical Illness; D024901:Drug Resistance, Multiple, Bacterial; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D003091:Colistin