title: Beta-lactam and fluoroquinolone combination antibiotic therapy for bacteremia caused by gram-negative bacilli.
abstract: The role of combination antibiotic therapy with a beta-lactam and a fluoroquinolone for bacteremia caused by gram-negative bacilli, to our knowledge, has not been previously described. Much of the previous study of combination therapy has included beta-lactams and aminoglycosides. We conducted a large retrospective cohort study to evaluate 28-day all-cause mortality in patients with monomicrobial bacteremia due to aerobic gram-negative bacilli who received either a combination of beta-lactams and fluoroquinolones or beta-lactam monotherapy. We enrolled adult patients admitted to Mayo Clinic hospitals from 1 January 2001 to 31 October 2006 in the study. After stratification of patients by Pitt bacteremia scores, we used Cox regression models to estimate the hazard ratios (HR) for 28-day all-cause mortality after adjusting for the propensity to receive combination therapy. We identified 398 and 304 unique patients with bacteremia caused by gram-negative bacilli who received single and combination antibiotic therapy, respectively. In less severely ill patients with Pitt bacteremia scores of <4, combination therapy was associated with lower 28-day mortality than single therapy (4.2% [9 of 214] versus 8.8% [28 of 319]; adjusted HR, 0.44; 95% confidence interval [CI], 0.20 to 0.98; P = 0.044). In critically ill patients with Pitt bacteremia scores of >or=4, there was no difference in 28-day mortality between combination and single therapy (25.6% [23 of 90] versus 27.8% [22 of 79]; adjusted HR, 0.87; 95% CI, 0.47 to 1.62; P = 0.660). These findings were consistent for 14-day all-cause mortality. In this large cohort, we found for the first time that combination therapy with beta-lactams and fluoroquinolones was associated with a reduction in 28-day all-cause mortality among less severely ill patients with bacteremia caused by gram-negative bacilli.
authors.affiliation: University of Kentucky Chandler Medical Center, Lexington, KY 40536, USA. majdi.alhasan@uky.edu
authors.forename: Majdi N
authors.initials: MN
authors.lastname: Al-Hasan
authors.forename: John W
authors.initials: JW
authors.lastname: Wilson
authors.forename: Brian D
authors.initials: BD
authors.lastname: Lahr
authors.forename: Kristine M
authors.initials: KM
authors.lastname: Thomsen
authors.forename: Jeanette E
authors.initials: JE
authors.lastname: Eckel-Passow
authors.forename: Emily A
authors.initials: EA
authors.lastname: Vetter
authors.forename: Imad M
authors.initials: IM
authors.lastname: Tleyjeh
authors.forename: Larry M
authors.initials: LM
authors.lastname: Baddour
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D016470:Bacteremia / Q000188:drug therapy* / Q000401:mortality; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D047090:beta-Lactams / Q000008:administration & dosage*
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D047090:beta-Lactams