title: Monotherapy versus beta-lactam-aminoglycoside combination treatment for gram-negative bacteremia: a prospective, observational study.
abstract: The aim of the present study was to test whether the combination of a beta-lactam drug plus an aminoglycoside has advantage over monotherapy for severe gram-negative infections. Of 2,124 patients with gram-negative bacteremia surveyed prospectively, 670 were given inappropriate empirical antibiotic treatment and the mortality rate in this group was 34%, whereas the mortality rate was 18% for 1,454 patients given appropriate empirical antibiotic treatment (P = 0.0001). The mortality rates for patients given appropriate empirical antibiotic treatment were 17% for 789 patients given a single beta-lactam drug, 19% for 327 patients given combination treatment, 24% for 249 patients given a single aminoglycoside, and 29% for 89 patients given other antibiotics (P = 0.0001). When patients were stratified according to risk factors for mortality other than antibiotic treatment, combination therapy showed no advantage over treatment with a single beta-lactam drug except for neutropenic patients (odds ratio [OR] for mortality, 0.5; 95% confidence interval [95% CI], 0.2 to 1.3) and patients with Pseudomonas aeruginosa bacteremia (OR, 0.7; 95% CI, 0.3 to 1.8). On multivariable logistic regression analysis including all risk factors for mortality, combination therapy had no advantage over therapy with a single beta-lactam drug. The mortality rate for patients treated with a single appropriate aminoglycoside was higher than that for patients given a beta-lactam drug in all strata except for patients with urinary tract infections. When the results of blood cultures were known, 1,878 patients were available for follow-up. Of these, 816 patients were given a single beta-lactam drug, 442 were given combination treatment, and 193 were given a single aminoglycoside. The mortality rates were 13, 15, and 23%, respectively (P = 0.0001). Both on stratified and on multivariable logistic regression analyses, combination treatment showed a benefit over treatment with a single beta-lactam drug only for neutropenic patients (OR, 0.2; 95% CI, 0.05 to 0.7). In summary, combination treatment showed no advantage over treatment with an appropriate beta-lactam drug in nonneutropenic patients with gram-negative bacteremia.
authors.affiliation: Department of Medicine, Rabin Medical Center, Beilinson Campus, Petah-Tiqva, Israel. leibovic@post.tau.ac.il
authors.forename: L
authors.initials: L
authors.lastname: Leibovici
authors.forename: M
authors.initials: M
authors.lastname: Paul
authors.forename: O
authors.initials: O
authors.lastname: Poznanski
authors.forename: M
authors.initials: M
authors.lastname: Drucker
authors.forename: Z
authors.initials: Z
authors.lastname: Samra
authors.forename: H
authors.initials: H
authors.lastname: Konigsberger
authors.forename: S D
authors.initials: SD
authors.lastname: Pitlik
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination / Q000627:therapeutic use*; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D016896:Treatment Outcome; D047090:beta-Lactams
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D047090:beta-Lactams