Sepsis (Sub-Category)

Monotherapy versus beta-lactam-aminoglycoside combination treatment for gram-negative bacteremia: a prospective, observational study

L Leibovici
M Paul
O Poznanski
M Drucker
Z Samra
H Konigsberger
SD Pitlik

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.

PubMed Link to Article:

Leibovici L, Paul M, Poznanski O, Drucker M, Samra Z, Konigsberger H, Pitlik SD. Monotherapy versus beta-lactam-aminoglycoside combination treatment for gram-negative bacteremia: a prospective, observational study. Antimicrob Agents Chemother. 1997 May;41(5):1127-33. Erratum in: Antimicrob Agents Chemother 1997 Nov;41(11):2595. PubMed PMID: 9145881; PubMed Central PMCID: PMC163862.