Prolonged beta-lactam antibiotics reduce mortality in sepsis

Prolonged IV infusion of antipseudomonal beta-lactam antibiotics significantly reduced all-cause mortality among patients with sepsis compared with short-term infusion, a meta-analysis found.

“Changes in both bacterial and host factors created the need for new antibiotics, revival of neglected old antibiotics and optimized use of the currently available ones,” Konstantinos Z. Vardakas, MD, of the Alfa Institute of Biomedical Sciences, Athens, Greece, and colleagues wrote in The Lancet Infectious Diseases. “Preliminary data from small randomized controlled trials and retrospective studies showed that the outcomes depend on the [beta-lactam] class, the quality of the included studies and the infection being studied.”

The researchers performed a systematic review and meta-analysis of 22 randomized controlled trials comparing short-term and prolonged infusion of antipseudomonal beta-lactam antibiotics in patients with sepsis. Vardakas and colleagues considered prolonged treatment to last at least 3 hours, whereas short-term infusion was defined as lasting 60 minutes or less. The main outcome was all-cause mortality at any time point.

Patients had a median or mean age of younger than 45 years in five studies, 45 to 65 years in 12 studies, and older than 65 years in one study. Four trials did not provide relevant data on age. Further, in most studies, the cause of patients’ sepsis was not reported in up to 81% of cases.

Prolonged infusion was associated with decreased all-cause mortality compared with short-term therapy, the researchers reported (RR = 0.7; 95% CI, 0.56-0.87). Vardakas and colleagues observed no heterogeneity (P = .93), and there was no evidence of publication bias (P = .44).

There was no significant difference in adverse events between short-term and prolonged infusion, the researchers reported (n = 7 trials; 980 patients; RR = 0.88; 95% CI, 0.71-1.09).

“We can foresee no harm with prolonged [beta-lactam] infusion and none has been shown,” Mical Paul, MD, of the Institute of Infectious Diseases at Rambam Health Care Campus, Israel, and Ursula Theuretzbacher, PhD, of the Center for Anti-Infective Agents in Vienna, wrote in an accompanying editorial. “With current evidence, it seems that we should standardize prolonged dosing of [beta-lactams] in ICUs.” – by Andy Polhamus

Disclosures: The authors report no relevant financial disclosures. Paul and Theuretzbacher report no relevant financial disclosures.