Assessment of Prolonged vs Short-Term Antipseudomonal β-lactam Infusion for Sepsis

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Bacterial infections are associated with substantial morbidity and mortality despite the availability of antibiotics.
Bacterial infections are associated with substantial morbidity and mortality despite the availability of antibiotics.

According to results of research published in Lancet Infectious Diseases, prolonged infusion of antipseudomonal β-lactams for treatment of sepsis was associated with significantly lower mortality than short-term infusions.

A meta-analysis and review of the literature, which yielded 22 randomized controlled trials (RCTs) totalling 1876 patients, evaluated the comparative effectiveness and safety of prolonged (≥3-hour or 24-hour continuous infusion) vs short-term (bolus or ≤60-minute intermittent infusion) treatment with any antipseudomonal β-lactam. 

Prolonged infusion was associated with lower mortality, regardless of cause, than the shorter-term treatment (risk ratio 0.70; 95% CI, 0.56-0.87). 

Nearly all subgroup and sensitivity analyses showed a trend to lower mortality with prolonged infusion, but data were not available to investigate specific pathogens, sites of infection, concomitant antibiotic therapy, and renal failure or renal replacement therapy. Clinical cure or improvement occurred in 18 of 22 RCTs, but differences in clinical cure rates were not significant. A funnel plot and Egger's test showed no evidence for publication biases (P = .44) and heterogeneity was not observed among studies (P = .93, I2=0%).

The investigators conclude that the weight of evidence for the benefit of prolonged infusion in patients with sepsis is high; however, further investigations are warranted – specifically,  the discrepancy between reduced mortality risk and a nonsignificant clinical cure rate, as well as subgroup analysis of patients by age, sepsis severity, degree of renal dysfunction, and immunocompetence.

 

Reference

Vardakas KZ, Voulgaris GL, Maliaros A, Samonis G, Falagas ME. Prolonged versus short-term intravenous infusion of antipseudomonal β-lactams for patients with sepsis: a systematic review and meta-analysis of randomised trialsLancet Infect Dis. 2018;18:108-120.

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