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Prolonged Infusion of β-lactams Lowers Mortality in Sepsis Patients

NOV 27, 2017 | NICOLA M. PARRY, BVSC, MRCVS, MSC, DACVP, ELS
Konstantinos Z. Vardakas, MDA recent study showed that, compared with short-term infusion, prolonged infusion of antipseudomonal β-lactams in patients with sepsis was associated with significantly less mortality.

Konstantinos Z Vardakas, MD, from Alfa Institute of Biomedical Sciences (AIBS), Athens, Greece, and colleagues published the results of their systematic review
and meta-analysis October 25 in Lancet Infectious Diseases.

“The risk of death in patients with sepsis treated with prolonged infusion of antipseudomonal β-lactams was 30% lower compared with patients treated with short-term infusion,” the authors write.

However, they noted that “[c]linical cure was not significantly higher with prolonged infusions.”

In an interview with Contagion®, Dr. Vardakas explained that prolonged infusion of antibiotics, especially β-lactams, is a relatively commonly used modality to improve the pharmacokinetics (PK), and subsequently the pharmacodynamics (PD), of these drugs.

“This is of particular interest in patients with sepsis, either in the intensive care unit or in the wards,” he said. “In these patients, the volume of distribution (lower albumin levels, increased capillary permeability, and higher extracellular volume) and renal clearance increase, resulting in lower antibiotic concentrations.”

However, findings from previous small randomized controlled trials (RCT), observational studies, and meta-analyses regarding the effectiveness of prolonged β-lactam infusion have varied widely.

Therefore, Dr. Vardakas and colleagues performed a meta-analysis to examine the effect of prolonged infusion of antipseudomonal β-lactams on mortality of patients with sepsis compared with short-term infusion.

In their study, they evaluated 22 RCTs that included 1,876 patients and compared the effect of prolonged (continuous or ≥3 hours) infusion versus short-term (≤60 min) infusion of antipseudomonal β-lactams (carbapenems, penicillins, cephalosporins, and monobactams) for treatment of patients with sepsis.


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