Continuous Infusion Versus Intermittent Bolus of Beta-Lactams in Critically Ill Patients with Respiratory Infections: A Systematic Review and Meta-analysis

Abstract

CI of beta-lactam antibiotics is associated with better cure rates and higher %fT > MIC when administered to critically ill patients with respiratory infections, but may be most beneficial in severely ill patients with more resistant Gram-negative bacterial infections.

Optimization of the treatment with beta-lactam antibiotics in critically ill patients—guidelines from the French Society of Pharmacology and Therapeutics (Société Française de Pharmacologie et Thérapeutique—SFPT) and the French Society of Anaesthesia and Intensive Care Medicine (Société Française d’Anesthésie et Réanimation—SFAR)

“…In contrast to the meta-analyses conducted prior to 2010 that have not reported any benefit of the continuous infusion [89, 90], the most recent meta-analysis conducted by Lee et al, which included 13 randomised controlled trials focusing on ICU patients suffering from respiratory infections, showed an improvement in terms of clinical cure in septic patients (RR 1.194, 95%CI [1.015–1.405]) and in patients at high risk of mortality (APACHE II score ≥ 20 or SAPS II score ≥ 52) (RR 1.162 [1.042–1.296]) treated with beta-lactam continuous infusion [91]. However, no difference was observed for the mortality rate for both septic patients and patients at high risk of mortality.…”

“…Two meta-analyses highlighted a significant improvement in the clinical cure rate of ICU patients suffering from lower respiratory tract infections treated by continuous administration of beta-lactam antibiotics compared to intermittent administration (RR 1.177 [1.065–1.300]—patients with lower respiratory tract infections [91]; and OR 2.45; [1.12–5.37]—nosocomial pneumonia due to Gram-negative bacteria [92]), although there was no effect on mortality.…”

Therapeutic drug monitoring-guided continuous infusion of piperacillin/tazobactam significantly improves pharmacokinetic target attainment in critically ill patients: a retrospective analysis of four years of clinical experience

“…CI infusion represents a reasonable approach of customized drug dosing in the ICU as to extend the time that the unbound fraction of PIP remains above the pathogen-specific minimum inhibitory concentration (MIC) (fT >MIC ) [6,7,13,14] up to 100% of the dosing interval [10,12,15]. Several studies demonstrated positive effects (clinical cure and survival rates) of CI compared to IB in the context of sepsis [16][17][18][19][20][21][22]. As evidence increases, the demand for dose optimization and TDM-guided individual dosing strategies grows [12,23,24]…”

Optimizing ceftolozane-tazobactam dosage during continuous renal replacement therapy: some nuances

“…Optimizing ceftolozane-tazobactam dosage during continuous renal replacement therapy: some nuances Gerardo Aguilar 1,2,3* , Rafael Ferriols 2,3,4 , Sara Martínez-Castro 1 , Carlos Ezquer 3,4 , Ernesto Pastor 1 , Jose A. Carbonell 1 , Manuel Alós 2,3,4 and David Navarro 2,3,5 We have read the recent letter by Honore et al [1] about our findings published in this journal regarding the influence of continuous renal replacement therapy (CRRT) on the pharmacokinetics of ceftolozane-tazobactam (C/ T) [2]. In our report, we decided to administer a 3 g/iv dose every 8 h taking into account two previous studies referenced in our paper [2] and another one which showed CRRT to be an independent predictor of clinical failure (OR 4.5, 95% CI 1.18-17.39, p = 0.02) when C/T is administered at 1.5 g every 8 h [3].…”

“…Therefore, we agree with Honore et al [1] that therapeutic drug monitoring (TDM) is critical when using C/T for patients receiving CRRT, especially when MICs of bacteria like multidrugresistant (MDR) Pseudomonas aeruginosa are considered very high. However, the recommendation of continuous (over 24 h) vs extended (over 2 to 4 h) or intermittent (over 30 to 60 min) infusion of beta-lactams is still under debate [5].…”