Comparison of extended versus intermittent infusion of antipseudomonal beta-lactams for the treatment of critically ill patients with respiratory infections: A systematic review and meta-analysis

Abstract

Objectives: Alternative dosing strategies for β-lactamsthe most common antibiotics used to treat critically ill patients with respiratory tract infectionshave been recommended to maximize the duration of exposure and reduce drug resistance. The objective of this study was to evaluate whether extended infusion of antipseudomonal β-lactams improves mortality and clinical efficacy. Methods: Two independent authors identified eligible trials by searching the PubMed, Cochrane Library, Scopus, and ICHUSHI databases, in both English and Japanese, up to June 2019. Data were extracted from both randomized controlled and observational trials comparing extended infusion (!3 h) with intermittent infusion in critically ill patients. The primary outcome was all-cause mortality. Risk differences (RD) and 95% confidential intervals (CI) were calculated using a random-effects model and subgroup analyses were performed. Sensitivity and heterogeneity were also evaluated. Results: Nine studies involving 1508 participants were included in the meta-analysis. Mortality was lower for extended infusion than for intermittent infusion (RD À0.10; 95% CI À0.15 to À0.04). However, no significant between-group differences in clinical success, length of ICU stay, length of hospital stay, and antibiotic duration were observed. Conclusions: Extended infusions of β-lactams were associated with reduced mortality rates but not with clinical success.

Method Development for Determination of Doripenem in Human Plasma via Capillary Electrophoresis Coupled with Field-Enhanced Sample Stacking and Sweeping

“…Since doripenem is an antibiotic of last resort for the treatment of multidrug-resistant bacterial infections, its plasma concentration is ideally maintained above the MIC during dosing intervals due to its time-dependent efficacy [ 10 ]. Apart from the clinical standard practice of intermittent intravenous (IV) administration, continuous IV infusions may be beneficial to maintain adequate drug concentrations and reduce fluctuations in plasma [ 11 , 38 ]. Patient 1 (P1) and patient 2 (P2) received doripenem 1.5 g per day by continuous IV infusions.…”

Model-Informed Translation of In Vitro Effects of Short-, Prolonged- and Continuous-Infusion Meropenem against Pseudomonas aeruginosa to Clinical Settings

“…A meta-analysis of 22 randomised trials associated prolonged infusions (≥3 h) of antipseudomonal beta-lactams with lower all-cause mortality than short-term infusion (≤60 min) for patients with sepsis [ 24 ]. Similarly, two smaller meta-analyses reported a significant reduction of hospital mortality or improvement of clinical cure when using >1-h infusions in studies published in or after 2015 [ 25 ] and lower mortality for extended infusions (≥3 h) [ 26 ]. However, most of these studies did not differentiate between different types of prolonged infusions (e.g., 3-h or continuous infusion).…”