Category: Professional Posters
Purpose: Since beta-lactams are the most common antimicrobial drugs used in critically ill patients with respiratory tract infections, alternative dosing strategies have been recommended for dose optimization. The objective of this systematic review and meta-analysis was to focus on extended infusion and capture additional data to evaluate whether the extended infusion antipseudomonal beta-lactams have improved mortality and better clinical efficacy compared to intermittent infusion in critically ill patients with predominant respiratory infection.
Methods: Two authors independently performed a literature search of trials using PubMed, Cochrane Library, Scopus and ICHUSHI in English and Japanese language from inception to February 2019.We retrieved both published and unpublished trials comparing extended infusion (3 or more hours) to intermittent infusion (up to 60 minutes) in critically ill patients. Two independent reviewers extracted and investigated the data. A meta-analysis was conducted using Review Manager 5.3 and R statistical software. Risk deference (RD) and 95% confidential interval (CI) were calculated regarding all outcomes by using random effect model. Statistical heterogeneity among studies was assessed by using I² statistic and Q statistic (χ2 test). The quality of each study was assessed. Sensitivity analysis and publication bias were evaluated. This meta-analysis is reported according to Preferred Items of Systematic reviews and Meta-analyses (PRISMA) guidelines and registered with the PROSPERO database, number CRD42019119166.
Results: 3,244 articles were identified and screened. Ten studies (3 Randomized Controlled Trials and 7 non- Randomized Controlled Trials) involving 1,558 participants were included in the meta-analysis. Studies comparing extended to intermittent infusion of penicillins, cephalosporins and carbapenems in critically ill patients having predominant respiratory tract infection were included. We excluded articles if no clinical outcome was reported and studies comparing continuous (lasting for 24 hours) infusion to intermittent infusion. Additionally, studies comparing between 2 different beta-lactams or not comparing extended to intermittent infusion were excluded.
Compared to intermittent infusion regimen, severely ill patients receiving extended infusion were associated with lower all-cause mortality RD, -0.10 [95% CI, -0.15 to-0.04]. Heterogeneity was (p=0.04, I²=51%). However, no significant difference in clinical success RD 0.10, [95% CI, -0.06 to 0.26], ICU length of stay RD -2.37, [95% CI, -5.17 to 0.42], hospital length of stay RD -1.68, [95% CI, -3.85 to 0.48] and antibiotic duration RD 0.05, [95% CI, -1.80 to 1.90] was observed between the two groups. The sensitivity analysis showed the results were stable.
Conclusion: Extended infusion beta-lactams compared to intermittent infusion were associated with significantly reduced mortality rates in severely ill patient with predominant respiratory infection, but no statistical difference in clinical success rate. Well-designed randomized controlled trials are warranted to confirm these findings.