Abstract
BackgroundThe prolonged β-lactam infusion strategy has emerged as the standard treatment for sepsis or septic shock despite its unknown efficacy. This study aimed to assess the efficacy of prolonged versus intermittent β-lactam antibiotics infusion on outcomes in sepsis or septic shock patients by conducting a systematic review and meta-analysis.MethodsA thorough search was conducted on MEDLINE, the Cochrane Central Register of Controlled Trials, and the Igaku Chuo Zasshi databases. Randomized controlled trials (RCTs) comparing mortality between prolonged and intermittent infusion in adult patients with sepsis or septic shock were included. The primary outcome was hospital mortality. The secondary outcomes were the attainment of the target plasma concentration, clinical cure, adverse events, and occurrence of antibiotic-resistant bacteria. We performed a subgroup analysis stratified according to the year of publication before or after 2015 and a trial sequential analysis (TSA). The Der Simonian–Laird random-effects models were subsequently used to report the pooled risk ratios (RR) with confidence intervals (CI).ResultsWe identified 2869 studies from the 3 databases, and 13 studies were included in the meta-analysis. Hospital mortality did not decrease (RR 0.69 [95%CI 0.47–1.02]) in the prolonged infusion group. The attainment of the target plasma concentration and clinical cure significantly improved (RR 0.40 [95%CI 0.21–0.75] and RR 0.84 [95%CI 0.73–0.97], respectively) in the prolonged infusion group. There were, however, no significant differences in the adverse events and the occurrence of antibiotic-resistant bacteria between the groups (RR 1.01 (95%CI 0.95–1.06) and RR 0.53 [95%CI 0.10–2.83], respectively). For the subgroup analysis, a significant improvement in hospital mortality or clinical cure was reported in studies published in or after 2015 (RR 0.66 [95%CI 0.44–0.98] and RR 0.67 [95%CI 0.50–0.90], respectively). The results of the TSA indicated an insufficient number of studies for a definitive analysis.ConclusionsThe prolonged infusion of β-lactam antibiotics significantly improved upon attaining the target plasma concentration and clinical cure without increasing the adverse event or the occurrence of antibiotic-resistant bacteria. Prolonged infusion could not improve hospital mortality although an improvement was shown for studies published in or after 2015. Further studies are warranted as suggested by our TSA results.
Highlights
Sepsis and septic shock can cause high morbidity and mortality rates; the early and appropriate use of effective antibiotics is important [1]. β-Lactam antibiotics are antibiotics commonly used by sepsis or septic shock patients in intensive care units (ICU) [2]
The prolonged infusion of β-lactam antibiotics significantly improved upon attaining the target plasma concentration and clinical cure without increasing the adverse event or the occurrence of antibioticresistant bacteria
177 patients from two Randomized controlled trial (RCT) [16, 19] were included in the attainment of the target plasma concentration, 886 patients from nine RCTs [16, 18,19,20,21,22,23, 26, 28] were included in clinical cure, 691 patients from three RCTs [21, 22, 24] were included in the adverse event groups, and 198 patients from one RCT [18] were included in the occurrence of antibiotic-resistant bacteria group
Summary
Sepsis and septic shock can cause high morbidity and mortality rates; the early and appropriate use of effective antibiotics is important [1]. β-Lactam antibiotics are antibiotics commonly used by sepsis or septic shock patients in intensive care units (ICU) [2]. The current international guidelines on the management of sepsis and septic shock (Surviving Sepsis Campaign, 2016) recommended that dosing strategies of antimicrobials be optimized based on the accepted pharmacokinetic/pharmacodynamics principles and the specific drug properties [5]. This has not been clearly defined for the prolonged β-lactam antibiotics infusion strategy. The prolonged β-lactam infusion strategy has emerged as the standard treatment for sepsis or septic shock despite its unknown efficacy. This study aimed to assess the efficacy of prolonged versus intermittent βlactam antibiotics infusion on outcomes in sepsis or septic shock patients by conducting a systematic review and meta-analysis
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