Prolonged Infusion Piperacillin-Tazobactam Decreases Mortality and Improves Outcomes in Severely Ill Patients: Results of a Systematic Review and Meta-Analysis.

OBJECTIVE: Piperacillin-tazobactam is a commonly used antibiotic in critically ill patients; however, controversy exists as to whether mortality in serious infections can be decreased through administration by prolonged infusion compared with intermittent infusion. The purpose of this systematic review and meta-analysis was to describe the impact of prolonged infusion piperacillin-tazobactam schemes on clinical endpoints in severely ill patients. DESIGN: We conducted a systematic literature review and meta-analysis searching MEDLINE, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library from inception to April 1, 2017, for studies. INTERVENTIONS: Mortality rates were compared between severely ill patients receiving piperacillin-tazobactam via prolonged infusion or intermittent infusion. Included studies must have reported severity of illness scores, which were transformed into average study-level mortality probabilities. MEASUREMENTS AND MAIN RESULTS: Two investigators independently screened titles, abstracts, and full texts of studies meeting inclusion criteria for this systematic review and meta-analysis. Variables included author name, publication year, study design, demographics, total daily dose(s), average estimated creatinine clearance, type of prolonged infusion, prevalence of combination therapy, severity of illness scores, infectious sources, all-cause mortality, clinical cure, microbiological cure, and hospital and ICU length of stay. The review identified 18 studies including 3,401 patients who received piperacillin-tazobactam, 56.7% via prolonged infusion. Across all studies, the majority of patients had an identified primary infectious source. Receipt of prolonged infusion was associated with a 1.46-fold lower odds of mortality (95% CI, 1.20-1.77) in the pooled analysis. Patients receiving prolonged infusion had a 1.77-fold higher odds of clinical cure (95% CI, 1.24-2.54) and a 1.22-fold higher odds of microbiological cure (95% CI, 0.84-1.77). Subanalyses were conducted according to high (≥ 20%) and low (< 20%) average study-level mortality probabilities. In studies reporting higher mortality probabilities, effect sizes were variable but similar to the pooled results. CONCLUSIONS: Receipt of prolonged infusion of piperacillin-tazobactam was associated with reduced mortality and improved clinical cure rates across diverse cohorts of severely ill patients.

Cefazolin vs. anti-staphylococcal penicillins for treatment of methicillin-susceptible Staphylococcus aureus bloodstream infections in acutely ill adult patients: Results of a systematic review and meta-analysis.

A systematic literature review and meta-analysis was conducted to evaluate the comparative efficacy and tolerability of cefazolin vs. anti-staphylococcal penicillins (ASPs) for methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSI). Utilizing published regression models, included studies were stratified into subgroups of high and low pre-probability of mortality. Cefazolin was associated with significantly lower rates of treatment failure (odds ratio [OR]: 0.70; 95% confidence interval [CI]: 0.61-0.82; P<0.001; I2 = 14%) and crude, all-cause mortality (OR: 0.69; 95% CI: 0.59-0.81; P<0.001; I2 = 18%) compared with ASP therapy. Overall risk of treatment-related adverse drug reactions was numerically lower with cefazolin (OR: 0.39; 95% CI: 0.15-1.00; P = 0.05). Subgroup sensitivity analyses of studies conducted in less severely ill patients were similar to the combined analysis. The role of cefazolin in the most severely ill patients with MSSA BSI should be prospectively evaluated.