Piperacillin/tazobactam vs carbapenems for patients with bacterial infection: Protocol for a systematic review

Introduction Early empirical broad‐spectrum antimicrobial therapy is recommended for patients with severe infections, including sepsis. β‐lactam/β‐lactamase inhibitor combinations or carbapenems are often used to ensure coverage of likely pathogens. Piperacillin/tazobactam is proposed as a carbapenem‐sparing agent to reduce the incidence of multidrug‐resistant bacteria and superinfections. In the recently published MERINO trial, increased mortality from piperacillin/tazobactam was suggested in patients with bacteraemia with resistant Escherichia coli or Klebsiella species. Whether these findings also apply to empirical piperacillin/tazobactam in patients with other severe infections, including sepsis, is unknown. We aim to assess the benefits and harms of empirical and definitive piperacillin/tazobactam vs carbapenems for patients with severe bacterial infections. Methods and analysis This protocol has been prepared according to the Preferred Reporting Items for Systematic Review and Meta‐Analysis Protocols statement, the Cochrane Handbook and the Grading of Recommendations, Assessment, Development, and Evaluation approach. We will include randomised clinical trials assessing piperacillin/tazobactam vs carbapenems in patients with severe bacterial infections of any origin. The primary outcome will be all‐cause short‐term mortality ≤ 90 days. Secondary outcomes will include all‐cause long‐term mortality > 90 days, adverse events, quality of life, use of life support, secondary infections, antibiotic resistance, and length of stay. We will conduct meta‐analyses, including pre‐planned subgroup and sensitivity analyses for all assessed outcomes. The risk of random errors in the meta‐analyses will be assessed by trial sequential analysis.