Comparative efficacy and safety of combination therapy with high-dose sulbactam or colistin with additional antibacterial agents for multiple drug-resistant and extensively drug-resistant Acinetobacter baumannii infections: A systematic review and network meta-analysis

J Glob Antimicrob Resist. 2021 Mar:24:136-147. doi: 10.1016/j.jgar.2020.08.021. Epub 2020 Sep 2.

Abstract

Objectives: This study aimed to compare the efficacy and safety of combination therapy with high-dose sulbactam or colistin with additional antibacterial agents for treating multidrug-resistant or extensively drug-resistant Acinetobacter baumannii (MDR-AB or XDR-AB) infections.

Methods: We systematically searched PubMed, Embase, Cochrane, and Web of Science (through March 30, 2020) for studies that examined high-dose sulbactam or colistin with additional antibacterial agents as therapy for patients with infections with MDR-AB and XDR-AB. Through a network meta-analysis (NMA), using both direct and indirect evidence, we determined risk ratios and 95% confidence intervals. Primary outcomes included clinical improvement, clinical cure, microbiological eradication, and mortality from any cause. Secondary outcomes included nephrotoxicity.

Results: The NMA included 18 studies and 1835 patients. We found that high-dose sulbactam (≥6 g per day), combined with another single antibacterial agent (levofloxacin or tigecycline), which were the highest ranking in clinical improvement and clinical cure. Still colistin-based combination in drug-resistant Acinetobacter baumannii therapy occupied the main position (the number of studies and patients) in most studies. Colistin combined with additional antibacterial agents was associated with a higher risk of nephrotoxicity.

Conclusions: Therapeutic regimens including high-dose sulbactam in combination with additional antibacterial agents (including colistin) might be one of the promising options for the treatment of MDR-AB or XDR-AB infections and high-quality study will be needed to confirm clinical efficacy.

Keywords: Acinetobacter baumannii; Colistin; Extensively drug- resistant; Multidrug-resistant; Network meta-analysis; Sulbactam.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Acinetobacter Infections* / drug therapy
  • Acinetobacter baumannii*
  • Anti-Bacterial Agents / adverse effects
  • Colistin / pharmacology
  • Drug Resistance, Multiple, Bacterial
  • Drug Therapy, Combination
  • Humans
  • Microbial Sensitivity Tests
  • Minocycline / pharmacology
  • Network Meta-Analysis
  • Pharmaceutical Preparations*
  • Sulbactam / adverse effects

Substances

  • Anti-Bacterial Agents
  • Pharmaceutical Preparations
  • Minocycline
  • Sulbactam
  • Colistin