The efficacy and safety of tazobactam/ceftolozane in combination with metronidazole in Japanese patients with complicated intra-abdominal infections

J Infect Chemother. 2019 Feb;25(2):111-116. doi: 10.1016/j.jiac.2018.10.012. Epub 2018 Dec 6.

Abstract

Tazobactam/ceftolozane, a novel antimicrobial therapy, is active against Pseudomonas aeruginosa and most extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. We report the results of the efficacy and safety of tazobactam/ceftolozane in Japanese patients with complicated intra-abdominal infections (cIAI). A multicenter, open-label, noncomparative study (MK-7625A Protocol 013, ClinicalTrials.gov Identifier: NCT02739997) to investigate the efficacy and safety of tazobactam/ceftolozane used in combination with metronidazole in Japanese patients with cIAI was conducted. One hundred Japanese patients with cIAI received tazobactam/ceftolozane 1.5 g (tazobactam 0.5 g/ceftolozane 1 g) plus metronidazole 500 mg intravenously every 8 h for 60 min for 4-14 days. The clinical response rate at the Test-of-Cure visit (TOC; Day 28 ± 2 days) was 92.0% (81/88 subjects). By disease type, the clinical response rates were 92.3% (24/26) for cholecystitis, 100% (6/6) for liver abscess, 93.5% (58/62) for intra-abdominal abscess and 90.2% (55/61) for peritonitis. The per-subject microbiological response rate at the TOC was 90.2% (55/61). Per-pathogen microbiological response rates in the most common baseline pathogens were Escherichia coli 90.2% (37/41), Kebsiella pneumoniae 91.7% (11/12), Streptococcus anginosus 100% (11/11), Streptococcus constellatus 90.0% (9/10) and Bacteroides fragilis 95.2% (20/21). The most common drug-related AEs were aspartate aminotransferase increased (11.0%) and alanine aminotransferase increased (9.0%). No serious drug-related AE was reported during the study. The favorable effect of tazobactam/ceftolozane in the treatment of cIAI suggests that the agent will be useful in clinical practice in Japan.

Keywords: Ceftolozane; Complicated intra-abdominal infection; ESBL; Japanese patients.

Publication types

  • Clinical Trial, Phase III

MeSH terms

  • Aged
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Bacteria / drug effects
  • Cephalosporins / adverse effects*
  • Cephalosporins / pharmacology
  • Cephalosporins / therapeutic use
  • Female
  • Humans
  • Intraabdominal Infections / drug therapy*
  • Intraabdominal Infections / microbiology
  • Japan
  • Male
  • Metronidazole / adverse effects*
  • Metronidazole / pharmacology
  • Metronidazole / therapeutic use
  • Middle Aged
  • Tazobactam / adverse effects*
  • Tazobactam / pharmacology
  • Tazobactam / therapeutic use
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Cephalosporins
  • ceftolozane, tazobactam drug combination
  • Metronidazole
  • Tazobactam

Associated data

  • ClinicalTrials.gov/NCT02739997