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

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.

• Authors: Hiroshige Mikamo, Kazuteru Monden, Yoshiaki Miyasaka, Tetsuya Horiuchi, Go Fujimoto, Takahiro Fukuhara, Tomoko Yoshinari, Elizabeth G Rhee, Toshiyuki Shizuya
• Journal: Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy (J Infect Chemother) Vol. 25 Issue 2 Pg. 111-116 (Feb 2019) ISSN: 1437-7780 [Electronic] Netherlands
• PMID: 30528561 (Publication Type: Clinical Trial, Phase III, Journal Article)
• Copyright: Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

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

Topics

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