We report efficacy and safety results for a combination of a novel cephalosporin class antibiotic and a β-Lactamase inhibitor, tazobactam/ceftolozane (1:2) at a dose of 1.5 g intravenously every 8 h in Japanese patients with uncomplicated pyelonephritis and complicated urinary tract infection. This study design was a nonrandomized, multicenter, open-label trial, and the treatment period was 7 days. Of 115 patients enrolled in this study, 114 received tazobactam/ceftolozane, and 90 were included in the efficacy analyses. Ninety-nine isolates (bacterial count ≥105 CFU/mL) were identified by urine culture. The main baseline uropathogens were Escherichia coli (80 isolates), Klebsiella pneumoniae (8 isolates), and Proteus mirabilis (3 isolates). Of these, 13 isolates were ESBL-producers. The favorable per-patient microbiological response rate at 7 days after the final administration of tazobactam/ceftolozane was 80.7% (71/88). The response rate in uncomplicated pyelonephritis was 90.0% (36/40), complicated pyelonephritis 63.6% (14/22), and complicated cystitis 80.8% (21/26). The favorable clinical response rate was 96.6% (86/89), and composite response rate (based on microbiological and clinical response) was 80.7% (71/88). The eradication rate by uropathogen was 83.5% (66/79) in E. coli, 42.9% (3/7) in K. pneumoniae, and 100% (3/3) in P. mirabilis. The incidence of drug-related adverse events was 17.5% (20/114 patients). The most common drug-related adverse events were diarrhea and alanine aminotransferase increased in 5.3% (6/114 patients each). Drug-related serious adverse events and deaths were not observed. These results support the safety and efficacy of tazobactam/ceftolozane and suggest it will be a useful treatment for uncomplicated pyelonephritis and complicated urinary tract infection.
Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy. 2018 Nov 09 [Epub ahead of print]
Soichi Arakawa, Kazuya Kawahara, Motoshi Kawahara, Mitsuru Yasuda, Go Fujimoto, Asako Sato, Ruriko Yokokawa, Tomoko Yoshinari, Elizabeth G Rhee, Norihiro Aoyama
Sanda City Hospital, Hyogo, Japan., Kawahara Clinic, Kagoshima, Japan., Kawahara Urology Clinic, Kagoshima, Japan., Center for Nutrition Support and Infection Control, Gifu University Hospital, Gifu, Japan., Japan Development, MSD K.K., Tokyo, Japan., Global Clinical Development, Merck & Co., Inc., Kenilworth, NJ, USA., Japan Development, MSD K.K., Tokyo, Japan. Electronic address: .