title: Efficacy and safety of metronidazole injection for the treatment of infectious peritonitis, abdominal abscess and pelvic inflammatory diseases in Japan.
abstract: Although metronidazole (MNZ) has been used worldwide for more than 4 decades as a standard therapy for trichomoniasis, anaerobic and amebic infections, resistance to MNZ is still low. MNZ is available as oral, intravenous, and vaginal formulations, but the intravenous formulation of MNZ has not been approved in Japan. We conducted a phase 3 study to evaluate the efficacy and safety of intravenous MNZ combined with ceftriaxone (CTRX) in Japanese subjects with infectious peritonitis, abdominal abscess or pelvic inflammatory diseases (PIDs) to obtain regulatory approval. A combination of MNZ/CTRX at doses of 500 mg 3 or 4 times a day/1 or 2 g twice a day was administered intravenously to a total of 38 hospitalized subjects. MNZ/CTRX was well tolerated and exhibited excellent clinical and bacteriological efficacy with clinical efficacy rates of 100% (20/20) in infectious peritonitis or abdominal abscess subjects and 90.0% (9/10) in PID subjects, and the eradication rates in infectious peritonitis or abdominal abscess subjects and PID subjects were 100% (16/16) and 100% (4/4), respectively, at the test of cure. MNZ/CTRX was effective in 1 subject in whom a metallo-β-lactamase-producing Bacteroides fragilis strain (MIC of MNZ, 2 μg/ml) was identified. The most common treatment-related adverse event was diarrhea (23.7%), followed by nausea (5.3%). No new safety signals were identified. MNZ/CTRX demonstrated excellent efficacy and was well tolerated in Japanese infectious peritonitis, abdominal abscess and PID subjects. This treatment regimen can be useful for anaerobic infections. Clinical registration number: NCT01473836.
authors.affiliation: Department of Clinical Infectious Diseases, Aichi Medical University Graduate School of Medicine, Aichi, Japan.
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Mikamo
authors.affiliation: Clinical Research, Development Japan, Pfizer Japan Inc., Tokyo, Japan. Electronic address: miyako.matsumizu@pfizer.com.
authors.forename: Miyako
authors.initials: M
authors.lastname: Matsumizu
authors.affiliation: Clinical Statistics, Development Japan, Pfizer Japan Inc., Tokyo, Japan.
authors.forename: Yoshiomi
authors.initials: Y
authors.lastname: Nakazuru
authors.affiliation: Department of Clinical Infectious Diseases, Aichi Medical University Graduate School of Medicine, Aichi, Japan; Clinical Research, Development Japan, Pfizer Japan Inc., Tokyo, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Nagashima
mesh_terms: D018784:Abdominal Abscess / Q000188:drug therapy* / Q000382:microbiology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001419:Bacteria / Q000187:drug effects / Q000302:isolation & purification; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008795:Metronidazole / Q000009:adverse effects* / Q000627:therapeutic use*; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D000292:Pelvic Inflammatory Disease / Q000188:drug therapy* / Q000382:microbiology; D010538:Peritonitis / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology; D055815:Young Adult
chemical_list: D000890:Anti-Infective Agents; D008795:Metronidazole
keywords: Abdominal abscess; Ceftriaxone; Infectious peritonitis; Metronidazole; Metronidazole/ceftriaxone combination therapy; Pelvic inflammatory diseases