The in vitro activity of FK037, a new parenteral cephalosporin, against anaerobic bacteria

• Published in: CHEMOTHERAPY Vol. 42; no. Supplement3; pp. 37 - 45
• Main Authors: Kato, Naoki, Kato, Haru, Tanaka, Kaori, Watanabe, Kunitomo, Ueno, Kazue
• Format: Journal Article
• Language: Japanese
• Published: Japanese Society of Chemotherapy 1994
• Subjects: Bacteroides fragilis; Clostridium difficile
• ISSN: 0009-3165; 1884-5894
• DOI: 10.11250/chemotherapy1953.42.Supplement3_37

The in vitro activity of FK037, a new parenteral cephalosporin, was compared with that of cefpirome (CPR), ceftazidime (CAZ) and flomoxef (FMOX) against anaerobic bacterium. A fastidious facultative anaerobic bacteria, Gardnerella vaginalis was also studied. FK037 had broad spectrum against reference strains of anaerobes, inhibiting many anaerobic bacterial strains at 3.13μg/ml or less. However, FK037 had weak activity against Eubacterium lentum ATCC 25559, Clostridium difficile GAI 10029, the Bacteroides fragilis group, Prevotella bivia ATCC 29303, and Fusobacterium varium ATCC 8501, with the MICs of 50μg/ml or more. FK037 was active against fresh clinical isolates of Peptostreptococcus anaerobius, Peptostreptococcus asaccharolyticus, Clostridium perfringens, Mobiluncus spp, Porphyromonas gingivalis, and G. vaginalis, a fastidious facultative anaerobic bacteria; 90% of each bacteria were inhibited by 0.78μg/ml or less of FK037. FK037 inhibited 50% of B. fragilis at 25μg/ml. The activity of FK037 was comparable to that of CPR and CAZ but less than that of FMOX. The activity of FK037 against Fusobacterium nucleatum and F. varium decreased when inoculum size was increased from 106 to 108 CFU/ml. Little influence of inoculum size on the activity of FK037 was observed for the other strains tested. Medium pH affected the activity of FK037 against F. varium and Bacteroides gracilis but not against the other organisms tested. FK037 was bactericidal at 4 times the MIC against B. fragilis. FK037 was more stable than CPR but less stable than CAZ against hydrolysis by β-lactamases, cefuroximase type I, derived from B. fragilis. A 5-day dosing of FK037 induced emergence of C. difficile in higher number than that of CAZ and FMOX in mouse ceca on 7-day after finishing administration of the compounds.