[Antimicrobial activity of fosfomycin under various conditions against standard strains, beta-lactam resistant strains, and multidrug efflux system mutants].
The purpose of this study was to evaluate the possible benefit of fosfomycin (FOM) as prophylactic antibiotic in terms of antimicrobial activity and the potential of inducibility of beta-lactamase, compared with cefazolin, cefotiam, cefmetazole, and piperacillin that are commonly used as perioperative agents. The in vitro activity of FOM against aerobic Gram-negative bacteria using Mueller-Hinton agar or nutrient agar supplemented with glucose-6-phosphate (G6P) as tested medium increased within a range from 2 to 256 times the activity in the medium without G6P. However, the susceptibility of Gram-positive bacteria to FOM remained largely unchanged with or without G6P. There was no aerobic- or anaerobic-bacteria which changed susceptibility against beta-lactam antibiotics under various tested medium conditions. FOM demonstrated strong bactericidal activity against Escherichia coli and Pseudomonas aeruginosa in a dose dependent manner, and decreased viable cell counts of Staphylococcus aureus. In the case of P. aeruginosa, transmission electron micrographs study revealed that numerous lysed cells were present 2 hours after treatment with FOM at four times the MIC. First and second generation cephalosporins induced AmpC-type beta-lactamase in a dose dependent manner among beta-lactamase inducible strains of P. aeruginosa and Enterobacter cloacae. On the other hand, inducible activity of FOM on beta-lactamase production was less than 1/25 to 1/65 compared with those of cephalosporins. In addition, FOM maintained strong antimicrobial activity for over then 20 years after marketing, because of the excellent stability against various types of beta-lactamase produced by plasmid-carrying bacteria and clinical isolates. FOM was not extruded by four types of efflux systems, such as MexAB-OprM, MexCD-OprJ, MexXY/ OprM and MexEF-OprN, however beta-lactam antibiotics were substrates of MexAB-OprM and MexCD-OprJ. In conclusion, FOM provides adequate coverage for both aerobic Gram-positive and Gram-negative bacteria causing postoperative infections. Further, FOM would not select/concentrate beta-lactamase producing bacteria in the clinical fields and would not be a substrate for multidrug efflux system of P. aeruginosa.
Infectious Disease Research Laboratories, Meiji Seika Kaisha, LTD., 760 Morooka-cho, Kohoku-ku, Yokohama 222-8567, Japan.
Takeshi
T
Mikuniya
Toru
T
Hiraishi
Kazunori
K
Maebashi
Takashi
T
Ida
Toshihiko
T
Takata
Muneo
M
Hikida
Sakuo
S
Yamada
Naomasa
N
Gotoh
Takeshi
T
Nishino
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001431:Bacteriological Techniques; D004305:Dose-Response Relationship, Drug; D024901:Drug Resistance, Multiple, Bacterial; D005578:Fosfomycin / Q000494:pharmacology*; D006088:Gram-Negative Aerobic Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D018440:beta-Lactam Resistance
D000900:Anti-Bacterial Agents; D005578:Fosfomycin