Determination of intracellular and extracellular beta-lactamase activities of Pseudomonas aeruginosa after exposure to beta-lactams in vitro and in vivo.
Beta-lactamase production in Pseudomonas aeruginosa was determined in in-vitro models and in rat pouch infection models after exposure to ceftazidime, imipenem, and piperacillin. Exposure of 28 P. aeruginosa strains to 1/4 minimum inhibitory concentration (MIC) of ceftazidime, imipenem, and piperacillin for 24 h enhanced intracellular beta-lactamase activities in 14, 22, and 6 strains, respectively, of the 28 clinical strains tested, and enhanced extracellular beta-lactamase activities which were not detected without exposure to antibiotics, in 7, 23, and 1 of the 28 strains, respectively. Extracellular beta-lactamase activity from P. aeruginosa S-1278, producing an inducible beta-lactamase, scarcely increased after exposure to ceftazidime and piperacillin 24 h after incubation, while the activity increased after exposure to imipenem over the range of 1/8 to 8 MIC. In the rat granuloma pouch models infected with P. aeruginosa S-1278, ceftazidime and piperacillin, after single administration (20 mg/kg) and serial administration (20 mg/kg per day x 3 days), did not enhance extracellular beta-lactamase activities. However, the activities were enhanced with single and serial administrations of imipenem, and levels over 10 mU/ml were detected until the third day. The beta-lactamase activity, similar to the activity found in rat pouches after serial administration of imipenem, inactivated various cephalosporins. In conclusion, extracellular beta-lactamase activity was detected both in vitro and in vivo after exposure to a good inducer, and extracellular beta-lactamase remained at infection site at levels that could inactivate cephalosporins.
Matsumura
N
N
Third Research Department, Research Laboratories, Toyama Chemical Co., Ltd., 2-4-1 Shimookui, Toyama 930-8508, Japan. NAOKI MATUMURA@toyama-chemical.co.jp
Minami
S
S
Araki
H
H
Hori
R
R
Ogake
N
N
Watanabe
Y
Y
D000818:Animals; D000900:Anti-Bacterial Agents / Q000145:classification / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured / Q000187:drug effects; D006099:Granuloma / Q000188:drug therapy; D008297:Male; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D001618:beta-Lactamases / Q000187:drug effects / Q000378:metabolism*; D047090:beta-Lactams / Q000145:classification / Q000494:pharmacology* / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D001618:beta-Lactamases