Activity of cefepime and carbapenems in experimental pneumonia caused by porin-deficient Klebsiella pneumoniae producing FOX-5 β-lactamase

Abstract

The in-vivo activities of cefepime, imipenem and meropenem against the porin-deficient strain Klebsiella pneumoniae C2 and its derivative K. pneumoniae C2(pMG252) coding for the AmpC-type β-lactamase FOX-5 were determined. Bactericidal activities were determined with the kill-curve method. A pneumonia model in guinea-pigs was developed, and Cmax, t1/2, and ΔT/MIC were calculated for the three agents tested. Animals were treated for 72 h with sterile saline (control group) or with cefepime, imipenem or meropenem (240 mg/kg/day, intramuscularly, three times daily). Bacterial counts in lungs (log10 CFU/g tissue) were determined by serial dilution. MICs (mg/L) of cefepime, imipenem and meropenem against K. pneumoniae C2/K. pneumoniae C2(pMG252), determined by macrodilution, were: 0.5/4, 0.5/0.5 and 0.25/0.5, respectively. Bacterial counts in the lungs of animals infected with K. pneumoniae C2 and treated with antimicrobial agents were always lower than in the control group (cefepime, 4.4 ± 0.5; imipenem, 4.6 ± 0.4; meropenem, 4.7 ± 0.5; control group, 5.6 ± 0.8; p < 0.01). No significant differences were observed among the groups receiving therapy (p >0.05). Bacterial lung clearance was higher in treated animals than in control animals following infection with K. pneumoniae C2(pMG252 (cefepime, 4.5 ± 0.4; imipenem, 4.0 ± 0.3; meropenem, 4.6 ± 0.4; control group, 6.1 ± 0.6; p < 0.01), with imipenem producing better clearance than either cefepime or meropenem (p < 0.05). Thus, in the guinea-pig pneumonia model, cefepime, imipenem and meropenem were each effective against the porin-deficient K. pneumoniae strain C2 and its derivative expressing the plasmid-mediated AmpC type β-lactamase FOX-5. © 2004 Copyright by the European Society of Clinical Microbiology and Infectious Diseases.