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
beta-lactamase FOX-5 were determined. Bactericidal activities were determined with the kill-curve method. A
pneumonia model in guinea-pigs was developed, and Cmax, t(1/2) and DeltaT/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
beta-lactamase FOX-5.