Activity of cefepime and carbapenems in experimental pneumonia caused by porin-deficient Klebsiella pneumoniae producing FOX-5 beta-lactamase.
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.
Pichardo
C
C
Service of Infectious Diseases, Hospitales Universitarios Virgen del Rocío, Spain.
del Carmen Conejo
M
M
Bernabéu-Wittel
M
M
Pascual
A
A
Jiménez-Mejías
M E
ME
de Cueto
M
M
Pachón-Ibáñez
M E
ME
García
I
I
Pachón
J
J
Martínez-Martínez
L
L
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015780:Carbapenems / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000077723:Cefepime; D002511:Cephalosporins / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D015169:Colony Count, Microbial; D006168:Guinea Pigs; D006801:Humans; D015378:Imipenem / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D007710:Klebsiella Infections / Q000188:drug therapy / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000201:enzymology; D008168:Lung / Q000382:microbiology; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D018272:Porins / Q000235:genetics; D013845:Thienamycins / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D002511:Cephalosporins; D018272:Porins; D013845:Thienamycins; D015378:Imipenem; D000077723:Cefepime; C444464:beta-lactamase FOX-5; D001618:beta-Lactamases; D000077731:Meropenem