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

• Authors: C Pichardo, M del Carmen Conejo, M Bernabéu-Wittel, A Pascual, M E Jiménez-Mejías, M de Cueto, M E Pachón-Ibáñez, I García, J Pachón, L Martínez-Martínez
• Journal: Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases (Clin Microbiol Infect) Vol. 11 Issue 1 Pg. 31-8 (Jan 2005) ISSN: 1198-743X [Print] England
• PMID: 15649301 (Publication Type: Journal Article)

Chemical References

• Anti-Bacterial Agents
• Carbapenems
• Cephalosporins
• Porins
• Thienamycins
• Imipenem
• Cefepime
• beta-lactamase FOX-5
• beta-Lactamases
• Meropenem

Topics

• Animals
• Anti-Bacterial Agents (pharmacology, therapeutic use)
• Carbapenems (pharmacokinetics, pharmacology, therapeutic use)
• Cefepime
• Cephalosporins (pharmacokinetics, pharmacology, therapeutic use)
• Colony Count, Microbial
• Guinea Pigs
• Humans
• Imipenem (pharmacokinetics, pharmacology, therapeutic use)
• Klebsiella Infections (drug therapy, microbiology)
• Klebsiella pneumoniae (drug effects, enzymology)
• Lung (microbiology)
• Meropenem
• Microbial Sensitivity Tests
• Pneumonia, Bacterial (drug therapy, microbiology)
• Porins (genetics)
• Thienamycins (pharmacokinetics, pharmacology, therapeutic use)
• Treatment Outcome
• beta-Lactamases (genetics, metabolism)