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Antimicrobial Agents and Chemotherapy, August 2005, p. 3311-3316, Vol. 49, No. 8
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.8.3311-3316.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Efficacy of Cefepime and Imipenem in Experimental Murine Pneumonia Caused by Porin-Deficient Klebsiella pneumoniae Producing CMY-2 ß-Lactamase

Cristina Pichardo,^1* José Manuel Rodríguez-Martínez,⁴ María E. Pachón-Ibañez,¹ Carmen Conejo,⁴ José Ibáñez-Martínez,³ Luis Martínez-Martínez,^2,4, Jerónimo Pachón,^1,5 and Álvaro Pascual^2,4

Infectious Diseases Services, Hospitales Universitarios Virgen del Rocío, Departments of,¹ Microbiology,² Pathology, Hospital Universitario Virgen Macarena, Seville, and Departments of,³ Microbiology,⁴ Medicine, School of Medicine, University of Seville, Seville, Spain⁵

Received 7 June 2004/ Returned for modification 27 September 2004/ Accepted 15 May 2005

Previous studies have shown decreased in vitro activity of zwitterionic cephalosporins and carbapenems against porin-deficient Klebsiella pneumoniae expressing a plasmid-mediated AmpC-type ß-lactamase (PACBL). The in vitro and in vivo activities of cefepime and imipenem were evaluated against the porin-deficient strain K. pneumoniae C2 and its CMY-2-producing derivative [K. pneumoniae C2(pMG248)]. The MICs (in micrograms/milliliter) of cefepime and imipenem against K. pneumoniae C2 were 0.125 and 0.25, respectively, while the corresponding values against K. pneumoniae C2(pMG248) were 8 and 16. Cefepime showed a greater inoculum effect than imipenem against both strains. Imipenem showed a significant postantibiotic effect (>2 h) against K. pneumoniae C2(pMG248) at 1x, 2x, 4x, 6x, and 8x MIC. The maximum concentrations of drug in serum of cefepime and imipenem in a pneumonia model using mice were 124.1 and 16.9 µg/ml, respectively. T/MIC for K. pneumoniae C2 and C2(pMG248) were 1.29 h and 0.34 h for imipenem and 2.96 h and 1.27 h for cefepime. Both imipenem (30 mg/kg of body weight every 3 h) and cefepime (60 mg/kg every 4 h), administered for 72 h, increased the survival rate (86.6% and 100%) compared with untreated control animals (26.6%, P < 0.003) infected with K. pneumoniae C2. For the CMY-2-producing strain, imipenem, but not cefepime, increased the survival rate compared to the controls (86.6% and 40% versus 40%, P < 0.01). Bacterial concentration of the lungs was significantly decreased by both antimicrobials. In conclusion, imipenem was more active in terms of survival than cefepime for the treatment of murine pneumonia caused by a porin-deficient K. pneumoniae expressing PACBL CMY-2.

Present address: Service of Microbiology, University Hospital Marqués de Valdecilla, Santander, Spain.

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