Treatment of experimental pneumonia in rats caused by a PER-1 extended-spectrum beta-lactamase-producing strain of Pseudomonas aeruginosa.
J Antimicrob Chemother
; 44(1): 91-7, 1999 Jul.
Article
em En
| MEDLINE
| ID: mdl-10459815
ABSTRACT
The antibacterial activity of imipenem, cefepime and piperacillin-tazobactam alone or in combination with amikacin against a Pseudomonas aeruginosa strain producing an extended-spectrum beta-lactamase (PER-1) were compared using an experimental model of pneumonia in non-leucopenic rats. Animals were infected intratracheally with 8.0 +/- 0.4 log10 cfu of P. aeruginosa, and therapy was initiated 3 h later, by which time animal lungs showed bilateral pneumonia containing >7 log10 P. aeruginosa cfu/g of tissue. Since rats eliminate antibiotics much more rapidly than humans, renal impairment was induced in all animals to simulate the pharmacokinetic parameters of humans. MICs determined using an inoculum of 4 log10 cfu/mL were as follows imipenem, 1 mg/L; cefepime, 8 mg/L; piperacillin-tazobactam, 32 mg/L; and amikacin, 16 mg/L. A noticeable inoculum effect was observed with the four antimicrobial agents tested, which was greatest for cefepime and piperacillin-tazobactam. In-vitro studies indicated that imipenem was the beta-lactam with the greatest bactericidal effect and that amikacin was synergic only in combination with cefepime and imipenem. Cefepime and piperacillin-tazobactam alone failed to decrease bacterial counts in the rats' lungs 60 h after therapy onset, whereas imipenem and, to a lesser extent, amikacin significantly reduced the number of viable microorganisms. Combination of amikacin with any of the three beta-lactams tested was synergic, despite a high amikacin MIC for the infecting strain. These results paralleled our in-vitro data showing a marked inoculum effect for cefepime and piperacillin-tazobactam. Based on the results of this study, the best treatment for infections caused by this type of extended-spectrum beta-lactamase-possessing strain would be imipenem plus amikacin.
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Base de dados:
MEDLINE
Métodos Terapêuticos e Terapias MTCI:
Plantas_medicinales
Assunto principal:
Pseudomonas aeruginosa
/
Infecções por Pseudomonas
/
Beta-Lactamases
/
Pneumonia Bacteriana
/
Quimioterapia Combinada
/
Antibacterianos
Idioma:
En
Revista:
J Antimicrob Chemother
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
França