Journal of Antimicrobial Chemotherapy, Vol 39, 363-369, Copyright © 1997 by The British Society for Antimicrobial Chemotherapy
O Mimoz, A Jacolot, C Padoin, J Caillon, K Louchahi, M Tod, K Samii and O Petitjean
We developed an experimental model of pneumonia to evaluate the efficacy of
new antibiotic regimens against Enterobacter cloacae. Rats were infected by
administering 8.5 log10 cfu E. cloacae intratracheally, and therapy was
initiated 24 h later. At that time, animals' lungs showed bilateral
pneumonia containing more than 7 log10 cfu/g of tissue. Because rats
eliminate amikacin and cefepime much more rapidly than humans, renal
impairment was induced in all animals to simulate the pharmacokinetic
parameters in humans. Using this model, we compared the bactericidal
activities of cefepime and amikacin alone or in combination against the
same cefotaxime-susceptible E. cloacae strain. The MICs of cefepime and
amikacin for this strain were 0.5 and 2 mg/L, respectively. In-vitro
killing studies showed that antibiotic combinations were synergic only at
intermediate concentrations. At peak concentrations, the combination was
only as effective as amikacin alone. At trough concentrations, a
non-significant trend towards the superiority of the combination over
cefepime alone was found. In-vivo studies showed that each antibiotic alone
failed to decrease bacterial counts in the lungs except at 6 h, whereas the
combination of both antibiotics induced a significant decrease in the lung
bacterial count 6, 12 and 24 h after the onset of therapy when compared
with tissue bacterial numbers in untreated animals or animals treated with
either antibiotic alone. In-vivo synergy between cefepime and amikacin was
observed at the three time points studied. No resistant clones emerged
during treatment with any of the antibiotic regimens studied.
JOURNAL ARTICLE
Cefepime and amikacin synergy against a cefotaxime-susceptible strain of Enterobacter cloacae in vitro and in vivo
Service d'Anesthesie-Reanimation Chirurgicale, Hopital Bicetre, Universite Paris-Sud, Le Kremlin-Bicetre, France.
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