Journal of Antimicrobial Chemotherapy, Vol 41, 367-372, Copyright © 1998 by The British Society for Antimicrobial Chemotherapy
O Mimoz, A Jacolot, C Padoin, M Tod, K Samii and O Petitjean
The activities of cefepime and amikacin alone or in combination against an
isogenic pair of Enterobacter cloacae strains (wild type and stably
derepressed, ceftazidime-resistant mutant) were compared using an
experimental model of pneumonia in non-leucopenic rats. Animals were
infected by administering 8.4 log10 cfu of E. cloacae intratracheally, and
therapy was initiated 12 h later. At that time, the animals' lungs showed
bilateral pneumonia and contained more than 7 log10 E. cloacae cfu/g
tissue. Because rats eliminate amikacin and cefepime much more rapidly than
humans, renal impairment was induced in all animals to simulate the
pharmacokinetic parameters of humans. In-vitro susceptibilities showed an
inoculum effect with cefepime proportional to the bacterial titre against
the two strains, but more pronounced with the stably derepressed mutant
strain, whereas with bacterial concentrations of up to 7 log10 cfu/mL, no
inoculum effect was observed with amikacin. In-vitro killing indicated that
antibiotic combinations were synergic only at intermediate concentrations.
At peak concentrations, the combination was merely as effective as amikacin
alone. At trough concentrations, a non-significant trend towards the
superiority of the combination over each antibiotic alone was noted.
Moreover, cefepime was either bacteriostatic or permitted regrowth of the
organisms in the range of antibiotic concentrations tested. Although each
antibiotic alone failed to decrease bacterial counts in the lungs,
regardless of the susceptibility of the strain used, the combination of
both antibiotics was synergic and induced a significant decrease in the
lung bacterial count 24 h after starting therapy when compared with tissue
bacterial numbers in untreated animals or animals treated with either
antibiotic alone. No resistant clones emerged during treatment with any of
the antibiotic regimens studied.
ORIGINAL ARTICLES
Cefepime and amikacin synergy in vitro and in vivo against a ceftazidime-resistant strain of Enterobacter cloacae
Service d'Anesthesie-Reanimation Chirurgicale, Hopital Bicetre, Le Kremlin-Bicetre, France. darkb@imaginet.fr
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