Enhanced in-vitro bactericidal activity of amikacin combined with latamoxef, cefotaxime and aztreonam against multi-resistant Enterobacter cloacae

The in-vitro interactions of amikacin with latamoxef, cefotaxime and aztreonam were studied for 20 multiresistant strains of Enterobacter cloacae isolated from clinical specimens of nosocomial origin. All the strains were resistant to amikacin, cefotaxime and aztreonam while 14 were resistant and six sensitive to latamoxef. Interactions were studied simultaneously by the killing curve technique after exposure to 16 mg/l of each antibiotic, whenever the MIC was above 16 mg/l and 1/4 the MICs whenever the MIC was less than or equal to 16 mg/l. Enhanced killing was defined as a greater than or equal to 2 log increase in bactericidal effect after three or five and a half or 24 h incubation with both drugs, as compared to the single most effective antibiotic alone. Aztreonam enhanced the rate of killing by amikacin for 13 strains, latamoxef for 12 strains and cefotaxime for 11 strains. For seven strains, all interactions exhibited enhanced killing over time. No antagonism was observed. The interaction results were independent of the MICs as well as of the underlying resistance mechanism to either of the combined antibiotics. The significance of these in-vitro results requires confirmation in vivo.