[Selection of resistance mutants and bacteriostatic and bactericidal activity of meropenem and imipenem against...

To evaluate the inhibitory and bactericidal activity of meropenem and imipenem against multiresistant isolates of Acinetobacter spp and to compare the frequency of mutation for both antibiotics.

Minimum inhibitory concentrations were determined by the agar dilution method. Bactericidal activities were evaluated by killing curves method employing 8 times the MIC. One-step resistant mutant selection was performed by spreading more than 5 x 10(8) ufc/ml on agar Mueller Hinton plates containing 2, 4 and 8 times the MIC of meropenem or imipenem.

In the group of sensitive strains (MIC < 4 mg/l for imipenem and meropenem) we detected lower MIC for imipenem than meropenem (61.5% of the strains). Strains with reduced susceptibility to imipenem (MIC = 4 mg/l) were more sensitive to meropenem with MICs equivalents to the sensitive group. Bactericidal activity was detected in 6 hs for imipenem and in 24 hs for meropenem. Meropenem was bactericidal in 4 clinical isolates with MICs = 4 mg/l for imipenem and imipenem was bactericidal in laboratory mutants resistant to meropenem. It was no possible to select mutants resistant to imipenem but for meropenem the rate of mutation was 1.4 x 10(-9) to 1.0 x 10(-8). Mutants resistant to meropenem were susceptible to imipenem and 57% of them were stable.

From the laboratory point of view we consider that imipenem is more active than meropenem because it presents lower MICs, better bactericidal activity, and no risk to select resistance. However meropenem could be useful in some strains resistant to imipenem (MIC = 4 mg/l). Cross-resistance was no detected so we consider that both antibiotics should be tested against Acinetobacter spp. because they are not equivalents.