Selection and transformation of non-beta-lactamase-mediated insusceptibility to beta-lactams in Haemophilus influenzae: lack of cross-resistance between carbapenems and other agents.


Non-beta-lactamase-mediated insusceptibility to beta-lactams was studied in Haemophilus influenzae. Mutants resistant to ampicillin were selected in a susceptible isolate, while phenotypically similar resistance was transformed from four wild-type isolates into a susceptible recipient. Ampicillin-selected mutants generally had reduced susceptibility to penicillins, cephalosporins and aztreonam. Reduced susceptibility to meropenem was less common, and susceptibility to imipenem was unaffected. MICs of three cephalosporins and aztreonam were much higher for the ampicillin-resistant transformants than for the recipient strain, and were generally equal to, or within one doubling dilution of, the concentrations that inhibited the donor parents. In contrast, reduced susceptibility to imipenem observed with one parent (MIC of 4 mg/l) was not transferred to the recipient (MIC of 0.5 mg/l). Meropenem inhibited 22 of 24 transformants tested at less than or equal to 0.12 mg/l, compared with MICs of greater than or equal to 0.5 mg/l for the donor parents and 0.03 mg/l for the recipient. These results indicated that the mechanisms that confer non-beta-lactamase-mediated insusceptibility to penicillins, cephalosporins and aztreonam in H. influenzae have little or no effect on susceptibility to carbapenems.


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