Screening of Neisseria gonorrhoeae for tolerant response to beta-lactam antibiotics

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Abstract
Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of penicillin, ampicillin, cefoxitin, and cefuroxime were determined for 103 beta-lactamase-negative Neisseria gonorrhoeae clinical isolates belonging to five different auxotypes. MBC determinations were base on killing 99.9% of the inoculum after 24 h of incubation. The MBC/MIC ratio was less than or equal to 8 for ampicillin, cefoxitin, and cefuroxime in all 103 strains. Two isolates which were very susceptible to penicillin (MIC, less than or equal to 0.015 micrograms/ml) had MBCs which were considerably greater than the MICs (MBC/MIC ratios, 32 and 64) for penicillin. A beta-lactamase-negative resistant subpopulation having the same auxotype as the total population was isolated from each of these two strains. Killing curve studies were in agreement with the existence of susceptible and resistant subpopulations, which may explain the high MBC/MIC ratios.