Pneumococcal resistance to the third-generation cephalosporins: clinical, laboratory and molecular aspects.

Widespread use of third-generation cephalosporins appears to have selected cephalosporin-resistant pneumococci associated with the failure of these agents in the management of meningitis. Breakpoints of 0.5 mg/l for intermediate and 2 mg/l for full resistance are proposed for the treatment of pneumococcal meningitis. As no disc tests reliably identify these breakpoints, MIC or E test confirmation of third-generation cephalosporin resistance is recommended for all strains found resistant to a 1 mug oxacillin disk. Resistant strains can be selected in a single transformation event, with PBP 2X gene rearrangements conferring low level resistance and PBP 1A gene rearrangements conferring full resistance.