Impact of new Clinical Laboratory Standards Institute Streptococcus pneumoniae penicillin susceptibility testing breakpoints on reported resistance changes over time.

The analysis comprised a total of 97,843 U.S. isolates from the Surveillance Network(®) database for the period 1996-2008. Penicillin resistance, when defined using the old Clinical Laboratory Standards Institute breakpoint (≥2 μg/ml), had an initial rise that started in 1996, peaked in 2000, declined until 2003, and rebounded through 2008 (15.6%, 23.2%, 15.4%, and 16.9%, respectively). Using the new Clinical Laboratory Standards Institute criteria and applying a breakpoint of ≥8 μg/ml to blood and bronchial isolates, resistance was unchanged (0.24% in 2003) but rose to 1.52% in 2008. Using the new meningitis criteria (≥0.12 μg/ml), resistance prevalence was 34.8% in 2008, whereas it was 12.3% using the old criteria (≥2 μg/ml) for cerebrospinal fluid isolates. The rise, fall, and subsequent rebound of penicillin resistance in the United States, presumably influenced by the introduction of the conjugate pneumococcal vaccine, is clearly seen with the old definition, but only the rebound is seen when the new criteria are applied. In the postvaccine period, isolates with minimum inhibitory concentrations of 1 and 2 μg/ml decline, whereas those with minimum inhibitory concentrations of 0.12-0.5 increase, which may signal the loss of resistant vaccine serotypes and the acquisition of resistance by nonvaccine serotypes.