Study objectives: The Memphis region historically has had high pneumococcal antibiotic resistance rates. In recent years, we have seen a significant shift in antibiotic use away from β-lactams toward the newer quinolones and macrolides. We hypothesized that these changes would cause a shift in pneumococcal antibiotic resistance patterns.Design: Retrospective cohort study.Setting: A large private hospital system.Patients and methods: We analyzed the antibiotic susceptibility patterns of 2,152 pneumococcal isolates obtained in the Memphis area from 1996 to 2001. Isolates were categorized as invasive or noninvasive and antibiotic resistance was classified according to the 2000 guidelines of the National Committee for Clinical Laboratory Standards.Results: Over the study period, the proportion of penicillin-susceptible noninvasive pneumococcal isolates taken from children increased from 22 to 44% (p = 0.0004 [for trend across the 6-year period]). In noninvasive isolates taken from adults, penicillin susceptibility increased from 22 to 55% (p = 0.002), with a trend toward increasing sensitivity to cefotaxime (p = 0.02) in noninvasive isolates over the same period. The proportion of isolates with high-level penicillin resistance (ie, minimum inhibitory concentration, ≥ 4 μg/mL) also decreased between 1996 and 2001 (p = 0.003). Clindamycin resistance in adult noninvasive isolates also declined (p = 0.002). The only adverse trend observed over this period was an increase in erythromycin resistance in noninvasive isolates from adults (p = 0.01). Resistance rates were significantly higher in children than in adults and were higher in noninvasive isolates than in invasive isolates.Conclusions: The stabilization of β-lactam resistance rates in our region suggests that a continuous increase in pneumococcal resistance to antibiotics is not inevitable and may be avoidable.