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Between February and June of 1997, a large number of community-acquired respiratory tract isolates of Haemophilus influenzae (n = 1,077) and Moraxella catarrhalis (n = 503) from 27 U.S. and 7 Canadian medical centers were characterized as part of the SENTRY Antimicrobial Surveillance Program. Overall prevalences of β-lactamase production were 33.5% in H. influenzae and 92.2% in M. catarrhalis with no differences noted between isolates recovered in the United States and those from Canada. Among a total of 21 different antimicrobial agents tested, including six cephalosporins, a β-lactamase inhibitor combination, three macrolides, tetracycline, trimethoprim-sulfamethoxazole (TMP-SMX), rifampin, chloramphenicol, five fluoroquinolones, and quinupristin-dalfopristin, resistance rates of >5% with H. influenzae were observed only with cefaclor (12.8%) and TMP-SMX (16.2%).