ANTIBIOTIC-RESISTANCE AMONG CLINICAL ISOLATES OF HAEMOPHILUS-INFLUENZAE IN THE UNITED-STATES IN 1994 AND 1995 AND DETECTION OF BETA-LACTAMASE-POSITIVE STRAINS RESISTANT TO AMOXICILLIN-CLAVULANATE - RESULTS OF A NATIONAL MULTICENTER SURVEILLANCE STUDY

A total of 1,537 clinical isolates of Haemophilus influenzae were reco vered in 30 U.S. medical center laboratories between 1 November 1994 a nd 30 April 1995 and were characterized in a central laboratory with r espect to serotype and beta-lactamase production and the in vitro acti vities of 15 oral antimicrobial agents, Overall, 36.4% of the isolates were found to produce beta-lactamase, The rank order of activity of s is cephalosporins on the basis of MICs was cefixime > cefpodoxime > ee furoxime > loracarbef greater than or equal to cefaclor > cefprozil. O n the basis of current National Committee for Clinical Laboratory Stan dards (NCCLS) breakpoints, the overall percentages of isolates found t o be resistant or intermediate to these agents were as follows: 0.1, 0 .3, 6.4, 16.3, 18.3, and 29.8, respectively (National Committee for Cl inical: Laboratory Standards, Methods for dilution antimicrobial susce ptibility tests for bacteria that grow aerobically, 4th ed. M7-A4, 199 5), Azithromycin was, on a weight basis, the most potent of the macrol ides tested in this study, followed by erythromycin and then clarithro mycin, Azithromycin was typically fourfold more active than erythromyc in, which was, in turn, slightly more active than clarithromycin, Howe ver, when compared an the basis of the frequency of resistance determi ned by using current NCCLS breakpoints, there was essentially no diffe rence between azithromycin and clarithromycin, i.e., 0.5 and 1.9%, res pectively (P = 0.086), Interpretive breakpoints for erythromycin MIC t ests versus H. influenzae have not been developed, Resistance to other non-beta-lactam agents was variable, as follows: trimethoprim-sulfame thoxazole, 9.0%; chloramphenicol, 0.2%; tetracycline, 1.3%; and rifamp in, 0.3%. Two conspicuous findings in this study were the identificati on of 39 strains of H. influenzae that were beta-lactamase negative bu t ampicillin intermediate or resistant (BLNAR) and, even more surprisi ngly, 17 beta-lactamase-positive isolates that were resistant to amoxi cillin-clavulanate (BLPACR), Strains of H. influenzae in the first gro up have heretofore been very uncommon; organisms in the second group h ave not previously been described in the literature. The percentages o f all study isolates comprised of BLNAR and BLPACR organisms were 2.5 and 1.1, respectively, Overall resistance to ampicillin was thus 38.9% , and that to amoxicillin-clavulanate was 4.5%.