Macrolide Susceptibility and β-Lactamase Production among Haemophilus influenzae Isolates in the United States, 1996–1997

Haemophilus influenzae is one of several causes of otitis media, sinusitis, acute exacerbation of chronic bronchitis, and pneumonia. These diseases often are treated empirically with oral antibiotics, and the results of national surveillance studies of antibiotic susceptibility provide a basis for rational therapy. The aim of the present study was to determine the prevalence of β-lactamase production and the macrolide susceptibility of recent isolates of H. influenzae in the United States. (This work was presented in part at the Fourth International Conference on the Macrolides, Azalides, Streptogramins and Ketolides, 21 to 23 January 1998, Barcelona, Spain.) Methods. The MICs of azithromycin, clarithromycin, and erythromycin against consecutive clinical isolates of H. influenzae recovered from the sputum of patients with community-acquired respiratory tract infections were determined by 68 hospital laboratories between 1 March 1996 and 31 July 1997. All determinations were performed according to National Committee for Clinical Laboratory Standards (NCCLS) guidelines (5) by the broth dilution method using microtiter trays prepared for the study by PML Microbiologicals (Tualatin, Oreg.). Susceptibility was evaluated on the basis of NCCLS interpretive breakpoints (no breakpoint has been established for erythromycin) (6). β-Lactamase production was determined by a nitrocefin-based filter paper spot test. Results and discussion. The in vitro activities of the study antibiotics are presented in Table ​Table1.1. On the basis of weight, azithromycin was more active than erythromycin, and both were more active than clarithromycin. Comparison of the data in Tables ​Tables11 and ​and22 suggests that the in vitro activities of azithromycin and clarithromycin have not changed significantly since they became commercially available in 1992 and 1991, respectively. TABLE 1 In vitro activities (MICs)a of macrolides against isolates of H. influenzae, 1996–1997 TABLE 2 Published in vitro activities (MICs)a of azithromycin and clarithromycin against isolates of H. influenzae There was little variation by region in the percentages of susceptibility to either antibiotic (Table ​(Table3),3), and in all regions, a greater proportion of the H. influenzae isolates was susceptible to azithromycin than to clarithromycin. Our results are similar to those of Doern and associates (2), who found the susceptibilities to azithromycin and clarithromycin of 1,537 isolates of H. influenzae at 30 centers in 1994 and 1995 to be >99.5 and 71%, respectively. The difference in susceptibility of H. influenzae to the two antibiotics is possibly attributable to the presence of an extra positive charge on the azithromycin molecule, which has been reported to enhance its ability to penetrate the gram-negative bacterial cell wall (3). TABLE 3 Susceptibility to azithromycin and clarithromycin of isolates of H. influenzae, 1996–1997 Overall, 32% of the H. influenzae isolates produced β-lactamase, a prevalence similar to that observed by Doern and colleagues in their 1994 and 1995 isolates (34.6%) (2). In our study, there was little geographic variation in the prevalence of β-lactamase production. In the East (28 hospitals, 835 isolates), 36% of isolates were β-lactamase positive (median, 35%; range, 13–66%). In the Midwest (26 hospitals, 757 isolates), 31% of isolates were β-lactamase positive (median, 30%; range, 7–50%). In the West (14 hospitals; 406 isolates), 29% of isolates were β-lactamase positive (median, 29%; range 7–57%).