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Antimicrobial Agents and Chemotherapy, December 1998, p. 3313-3314, Vol. 42, No. 12
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Macrolide Susceptibility and 
-Lactamase
Production among Haemophilus influenzae Isolates in the
United States, 1996-1997
Patricia A.
Hogan* and
Daniel J.
Sheehan
U.S. Pharmaceuticals Group, Pfizer Inc.,
New York, New York 10017
Received 23 April 1998/Returned for modification 10 August
1998/Accepted 10 September 1998
 |
ABSTRACT |
In 1996 and 1997, 68 hospital laboratories throughout the United
States determined the 
-lactamase production and susceptibility to
macrolides of 1,998 isolates of Haemophilus influenzae
obtained from patients with community-acquired respiratory tract
infections. The MICs at which 90% of the isolates are inhibited of
azithromycin, erythromycin, and clarithromycin were 4, 8, and 16 µg/ml, respectively. By National Committee for Clinical Laboratory
Standards interpretive criteria, 99 and 78% of the isolates were
susceptible to azithromycin and clarithromycin, respectively. The
prevalence of -lactamase production was 32%.
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TEXT |
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 -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). -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 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 1 and 2 suggests that the in vitro activities of azithromycin and clarithromycin have not changed significantly since they became commercially available in 1992 and
1991, respectively.
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TABLE 2.
Published in vitro activities
(MICs)a of azithromycin and clarithromycin
against isolates of H. influenzae
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|
There was little variation by region in the percentages of
susceptibility to either antibiotic (Table
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).
Overall, 32% of the
H. influenzae isolates produced
-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
-lactamase
production. In the East (28 hospitals, 835 isolates),
36% of isolates
were
-lactamase positive (median, 35%; range,
13-66%). In the
Midwest (26 hospitals, 757 isolates), 31% of
isolates were
-lactamase
positive (median, 30%; range, 7-50%). In
the West (14 hospitals;
406 isolates), 29% of isolates were
-lactamase positive (median,
29%; range 7-57%).
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ACKNOWLEDGMENTS |
We are grateful to Falk Communications and all the participating
clinical laboratories for their contribution to the study.
| |
FOOTNOTES |
*
Corresponding author. Mailing address: U.S.
Pharmaceuticals Group, Pfizer Inc., New York, NY 10017. Phone: (212)
573-3923. Fax: (212) 573-5916. E-mail: hoganp{at}pfizer.com.
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Antimicrobial Agents and Chemotherapy, December 1998, p. 3313-3314, Vol. 42, No. 12
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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