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JAC Advance Access published online on May 25, 2005
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dki167
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© The Author 2005. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oupjournals.org
Received December 15, 2004
Revised April 19, 2005
Accepted April 19, 2005

Original article

Susceptibility of European {beta}-lactamase-positive and -negative Haemophilus influenzae isolates from the periods 1997/1998 and 2002/2003

A. C. Fluit 1*, A. Florijn 1, J. Verhoef 1, and D. Milatovic 1

1 Eijkman-Winkler Center, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands

* To whom correspondence should be addressed.
A. C. Fluit, E-mail: A.C.Fluit{at}lab.azu.nl


  Abstract

Aims: To test prospectively the activity of cefixime and comparators against Haemophilus influenzae from Europe and to compare the susceptibilities of isolates from 1997/1998 with isolates from 2002/2003 paying special attention to the epidemiology of amoxicillin resistance.

Methods: MICs of antibiotics were determined using broth microdilution. For {beta}-lactamase-negative isolates with reduced susceptibility to amoxicillin, the nucleotide sequence of the penicillin-binding domain of PBP3 was determined.

Results: The prevalence of {beta}-lactamase-positive isolates in certain countries has reached 38%. During the period 1997/1998, 8.8% of the isolates were {beta}-lactamase-negative and non-susceptible to amoxicillin (BLNAR). During the period 2002/2003, 9.6% of the isolates were BLNAR. The emergence of the BLNAR phenotype of H. influenzae was demonstrated in all countries with a prevalence ranging from 2% to 20%. The penicillin-binding domain of PBP3 from 30 sequenced isolates showed known amino acid substitutions, although no amino acid changes were observed in two BLNAR isolates. Clonal spread of BLNAR strains was limited or absent in our study. Both {beta}-lactamase-producing and BLNAR strains of H. influenzae were fully susceptible to cefixime. However, neither {beta}-lactamase-producing nor BLNAR isolates were fully susceptible to the other cephalosporins tested. All isolates were also fully susceptible to levofloxacin, moxifloxacin, azithromycin and telithromycin.

Conclusions: The prevalence of the BLNAR phenotype in Europe is increasing, but no new amino acid substitutions were detected in the penicillin-binding domain of PBP3. Cefixime remains a useful treatment option for respiratory tract infections, including in areas with increasing resistance problems.

Keywords: PBP3; surveillance; cefixime.
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