Antimicrobial Susceptibility of Haemophilus influenzae in the Respiratory Tracts of Patients with Cystic Fibrosis

Antimicrobial Susceptibility of Haemophilus influenzae in the Respiratory Tracts of Patients with Cystic Fibrosis

Lieke V. M. Mé°ˆler,1,2 Annette G. Regelink,1 Henny Grasselier,1 Loek van Alphen,1,* and Jacob Dankert1

Department of Medical Microbiology, University of Amsterdam, Academic Medical Center, Amsterdam,1 and Department of Medical Microbiology, University Hospital Groningen and Laboratory for Public Health, Groningen,2 The Netherlands

Received 3 March 1997/Returned for modification 19 July 1997/Accepted 26 November 1997

We analyzed the antimicrobial susceptibilities of Haemophilus influenzae isolates from 157 sputum specimens prospectively collected from 39 cystic fibrosis (CF) patients during a 2-year study. These isolates were characterized by random amplified polymorphic DNA analysis and major outer membrane protein (MOMP) analysis to identify H. influenzae strains and MOMP variants and to assess their persistence in the respiratory tract. Among the 247 H. influenzae isolates, 16 (6.5%) produced beta -lactamase. The 231 beta -lactamase-negative isolates represented 85 H. influenzae strains, 61 MOMP variants derived from 27 of these strains, and 85 persistent isolates identical to strains or MOMP variants. All beta -lactamase-negative isolates were tested for susceptibility to ampicillin, amoxicillin-clavulanic acid, cefuroxime, cefotaxime, cefaclor, imipenem, tetracycline, and trimethoprim-sulfamethoxazole by disk diffusion testing. Eleven (13%) H. influenzae strains, 18 (30%) MOMP variants, and 30 (35%) persistent isolates were resistant to one or more of the antibiotics tested. Antimicrobial susceptibility was decreased among MOMP variants and persistent isolates compared to nonpersistent H. influenzae strains, and changes in susceptibility occurred irrespective of MOMP variation. We conclude that the decreased antimicrobial susceptibility of H. influenzae during persistence contributes to the poor eradication of H. influenzae from the respiratory tracts of CF patients.

* Corresponding author. Mailing address: Laboratory for Vaccine Development and Mechanisms of Immunity (L.V.M.), National Institute for Public Health and Environment (RIVM), P.O. Box 1, NL-3720 BA Bilthoven, The Netherlands. Phone: 31-30-2742701. Fax: 31-30-2744429. E-mail: Loek.van.Alphen@RIVM.NL.