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

Lieke V. M. M鰈ler, Annette G. Regelink, Henny Grasselier, Loek van Alphen, and Jacob Dankert. Antimicrobial Susceptibility of Haemophilus influenzae in the Respiratory Tracts of Patients with Cystic Fibrosis. Antimicrob. Agents Chemother., Feb 1998; 42: 319 - 324
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Antimicrobial Susceptibility of Haemophilus influenzae in the Respiratory Tracts of Patients with Cystic Fibrosis

Lieke V. M. M鰈ler,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 prospectivelycollected from 39 cystic fibrosis (CF) patients during a 2-yearstudy. These isolates were characterized by random amplified polymorphicDNA analysis and major outer membrane protein (MOMP) analysisto identify H. influenzae strains and MOMP variants and to assesstheir persistence in the respiratory tract. Among the 247 H. influenzaeisolates, 16 (6.5%) produced $beta$ -lactamase. The 231 $beta$ -lactamase-negativeisolates represented 85 H. influenzae strains, 61 MOMP variantsderived from 27 of these strains, and 85 persistent isolates identicalto strains or MOMP variants. All $beta$ -lactamase-negative isolateswere tested for susceptibility to ampicillin, amoxicillin-clavulanicacid, 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 antibioticstested. Antimicrobial susceptibility was decreased among MOMPvariants and persistent isolates compared to nonpersistent H.influenzae strains, and changes in susceptibility occurred irrespectiveof MOMP variation. We conclude that the decreased antimicrobialsusceptibility of H. influenzae during persistence contributesto the poor eradication of H. influenzae from the respiratorytracts of CF patients.

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