Rapidly Increasing Prevalence of β-Lactamase-Nonproducing, Ampicillin-Resistant <i>Haemophilus influenzae</i> Type b in Patients with Meningitis

Antimicrobial Agents and Chemotherapy - Tập 48 Số 5 - Trang 1509-1514 - 2004
Keiko Hasegawa1, Naoko Chiba1, Reiko Kobayashi2, Somay Yamagata Murayama1, Satoshi Iwata3, Keisuke Sunakawa1, Takashi Takahashi1
1Kitasato Institute for Life Sciences &amp; Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku
2Pharmaceutical Research Center, Meiji Seika Kaisha Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama, Japan
3National Medical Center of Japan, Tokyo

Tóm tắt

ABSTRACT A total of 395 Haemophilus influenzae strains from 226 Japanese institutions participating in the Nationwide Surveillance Study Group for Bacterial Meningitis were received from 1999 to 2002. All strains were analyzed by PCR to identify the resistance genes, and their susceptibilities to β-lactam agents were determined. Of these strains, 29.1% were β-lactamase nonproducing and ampicillin (AMP) susceptible (BLNAS) and lacked all resistance genes; 15.4% were β-lactamase producing and AMP resistant and had the bla TEM-1 gene; 30.6% were β-lactamase nonproducing and AMP resistant (low-BLNAR) and had a Lys-526 or His-517 amino acid substitution in ftsI encoding PBP 3; 13.9% were β-lactamase nonproducing and AMP resistant (BLNAR) and had an additional substitution of Thr-385 in ftsI ; 9.1% were amoxicillin-clavulanic acid resistant (BLPACR I) and had the bla TEM-1 gene and a Lys-526 or His-517 amino acid substitution in ftsI ; and 1.8% showed resistance similar to that of the BLPACR I group (BLPACR II) but had bla TEM-1 gene and ftsI substitutions, as was the case for the BLNAR strains. All but three strains were serotype b. The prevalence of BLNAR strains has increased rapidly: 0% in 1999, 5.8% in 2000, 14.1% in 2001, and 21.3% in 2002. The MICs at which 90% of BLNAR isolates were inhibited were as follows: AMP, 16 μg/ml; cefotaxime, 1 μg/ml; ceftriaxone, 0.25 μg/ml; and meropenem, 0.5 μg/ml. All of these values were higher than those for the BLNAS counterpart strains. The relatively wide distributions of the β-lactam MICs for BLNAR strains presumably reflect variations in ftsI gene mutations. Pulsed-field gel electrophoresis suggested the rapid spread of specific H. influenzae type b strains throughout Japan. Expedited vaccination, rapid identification, and judicious antibiotic use could slow their spread.

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