The minimum inhibitory concentration (MIC) of five antibiotics and the presence of resistance genes was determined in 163 Haemophilus influenzae isolates collected over 13 years (1987–2000) in four two-yearly sampling periods from patients with respiratory tract infections. The prevalence of β-lactamase-negative ampicillin-susceptible strains was approximately 80% over the sampling period although fewer strains (65·9%) were recovered in the period 1995–1997. TEM-1 type β-lactamase-producing strains were less frequent starting at 15·6% and declining to 2·2% in the final sampling period. Low-β-lactamase-negative ampicillin-resistant (BLNAR) strains were uncommon in 1987–1989 (2·2%), peaked to 19·5% in 1995–1997, but fell back to 11·1% by 2000. Fully BLNAR strains were not detected until the last sampling period (6·7%). The MICs of ampicillin, levofloxacin, cefditoren and ceftriaxone remained stable but there was an eight-fold increase in the MIC of cefdinir over the sampling period. Pulsed-field gel electrophoresis of DNA digests showed that three representative BLNAR strains were genetically distinct and 11 DNA profiles were identified among 17 low-BLNAR strains. These data suggest that the number of genetically altered BLNAR and low-BLNAR strains are increasing in Japan.
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