Increasing prevalence of ampicillin-resistant, non-beta-lactamase-producing strains of Haemophilus influenzae in children in Japan

Among Haemophilus influenzae isolated from children with respiratory tract infections, the evolution of ampicillin resistance was investigated during 1996 and 1997 in Japan. beta-Lactamase production was assessed and minimum inhibitory concentrations (MICs) of eight antimicrobial agents were determined using a broth microdilution method in Mueller-Hinton-lysed horse blood medium. Of 74 H. influenzae, 11 strains (14.9%) produce beta-lactamase and were thus highly resistant to ampicillin (MIC of >4.0 mu g/ mi). In addition, moderate resistance to ampicillin, defined as an MIC of greater than or equal to 1.0 mu g/ml, was noted in 44.4% of a II beta-lactamase-negative isolates. These beta-lactamase-negative ampicillin-resistant (BLNAR) organisms were resistant to other cephalosporins such as cefpodoxime and cefdinir, while beta-lactamase-producing strains were susceptible to them. Cefditoren, cefteram, and minocycline were active against all strains studied, whereas cefaclor and clarithromycin were inactive against all H. influenzae isolates in this study. Results indicate that BLNAR strains have emerged among children with respiratory tract infections in Japan.