In vitro susceptibilities to 23 antimicrobial agents of Haemophilus influenzae from pediatric patients in Japan

Abstract

One hundred eighty-six clinical isolates of Haemophilus influenzae (H. influenzae) collected from January 1996 through December 1997 from 182 pediatric patients and 16 isolates from blood or cerebrospinal fluid (CSF) of 13 patients with bacteremia and purulent meningitis collected during the last ten years were examined for in vitro susceptibilities to 23 antibiotic agents, including 3 penicillins, 9 cephalosporins, 4 carbapenems and others, as well as for their encapsulated types and β-lactamase production. Ceftriaxone (a third generation cephalosporin) had the highest activity against the strains in this study (minimal inhibitory concentration, MIC90 of 0.025 μg/ml) and cefditoren (a new oral cephalosporin) was the most active oral antimicrobial agent (MIC90 of 0.05 μg/ml). Meropenem had a much higher activity against H. influenzae (MIC90 of 0.2 μg/ml) than the other carbapenems (imipenem, MIC90 of 1.56 μg/ml, panipenem, MIC90 of 1.56 μg/ml, and biapenem, MIC90 of 3.13 μg/ml). Regarding the serotyping of the encapsulated strains, 172 strains (85.1%) were nontypeable and 30 (14.9%) were serotyped (24 strains of type b, 4 strains of type e, one each of type a and c). Fifteen of the strains isolated from blood and CSF were type b and one was nontypeable. Sixteen of 202 strains (7.9%) produced β-lactamase and all of them produced both penicillinase and cephalosporinase. The production of β-lactamase in this study was lower than that reported in previous studies [1-3]. In this study, some strains were found against which the MICs of carbapenems were very high (highest MIC of imipenem was 12.5 μg/ml, of panipenem was 6.25 μg/ml and of biapenem was 25 μg/ml). Therefore, we assayed the binding affinities of imipenem for each of penicillin-binding proteins (PBPs) about one of these resistant strains. In resistant strains, inhibitory concentrations (IC50) of imipenem for PBP4 and 5 were much higher than those in susceptible strains. Thus, the results demonstrate the decrease of the affinity of imipenem for PBP4 and 5. It seems, therefore, that the major factor in the resistance to imipenem of H. influenzae was the low affinity of PBP4 and 5 for the drug.