In vitro investigation of the indirect pathogenicity of beta-lactamase-producing microorganisms in the nasopharyngeal microflora

Abstract

Nasopharyngeal microflora contains some beta-lactamase-producing microorganisms. In this study, we investigated in vitro on the indirect pathogenicities of Haemophilus parainfluenzae (H. parainfluenzae) and Moraxella catarrhalis (M. catarrhalis) against the antipneumococcul activities of some beta-lactams. We compared the antimicrobial and bactericidal activities of beta-lactams against penicillin-susceptible Streptococcus pneumoniae (PSSP) with or without presence of the enzymes of two species of beta-lactamase-producing microorganisms, H. parainfluenzae and M. catarrhalis. When adding the enzymes extracted from these two beta-lactamase-producing microorganisms in equivalent amounts of 10(7) CFU/spot, the minimum inhibitory concentrations of amoxicillin (AMPC) and cefaclor (CCL) increased to >64 microg/mL. Even third-generation cephalosporins, such as cefditren (CDTR) and ceftriaxone (CTRX) showed marked increases with the enzyme of M. catarrhalis. In time-kill kinetics, same phenomenon was observed in mixed culture indicating the indirect pathogenicities of distinct bacteria, not extracted enzymes, on the cidal activities of beta-lactams against PSSP. Clavulanic acid (CVA)/AMPC, faropenem (FRPM), and imipenem (IPM) were not affected by these beta-lactamase-producing strains with respect to their activities against PSSP. However, these two beta-lactamase-producing strains and their enzymes did not show any significant influence on the antipneumococcul activities of beta-lactams, until the number of bacterial cells reached >10(8) CFU/mL. Our results suggest that these two species of beta-lactamase-producing microorganisms in the nasopharyngeal microflora may act as indirect pathogens on the antipneumococcul activities of beta-lactams with reflecting their substrate profiles, but this is dependent on sufficient amounts of enzyme for their influence as indirect pathogens.