title: In vitro investigation of the indirect pathogenicity of beta-lactamase-producing microorganisms in the nasopharyngeal microflora.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Otorhinolaryngology, Department of Translational Medical Science, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan. tetsuumi@aol.com
authors.forename: Satoru
authors.initials: S
authors.lastname: Kaieda
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Yano
authors.forename: Naohiro
authors.initials: N
authors.lastname: Okitsu
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hosaka
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Okamoto
authors.forename: Matsuhisa
authors.initials: M
authors.lastname: Inoue
authors.forename: Haruo
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D000658:Amoxicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002433:Cefaclor / Q000494:pharmacology; D002443:Ceftriaxone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D044134:Haemophilus paragallinarum / Q000187:drug effects* / Q000201:enzymology; D015378:Imipenem / Q000494:pharmacology; D007769:Lactams / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D001936:Moraxella catarrhalis / Q000187:drug effects* / Q000201:enzymology; D010406:Penicillins / Q000494:pharmacology; D013997:Time Factors; D001618:beta-Lactamases / Q000096:biosynthesis*; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D007769:Lactams; D010406:Penicillins; D047090:beta-Lactams; D002433:Cefaclor; D015378:Imipenem; D002443:Ceftriaxone; D000658:Amoxicillin; D001618:beta-Lactamases; C107057:fropenem