title: Beta-lactam effects on mixed cultures of common respiratory isolates as an approach to treatment effects on nasopharyngeal bacterial population dynamics.
abstract: BACKGROUND
  Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae are bacteria present in the nasopharynx as part of normal flora. The ecological equilibrium in the nasopharynx can be disrupted by the presence of antibiotics.
  
  
  RESULTS
  A computerized two-compartment pharmacodynamic model was used to explore beta-lactam effects on the evolution over time of a bacterial load containing common pharyngeal isolates by simulating free serum concentrations obtained with amoxicillin (AMX) 875 mg tid, amoxicillin/clavulanic acid (AMC) 875/125 mg tid and cefditoren (CDN) 400 mg bid regimens over 24 h. Strains and MICs (microg/ml) of AMX, AMC and CDN were: S. pyogenes (0.03, 0.03 and 0.015), S. pneumoniae (2, 2 and 0.25), a beta-lactamase positive H. influenzae (BL(+); >16, 2 and 0.06) and a beta-lactamase positive AMC-resistant H. influenzae (BLPACR, >16, 8 and 0.06). Mixture of identical 1:1:1:1 volumes of each bacterial suspension were prepared yielding an inocula of approximately 4 x 10(6) cfu/ml. Antibiotic concentrations were measured both in bacterial and in bacteria-free antibiotic simulations. beta-lactamase production decreased AMX concentrations and fT(>MIC) against S. pneumoniae (from 43.2% to 17.7%) or S. pyogenes (from 99.9% to 24.9%), and eradication was precluded. The presence of clavulanic acid countered this effect of co-pathogenicity, and S. pyogenes (but not BL(+) and S. pneumoniae) was eradicated. Resistance of CDN to TEM beta-lactamase avoided this co-pathogenicity effect, and CDN eradicated S. pyogenes and H. influenzae strains (fT(>MIC) >58%), and reduced in 94% S. pneumoniae counts (fT(>MIC) approximately 25%).
  
  
  CONCLUSIONS
  Co-pathogenicity seems to be gradual since clavulanic acid countered this effect for strains very susceptible to AMX as S. pyogenes but not for strains with AMX MIC values in the limit of susceptibility as S. pneumoniae. There is a potential therapeutic advantage for beta-lactamase resistant cephalosporins with high activity against streptococci.
authors.affiliation: Microbiology Department, School of Medicine, University Complutense, Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Sevillano
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Aguilar
authors.forename: Luis
authors.initials: L
authors.lastname: Alou
authors.forename: María-José
authors.initials: MJ
authors.lastname: Giménez
authors.forename: Natalia
authors.initials: N
authors.lastname: González
authors.forename: Martha
authors.initials: M
authors.lastname: Torrico
authors.forename: Fabio
authors.initials: F
authors.lastname: Cafini
authors.forename: Pilar
authors.initials: P
authors.lastname: Coronel
authors.forename: José
authors.initials: J
authors.lastname: Prieto
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D019818:Clavulanic Acid / Q000494:pharmacology; D003198:Computer Simulation; D006193:Haemophilus influenzae / Q000187:drug effects / Q000302:isolation & purification; D009305:Nasopharynx / Q000187:drug effects / Q000382:microbiology*; D012141:Respiratory Tract Infections / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000302:isolation & purification; D001618:beta-Lactamases / Q000032:analysis; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D019818:Clavulanic Acid; D001618:beta-Lactamases