RT Journal Article
T1 β-Lactam Effects on Mixed Cultures of Common Respiratory Isolates as an Approach to Treatment Effects on Nasopharyngeal Bacterial Population Dynamics
A1 Sevillano Fernández, David
A1 Aguilar, Lorenzo
A1 Alou Cervera, Luis
A1 Giménez, María José
A1 González Hidalgo, Natalia
A1 Torrico, Martha
A1 Cafini, Fabio
A1 Coronel, Pilar
A1 Prieto Prieto, José
A2 Keertan Dheda, 
AB 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.Methodology/principal findings: 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/significance: 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.
PB PLOS
SN 1932-6203
YR 2008
FD 2008-12-04
LK https://hdl.handle.net/20.500.14352/107143
UL https://hdl.handle.net/20.500.14352/107143
LA eng
NO Sevillano D, Aguilar L, Alou L, Giménez MJ, González N, Torrico M, Cafini F, Coronel P, Prieto J. Beta-lactam effects on mixed cultures of common respiratory isolates as an approach to treatment effects on nasopharyngeal bacterial population dynamics. PLoS One. 2008;3(12):e3846. doi: 10.1371/journal.pone.0003846.
NO Tedec-Meiji Farma S.A.
DS Docta Complutense
RD 10 abr 2025