Beta-lactam effects on mixed cultures of common respiratory isolates as an approach to treatment effects on nasopharyngeal bacterial population dynamics.
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-c...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2008-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2587697?pdf=render |
| _version_ | 1811266754738913280 |
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| author | David Sevillano Lorenzo Aguilar Luis Alou María-José Giménez Natalia González Martha Torrico Fabio Cafini Pilar Coronel José Prieto |
| author_facet | David Sevillano Lorenzo Aguilar Luis Alou María-José Giménez Natalia González Martha Torrico Fabio Cafini Pilar Coronel José Prieto |
| author_sort | David Sevillano |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T20:49:00Z |
| format | Article |
| id | doaj.art-3dce5a6806964c5c878222ef4a7af6b7 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T20:49:00Z |
| publishDate | 2008-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-3dce5a6806964c5c878222ef4a7af6b72022-12-22T03:17:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-01-01312e384610.1371/journal.pone.0003846Beta-lactam effects on mixed cultures of common respiratory isolates as an approach to treatment effects on nasopharyngeal bacterial population dynamics.David SevillanoLorenzo AguilarLuis AlouMaría-José GiménezNatalia GonzálezMartha TorricoFabio CafiniPilar CoronelJosé PrietoBACKGROUND: 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.http://europepmc.org/articles/PMC2587697?pdf=render |
| spellingShingle | David Sevillano Lorenzo Aguilar Luis Alou María-José Giménez Natalia González Martha Torrico Fabio Cafini Pilar Coronel José Prieto Beta-lactam effects on mixed cultures of common respiratory isolates as an approach to treatment effects on nasopharyngeal bacterial population dynamics. PLoS ONE |
| title | Beta-lactam effects on mixed cultures of common respiratory isolates as an approach to treatment effects on nasopharyngeal bacterial population dynamics. |
| title_full | Beta-lactam effects on mixed cultures of common respiratory isolates as an approach to treatment effects on nasopharyngeal bacterial population dynamics. |
| title_fullStr | Beta-lactam effects on mixed cultures of common respiratory isolates as an approach to treatment effects on nasopharyngeal bacterial population dynamics. |
| title_full_unstemmed | Beta-lactam effects on mixed cultures of common respiratory isolates as an approach to treatment effects on nasopharyngeal bacterial population dynamics. |
| title_short | Beta-lactam effects on mixed cultures of common respiratory isolates as an approach to treatment effects on nasopharyngeal bacterial population dynamics. |
| title_sort | beta lactam effects on mixed cultures of common respiratory isolates as an approach to treatment effects on nasopharyngeal bacterial population dynamics |
| url | http://europepmc.org/articles/PMC2587697?pdf=render |
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