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Effects of b-lactams on mixed cultures of common respiratory isolates as an approach to treatment effects on nasopharyngeal carriage

Abstract number: P1047

Sevillano D., Aguilar L., Alou L., Giménez M.J., González N., Torrico M., Cafini F., Coronel P., Prieto J.

Objectives: To explore b-lactam effects on the evolution over time of a bacterial load containing common pharyngeal isolates.

Methods: A computerised two-compartment pharmacodynamic model 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 was used. Strains and MICs (mg/l) of AMX, AMC and CDN were: S. pyogenes (0.03, 0.03 and 0.015), penicillin-resistant S. pneumoniae (PRP; 2, 2 and 0.25), a b-lactamase positive H. influenzae (BL+; >16, 2 and 0.06) and a b-lactamase positive AMC-resistant H. influenzae (BLPACR, >16, 8 and 0.06). A mixture of identical 1:1:1:1 volumes of bacterial suspensions of each strain were prepared yielding an inoculum approx. 4×106 cfu/ml. Antibiotic concentrations were measured both in bacteria-free antibiotic simulations (SBF) and in antibiotic simulations with the mixed inocula (SMI) and T>MIC calculated.

Results: T>MIC (% dosing interval) and mean % initial inocula reduction (%IIR; cfu/ml) are shown in the Table.

b-lactamase production decreased AMX concentrations and T>MIC against PRP or S. pyogenes, and eradication was precluded. The presence of clavulanic acid countered this effect, and S. pyogenes was eradicated (but not BL+ and PRP). CDN resistance to TEM b-lactamase avoided this effect, and eradicated S. pyogenes, BL+ and BLPACR, and reduced in 94.1%S. pneumoniae counts.

Conclusions: Co-pathogenicity seems to be gradual since calvulanic acid countered this effect for strains very susceptible to AMX as S. pyogenes but not for strains with AMX MICs values in the limit of susceptibility as PRP. There is a potential therapeutic advantage for b-lactamase resistant cephalosporins with high intrinsic activity against streptococci.

Session Details

Date: 19/04/2008
Time: 00:00-00:00
Session name: 18th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Barcelona, Spain
Presentation type:
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