Pharmacodynamic and kinetic basis for the selection of pneumococcal resistance in the upper respiratory tract.

The oropharynx is both the reservoir where antibiotic-resistant Streptococcus pneumoniae strains are selected and the focus for further spread of these organisms. In order to select antibiotic-resistant organisms, the antibiotic must be able to eradicate the susceptible population. How an antibiotic acts on oropharyngeal flora is not fully understood, although data on salivary antibiotic concentrations could be useful for establishing some correlation. Many beta-lactam antibiotics are very active against S. pneumoniae, and although their saliva concentrations are very low, there may be enough to eradicate the majority of beta-lactam-sensitive strains. Other antibiotics achieve salivary concentrations in the range 10-30% of serum concentrations (erythromycin, clindamycin, doxycycline and rifampicin), and are also able to eradicate the antibiotic-susceptible population. Antibiotics achieving higher salivary concentrations (>/=40% of the serum levels) are not very active against S. pneumoniae (ciprofloxacin) or are able to eradicate antibiotic-sensitive and -intermediate strains (clarithromycin, azithromycin and telithromycin). Only antibiotics for which there are no highly resistant pneumococcal strains, for instance some beta-lactams administered at very high dose and for a short course, are associated with a lower risk of antibiotic resistance selection. To diminish the risk, the antibiotics should be dosed in order to obtain inhibitory quotients (maximal serum concentration/MIC ratios) >/= 4, which depends not only on the antibiotic concentration achieved but also on the lack of highly resistant organisms.