Effect of rifampicin chemoprophylaxis on the aerobic bacterial flora of the oropharynx

Expression of serogroup B meningococcal capsular polysaccharide undergoes frequent phase variation involving reversible frameshift mutations within a homopolymeric repeat in the siaD gene. A high rate of phase variation is the consequence of a biochemical defect in methyl-directed mismatch repair. The mutator phenotype is associated to the absence of DNA adenine methyltransferase (Dam) activity in all pathogenic isolates and in 50% of commensal strains. Analysis of the meningococcal dam gene region revealed that in all Dam- strains a gene encoding a putative restriction endonuclease (drg) that cleaves only the methylated DNA sequence 5'-GmeATC-3' replaced the dam gene. Insertional inactivation of the dam and/or drg genes indicated that high rates of phase variation and hypermutator phenotype are caused by absence of a functional dam gene.

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Hypermutation in Pathogenic Bacteria

Bucci

et al. 1999

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

Soriano

Rodríguez-Cerrato

2002

Journal of Antimicrobial Chemotherapy

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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.

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Effect of rifampicin chemoprophylaxis on the aerobic bacterial flora of the oropharynx

Cited by 2 publications

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Hypermutation in Pathogenic Bacteria

Hypermutation in Pathogenic Bacteria

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

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