Why do we fail with penicillin in the treatment of group A streptococcus infections?

Acute pharyngotonsillitis caused by beta-haemolytic group A streptococcus ( GAS) is a common childhood disease. Phenoxymethyl penicillin remains the dr ug of choice, as no resistance has been reported so far. Nevertheless, the failure of penicillin to eradicate streptococci from the throat occurs in u p to 35% of patients with pharyngotonsillitis, and might present clinical c oncern. Various explanations have been proposed over the years to account f or this perplexing phenomenon. Among these are coexistence of oropharyngeal P-lactamase-producing bacteria that degrade penicillin, growth interferenc e by aerobic and anaerobic commensals, penicillin tolerance, reinfection, a nd poor antibiotic compliance. Although CAS has been considered an extracel lular pathogen, recent studies have demonstrated that strains of this bacte rium can internalize epithelial cells both in vitro and in vivo. The intrac ellular niche may protect the bacterium from penicillin that does not gain high intracellular concentration. In support of this hypothesis, GAS strain s were shown to survive 4-7 days inside cultured epithelial cells. In addit ion, it was found that GAS strains isolated from patients with eradication failure harbour the internalization-associated gene, prtF1/sfbI, in higher prevalence than do strains recovered from patients with successful eradicat ion. Thus, internalization and intracellular survival represent a novel exp lanation for penicillin eradication failure.