Why Have Group A Streptococci Remained Susceptible to Penicillin? Report on a Symposium

Abstract

In spite of 50 years of extensive use of penicillin, group A streptococci remain exquisitely susceptible to this antibiotic. This observation that continuing susceptibility has occurred despite the development of resistance to other antimicrobial agents prompted a day-long meeting at Rockefeller University (New York) in October 1996. Among the most likely explanations for this remarkable state of continued susceptibility to penicillin are that beta-lactamase may not be expressed or may be toxic to the organism and/or that low-affinity penicillin-binding proteins either are not expressed or render organisms nonviable. Other potential explanations are that circumstances favorable for the development of resistance have not yet occurred and/or that there are inefficient mechanisms for or barriers to genetic transfer. Recommended future actions include (1) additional laboratory investigations of gene transfer, penicillin-binding proteins, virulence factors, and homeologous recombination and mismatch repair; (2) increased surveillance for the development of penicillin resistance; (3) application of bioinformatics to analyze streptococcal genome sequences; and (4) development of vaccines and novel antimicrobial agents. Thus far the susceptibility of group A streptococci to penicillin has not been a major clinical or epidemiological problem. A similar observation, however, could have been made decades ago about Streptococcus pneumoniae. It is therefore vital for the scientific community to closely examine why penicillin has remained uniformly highly active against group A streptococci in order to maintain this desirable state.

A Novel Integrative Conjugative Element Mediates Genetic Transfer from Group G Streptococcus to Other β-Hemolytic Streptococci

“…Penicillin has remained the drug of choice for treatment and prevention of ␤-hemolytic infections for over 50 years. Unlike related bacteria, the ␤-hemolytic streptococci have not developed resistance to penicillin; the reasons for this remain unknown (31). As penicillin resistance has not arisen naturally in ␤-hemolytic streptococci, even in the face of long-term penicillin treatment, mutation of existing genes seems to be an unlikely source of future resistance.…”

The M protein of group A Streptococcus is a key virulence factor and a clinically relevant strain identification marker

“…43,45 Therefore, penicillin remains the treatment of choice and is generally effective. However, many people are allergic to penicillin and for these subpopulations macrolides and other antibiotics provide critical alternatives.…”

Antibiotic Susceptibility of Streptococcus Pyogenes Strains Isolated From Throat Cultures of Children With Tonsillopharyngitis

“…Interestingly, Streptococcus pyogenes remains susceptible to penicillin during the past 70 or 80 years. The reason for this unique lack of development of resistance to penicillin is unknown (14). On the other hand, numerous reports have demonstrated a significant prevalence of erythromycin resistant S. pyogenes around the world during the past three decades (4)(5)(6)(7)(8)(9)(10).…”