Macrolide-resistant Streptococcus pyogenes: prevalence and treatment strategies

Abstract

Although penicillin remains the first-choice treatment for Streptococcus pyogenes infection, macrolides are important alternatives for allergic patients and lincosamides are recommended together with β-lactams in invasive infections. S. pyogenes may exhibit macrolide resistance because of active efflux (mef genes) or target modification (erm genes), the latter conferring cross resistance to lincosamides and streptogramin B. Worldwide, resistance is restricted to a limited number of genetic lineages, despite resistance genes being encoded on mobile genetic elements. For reasons that are not completely clear, resistance and the associated phenotypes are highly variable across countries. Although resistance remains high in several countries, particularly in Asia, an overall decreasing trend of resistance has been noted in recent years, mostly in Europe. This decrease is not always accompanied by declines in macrolide consumption, suggesting significant roles of other factors in determining the dynamics of macrolide-resistant clones. Continued surveillance is needed to obtain further insights into the forces governing macrolide resistance in S. pyogenes.

Keywords:

• antimicrobial therapy
• emm typing
• lancefield group A
• macrolide resistance
• molecular epidemiology
• resistance phenotypes
• resistant determinants
• Streptococcus pyogenes

Financial & competing interests disclosure

J Melo-Cristino has received research grants administered through university and honoraria for serving on speaker’s bureaus of Pfizer, Bial, GlaxoSmithKline and Novartis. M Ramirez has received honoraria for serving on the speaker’s bureau of Pfizer and for consulting for GlaxoSmithKline. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Macrolide resistance in Group A Streptococcus (GAS) is mostly mediated by the acquisition of mobile genetic elements encoding either methyltransferases that act on 23S rRNA (erm genes) resulting in cross-resistance to all macrolides, lincosamides and streptogramins B – the MLS_B phenotype; or pumps that remove the antimicrobial from the cell (mef genes) resulting in resistance to 14- and 15-membered lactone ring macrolides, but not to 16-member macrolides, nor to lincosamides or streptogramins B – the M phenotype.

• There are large variations in macrolide resistance rates across geographic regions, with generally low resistance in America, higher in Europe and highest in Asia, particularly in China where multicenter studies report resistance between 80 and 95%.

• The prevalence of resistant isolates and of the macrolide resistance phenotypes they express is different in the various countries and has varied with time even within the same country.

• There has been a general, although not universal, tendency for decline in macrolide resistance in GAS in recent years, including in countries that have not diminished their macrolide use, suggesting that other yet unidentified forces may play key roles in determining the overall macrolide resistance rate.

• Although several distinct genetic lineages express macrolide resistance, a limited number of macrolide-resistant clones are widely disseminated, such that the resistant bacterial population is distinct from the susceptible one.

• A recent study of an ongoing outbreak of scarlet fever in China suggested an important role of macrolide resistance in selecting the lineages responsible for the outbreak, indicating that resistance may be a key trait for success of a particular lineage in certain contexts.

• Penicillin remains the treatment of choice for infections caused by Streptococcus pyogenes and resistance to this antimicrobial has not been described although an association with clindamycin is recommended in more severe infections.

• Antimicrobial therapy for proven GAS pharyngitis remains controversial, with guidelines from different countries taking different views, but macrolides and lincosamides are universally considered suitable alternatives to penicillin.

Notes