Abstract
Group A Streptococcus (GAS; Streptococcus pyogenes) is a nearly ubiquitous human pathogen responsible for a significant global disease burden. No vaccine exists, so antibiotics are essential for effective treatment. Despite a lower incidence of antimicrobial resistance than many pathogens, GAS is still a top 10 cause of death due to infections worldwide. The morbidity and mortality are primarily a consequence of the immune sequelae and invasive infections that are difficult to treat with antibiotics. GAS has remained susceptible to penicillin and other β-lactams, despite their widespread use for 80 years. However, the failure of treatment for invasive infections with penicillin has been consistently reported since the introduction of antibiotics, and strains with reduced susceptibility to β-lactams have emerged. Furthermore, isolates responsible for outbreaks of severe infections are increasingly resistant to other antibiotics of choice, such as clindamycin and macrolides. This review focuses on the challenges in the treatment of GAS infection, the mechanisms that contribute to antibiotic failure, and adjunctive therapeutics. Further understanding of these processes will be necessary for improving the treatment of high-risk GAS infections and surveillance for non-susceptible or resistant isolates. These insights will also help guide treatments against other leading pathogens for which conventional antibiotic strategies are increasingly failing.
Highlights
Streptococcus pyogenes is a ubiquitous human pathogen responsible for over half a million deaths per year worldwide (Carapetis et al, 2005)
Group A Streptococcus (GAS) has no resistance to penicillin, but treatment failure remains a major concern
Since penicillin treatment can lead to lysis and toxin release (Coyle, 2003), protein synthesis inhibitors like clindamycin (Kishi et al, 1999) that decrease toxin production can help mitigate excessive immune stimulation (Coyle, 2003)
Summary
Streptococcus pyogenes (group A Streptococcus, GAS) is a ubiquitous human pathogen responsible for over half a million deaths per year worldwide (Carapetis et al, 2005). Current treatment depends on conventional antibiotics and symptom management. While the β-lactam penicillin remains the antibiotic of choice for mild to moderate infections, severe or prolonged infections require additional measures for effective clearance. The standard recommendation is to utilize the lincosamide clindamycin in combination with penicillin. Group A Streptococcus Therapeutic Failure (Stevens et al, 2014). Any resistance is a serious issue because of the reliance on these antibiotics, so surveillance is important. GAS has no resistance to penicillin, but treatment failure remains a major concern. Clindamycin has been very effective, but the global rates of resistance continue to rise and make the implementation of universal guidelines a challenge. Emergent challenges and opportunities for the treatment of GAS are the focus of this review
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