• Group A Streptococcus infection is one of the top ten causes of infection-related mortality worldwide.
• Group A Streptococcus is commonly used as an alternative label for Streptococcus pyogenes (S. pyogenes), the predominant group A Streptococcus species.
• As a genitourinary tract infection, S. pyogenes is most commonly found as a postpartum and gynecological infection.
• S. pyogenes can cause puerperal sepsis following genitourinary tract infection.
• Bacterial culture remains the most common method for detection and identification of S. pyogenes infection.
• Antibiotic resistance testing of S. pyogenes infections is rarely performed, inasmuch as S. pyogenes retains susceptibility to penicillin.
Group A Streptococcus (GAS) is a significant cause of global mortality and morbidity, causing approximately 750 million infections worldwide annually, with infections causing disease ranging from pharyngitis to:
• post-streptococcal glomerulonephritis (PSGN)
• toxic shock syndrome, rheumatic heart disease,
• necrotizing fasciitis, and
• urinary tract infections.1,2
Rheumatic fever accounts for over half of the 500,000 annual deaths worldwide from GAS infections.3 GAS is carried asymptomatically in up to 20% of school-age children and in about 25% of adults who have regular contact with infected school-age children.4
Streptococcus bacteria form a genus of Gram-positive spherical bacteria that are commonly classified based on their hemolytic properties. While infection with alpha-hemolytic strep causes partial hemolysis, infection with beta-hemolytic strep bacteria causes complete hemolysis. Strep A bacteria, which includes S. pyogenes and S. dysgalactiae, are beta-hemolytic bacteria.5
GAS is used as an alternative for S. pyogenes, the most predominant group A Streptococcus species.2 Primary sites of S. pyogenes colonization are the oropharynx, genital mucosa, rectum, and skin.6
• Infection is specific to humans, and transmission is through either respiratory droplets or direct human-to-human contact.3 There is no known reservoir for S. pyogenes outside of human.4
• Is a well-established cause for vulvovaginitis in prepubescent females. However, it may be an emerging pathogen in adult women, having been rarely described.7 In adults, S. pyogenes infection is a rare but serious form of postpartum and gynecological infection. A small study found S. pyogenes infection in about 8% of women in a gynecological practice, with common gynecological procedures associated with infection. The authors noted that there are currently no guidelines for either follow-up or prophylaxis for women with previous infections.8
• Can penetrate deep body tissues following proliferation in the genitourinary tract in women. This places women at significant risk of puerperal sepsis caused by S. pyogenes.9,10 One reason for this is that S. pyogenes infections are exacerbated by prostaglandin-E2, which is an immunomodulatory lipid that regulates maternofetal tolerance, parturition, and innate immunity.11
• Can also inhibit host immune response by decreasing inflammasome-dependent interleukin-1 beta (IL-1 beta) release from macrophages. The mechanism by which this occurs involves bacterial expression of a pore-forming toxin (streptolysin O; SLO) and a cotoxin (NAD+-glycohydrolase; NADase).12 NADase has been shown to promote intracellular survival of S. pyogenes.13
• It is important that partners of people with S. pyogenes UTI be tested. A partner may be an asymptomatic passive carrier, resulting in recurrent infections.7
Value of genotyping and phenotyping
S. pyogenes does grow in culture, but requires complex media that contains blood products, and grows best in an environment of 10% carbon dioxide. Pinpoint colonies are produced in blood agar plates, with zones of complete (beta) hemolysis surrounding each colony.14
Antibiotic resistance testing of S. pyogenes is reportedly not commonly performed, even though it has been reported to be resistant to macrolides, fluoroquinolones, clarithromycin, and clindamycin. The reason is that S. pyogenes retains susceptibility to penicillin. This only becomes an issue for patients who are allergic to penicillins.2,15–17
It may be the case that additional resistances will develop, including to penicillin. Different strains of S. pyogenes carry significant genetic diversity, and a variety of mobile genetic elements (such as phage-like chromosomal islands and integrative and conjugative elements [ICEs]) are prominent features of the S. pyogenes genome. This contribute to antibiotic resistance and to modulation of host cell gene expression.
ICEs, in particular, have been found to harbor genes conferring antibiotic resistance on S. pyogenes. ICEs are also associated with other mobile genetic elements that cans result in antibiotic resistance. As examples, there are at least 49 independent genetic elements in S. pyogenes that confer resistance to macrolide antibiotics, and over 80 genes that confer resistance to tetracycline. In addition, genetic variation in expression of surface M proteins can make S. pyogenes resistant to phagocytosis.2
Historically, diagnosis has proceeded based on culture and serology. Sensitivity to Bacitracin has been used to differentiate group A strep from other groups. Differentiation between S. pyogenes and other streptococci is performed by serological identification of Lancefield surface antigens. The PYR test, a rapid enzymatic colorimetric assay, can be used to distinguish S. pyogenes from other beta-hemolytic streptococci. That is, culture can demonstrate the presence of beta-hemolytic bacteria, and the PYR test can be used to determine if those bacteria are S. pyogenes.5,17
Genotyping assays can also be used for more rapid identification of S. pyogenes.17
Treatment of S. pyogenes infection is very straightforward, inasmuch as S. pyogenes continues to be susceptible to penicillins. A patient that is allergic to penicillin will require a different antibiotic, at which point antibiotic resistance may become an issue. S. pyogenes has been reported to be resistant to macrolides, fluoroquinolones, clarithromycin, and clindamycin.2,15–17
1. Sims Sanyahumbi, A., Colquhoun, S., Wyber, R. & Carapetis, J. R. Global Disease Burden of Group A Streptococcus. in Streptococcus pyogenes : Basic Biology to Clinical Manifestations (eds. Ferretti, J. J., Stevens, D. L. & Fischetti, V. A.) (University of Oklahoma Health Sciences Center, 2016).
2. Bessen, D. E. et al. Molecular Epidemiology and Genomics of Group A Streptococcus. Infect Genet Evol 33, 393–418 (2015).
3. Bessen, D. E. Population Biology of the Human Restricted Pathogen, Streptococcus pyogenes. Infect Genet Evol 9, 581–593 (2009).
4. Wilkening, R. V. & Federle, M. J. Evolutionary constraints shaping Streptococcus pyogenes host interactions. Trends Microbiol 25, 562–572 (2017).
5. Patterson, M. J. Streptococcus. in Medical Microbiology (ed. Baron, S.) (University of Texas Medical Branch at Galveston, 1996).
6. Efstratiou, A. & Lamagni, T. Epidemiology of Streptococcus pyogenes. in Streptococcus pyogenes : Basic Biology to Clinical Manifestations (eds. Ferretti, J. J., Stevens, D. L. & Fischetti, V. A.) (University of Oklahoma Health Sciences Center, 2016).
7. Verkaeren, E. et al. Recurrent Streptococcus pyogenes genital infection in a woman: test and treat the partner! International Journal of Infectious Diseases 29, 37–39 (2014).
8. Lev-Sagie, A. et al. Group A streptococcus: is there a genital carrier state in women following infection? Eur. J. Clin. Microbiol. Infect. Dis. 36, 91–93 (2017).
9. Carey, A. J. et al. Interleukin-17A Contributes to the Control of Streptococcus pyogenes Colonization and Inflammation of the Female Genital Tract. Sci Rep 6, (2016).
10. Mason, K. L. & Aronoff, D. M. Postpartum Group A Streptococcus Sepsis and Maternal Immunology. Am J Reprod Immunol 67, 91–100 (2012).
11. Mason, K. L. et al. Intrauterine Group A Streptococcal Infections are Exacerbated by Prostaglandin E2. J Immunol 191, 2457–2465 (2013).
12. Hancz, D. et al. Inhibition of Inflammasome-Dependent Interleukin 1β Production by Streptococcal NAD+-Glycohydrolase: Evidence for Extracellular Activity. mBio 8, (2017).
13. Sharma, O., O’Seaghdha, M., Velarde, J. J. & Wessels, M. R. NAD+-Glycohydrolase Promotes Intracellular Survival of Group A Streptococcus. PLoS Pathog 12, (2016).
14. Biedenbach, D. J. et al. In Vitro Activity of Oral Antimicrobial Agents against Pathogens Associated with Community-Acquired Upper Respiratory Tract and Urinary Tract Infections: A Five Country Surveillance Study. Infect Dis Ther 5, 139–153 (2016).
15. Richter, S. S. et al. Fluoroquinolone Resistance in Streptococcus pyogenes. Clinical Infectious Diseases 36, 380–383 (2003).
16. Hsueh, P.-R. et al. Multicenter surveillance of antimicrobial resistance of Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis to 14 oral antibiotics. J. Formos. Med. Assoc. 103, 664–670 (2004).
17. Spellerberg, B. & Brandt, C. Laboratory Diagnosis of Streptococcus pyogenes (group A streptococci). in Streptococcus pyogenes : Basic Biology to Clinical Manifestations (eds. Ferretti, J. J., Stevens, D. L. & Fischetti, V. A.) (University of Oklahoma Health Sciences Center, 2016).