Streptococcus pyogenes, a group A Streptococcus (GAS) species, is the most important human pathogen within the Streptococcus genus. The most common diseases caused by S. pyogenes are pharyngitis and skin conditions, with possible sequelae of poststreptococcal glomerulonephritis and acute rheumatic fever. Streptococci also have the ability to invade tissues and cause bacteremia. Recently an increase in Streptococcus group B infections has been observed.
Presentation
Many species belong to the Streptococcus genus, which are Gram-positive, nonmotile cocci. They can be classified according to more than one scheme [1]. Their hemolytic capabilities on sheep blood agar define their division into three groups (β-, α-, and γ-hemolytic streptococci). Further classification subdivides these groups according to cell wall carbohydrate antigens into A, B, C, and other groups. The most important representative is S. pyogenes, which is a group A (beta-hemolytic) streptococcus (GABHS).
S. pyogenes causes a variety of diseases, the most common being pharyngitis and skin infections. The manifestations of pharyngitis are variable, from mild discomfort at swallowing to exudative pharyngitis with high fever [2]. In addition to throat pain, the manifestations may include chills, headache, and, in young children, abdominal pain, and vomiting. The possibility of local suppurative complications, such as peritonsillar abscess, should be checked if there is an intense pain [2]. Rarely, the pharyngitis is associated with scarlet fever.
Scarlet fever used to be a serious complication of streptococcal pharyngitis, but with the use of antibiotics, it is not considered an important threat today. However, serious conditions can develop following streptococcal infections. One is acute poststreptococcal glomerulonephritis [3], which presents with edema, hypertension, hematuria, and other urinary abnormalities. The disease is on the decline. Another sequel is rheumatic fever, an autoimmune disease initiated by S. pyogenes but dependent on the host’s immune responses. The development of the disease is associated with certain serotypes of the M protein, a cell wall component of S. pyogenes. Rheumatic fever can present as an inflammation of the joints, heart, central nervous system, or skin [3]. A large proportion of acquired heart disease cases in children originates from rheumatic fever [4]. Neuropsychiatric disorders can also follow streptococcal infections.
Superficial manifestations of streptococcal infection, other than pharyngitis, are skin conditions, such as impetigo, and erysipelas.
The most serious consequences of streptococcal infections stem from their ability to cause invasive diseases. These include sepsis, bacteremic pneumonia, necrotizing fasciitis and streptococcal toxic shock syndrome. Most of the mortality from streptococcal infections is associated with invasive disease and rheumatic fever [5]. The characteristics of an invasive streptococcal disease include systemic toxicity, hypotension, shock, multiple organ failure, rapid necrosis, and gangrene [3]. Several bacterial factors (for example pyrogenic exotoxins and nucleases) are thought to contribute to the pathogenesis of an invasive disease. [3].
Group B Streptococcus infections, caused by Streptococcus agalactiae, were thought to occur mainly in women after childbirth and in newborn babies. However, recently, the infection has appeared in nonpregnant adults, usually associated with comorbidities.
Entire Body System
- Fever
Rheumatic fever can present as an inflammation of the joints, heart, central nervous system, or skin. A large proportion of acquired heart disease cases in children originates from rheumatic fever. [symptoma.com]
fever) by using antibiotics. [merckmanuals.com]
We described a 21-year-old Japanese patient with sore throat, fever, and diffuse erythema on the neck, trunk, and limbs. Erythema markedly appeared on the neck, axillary, antecubital, and popliteal fossae. [ncbi.nlm.nih.gov]
Scarlet fever Rheumatic fever gives you painful, swollen joints. Children with rheumatic fever may have uncontrollable, jerky movements of their arms and legs. Rheumatic fever sometimes damages the heart's valves. [msdmanuals.com]
- Swelling
RESULTS: Magnetic resonance imaging showed diffuse symmetrical swelling and edema of the cerebellum resulting in compression of the fourth ventricle and hydrocephalus. [ncbi.nlm.nih.gov]
Pharyngitis Physical findings of pharyngitis include erythema, edema, and swelling of the pharynx. The tonsils are enlarged, and a grayish white exudate may be present. [emedicine.medscape.com]
Keep all wounds clean and watch for redness, swelling, fever or increasing pain or drainage at the wound site. Get the chickenpox vaccine if you are not already protected. [healthlinkbc.ca]
- Severe Pain
[…] red area on your skin (cellulitis), or yellow, crusty sores (impetigo) Infection under your skin (necrotizing fasciitis): Chills, fever, and severe pain and tenderness in the part of your body that’s infected Necrotizing fasciitis is very serious. [msdmanuals.com]
Necrotizing fasciitis: Severe pain and swelling, often rapidly increasing Fever Redness at a wound site STSS: Fever Abrupt onset of generalized or localized severe pain, often in an arm or leg Dizziness with or without confusion Influenza-like syndrome [dph.illinois.gov]
Early signs of necrotizing fasciitis may include fever, severe pain and swelling, and redness at the wound site. Early signs of streptococcal toxic shock syndrome may include fever, dizziness, confusion, red rash and abdominal pain. [algomapublichealth.com]
- Wound Infection
Puerperal fever - uterus is infected C. Surgical scarlet fever - surgical wound is infected D. Myositis - muscle is destroyed E. Necrotizing fasciitis - muscle sheath is destroyed 2. Local infections (pyodermas) A. [atsu.edu]
The most common GAS infection is strep throat. Other types of common infections include skin and wound infections, ear and sinus infections, and infections in the lymph glands. [healthlinkbc.ca]
Tag words: Streptococcus, Streptococcus pyogenes, S pyogenes, strep, Group A strep, GAS, strep throat, streptococcal streptococci, Gram-positive cocci, cocci, wound infection, acute rheumatic fever, acute glomerulonephritis, scarlet fever, pharyngitis [textbookofbacteriology.net]
Streptococci are gram-positive aerobic organisms that cause many disorders, including pharyngitis, pneumonia, wound and skin infections, sepsis, and endocarditis. Symptoms vary with the organ infected. [msdmanuals.com]
- Malaise
He had persistent fever (39.5 degrees C) and general malaise for 2 weeks. Intraoral examination revealed extremely inflamed and enlarged gingiva with spontaneous bleeding and suppuration. [ncbi.nlm.nih.gov]
COMPLICATION : Acute Glomerulonephritis The major clinical and laboratory manifestations of acute post-streptococcal glomerulonephritis are: CLINICAL FEATURES LABORATORY FINDINGS Abrupt onset Hematuria, cylindruria Headache, malaise Proteinuria Edema, [atsu.edu]
Children may also have chills, fever, headache, nausea, vomiting, and a general feeling of illness (malaise). The throat is beefy red, and the tonsils are swollen, with or without patches of pus. [merckmanuals.com]
Early symptoms of TSS are nonspecific and often begin with influenza-like symptoms of mild fever and malaise. However, TSS often suddenly advances with symptoms of high fever, nausea, vomiting, diarrhea, skin rash, and a low blood pressure. [medicinenet.com]
Respiratoric
- Sore Throat
[…] there's little proof they help) You can buy them from a supermarket or from a pharmacist without a prescription. your sore throat doesn't improve after a week you often get sore throats you're worried about your sore throat you have a sore throat and [nhs.uk]
Most often they cause sore throat (strep throat) or skin infections. But they can cause life-threatening infections in other parts of your body. [msdmanuals.com]
While many sore throats will get better without treatment, some throat infections—including strep throat—may need antibiotic treatment. [my.clevelandclinic.org]
- Cough
If people with a sore throat have a cough, red eyes, hoarseness, diarrhea, or a stuffy nose, the cause is probably a viral infection, not a streptococcal infection. [merckmanuals.com]
(If you have a sore throat as well as a cough, red eyes, hoarseness, diarrhoea, or a blocked-up nose then the cause is likely to be a viral infection, not streptococcal.) [netdoctor.co.uk]
These germs can be spread from child to child by sneezing, coughing and talking. Strep germs can also live long enough on objects like doorknobs, toys, cups, and eating utensils for kids to get them that way too. [kidspot.com.au]
- Throat Irritation
GAS infections can produce many different signs and symptoms: Pharyngitis (strep throat/ tonsillitis ): sore throat, irritation with swallowing, white patches on tonsils (exudates), swollen lymph nodes on the neck, fever; pharyngitis with fever and white [medicinenet.com]
Gastrointestinal
- Overeating
Abstract There has been an increasing incidence worldwide of invasive group A streptococcal disease in pregnancy and the puerperal period over the past 30 years. [ncbi.nlm.nih.gov]
Learn more How to Treat Your Child's Fever Should you use an over-the-counter fever reducer or is it better to let the fever run its course? Our pediatrician weighs in. [northwell.edu]
- Nausea
However, when it does, streptococcus can cause: pneumonia sepsis (a serious infection of the blood) meningitis toxic shock syndrome (toxins released into the blood causing fever, nausea and vomiting) a serious infection of the deeper layers of the skin [healthdirect.gov.au]
Early signs of Streptococcal toxic shock syndrome may include low blood pressure and shock, dizziness, confusion, red rash, nausea, vomiting and abdominal pain. [simcoemuskokahealth.org]
Signs can include: A sore throat Swollen glands Fever Nausea, vomiting Rash Try not to share any personal items with someone who is sick. [webmd.com]
[…] on quickly Painful swallowing Red and swollen tonsils, sometimes with white patches or streaks of pus Tiny red spots on the area at the back of the roof of the mouth (soft or hard palate) Swollen, tender lymph nodes in your neck Fever Headache Rash Nausea [mayoclinic.org]
- Abdominal Pain
Thirty-one (66%) women had fever as their sole presenting symptom, eight (17%) had fever and abdominal pain, seven (15%) had fever and abnormal vaginal bleeding, and one patient (2%) presented with a rash. [ncbi.nlm.nih.gov]
Early signs of necrotizing fasciitis may include fever, severe pain and swelling, and redness at the wound site. Early signs of streptococcal toxic shock syndrome may include fever, dizziness, confusion, red rash and abdominal pain. [algomapublichealth.com]
In addition to throat pain, the manifestations may include chills, headache, and, in young children, abdominal pain, and vomiting. [symptoma.com]
Early signs of Streptococcal toxic shock syndrome may include low blood pressure and shock, dizziness, confusion, red rash, nausea, vomiting and abdominal pain. [simcoemuskokahealth.org]
Strep throat starts suddenly with a high fever, headache, swollen red throat and tonsils, swollen lymph nodes in the neck, white or yellow patches at the back of the throat and, in children, abdominal pain. [healthlinkbc.ca]
- Blood in Stool
HIV, urethreal Gonococcal and Chlamydia testing, Rheumatoid Factor, ANA, C. difficile toxins, blood cultures, stool cultures, and throat cultures were negative. [casesjournal.biomedcentral.com]
Skin
- Skin Lesion
A 13-year-old boy was admitted with fever, skin lesions, polyarthritis and muscle involvement. A muscle biopsy demonstrated a necrotizing vasculitis and antistreptolysin titre was tremendously increased. [ncbi.nlm.nih.gov]
Acute onset of skin lesions caused by streptococcal infection can be either the first manifestation in a previously unaffected person or an acute exacerbation of long-standing psoriasis. [mdedge.com]
Many GAS infections are spread when a child comes in direct contact with the skin lesions or secretions from the throat or nose of an infected person. [healthychildren.org]
People with skin lesions or blisters should not handle food until the infection has cleared. [betterhealth.vic.gov.au]
Symptoms start with red sores or pimple-like lesions (sores) surrounded by reddened skin These lesions can be anywhere on the body, but are found mostly on the face, arms, and legs. [healthieryou.com]
- Skin Rash
Flesh-eating bacteria is characterized by fever, extreme pain, and swelling and redness at a site where skin is broken. Symptoms of toxic shock include abdominal pain, confusion, dizziness, and widespread red skin rash. [medical-dictionary.thefreedictionary.com]
However, TSS often suddenly advances with symptoms of high fever, nausea, vomiting, diarrhea, skin rash, and a low blood pressure. [medicinenet.com]
Flesh-eating bacteria is characterized by fever, extreme pain, swelling, and redness at a site where skin is broken. Symptoms of toxic shock include abdominal pain, confusion, dizziness, and widespread red skin rash. [encyclopedia.com]
- Eczema
Underlying skin diseases that predispose to streptococcal pyoderma, such as tinea capitis and eczema, may become more apparent. [atsu.edu]
Impetigo Drug reaction Guttate psoriasis Nummular eczema Pityriasis rosea A: The most likely diagnosis is guttate psoriasis. [mdedge.com]
The bacteria get into scrapes, cold sores, insect bites or patches of eczema. For more information, see HealthLinkBC File #81 Impetigo. Toxic shock syndrome (TSS) is a rare and serious result of an invasive GAS infection. [healthlinkbc.ca]
An infection can also occur when the bacteria invade the skin as a result of the skin barrier being disrupted by another underlying skin condition, such as head lice, scabies or eczema. [hse.ie]
- Petechiae
Cutaneous petechiae are not uncommon, and a scarlatiniform rash may be present. When the characteristic rash of scarlet fever exists, a clinical diagnosis can be made with increased confidence. [emedicine.medscape.com]
Mouth wide open showing the throat Note the petechiae, or small red spots, on the soft palate. [en.wikipedia.org]
Commonly, the tonsils may have a bumpy look on their surface - somewhat like a golf ball White or yellow colored spots on the tonsils (tonsillar exudate) Petechiae (look like 1-2 mm bright red "dots" which represent ruptured capillaries) scattered on [medicinenet.com]
- Eruptions
However, other skin signs of scarlet fever such as red strawberry tongue and linear petechial eruption did not appear. Before his visit to our clinic, he had been diagnosed as pharyngitis and treated with cefaclor 750 mg daily for six days. [ncbi.nlm.nih.gov]
Typical scarlet fever is not generally difficult to diagnose, but it may be confused with roseola, Kawasaki syndrome, drug eruptions, and toxigenic S aureus infections. [emedicine.medscape.com]
Other organisms involved in guttate psoriasis are Staphylococcus aureus, Candida, and viruses such as human papillomavirus, human immunodeficiency virus, and human endogenous retrovirus. 2 Several commonly used drugs are also implicated in psoriasiform eruptions [mdedge.com]
A severe and potentially fatal variant of the disease, Staphylococcal scalded skin syndrome, occurs in infants, which is characterized by the development of a generalized bullous eruption. [apps.who.int]
Musculoskeletal
- Arthralgia
We report the case of an immunocompetent child who showed monoarticular arthritis and fever, preceded by pharyngitis and arthralgias. [ncbi.nlm.nih.gov]
The minor criteria include arthralgia, fever, elevated erythrocyte sedimentation rate, elevated C-reactive protein, or a prolonged PR interval [ 1 ]. [casesjournal.biomedcentral.com]
Other minor Jones Criteria are fever, elevated ESR and arthralgia. One of the most serious complications is pancarditis, or inflammation of all three heart tissues. [en.wikipedia.org]
- Muscle Strain
Numerous cases have developed within 24 - 72 hours of minor non-penetrating trauma resulting in hematoma, deep bruise to the calf or even following muscle strain (87). [antimicrobe.org]
Face, Head & Neck
- Facial Pain
Over-the-counter painkillers such as paracetamol, ibuprofen or aspirin can be used to relieve a headache, high temperature and any facial pain or tenderness. [hse.ie]
Over-the-counter painkillers such as paracetamol, ibuprofen or aspirin can be used to relieve a headache, high temperature and any facial pain or tenderness. Read more about the treatment of sinusitis. [your.md]
Urogenital
- Oliguria
COMPLICATION : Acute Glomerulonephritis The major clinical and laboratory manifestations of acute post-streptococcal glomerulonephritis are: CLINICAL FEATURES LABORATORY FINDINGS Abrupt onset Hematuria, cylindruria Headache, malaise Proteinuria Edema, oliguria [atsu.edu]
Some experts recommend use when there has been no clinical response after the first 6 hours of supportive therapy, or in cases in which an undrainable focus or persistent oliguria with pulmonary edema are present. [clinicaladvisor.com]
Neurologic
- Headache
Abstract We previously found that 97% of children diagnosed with chronic tension-type headaches had meningismus. [ncbi.nlm.nih.gov]
Children may also have chills, fever, headache, nausea, vomiting, and a general feeling of illness (malaise). The throat is beefy red, and the tonsils are swollen, with or without patches of pus. [merckmanuals.com]
In addition to throat pain, the manifestations may include chills, headache, and, in young children, abdominal pain, and vomiting. [symptoma.com]
Often you get 39-40 degrees of fever and headache. Scarlet fever (scarlantina) can act together with halsbetændelsen, and is due to toxins (poisons) produced by the bacterium. [healthanddisease.com]
- Confusion
SPE B is potentially allergenic and may confuse the clinicians due to its clinical mimicry of drug-induced AIN. Although very rare, AIN might be included into the differential diagnosis of patients with streptococcal sepsis and acute renal failure. [ncbi.nlm.nih.gov]
Early signs of Streptococcal toxic shock syndrome may include low blood pressure and shock, dizziness, confusion, red rash, nausea, vomiting and abdominal pain. [simcoemuskokahealth.org]
Toxic shock syndrome – caused by both types of the bacteria, releases toxins into the blood, which can cause a sudden fever, vomiting, diarrhoea, fainting, dizziness, confusion and a rash. [express.co.uk]
Necrotizing fasciitis: Severe pain and swelling, often rapidly increasing Fever Redness at a wound site STSS: Fever Abrupt onset of generalized or localized severe pain, often in an arm or leg Dizziness with or without confusion Influenza-like syndrome [dph.illinois.gov]
- Dizziness
Early signs of Streptococcal toxic shock syndrome may include low blood pressure and shock, dizziness, confusion, red rash, nausea, vomiting and abdominal pain. [simcoemuskokahealth.org]
Toxic shock syndrome – caused by both types of the bacteria, releases toxins into the blood, which can cause a sudden fever, vomiting, diarrhoea, fainting, dizziness, confusion and a rash. [express.co.uk]
Necrotizing fasciitis: Severe pain and swelling, often rapidly increasing Fever Redness at a wound site STSS: Fever Abrupt onset of generalized or localized severe pain, often in an arm or leg Dizziness with or without confusion Influenza-like syndrome [dph.illinois.gov]
- Vertigo
(Radio-Canada) At that time he suffered severe anxiety, symptoms of obsessive compulsive disorder (OCD), vertigo, pain in his throat and ears, hallucinations and concentration problems. His parents said the problems seemed to happen overnight. [cbc.ca]
Workup
Early diagnosis of streptococcal infections is important not just for the treatment of the acute disease, but also to prevent complications [6], such as rheumatic fever [7]. Therefore, while culture is regarded as the most reliable method for the identification of Streptococcus species [3], decisions regarding treatment sometimes have to be made before the results are available because of the time required for growth of the bacterial cultures [7].
Several quick assays have been developed based on the immunological detection of the group-specific cell wall carbohydrate of GAS organisms. These assays use latex agglutination, enzyme immunoassay, and optical immunoassay; DNA is detected by PCR methods and chemiluminescent DNA probes [8]. These methods are very specific, but of variable sensitivity, although this has been reported to be high in some assays [6] [7] [8] [9]. Recommendations by the Infectious Diseases Society of America advocate the use of rapid antigen detection tests and/or cultures for the diagnosis of streptococcal pharyngitis, with negative immunological tests to be followed up by culturing the organism in populations at high risk for acute rheumatic fever (children and adolescents) [10].
Assaying for antistreptococcal antibodies in serum is most valuable for the diagnosis of rheumatic fever and other poststreptococcal diseases. In cases of necrotizing fasciitis, a frozen section biopsy can be used to identify or confirm the presence of the organism.
Microbiology
- Gram-Positive Bacteria
Vancomycin View full drug information Vancomycin acts by inhibiting proper cell wall synthesis in gram-positive bacteria. [emedicine.medscape.com]
Location: Lecture Hall 4Z, Alfred Nobels Allé 8, Karolinska University Hospital, Huddinge Abstract Streptococcus pyogenes and Staphylococcus aureus are Gram-positive bacteria that share many features, including clinical presentations and pathogenic mechanisms [openarchive.ki.se]
positive bacteria belonging to the family streptococcaceae. [icd10data.com]
Cotrimoxazole provides good coverage against gram-positive bacteria (e.g. Streptococcus pneumoniae), gram-negative bacteria (e.g. Escherichia coli and non-typhoid Salmonella), protozoa (e.g. [ar.glosbe.com]
- Gram-Positive Coccus
Group A Strep (GAS) Infection Related Articles Group A Strep (GAS) Infection Facts Streptococcus pyogenes, also known as group A beta-hemolytic Streptococcus, or group A strep ( GAS ) is a gram-positive coccus (spherical bacteria) that is ubiquitous, [emedicinehealth.com]
GENERAL DESCRIPTION Microbiology Streptococcus pyogenes, or Group A streptococcus (GAS), is a facultative, Gram-positive coccus which grows in chains and causes numerous infections in humans including pharyngitis, tonsillitis, scarlet fever, cellulitis [antimicrobe.org]
Treatment
Even with prompt treatment of invasive group A Streptococcus, it remains the most common cause of infection that results in severe maternal morbidity and death in the world. [ncbi.nlm.nih.gov]
Prognosis
Abstract Pancarditis is a rare condition with a poor prognosis combining endocarditis, myocarditis with abscess formation, and purulent pericarditis. [ncbi.nlm.nih.gov]
What is the prognosis for group A streptococcal infections? The prognosis for mild GAS infections is usually good to excellent. [medicinenet.com]
Etiology
It may be prudent to consider penicillin prophylaxis in patients with periarteritis nodosa when a streptococcal etiology is documented or highly suspected. [ncbi.nlm.nih.gov]
Epidemiology
In recent epidemiological studies, Streptococcus dysgalactiae subsp. equisimilis (SDSE) has been isolated from severe invasive streptococcal infection. [ncbi.nlm.nih.gov]
Berrios et al. [ 11 ] studied the epidemiology and bacteriology of ARF and AGN in Santiago, Chile. [academic.oup.com]
Pathophysiology
The pathophysiology of the involuntary movements may be associated with sensorimotor cortex hyperexcitability. [ncbi.nlm.nih.gov]
Because the pathophysiology of invasive GAS infection is largely toxin mediated, the use of a protein synthesis inhibitor (eg, clindamycin) offers a theoretical advantage. [emedicine.medscape.com]
An immunological view of the pathophysiology of psoriasis. Clin Exp Dermatol 2001 ; 26 : 326 –32. ↵ Olivier C. Rheumatic fever - is it still a problem? J Antimicrob Chemother 2000 ; 45 (suppl): 13 –21. ↵ Leung DY, Travers JB, Norris DA. [jmg.bmj.com]
Prevention
Hand washing remains the cornerstone of prevention as transmission can occur directly from an asymptomatic colonized healthcare provider, other patients, or a community-acquired source. [ncbi.nlm.nih.gov]
Figure 1 derived from Centers for Disease Control and Prevention. Prevention of perinatal group B streptococcal disease: a public health perspective. [aafp.org]
The global strategies for prevention of GAS on a larger scale remain complex (19). [isid.org]
References
- Hamada S, Kawabata S, Nakagawa I. Molecular and genomic characterization of pathogenic traits of group A Streptococcus pyogenes. Proc Jpn Acad Ser B Phys Biol Sci. 2015;91(10):539-559.
- Wessels MR. Streptococcal pharyngitis. N Engl J Med.2011;364(7):648-655.
- Cunningham MW. Pathogenesis of group A streptococcal infections. Clin Microbiol Rev. 2000;13(3):470-511.
- Pavone P, Parano E, Rizzo R, Trifiletti RR. Autoimmune neuropsychiatric disorders associated with streptococcal infection: Sydenham chorea, PANDAS, and PANDAS variants. J Child Neurol. 2006;21(9):727-736.
- O’Loughlin RE, Roberson A, Cieslak PR, et al. The epidemiology of invasive group A streptococcal infection and potential vaccine implications: United States, 2000-2004. Clin Infect Dis. 2007;45(7):853-862
- Smith JM, Bauman MC, Fuchs PC. An OIA for the direct detection of group A strep antigen. Lab. Med. 1995;26: 408–410.
- Orda U, Gunnarsson R, Orda S, Fitzgerald M, Rofe G, Dargan A. Etiologic predictive value of a rapid immunoassay for the detection of group A Streptococcus antigen from throat swabs in patients presenting with a sore throat. Int J Infect Dis. 2016;45:32-35.
- Leung AK, Newman R, Kumar A, Davies HD. Rapid antigen detection testing in diagnosing group A beta-hemolytic streptococcal pharyngitis. Expert Rev Mol Diagn. 2006 Sep;6(5):761-766.
- Lasseter GM, McNulty CAM, Hobbs FDR, Mant D, Little P. In vitro evaluation of five rapid antigen detection tests for group A beta-haemolytic streptococcal sore throat infections. Family Practice. 2009; 26: 437–444.
- Shulman ST, Bisno AL, Clegg HW, et al. Clinical practice guideline for the diagnosis and management of group a streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. Clin Infect Dis. 2012;55(10):e86-e102.