(See also Pneumococcal Infections Pneumococcal Infections Streptococcus pneumoniae (pneumococci) are gram-positive, alpha-hemolytic, aerobic, encapsulated diplococci. Pneumococcal infection is a major cause of otitis media, pneumonia, sepsis... read more , Rheumatic Fever Rheumatic Fever Rheumatic fever is a nonsuppurative, acute inflammatory complication of group A streptococcal pharyngeal infection, causing combinations of arthritis, carditis, subcutaneous nodules, erythema... read more , and Tonsillopharyngitis Tonsillopharyngitis Tonsillopharyngitis is acute infection of the pharynx, palatine tonsils, or both. Symptoms may include sore throat, odynophagia, cervical lymphadenopathy, and fever. Diagnosis is clinical, supplemented... read more .)
Classification of Streptococci
Three different types of streptococci are initially differentiated by their appearance when they are grown in culture on sheep blood agar:
Beta-hemolytic streptococci produce zones of clear hemolysis around each colony.
Alpha-hemolytic streptococci (commonly called viridans streptococci) are surrounded by green discoloration resulting from incomplete hemolysis.
Gamma-hemolytic streptococci are nonhemolytic.
Subsequent classification, based on carbohydrates in the cell wall, divides streptococci into 20 Lancefield groups A through H and K through V (see table *). In the Lancefield classification, enterococci Enterococcal Infections Enterococci are gram-positive, facultative anaerobic organisms. Enterococcus faecalis and E. faecium cause a variety of infections, including endocarditis, urinary tract infections... read more were initially included among the group D streptococci but are now classified as a separate genus even though they do express Lancefield group D antigens. Lancefield groups K through V are streptococcal species of limited virulence that can cause infections in people who are immunocompromised.
Viridans streptococci form a separate group that is difficult to classify. Some streptococci such as Streptococcus pneumoniae Pneumococcal Infections Streptococcus pneumoniae (pneumococci) are gram-positive, alpha-hemolytic, aerobic, encapsulated diplococci. Pneumococcal infection is a major cause of otitis media, pneumonia, sepsis... read more are alpha-hemolytic, ie, they are a type of viridans streptococci and do not express Lancefield antigens.
Many streptococci elaborate virulence factors, including streptolysins, DNAases, and hyaluronidase, which contribute to tissue destruction and spread of infection. A few strains release exotoxins that activate certain T cells, triggering release of cytokines, including tumor necrosis factor-alpha, interleukins, and other immunomodulators. These cytokines activate the complement, coagulation, and fibrinolytic systems, leading to shock, organ failure, and death.
Diseases Caused by Streptococci
The most significant streptococcal pathogen is S. pyogenes, which is beta-hemolytic and in Lancefield group A and is thus denoted as group A beta-hemolytic streptococci (GABHS).
The most common acute diseases due to GABHS are
In addition, delayed, nonsuppurative complications (rheumatic fever Rheumatic Fever Rheumatic fever is a nonsuppurative, acute inflammatory complication of group A streptococcal pharyngeal infection, causing combinations of arthritis, carditis, subcutaneous nodules, erythema... read more , acute glomerulonephritis Postinfectious Glomerulonephritis (PIGN) Postinfectious glomerulonephritis occurs after infection, usually with a nephritogenic strain of group A beta-hemolytic streptococcus. Diagnosis is suggested by history and urinalysis and confirmed... read more ) sometimes occur ≥ 2 weeks after infection.
GABHS can spread through the affected tissues and along lymphatic channels (causing lymphangitis Lymphangitis Lymphangitis is acute bacterial infection (usually streptococcal) of peripheral lymphatic channels. (See also Overview of Bacterial Skin Infections and Lymphadenitis.) Typical causes of lymphangitis... read more ) to regional lymph nodes (causing lymphadenitis Lymphadenitis Lymphadenitis is an acute infection of one or more lymph nodes. Symptoms include pain, tenderness, and lymph node enlargement. Diagnosis is typically clinical. Treatment is usually empiric.... read more ). GABHS can also cause local suppurative complications, such as peritonsillar abscess Peritonsillar Abscess and Cellulitis Peritonsillar abscess and cellulitis are acute pharyngeal infections most common among adolescents and young adults. Symptoms are severe sore throat, trismus, "hot potato" voice, and uvular... read more , otitis media Otitis Media (Acute) Acute otitis media is a bacterial or viral infection of the middle ear, usually accompanying an upper respiratory infection. Symptoms include otalgia, often with systemic symptoms (eg, fever... read more , sinusitis Sinusitis Sinusitis is inflammation of the paranasal sinuses due to viral, bacterial, or fungal infections or allergic reactions. Symptoms include nasal obstruction and congestion, purulent rhinorrhea... read more , and bacteremia Bacteremia Bacteremia is the presence of bacteria in the bloodstream. It can occur spontaneously, during certain tissue infections, with use of indwelling genitourinary or IV catheters, or after dental... read more . Suppuration depends on the severity of infection and the susceptibility of tissue.
Other serious GABHS infections include septicemia, puerperal sepsis, endocarditis Infective Endocarditis Infective endocarditis is infection of the endocardium, usually with bacteria (commonly, streptococci or staphylococci) or fungi. It may cause fever, heart murmurs, petechiae, anemia, embolic... read more , pneumonia Overview of Pneumonia Pneumonia is acute inflammation of the lungs caused by infection. Initial diagnosis is usually based on chest x-ray and clinical findings. Causes, symptoms, treatment, preventive measures, and... read more , and empyema.
Disease caused by other streptococcal species is less prevalent and usually involves soft-tissue infection or endocarditis (see table *). Some non-GABHS infections occur predominantly in certain populations (eg, group B streptococci in neonates and postpartum women).
GABHS are the most common cause of acute-onset bacterial pharyngitis. Other bacterial causes include groups C and G streptococci and Fusobacterium necrophorum. Most patients with GABHS pharyngitis are children between 3 years and 14 years of age who present with acute onset of sore throat, fever, beefy-red pharynx, and purulent tonsillar exudate. GABHS pharyngitis is rare in children younger than 3 years of age.
The cervical and submaxillary nodes may enlarge and become tender. Streptococcal pharyngitis can lead to peritonsillar abscess Peritonsillar Abscess and Cellulitis Peritonsillar abscess and cellulitis are acute pharyngeal infections most common among adolescents and young adults. Symptoms are severe sore throat, trismus, "hot potato" voice, and uvular... read more . Cough, laryngitis, and stuffy nose are not characteristic of streptococcal pharyngeal infection; their presence suggests another cause (usually viral or allergic).
Humans are the primary reservoir for group A streptococci, which spread person-to-person via saliva or nasal secretions from an infected person. An asymptomatic carrier state may exist in as many as 20% of people.
Scarlet fever, a predominantly childhood disease, usually follows a pharyngeal streptococcal infection; less commonly, it follows streptococcal infections at other sites (eg, the skin). Scarlet fever is caused by group A streptococcal strains that produce an erythrogenic toxin, leading to a diffuse pink-red cutaneous flush that blanches with pressure.
The rash is seen best on the abdomen or lateral chest and as dark red lines in skinfolds (Pastia lines) or as circumoral pallor. The rash consists of characteristic numerous small (1- to 2-mm) papular elevations, giving a sandpaper quality to the skin. The upper layer of the previously reddened skin often desquamates after fever subsides. The rash usually lasts 2 to 5 days.
Transmission of scarlet fever is enhanced in environments that result in close contact among people (eg, in schools or day care centers).
Scarlet fever is not as common as it was in the past, but in recent years there have been a number of significant outbreaks in the United States, Europe, and China. For example, since 2014 there has been an unprecedented and persistent increase in scarlet fever in England with the highest incidence for nearly 50 years. Over a century ago, scarlet fever was feared as a potentially lethal disease. Its mortality and morbidity waned, however, well before antibiotics became available. Since the advent of antibiotic therapy, the mortality rate of treated scarlet fever is < 1% (1 Scarlet fever reference 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... read more ).
A strawberry tongue (inflamed papillae protruding through a bright red coating) also occurs and must be differentiated from that seen in toxic shock syndrome Toxic Shock Syndrome (TSS) Toxic shock syndrome is caused by staphylococcal or streptococcal exotoxins. Manifestations include high fever, hypotension, diffuse erythematous rash, and multiple organ dysfunction, which... read more and Kawasaki disease Kawasaki Disease Kawasaki disease is a vasculitis, sometimes involving the coronary arteries, that tends to occur in infants and children between the ages of 1 year and 8 years. It is characterized by prolonged... read more .
Other symptoms are similar to those in streptococcal pharyngitis, and the course and management of scarlet fever are the same as those of other group A infections.
Scarlet fever reference
1. Lamagni T, Guy R, Chand M, et al: Resurgence of scarlet fever in England, 2014-16: A population-based surveillance study. Lancet Infect Dis 18(2):180–187, 2018. doi: 10.1016/S1473-3099(17)30693-X
Streptococcal skin infections
Skin infections include
Impetigo is a superficial skin infection that causes crusting or bullae.
Erysipelas Erysipelas Erysipelas is a type of superficial cellulitis with dermal lymphatic involvement. Diagnosis is clinical. Treatment is with oral or IV antibiotics. (See also Overview of Bacterial Skin Infections... read more is a superficial cellulitis that also involves the lymphatics. Patients have shiny, red, raised, indurated lesions with distinct margins. It is most often caused by GABHS, but other streptococcal and nonstreptococcal organisms are sometimes involved.
Cellulitis Cellulitis Cellulitis is acute bacterial infection of the skin and subcutaneous tissue most often caused by streptococci or staphylococci. Symptoms and signs are pain, warmth, rapidly spreading erythema... read more involves the deeper layers of skin and may spread rapidly because of the numerous lytic enzymes and toxins produced mainly by group A streptococci.
Necrotizing fasciitis Necrotizing Soft Tissue Infection Necrotizing soft tissue infection is typically caused by a mixture of aerobic and anaerobic organisms that cause necrosis of subcutaneous tissue, usually including the fascia. This infection... read more due to S. pyogenes is a severe dermal (and sometimes muscle) infection that spreads along fascial planes. Inoculation originates through the skin or bowel.
Necrotizing fasciitis is prevalent among people who use injection drugs.
Formerly known as streptococcal gangrene and popularized as the flesh-eating bacteria, the same syndrome may also be polymicrobial, involving a host of aerobic and anaerobic flora, including Clostridium perfringens. Polymicrobial infection is likely when the source is the bowel (eg, after intestinal surgery, bowel perforation, diverticulitis, or appendicitis).
Symptoms of necrotizing fasciitis begin with fever and exquisite localized pain out of proportion to physical findings; pain increases rapidly over time and is often the first (and sometimes only) manifestation. Diffuse or local erythema may be present. Thrombosis of the microvasculature causes ischemic necrosis, leading to rapid spread and disproportionally severe toxicity. In 20 to 40% of patients, adjacent muscles are invaded. Shock and renal dysfunction are common. Mortality is high, even with treatment.
Streptococcal toxic shock syndrome
Streptococcal toxic shock syndrome Streptococcal toxic shock Toxic shock syndrome is caused by staphylococcal or streptococcal exotoxins. Manifestations include high fever, hypotension, diffuse erythematous rash, and multiple organ dysfunction, which... read more (TSS), similar to that caused by S. aureus, may result from toxin-producing strains of GABHS and occasionally from other streptococci.
Patients are usually otherwise healthy children or adults with skin and soft-tissue infections. Predisposing risk factors for TSS in patients infected with these toxin-producing strains include diabetes, alcohol use disorder, penetrating and nonpenetrating trauma, surgical procedures, and varicella infection.
An initial influenza-like prodrome is followed by high fever, tachycardia, tachypnea, and severe pain. Tissue necrosis, shock, disseminated coagulation, and multisystem organ failure follow.
Delayed complications of streptococcal infection
The mechanism by which certain strains of GABHS cause delayed complications is unclear but may involve cross-reactivity of streptococcal antibodies against host tissue.
Rheumatic fever Rheumatic Fever Rheumatic fever is a nonsuppurative, acute inflammatory complication of group A streptococcal pharyngeal infection, causing combinations of arthritis, carditis, subcutaneous nodules, erythema... read more , an inflammatory disorder, occurs in < 3% of patients in the weeks after untreated GABHS pharyngitis. It has become much less common in developed countries, but incidence is still high in resource-limited regions.
Diagnosis of a first episode is based on a combination of arthritis, carditis, chorea, specific cutaneous manifestations, and laboratory test results (Jones criteria—see table ).
One of the most important reasons for treating GABHS pharyngitis (strep throat) is to prevent rheumatic fever.
Poststreptococcal acute glomerulonephritis Postinfectious Glomerulonephritis (PIGN) Postinfectious glomerulonephritis occurs after infection, usually with a nephritogenic strain of group A beta-hemolytic streptococcus. Diagnosis is suggested by history and urinalysis and confirmed... read more is an acute nephritic syndrome following pharyngitis or skin infection due to a certain limited number of nephritogenic strains of GABHS (eg, M protein serotypes 12 and 49). After a throat or skin infection with one of these strains, about 10 to 15% of patients develop acute glomerulonephritis. It is most common among children, occurring 1 to 3 weeks after infection. Nearly all children, but somewhat fewer adults, recover without permanent renal damage. Antibiotic treatment of GABHS infection has little effect on the development of glomerulonephritis.
PANDAS syndrome (pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections) refers to a subset of obsessive disorders in children Obsessive-Compulsive Disorder (OCD) and Related Disorders in Children and Adolescents Obsessive-compulsive disorder is characterized by obsessions, compulsions, or both. Obsessions are irresistible, persistent ideas, images, or impulses to do something. Compulsions are pathologic... read more or tic disorders in children Tic Disorders and Tourette Syndrome in Children and Adolescents Tics are defined as repeated, sudden, rapid, nonrhythmic muscle movements including sounds or vocalizations. Tourette syndrome is diagnosed when people have had both motor and vocal tics for... read more that is thought to be exacerbated by GABHS infection.
Certain forms of psoriasis Psoriasis Psoriasis is an inflammatory disease that manifests most commonly as well-circumscribed, erythematous papules and plaques covered with silvery scales. Multiple factors contribute, including... read more (eg, guttate) may also be related to beta-hemolytic streptococcal infections.
Diagnosis of Streptococcal Infections
Sometimes rapid antigen tests or antibody titers
Streptococci are readily identified by culture on a sheep blood agar plate.
Rapid antigen-detection tests that can detect GABHS directly from throat swabs are available (ie, for point-of-care use). Many tests use enzyme immunoassay, but more recently, tests using optical immunoassay have become available. These rapid tests have high specificity (> 95%) but vary considerably in sensitivity (55% to 80 to 90% for the newer optical immunoassay test) (1 Diagnosis reference 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... read more ). Thus, positive results can establish the diagnosis, but negative results, at least in children, should be confirmed by culture. Because streptococcal pharyngitis is less common among adults and adults are unlikely to have poststreptococcal complications, many clinicians do not confirm a negative rapid screening result in adults by culture unless use of a macrolide is being considered; in such cases, culture with susceptibility testing to detect macrolide resistance should be done.
The Centor criteria can be used to guide decisions about testing for GABHS or selecting empiric antibiotic treatment for patients with pharyngitis. The criteria are age, presence of tonsillar exudate, anterior cervical lymphadenopathy, fever > 104° C, and absence of cough.
Demonstrating antistreptococcal antibodies in serum during convalescence provides only indirect evidence of infection. Antistreptococcal antibody tests are not useful in diagnosing acute GABHS infection because antibody first develops several weeks after GABHS infection begins and a single high antibody titer is more likely to reflect a long antecedent infection. Antibodies are most useful in diagnosis of poststreptococcal diseases, such as rheumatic fever and glomerulonephritis.
Antistreptolysin O (ASO) and antideoxyribonuclease B (anti-DNase B) titers begin to increase about 1 week after the GABHS infection and peak about 1 to 2 months after the infection. Both titers may remain elevated for several months, even after uncomplicated infections. The ASO titer increases in only 75 to 80% of infections. For completeness in difficult cases, any one of the other tests (antihyaluronidase, antinicotinamide adenine dinucleotidase, antistreptokinase) can also be used.
Titers are measured in the acute phase and in the convalescent phase 2 to 4 weeks later; a positive result is defined as a ≥ 2-fold increase in the titer. A single titer greater than the upper limit of normal suggests an antecedent streptococcal infection or high streptococcal endemicity in the community.
Penicillin given within the first 5 days for symptomatic streptococcal pharyngitis may delay the appearance and decrease the magnitude of the ASO response.
Patients with streptococcal pyoderma usually do not have a significant ASO response but may have a response to other antigens (ie, anti-DNAase, antihyaluronidase).
1. Plainvert C, Duquesne I, Touak G, et al: In vitro evaluation and comparison of 5 rapid antigen detection tests for the diagnosis of beta-hemolytic group A streptococcal pharyngitis. Diagn Microbiol Infect Dis 83(2):105–111, 2015. doi: 10.1016/j.diagmicrobio.2015.06.012
Treatment of Streptococcal Infections
(See also the Infectious Diseases Society of America’s 2012 Practice Guidelines for the Diagnosis and Management of Group A Streptococcal Pharyngitis and the American Heart Association's 2020 Contemporary Diagnosis and Management of Rheumatic Heart Disease statement.)
Ordinarily, pharyngeal GABHS infections, including scarlet fever, are self-limited. Antibiotics shorten the course in young children, especially those with scarlet fever, but have only modest effect on symptoms in adolescents and adults. However, antibiotics help prevent local suppurative complications (eg, peritonsillar abscess), otitis media, and rheumatic fever.
Penicillin is the drug of choice for pharyngeal GABHS infections. No isolate of GABHS has shown penicillin resistance clinically. However, some streptococcal strains appear to have in vitro tolerance to penicillin (ie, significantly decreased bactericidal effect of penicillin); the clinical significance of such strains is unclear.
A single injection of benzathine penicillin G 600,000 units IM for small children (< 27 kg) or 1.2 million units IM for children weighing ≥ 27 kg, adolescents, and adults usually suffices.
Oral medications may be used if the patient can be trusted to maintain the regimen for the required 10 days. Choices include
Penicillin V 500 mg (250 mg for children < 27 kg) orally every 12 hours
Amoxicillin 50 mg/kg (maximum 1 g) once a day for 10 days (which is an effective substitute for penicillin V)
Oral narrow-spectrum cephalosporins (eg, cephalexin, cefadroxil) are also effective and can be used unless patients have an anaphylactic reaction to penicillin. Azithromycin can be used for a 5-day course of therapy, although macrolides are inactive against Fusobacterium necrophorum, a common cause of pharyngitis in adolescents and adults. Delaying treatment 1 to 2 days until laboratory confirmation increases neither the duration of disease nor the incidence of complications.
When penicillin and a beta-lactam are contraindicated, choices include
Clindamycin 600 mg (7 mg/kg for children) orally every 8 hours for 10 days
Clarithromycin 250 mg (7.5 mg/kg for children) orally every 12 hours for 10 days
Azithromycin 500 mg (15 mg/kg for children) orally once a day for 5 days
Cephalexin 500 mg (20 mg/kg for children; maximum dose is 500 mg/dose) orally every 12 hours for 10 days
Cefadroxil 1000 mg (30 mg/kg for children; maximum dose is 1000 mg/dose) orally once a day or 500 mg (15 mg/kg for children; maximum dose is 500 mg/dose) every 12 hours for 10 days
Because resistance of GABHS to macrolides has been detected, some authorities recommend in vitro confirmation of susceptibility if a macrolide is to be used and there is macrolide resistance in the community. Clindamycin 7 mg/kg orally every 8 hours is preferred in children who have relapses of chronic tonsillitis, possibly because of the following:
Clindamycin has good activity against penicillinase-producing staphylococci or anaerobes coinfecting the tonsillar crypts and inactivating penicillin G.
It appears to halt exotoxin production more rapidly than other medications.
Amoxicillin/clavulanate is also effective.
Trimethoprim/sulfamethoxazole (TMP/SMX), some of the fluoroquinolones, and tetracyclines are unreliable for treating GABHS infection.
Sore throat, headache, and fever can be treated with analgesics or antipyretics. Aspirin should be avoided in children. Bed rest and isolation are unnecessary. Close contacts who are symptomatic or have a history of poststreptococcal complications should be examined for streptococci.
Cellulitis is often treated without doing a culture because isolating organisms can be difficult. Thus, regimens effective against both streptococci and staphylococci are used; for example, one of the following may be used:
Dicloxacillin or cephalexin if methicillin-resistant Staphylococcus aureus (MRSA) is not likely
TMP/SMX, linezolid, minocycline, or clindamycin if MRSA is suspected (see treatment of cellulitis Treatment Cellulitis is acute bacterial infection of the skin and subcutaneous tissue most often caused by streptococci or staphylococci. Symptoms and signs are pain, warmth, rapidly spreading erythema... read more )
Necrotizing fasciitis should be treated in an intensive care unit. Extensive (sometimes repeated) surgical debridement is required. A recommended initial antibiotic regimen is a broad-spectrum beta-lactam (eg, piperacillin/tazobactam) or a carbapenem (eg, meropenem, imipenem) (until etiology is confirmed by culture) plus clindamycin. Vancomycin should be added if infection with MRSA is suspected. Although streptococci remain susceptible to beta-lactam antibiotics, animal studies show that penicillin is not always effective against a large bacterial inoculum because the streptococci are not rapidly growing and may lack penicillin-binding proteins, which are the target of penicillin activity.
Other streptococcal infections
For treating groups B, C, and G infections, antibiotics of choice are
Cephalosporins or macrolides are usually effective, but susceptibility tests must guide therapy, especially in very ill, immunocompromised, or debilitated people and in people with foreign bodies at the infection site. Surgical wound drainage and debridement as adjuncts to antimicrobial therapy may be lifesaving.
S. gallolyticus (formerly S. bovis) is relatively susceptible to antibiotics. Although vancomycin-resistant S. gallolyticus isolates have been reported, the organism remains susceptible to penicillin and aminoglycosides.
Most viridans streptococci are susceptible to penicillin G and other beta-lactams. Resistance is growing, and therapy for such strains should be dictated by results of in vitro susceptibility tests.
The most significant streptococcal pathogen is S. pyogenes, which is denoted as group A beta-hemolytic streptococci (GABHS).
The 2 most common acute diseases due to GABHS are pharyngitis and skin infections.
Delayed nonsuppurative complications, including rheumatic fever and poststreptococcal glomerulonephritis, can occur.
Rapid antigen tests (ie, for point-of-care use) are very specific but not highly sensitive; confirm negative results using culture, at least in children.
A penicillin or cephalosporin is preferred for pharyngitis; because macrolide resistance is increasing, susceptibility testing is recommended if that class of antibiotic is used.
For skin infection, give dicloxacillin or cephalexin if MRSA is not likely, but give TMP/SMX, linezolid, minocycline, or clindamycin if MRSA is suspected.
Treat groups B, C, and G streptococcal infections with the same antibiotics used for treating GABHS.
The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.
Infectious Diseases Society of America: Practice Guidelines for the Diagnosis and Management of Group A Streptococcal Pharyngitis (2012)
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