Basics
Description
Infection associated with isolation of group A � �-hemolytic streptococci (GABHS) from a normally sterile body site; includes 3 clinical syndromes: � �
- GABHS toxic shock syndrome (STSS)
- GABHS necrotizing fasciitis (NF)
- Infection characterized by extensive local necrosis of skin and subcutaneous soft tissues
- Isolation of GABHS from normally sterile sites in patients not meeting criteria for STSS or NF (e.g., meningitis, osteomyelitis, septic arthritis, myositis, surgical wound infections) with or without bacteremia
Diagnostic criteria for STSS: � �
- (I) Isolation of GABHS
- A: From a normally sterile site (e.g., blood, CSF, tissue, peritoneal fluid)
- B: From a nonsterile site (e.g., throat, vagina, sputum, open surgical wound)
- (II) Clinical signs of severity
- A: Hypotension
- B: Two or more of the following signs:
- Renal impairment
- Coagulopathy
- Hepatic involvement
- Adult respiratory distress syndrome
- A generalized erythematous macular rash that may desquamate
- Soft tissue necrosis, including NF or myositis, or gangrene
- A definite case fulfills criteria IA and II (A and B). A probable case fulfills criteria IB and II (A and B) and no other identifiable cause.
Epidemiology
- Overall mortality rates for invasive GABHS infections are lower in children (5 " �15%) than in adults (30 " �80%).
- Most cases occur in winter and early spring.
Incidence
- It is estimated that the annual incidence in the United States is 1.5 " �5.9 cases per 100,000 persons.
- Incidence is highest in infants and the elderly.
- 85% of cases are sporadic, 10% hospital-acquired, 4% in chronic care facilities, 1% in cases with a close index contact.
Risk Factors
- Risk factors for invasive GABHS infections include injuries resulting in bruising or muscle strain, surgical procedures, and viral infections such as varicella.
- High-risk groups include patients with diabetes mellitus, chronic cardiac or pulmonary disease, HIV infection or AIDS, and those with a history of IV drug use.
General Prevention
- Routine immunization against varicella
- Isolation of hospitalized patients
- In addition to standard precautions, droplet precautions for children with pneumonia
- Contact precautions should be used for at least 24 hours after the start of antimicrobial therapy in children with extensive or draining cutaneous infections.
- Several GABHS vaccine candidates are in varying stages of development. A 26-valent recombinant M protein vaccine is the only vaccine to have entered into clinical trials.
Pathophysiology
- The pathogenic mechanism has not been fully defined; however, an association with streptococcal pyrogenic exotoxins (SPE) has been suggested.
- SPE A, B, and C (responsible for rash of scarlet fever) along with streptococcal exotoxins, mitogen factor, and superantigen stimulate activation of T lymphocytes and macrophages to produce large quantities of cytokines resulting in shock and tissue damage.
- There may be no identifiable focus of infection.
Etiology
Streptococcus pyogenes is the only species of � �-hemolytic streptococci to be associated with invasive infections. � �
Diagnosis
History
- Historic features vary depending on the GABHS syndrome.
- May have preceding soft tissue infection such as cellulitis
- A preceding clinical pharyngitis is not common.
- Consider GABHS infection in any child with varicella who has any of the following:
- Localized skin findings of erythema, warmth, swelling, or induration
- Return of fever after having been afebrile
- A temperature of ≥39 � �C (102.7 � �F) beyond the 3rd day of illness
- Any fever persisting beyond the 4th day of illness
- In children without varicella, presentation can mimic influenza infection (fever, chills, myalgias). Abrupt onset of localized or severe pain and absence of respiratory symptoms or a contact history are clues to help distinguish STSS from influenza.
- Incubation period for STSS is unknown.
Physical Exam
- Vital signs
- Elevated temperature
- Tachycardia
- Hypotension (late sign)
- Toxic appearance is common but may not be present, especially early in the disease course.
- Skin exam varies:
- Often, there are no cutaneous findings.
- With varicella infection, vesicular lesions may have underlying erythema, warmth, or induration but can also appear normal.
- NF should be suspected in child who presents with diffuse swelling of an extremity followed by the development of bullae with fluid that rapidly evolves from clear to violaceous in color.
- Erythroderma, a generalized macular exfoliative and erythematous rash, is sometimes observed with STSS.
- Deep infections will have exam findings consistent with the specific focus (e.g., joint pain and limitation of mobility in septic arthritis, respiratory symptoms in GABHS pneumonia).
- Pain and/or hyperesthesias out of proportion to clinical findings may be noted.
Diagnostic Tests & Interpretation
Lab
- CBC (leukocytosis with immature neutrophils may be noted but WBC can also be normal)
- Electrolytes, BUN, creatinine, and glucose
- Liver function tests
- Screen for disseminated intravascular coagulation
- Creatine kinase level (may be elevated in NF)
- Blood culture
- Culture of wound and tissue aspirates
- Throat culture
- If culture negative, a rise in antibody titers to streptolysin O, deoxyribonuclease B, or other streptococcal extracellular products 4 " �6 weeks after infection may help confirm the diagnosis.
- These antibodies may remain elevated for several months and indicate an infection in the recent past.
Imaging
In cases of NF: Consider MRI to confirm diagnosis and extent of infection. � �
Differential Diagnosis
- Bacterial sepsis
- Toxic shock syndrome from Staphylococcus aureus
- Other soft tissue infections
- Cellulitis
- Erysipelas
- Clostridial or mixed anaerobic and aerobic fasciitis/gangrene
Alert
- Diagnosis is primarily clinical and requires a high degree of suspicion because of the rapid progression of infection.
- Diagnosis should be considered even in suspect cases with absence of rash, cellulitis, or superinfected varicella lesions.
- In cases of NF, extent of involvement in subcutaneous tissues may be underestimated. Infection may be more widespread than what is apparent on physical exam.
- In STSS cases, care should be taken to search for a localized infection as a possible source of toxin production.
Treatment
Medication
- Parenteral therapy at maximum doses for both GABHS and S. aureus should be instituted promptly with the capacity to do both of the following:
- Kill organism with bactericidal cell wall inhibitor.
- Decrease enzyme, toxin, or cytokine production with protein synthesis inhibitor.
- Recommended regimens:
- Oxacillin (150 mg/kg/24 h divided q6h) or nafcillin (200 mg/kg/24 h divided q4 " �6h; maximum 12 g/24 h) plusclindamycin (25 " �40 mg/kg/24 h divided q6h or q8h)
- In penicillin-allergic patients, consider vancomycin (40 mg/kg/24 h divided q6h) plusclindamycin.
- In areas with high prevalence of community-acquired methicillin-resistant S. aureusvancomycin should be used in place of � �-lactamase " �resistant penicillins.
- Once GABHS has been identified, antibiotic regimen should be changed to high-dose penicillin G (200,000 " �400,000 U/kg/24 h in 4 " �6 divided doses) plusclindamycin.
- No penicillin G " �resistant isolates of GABHS have been reported.
- There are strains resistant to clindamycin, so it should not be used alone until shown to be sensitive.
- Antibiotics should be continued for a minimum of 14 days in patients with bacteremia and for 14 days after last positive culture obtained during surgical debridement for patients with deep soft tissue infections.
- The use of IV immunoglobulin may be considered in cases refractory to aggressive therapy, for infection in an area that precludes drainage, or persistent oliguria with pulmonary edema. Various regimens have been used: 150 " �400 mg/kg/24 h for 5 days or 1 " �2 g/kg as single dose.
Additional Treatment
General Measures
- Volume resuscitation
- Replete electrolytes as indicated
- Inotropes as indicated
- Blood products as indicated for anemia or thrombocytopenia
- Airway support for severe depression of level of consciousness or respiratory insufficiency
Surgery/Other Procedures
Consider surgical consult early in management of NF. Extensive debridement of necrotic tissue is often indicated. Fasciotomy may be required to relieve compartment syndrome. � �
Ongoing Care
Prognosis
- Fulminant course with rapid deterioration is characteristic of invasive GABHS infections.
- Prognosis is improved with early recognition and aggressive management.
- Case fatality rate for invasive GABHS infections is 13.7% (36% for STSS and 24% for NF).
- Increased morbidity and mortality reported in cases of coinfection with H1N1 influenza
- Poor prognostic factors:
- Emm/M strain types 1, 3, or 12
- Increased age
- Occurrence in winter/early spring
- Development of GI symptoms
Complications
- From deep and systemic infections:
- Sepsis syndrome
- Hematologic seeding and development of focal infection
- Infection site " �specific complications (e.g., meningitis, neurologic impairment; septic arthritis, joint destruction)
- From NF:
- Severe tissue necrosis usually requires extensive surgical debridement and may require amputation of involved extremities.
- Compartment syndrome
- Functional disabilities
- Cosmetic sequelae
- From STSS:
- Multiorgan system failure
- Acute respiratory distress syndrome
- Disseminated intravascular coagulation
- Acute tubular necrosis and renal failure
- Hepatic failure
- Cardiac insufficiency
- Cerebral ischemia and edema
- Metabolic derangements
Additional Reading
- American Academy of Pediatrics. Group A streptococcal infections. In: Pickering � �LK, Baker � �CJ, Kimberlin � �DW, et al, eds. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th ed. Elk Gove Village, IL: American Academy of Pediatrics; 2012:668 " �680.
- American Academy of Pediatrics Committee on Infectious Diseases. Severe invasive group A streptococcal infections: a subject review. Pediatrics. 1998;101(1, Pt 1):136 " �140. � �[View Abstract]
- Burnett � �AM, Domachowske � �JB. Therapeutic considerations for children with invasive group A streptococcal infections: a case series report and review of the literature. Clin Pediatr. 2007;46(6):550 " �555. � �[View Abstract]
- Lamagni � �TL, Neal � �S, Keshishian � �C, et al. Predictors of death after severe Streptococcus pyogenes infection. Emerg Infect Dis. 2009;15(8):1304 " �1307. � �[View Abstract]
- Langlois � �DM, Andreae � �M. Group A streptococcal infections. Pediatr Rev. 2011;32(10):423 " �430. � �[View Abstract]
- Martin � �JM, Green � �M. Group A Streptococcus. Semin Pediatr Infect Dis. 2006;17(3):140 " �148. � �[View Abstract]
- 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. � �[View Abstract]
Codes
ICD09
- 041.01 Streptococcus infection in conditions classified elsewhere and of unspecified site, streptococcus, group A
- 041.02 Streptococcus infection in conditions classified elsewhere and of unspecified site, streptococcus, group B
- 040.82 Toxic shock syndrome
- 728.86 Necrotizing fasciitis
ICD10
- B95.0 Streptococcus, group A, causing diseases classd elswhr
- B95.1 Streptococcus, group B, causing diseases classd elswhr
- A48.3 Toxic shock syndrome
- M72.6 Necrotizing fasciitis
SNOMED
- 302809008 Streptococcus pyogenes infection (disorder)
- 426933007 Streptococcus agalactiae infection (disorder)
- 240451000 Streptococcal toxic shock syndrome (disorder)
- 449900006 necrotizing fasciitis due to Streptococcus pyogenes (disorder)
FAQ
- Q: For whom should the diagnosis of invasive GABHS be entertained?
- A: Consider GABHS in any child with varicella who experiences recrudescence of fever, fever ≥39 � �C (102.2 � �F) beyond the 3rd day of illness, or any fever beyond the 4th day of illness. A high index of suspicion should be maintained in patients with septicemia and in febrile patients with pain and hyperesthesia out of proportion to the clinical findings.
- Q: Is NSAID use in patients with varicella associated with GABHS?
- A: There are reports suggesting an association between the use of NSAIDs and the development of invasive GABHS diseases, but a causal relationship has not been established. There is evidence that NSAIDs impair granulocyte function and enhance production of cytokines. Additionally, they may mask signs of disease by suppressing the pain and fever that might encourage a patient with invasive GABHS infection to seek medical attention. No formal recommendations for restricting the use of NSAIDs are being made at this time.
- Q: Should close contacts of patients with invasive GABHS infections receive chemoprophylaxis?
- A: Although the risk of developing disease for household contacts is elevated in comparison to the general population, the risk is not sufficiently high to warrant routine testing or treatment for GABHS colonization. No clearly effective chemoprophylactic regimen has been identified. However, in high-risk populations (people >65 years or those with HIV, varicella, or diabetes mellitus), targeted chemoprophylaxis may be considered. Chemoprophylaxis is not recommended in schools or child care facilities.