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Given the potentially devastating consequences of severe invasive group A streptococcal disease, attention has been directed toward the role of chemoprophylaxis and the optimization of management strategies. In response to this issue, Canadian guidelines were previously developed. However, the uptake of these recommendations is variable across Canada. The present document summarizes key components of the recommendations for use by Canadian physicians. The importance of penicillin in the treatment of group A streptococcal disease is reaffirmed, and the role of clindamycin is discussed. In addition, in situations in which chemoprophylaxis may be considered, the preferred agents are summarized.
Key Words: Chemoprophylaxis; Group A streptococcus; Necrotizing fasciitis; Toxic shock
Since the resurgence of severe group A streptococcal disease in the 1980s, attention has been directed toward the role of chemoprophylaxis of contacts of invasive group A streptococcal disease, as well as the clinical management of individuals with this disease. In 2006, Canadian guidelines were developed to address the prevention and control of invasive disease due to group A streptococcus (GAS) . The present document highlights the management of contacts of cases of invasive group A streptococcal disease and the management of this disease based on these guidelines.
The most common clinical presentations of invasive group A streptococcal infections are necrotizing fasciitis (NF) or myositis, bacteremia with no septic focus and pneumonia. In Canada, the incidence of invasive group A streptococcal disease was 2.7 per 100,000 population, based on data from 2001  (the most recent year for which complete data are available). Rates were highest in young children and the elderly. The rate among infants younger than one year of age was 4.8 per 100,000, while the rate among children one to four years of age was 3.6 per 100,000. Among children, the annual incidence of NF has been shown to be higher in those younger than five years of age versus those five years to younger than 16 years of age (5.9 versus 1.8 per million; P=0.0002) .
Invasive group A streptococcal infection may present as a severe disease manifested by toxic shock syndrome (TSS) with or without an identifiable focus of infection . Surveillance data from Ontario suggest that 13% of cases of invasive group A streptococcal infection were streptococcal TSS and 6% were NF . Risk factors for invasive group A streptococcal disease among adults include HIV infection, cancer, heart disease, diabetes, lung disease, alcohol abuse, injection drug use and pregnancy-related risk factors. Among children, varicella is a prominent risk factor . Two studies  assessing secondary cases in household contacts reported rates of 0.66 and 2.94 per 1000, respectively, which were 20 to 100 times the rates in the overall populations studied. Most secondary cases occurred within seven days of the index case. There is little information on the risk of transmission in other settings, but secondary cases appear to be rare. A secondary case associated with varicella has been reported in a child care centre . Transmission also occurs in hospitals .
Currently, invasive group A streptococcal infection is reportable in all provinces and territories in Canada. Within each province or territory, procedures are in place for the rapid notification of cases to medical health officers and for timely reporting to the appropriate provincial/territorial public health official. Confirmed cases are reported at the national level.
The Public Health Agency of Canada’s (PHAC) “Guidelines for the prevention and control of invasive group A streptococcal disease”  are based on the following consensus definitions summarized below:
In the above context, clinical evidence of invasive disease includes the following:
a. streptococcal TSS, which is characterized by hypotension (systolic blood pressure of 90 mmHg or less in adults, or less than the fifth percentile for age in children) and at least two of the following signs:
b. soft-tissue necrosis, including NF, myositis or gangrene;
c. meningitis; or
d. a combination of the above.
With respect to the role of chemoprophylaxis, the Canadian guidelines suggest the following:
Variations in the approach to chemoprophylaxis exist across jurisdictions . The level of risk may vary for different groups of individuals, and there may be circumstances under which different decisions regarding chemoprophylaxis may be made. Chemoprophylaxis is not routinely recommended for contacts of cases that are not severe (eg, bacteremia or septic arthritis). These cases tend to have milder disease and so do their contacts .
Chemoprophylaxis is recommended for all children and staff in family or home daycare settings if the above criteria are met. Chemoprophylaxis is generally not recommended in group or institutional child care centres and preschools. However, this may be considered in specific situations such as the occurrence of more than one case of invasive group A streptococcal disease in children or staff of the child care centre within one month, or the occurrence of a concurrent varicella outbreak at the child care centre.
The first-generation cephalosporins (eg, cephalexin) are the preferred agents (Table 1). Alternative agents include second- and third-generation cephalosporins (eg, cefuroxime axetil and cefixime). Penicillin is less effective in eradicating GAS colonization than the cephalosporins . Macrolides, such as erythromycin, clarithromycin and azithromycin, may be used for chemoprophylaxis in individuals with beta-lactam allergy. However, this course of action would need to be periodically reassessed given the concern regarding macrolide-resistant GAS. Clindamycin may also be used for chemoprophylaxis in patients who are not able to tolerate beta-lactams.
| TABLE 1|
Recommended chemoprophylaxis regimens for close contacts of invasive group A streptococcal disease
First-generation cephalosporins: cephalexin, cephadroxil and cephradine
First-line treatment: Children and adults:
Recommended drug for pregnant and lactating women. Should be used with caution in patients allergic to penicillin
Second-line treatment: Children:
Erythromycin estolate is contraindicated in persons with pre-existing liver disease or dysfunction, and during pregnancy. Sensitivity testing is recommended in areas in which macrolide resistance is unknown or known to be 10% or greater
Second-line treatment: Children: 15 mg/kg daily in divided doses every 12 h, to a maximum of 250 mg orally twice daily for 10 days. Adults: 250 mg orally twice daily for 10 days
Contraindicated in pregnancy. Sensitivity testing is recommended in areas in which macrolide resistance is unknown or known to be 10% or greater
Second-line treatment: Children:
Alternative for persons who are unable to tolerate beta-lactam antibiotics
Adapted from reference 
Routine cultures are not required for contacts receiving antibiotic chemoprophylaxis. Cultures have no role in the identification of asymptomatic close contacts of sporadic cases occurring in the community.
The management of severe invasive group A streptococcal disease involves the following: supportive treatment with the use of fluid and electrolytes; specific therapy with antimicrobials; and the use of measures to minimize or neutralize the effects of toxin production, where indicated. Penicillin remains the treatment of choice . The addition of clindamycin is regarded as a more effective regimen than penicillin alone, because the antimicrobial activity of clindamycin is not affected by inoculum size, has a long postantimicrobial effect and acts by inhibiting protein synthesis . The latter is believed to be particularly relevant in cases of GAS in which there is no evidence of toxin-mediated disease. Clindamycin should not be used as monotherapy because a small proportion of group A streptococci are resistant to clindamycin (1% to 2%) , whereas, to date, there is no resistance to penicillin.
Intravenous immune globulin may be considered in the treatment of streptococcal TSS or severe toxin-mediated disease in the absence of shock. The mechanism of action of intravenous immune globulin is unclear. Suggested regimens include 150 mg/kg to 400 mg/kg per day for five days or a single dose of 1 g/kg to 2 g/kg .
Other specific treatments may be required depending on the clinical situation (eg, surgical debridement of necrotic tissue).
The decision to engage the National Centre for Streptococcus in the investigations of clusters or outbreaks of disease due to GAS rests with the local public health agencies. Group A streptococcal strains are characterized using serological and molecular techniques. The profile of a particular strain includes the identification of the M protein type and T protein, and anti-opacity factor testing for serum opacity-factor-positive GAS -.
Readers are encouraged to consult the PHAC “Guidelines for the prevention and control of invasive group A streptococcal disease”  as well as the related infection control guidelines -. These documents also address the prevention of noninvasive group A streptococcal disease within health care institutions.
Members: Robert Bortolussi MD (chair); Jane Finlay MD; Jane C McDonald MD; Heather Onyett MD; Joan L Robinson MD; Élisabeth Rousseau-Harsany MD (board representative)
Liaisons: Upton D Allen MD, Canadian Pediatric AIDS Research Group; Charles PS Hui MD, CPS Liaison to Health Canada, Committee to Advise on Tropical Medicine and Travel; Nicole Le Saux MD, Immunization Program, ACTive; Larry Pickering MD, American Academy of Pediatrics; Marina I Salvadori MD, CPS Liaison to Health Canada, National Advisory Committee on Immunization
Consultants: James Kellner MD; Noni E MacDonald MD; Dorothy L Moore MD
Principal authors: Upton D Allen MD; Dorothy L Moore MD
Disclaimer: The recommendations in this position statement do not indicate an exclusive course of treatment or procedure to be followed. Variations, taking into account individual circumstances, may be appropriate. Internet addresses are current at time of publication.