ARCHIVED - 7.0 Recommendations for Chemoprophylaxis
The objective of chemoprophylaxis is to prevent disease in colonized individuals and in those who have recently been exposed, thereby decreasing transmission of a strain known to cause severe infection.
The recommendations for chemoprophylaxis regimens have been extrapolated from treatment guidelines for acute GAS pharyngitis and evidence from clinical trials for the eradication of pharyngeal GAS colonization. Currently, there are no studies that have specifically assessed the effectiveness of chemoprophylaxis for the prevention of subsequent cases of invasive GAS disease, although antibiotic prophylaxis has been successfully used for outbreak control in LTCF in Canada and the United States(35,36,43,46). Further studies are needed.
First-generation cephalosporins, such as cephalexin, are the preferred antibiotic for GAS chemoprophylaxis. Second-and third-generation cephalosporins (e.g. cefuroxime axetil, cefixime) may also be considered, but they have a broader spectrum, increased likelihood of resistance and higher cost than first-generation cephalosporins(56,57). Cephalosporins are more effective than penicillin in eradicating GAS from pharyngeal carriers(56,58,59).Ameta-analysisof 35 trials involving 7,125 pediatric patients with GAS tonsillopharyngitis showed that the bacteriologic cure rate significantly favoured cephalosporins compared with penicillin (odds ratio [OR] = 3.02, 95% CI: 2.49-3.67) after 10 days of treatment. Eight of 11 individual cephalosporins showed superior bacteriological cure rates among children. The summary OR for clinical cure rate was 2.33 (95% CI: 1.84-2.97)(60). A meta-analysis of nine randomized controlled trials with adult patients showed that the bacteriologic eradication rate was nearly two times higher for cephalosporins than penicillin for the treatment of acute GAS tonsillopharyngitis after 10 days of treatment (summary OR = 1.83, 95% CI: 1.37-2.44); the clinical cure rate also favoured cephalosporins (summary OR = 2.29, 95% CI: 1.61-3.28)(57). Cephalosporins are acceptable for penicillin-allergic patients who do not manifest immediate-type hypersensitivity to beta-lactam antibiotics(61).
The macrolides erythromycin and clarithromycin are suitable alternative agents that have been shown to be clinically effective for treatment of GAS pharyngitis(62-67). However, macrolide resistance is a concern in Canada. According to surveillance data for invasive GAS submitted to NCS, erythromycin resistance has been relatively stable over the past 4 years, ranging from 9.8 to 11.1%(14-16). In areas where macrolide resistance is either unknown or known to be ≥ 10%, testing of the GAS isolate is recommended to determine appropriate treatment.
Clindamycin is another alternative agent recommended for patients infected with an erythromycin-resistant strain of S. pyogenes who are unable to tolerate beta-lactam antibiotics(61). A 10-day regimen of orally administered clindamycin (20 mg/kg per day) was effective in eradicating GAS from the oropharynx of persistently colonized, asymptomatic children (92%, 24/26) in a randomized, unblinded, controlled clinical trial(68). Gallegos et al.(69) found that clindamycin regimens of either 150 mg 4 times per day or 300 mg 2 times per day were equally efficacious, with a clinical cure rate of 93% among adults with acute streptococcal tonsillitis/pharyngitis in a double-blind, randomized, multicentre study. However, emergence of resistance would need to be monitored closely for this anti-microbial. In 2004-2005, 2.0% of GAS isolates tested for antimicrobial sensitivity at the NCS were resistant to clindamycin(16), as compared with 1.6% of isolates in 2003-2004(15), 1.9% in 2002-2003 and 0.9% in 2001-2002(14).
Oral penicillin VK (or amoxicillin in young children) may be considered for GAS chemoprophylaxis because of its proven efficacy, safety, narrow spectrum and low cost(70). However, penicillin is less effective in eradicating GAS from the upper respiratory tracts of chronic (asymptomatic) carriers. Carriers treated with penicillin are generally characterized by a lack of a serologic response and may account for a significant proportion of penicillin treatment failures(58,71-73). Streptococcal internalization within epithelial cells may contribute to eradication failure and persistent throat carriage(74). Some experts feel that penicillin should be considered an alternative first-line therapy, whereas other experts believe that penicillin monotherapy may be inferior on the basis of data from bacteriologic eradication in the treatment of GAS pharyngitis and in the eradication of carriage; however, the relevance of these data to chemoprophylaxis of contacts is unclear.
Azithromycin may be considered for the eradication of GAS from the pharynx using a shorter 5-day (70,75) course, but Canadian evidence has shown that azithromycin may select for macrolide resistance among streptococci more strongly than erythromycin and clarithromycin, and therefore it should not be considered as a first-or second-line therapy(76).
The chemoprophylactic agents and dosages recommended for preventing disease and decreasing transmission of GAS are listed in Table 6. It is important to ensure that contacts requiring chemoprophylaxis complete the recommended course.
|First-generation cephalosporins: cephalexin, cephadroxil, cephradine||First line. Children and adults: 25 to 50 mg/kg daily, to a maximum of 1 g/day in 2 to 4 divided doses × 10 days||Recommended drug for pregnant and lactating women. Should be used with caution in patients with allergy to penicillin. Use of cephalosporins with nephrotoxic drugs (e.g. aminoglycosides, vancomycin) may increase the risk of cephalosporin-induced nephrotoxicity.|
|Erythromycin||Second line. Children: 5 to 7.5 mg/kg every 6 hours or 10 to 15 mg/kg every 12 hours (base) × 10 days (not to exceed maximum of adult dose) Adults: 500 mg every 12 hours (base) × 10 days||Erythromycin estolate is contraindicated in persons with pre-existing liver disease or dysfunction and during pregnancy. Sensitivity testing is recommended in areas where macrolide resistance is unknown or known to be ≥ 10%.|
|Clarithromycin||Second line. Children: 15 mg/kg daily in divided doses every 12 hours, to a maximum of 250 mg po bid × 10 days Adults: 250 mg po bid × 10 days||Contraindicated in pregnancy. Sensitivity testing is recommended in areas where macrolide resistance is unknown or known to be ≥ 10%.|
|Clindamycin||Second line. Children: 8 to 16 mg/kg daily divided into 3 or 4 equal doses × 10 days (not to exceed maximum of adult dose) Adults: 150 mg every 6 hours × 10 days||Alternative for persons who are unable to tolerate beta-lactam antibiotics.|
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