Group A Strep Resistance to Macrolides

The most recent Treatment Guidelines issue on Drugs for Bacterial Infections (2010; 10:43) warned about high rates of resistance to macrolide antibiotics among pharyngeal isolates of group A streptococci. A recent article in Pediatrics reported 2 cases of acute rheumatic fever in children who had been treated with macrolides, one with erythromycin and one with azithromycin, for group A streptococcal pharyngitis (LK Logan et al, Pediatrics 2012; 129:e798-e802).

Rheumatic fever is rarely encountered now in the United States, but it remains common in the developing world, where it is the leading cause of acquired heart disease in children, and among special groups such as the Indigenous people (formerly called Aborigines) of Australia. The reasons for its disappearance in the US and other developed countries are not entirely understood. The widespread use of antimicrobial agents, particularly the penicillins, has undoubtedly played a role, but the greater availability of housing and the marked decrease in the number of people living under crowded conditions may be equally important.

The Pediatrics report should serve as a reminder that the strains of group A streptococci that can cause rheumatic fever are still with us, and they must be treated appropriately to prevent the reappearance of this crippling illness. The drug of choice is penicillin G, to which group A strep are exquisitely sensitive. Penicillin V, amoxicillin, or a first-generation cephalosporin are highly effective alternatives.

Macrolides are recommended alternatives for patients who are allergic to penicillin, but serious allergy to penicillin is rare in children, and the widespread use of macrolides to treat respiratory infections may have led to less appropriate use for treatment of pharyngitis. Azithromycin is especially tempting because of its convenient once-daily, 5-day course, but resistance can occur, and there is no evidence that this regimen prevents rheumatic fever. Cross-resistance is complete among the macrolides; some macrolide-resistant group A strep may be susceptible to clindamycin.  Penicillin is effective, safe, and inexpensive. Unless a patient has a history of an immediate reaction to penicillin, it should continue to be the drug of choice for treatment of group A streptococcal pharyngitis.

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