Acute rheumatic fever developed after macrolide resistance

Logan LK. Pediatrics. 2012;doi:10.1542/peds.2011-1198.

Two pediatric cases of macrolide resistance and/or treatment failure in group A streptococcal pharyngitis — with ensuing development of acute rheumatic fever — were reported in a recent review published online.

To assess the use of macrolides in the management of group A streptococcus (GAS), researchers reviewed available literature on worldwide macrolide resistance rates, molecular classifications and emm types associated with GAS pharyngeal isolates from 2000 to 2010. The researchers provided case reports on two patients treated with azithromycin for GAS pharyngitis — Patient 1 due to a presumed penicillin allergy and Patient 2 as a first-line treatment.

Although results of an echocardiogram, electrocardiogram and chest radiograph on Patient 1 were normal, a throat culture revealed an erythromycin-resistant, clindamycin-sensitive strain of GAS. Patient 1 was treated with clindamycin and aspirin, and after a negative throat culture, received erythromycin as secondary prophylaxis.

Patient 2 also demonstrated normal ECG and chest radiograph results, but received a throat culture. The echocardiogram exposed mild tricuspid and trivial mitral valve regurgitation, and the patient was treated with prednisone and administered penicillin V potassium for acute rheumatic fever treatment and secondary prophylaxis.

After a review for worldwide prevalence of macrolide resistance, researchers observed a wide spectrum in rates of GAS macrolide resistance — from 1.1% in Cyprus to as high as 97.9% in China. In the United States, single-center studies have revealed macrolide-resistance rates as high as 48%, whereas prospective multicenter US surveillance studies have demonstrated escalating resistance rates from 3% to 8.7% (from 2000 to 2003) to as high as 12% to 15% at the same centers in 2007.

Researchers attributed the increase in worldwide rates to several factors, including horizontal gene transfer and spread of dominant resistance clones, overconsumption of macrolide antibiotics and temporal variation in the distribution of emm types.

According to the researchers, “Practitioners should be cautioned to use macrolide antibiotics in the management of GAS infection only in the face of anaphylactic-type penicillin allergy because of increased rates of macrolide-resistance and the potential risk of serious complications such as [acute rheumatic fever] and [rheumatic heart disease] without adequate therapy.”

Disclosure: The researchers report no relevant financial disclosures.

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