Strep Throat: Where Does Azithromycin Fit?

Michael J. Postelnick, BSPharm

Disclosures

December 18, 2014

Question

What is the latest on azithromycin use for group A streptococcal pharyngitis?

Response from Michael J. Postelnick, BSPharm
Lecturer, Department of Medical Education, Northwestern University Feinberg School of Medicine; Senior Infectious Disease Pharmacist, Clinical Manager, Northwestern Memorial Hospital Department of Pharmacy, Chicago, Illinois

Streptococcal pharyngitis is one of the more common infections of childhood and can also occur in adults. The association between this disease and the development of rheumatic heart disease is well established. The exact relationship between streptococcal pharyngitis and rheumatic fever is not totally clear; however, failure to eradicate the organism from the pharynx has been identified as a significant risk factor. The incidence of rheumatic heart disease is considerably higher in countries where aggressive treatment with effective antibiotics is not always available or undertaken.

According to the most current Infectious Diseases Society of America (IDSA) guidelines, penicillin or amoxicillin remains the drug of choice for the treatment of group A streptococcal pharyngitis. A first-generation cephalosporin is recommended if a patient has a history of nonanaphylactic allergy to penicillin. Alternatives include clindamycin, clarithromycin, and azithromycin.

All recommended oral treatment courses extend for 10 days except for azithromycin, for which a 5-day treatment course is recommended.[1] This may lead clinicians to choose azithromycin for patients who have no clear contraindication to a penicillin or cephalosporin.

Whereas the penicillin and cephalosporin recommendations are rated as being based on high-level strong evidence, the azithromycin recommendation is rated as based on moderate evidence.[1] The remainder of this discussion will examine the appropriate utilization of azithromycin for this indication.

Azithromycin has broad activity against streptococcal species, including group A strep. It has shown efficacy in the treatment of a broad range of respiratory infections, as well as pharyngitis. Owing to the unique pharmacokinetics of azithromycin (half-life of about 60 hours) and its ability to concentrate intracellularly, shorter courses of therapy have routinely been implemented.

As stated above, the IDSA guidelines recommend a 5-day course of azithromycin at a dosage of 12 mg/kg/day.[1] (Editor’s note: The IDSA has published an erratum to this recommendation, noting that the dosage for azithromycin is 12 mg/kg once [max. 500 mg], and then 6 mg/kg [max. 250 mg] once daily for the next 4 days.) Three-day courses of treatment have also been examined. In a randomized, controlled, pediatric trial, Cohen and colleagues[2] examined a 3-day course of azithromycin 10 mg/kg/day or 20 mg/kg/day vs penicillin V 45 mg/kg/day administered in three doses daily for 10 days. Azithromycin 20 mg/kg/day was superior to 10 mg/kg/day microbiologically on day 14 and day 30 after the start of therapy, and was clinically superior on day 14. In addition, 20 mg/kg/day was equivalent to penicillin V at all endpoints.

A summary of the pediatric clinical trial data has suggested that the total dose of azithromycin that is administered is a determinant of outcome, with a total dose of 60 mg/kg being associated with a higher rate of success than is achieved with a lower dose.[3]

Unfortunately, the increased incidence of macrolide-resistant group A strep has limited the utility of azithromycin for the treatment of strep throat. The growth in rates of resistance has correlated with increased macrolide utilization. From data published between 2000 and 2011, worldwide macrolide resistance has ranged from 1.1% to 97.9%. In the United States, although rates of macrolide resistance generally range between 3% and 15%, some single-center studies report rates as high as 48%.[4]

Because use of azithromycin for patients infected with macrolide-resistant strains is likely to result in organism persistence and subsequent risk for development of rheumatic fever, treatment with azithromycin should be limited to patients with a documented history of anaphylactic reactions to penicillin.

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