Clinical and Bacteriological Effect of Clarithromycin in Streptococcal Pharyngitis: Review of Meta-Analysis of Clinical Trials

Written By :  Dr. Kamal Kant Kohli
Published On 2023-07-22 06:00 GMT   |   Update On 2024-03-12 10:35 GMT

Acute pharyngitis (sore throat) is one of the common reasons for visits to primary care physicians. Pharyngitis caused by Group A beta-hemolytic Streptococci [GABHS] is the most prominent subgroup of pharyngitis arising out of bacterial etiology. (1) Acute GABHS pharyngitis infection-related complications such as acute rheumatic fever (ARF) and glomerulonephritis pose a great challenge to clinicians. (2)

In view of the above considerations, correct diagnosis and prompt treatment of streptococcal pharyngitis are crucial for minimizing dissemination and re-infection; to mitigate the risk of long-term unfavorable sequelae of infection. (1)

An estimated 18 million people worldwide are believed to be affected by the serious Group A streptococcal (GAS) disease. The estimated prevalence of GAS pharyngitis and its carriage in India varies and is up to 13.7% and up to 34%, respectively. (2) Poor housing conditions and indoor pollution, such as smoking in the house and fuel used for cooking, contribute to the increased burden of pharyngitis in India. (3) Acute pharyngitis is usually associated with high-grade fever, pain in the throat while swallowing, severely enlarged tonsils, and tender lymphadenopathy. (3)

Antibiotics are frequently used in the treatment of streptococcal pharyngitis in order to eradicate the pathogen, prevent its spread and re-infection, and reduce any potential complications of initial infection. (1)

Clarithromycin in Streptococcal Pharyngitis-Data from Meta-analysis of Clinical Trials: (1)

A meta-analysis conducted on the series of five outpatient trials including Clarithromycin for the treatment of streptococcal pharyngitis indicated that Clarithromycin is an effective and well-tolerated treatment option for GABHS pharyngitis.

Of the five studies included, three used a double-blind methodology, one was single-blind (investigator-blind), and one was an open-label trial. Active comparators comprised penicillin V Potassium (VK) and erythromycin. In all, 1184 patients with signs and symptoms of streptococcal pharyngitis were enrolled in the five studies, of whom 600 patients were randomized to treatment with Clarithromycin 250 mg twice daily and 584 patients to treatment with penicillin VK (250 mg three or four times daily; n=412) or erythromycin (500 mg twice daily; n=172). The important findings have been emphasized below:

  • The numerical findings for bacteriological cure were notably in favour of Clarithromycin.
  • The intergroup difference in bacteriologic cure rate in pharyngitis patients was determined, and the results significantly favoured Clarithromycin over penicillin VK (95% vs 87%; p=0.009).
  • The bacteriological eradication in the five GABHS pharyngitis studies at Visit 3 (4–6 days post-treatment) showed better results with Clarithromycin than penicillin VK (81.8% vs 78.1%; p=0.25). The same comparison also favoured Clarithromycin over erythromycin. (85.8% vs 80.8%; p=0.23)
  • The study suggests that Clarithromycin's bacteriological superiority may partly be by virtue of the drug's pharmacokinetics and metabolism, including tissue penetration and formation of a bacteriologically relevant 14-hydroxy metabolite.
  • Complications of pharyngitis are common in lower-income areas of the world, where poverty in its broad sense along with related environmental proxies such as overcrowding and shared housing, can promote the spread of infection and cycles of re-infection. Effective use of Clarithromycin in this context may have a positive and long-lasting impact on the health of both upper respiratory tract infections patients and their contacts.
The meta-analysis concluded that Clarithromycin is useful and effective in treating GABHS pharyngitis in patients. (1)
Using Clarithromycin in Pharyngitis: What Do Global & Indian Guidelines Say?
  • The Infectious Diseases Society of America, and the National Institute for Health and Clinical Excellence (NICE) recommended oral Clarithromycin to manage acute pharyngitis in adults and pediatric patients. (4)
  • The Standard Treatment Guidelines for Acute Pharyngitis/ Acute Tonsillopharyngitis released by the Indian Academy of Pediatrics recommended oral Clarithromycin at 7.5 mg/kg/dose twice daily (maximum = 250 mg/dose) for 10 days in streptococcal pharyngitis. (5)
  • The Treatment Guidelines for Antimicrobial Use in Common Syndromes (2022) released by the Indian Council of Medical Research also recommended the use of Clarithromycin at the dose of 500 mg twice daily for adult patients and 7.5 mg/kg twice daily for pediatric patients (6)
  • The American Heart Association (AHA) recommended Clarithromycin in the treatment of streptococcal pharyngitis, primarily for the prevention of rheumatic fever. The recommended dosage of oral Clarithromycin is 15 mg/kg per day divided BID (maximum 250 mg BID) for 10 days in adults. (7)
Clinical Pointers:
  • Acute pharyngitis (sore throat) is a common reason for primary care consultations.
  • The most prominent group among bacterial origin pharyngitis is due to Group A beta-hemolytic Streptococci (GABHS).
  • Sore throat is one of the commonest reasons contributing to the use of antibiotics worldwide.
  • Data from a meta-analysis conducted on the series of outpatient trials to treat streptococcal pharyngitis indicated that Clarithromycin is effective in treating streptococcal pharyngitis. The meta-analysis also demonstrated that the bacteriological eradication rate of Clarithromycin is superior to other commonly used agents.
References:
1. Hoban DJ, Nauta J. Clinical And Bacteriological Impact Of Clarithromycin In Streptococcal Pharyngitis: Findings From A Meta-Analysis Of Clinical Trials. Drug Des Devel Ther. 2019;13:3551-3558. Published 2019 Oct 16. 
2. Singh AK, Kumar A, Agarwal L, Agarwal A, Sengupta C. Prevalence of group A streptococcal pharyngitis among schoolchildren of Barabanki district, Uttar Pradesh, India. J Acad Clin Microbiol 2015;17:110-4
3. Bhalla K, Bhardwaj P, Gupta A, Mehra S, Nehra D, Nanda S. Role of epidemiological risk factors in improving the clinical diagnosis of streptococcal sore throat in pediatric clinical practice. J Family Med Prim Care. 2019;8(10):3130-3135. Published 2019 Oct 31. 
4. Coutinho G, Duerden M, Sessa A, Caretta‐Barradas S, Altiner A. Worldwide comparison of treatment guidelines for sore throat. Int J Clin Pract. 2021;75(5):e13879
5. Indian Academy of Pediatrics. Standard Treatment Guidelines 2022 for Acute Pharyngitis/ Acute Tonsillopharyngitis. Access on 02nd July 2023 from 
6. Indian Council of Medical Research. Treatment Guidelines for Antimicrobial Use in Common Syndromes 2022. Accessed on 4th July 2023 from 
7. Gerber MA, Baltimore RS, Eaton CB, et al. Prevention of rheumatic fever and diagnosis and treatment of acute Streptococcal pharyngitis: a scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics.
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