WHO Model Prescribing Information: Drugs Used in the Treatment of Streptococcal Pharyngitis and Prevention of Rheumatic Fever
(1999; 18 pages) View the PDF document
Table of Contents
View the documentPreface
View the documentIntroduction
Close this folderManagement of group a streptococcal upper respiratory tract infection
View the documentDiagnosis
Close this folderAntimicrobial treatment of Group A streptococcal pharyngitis
View the document1. Primary prevention of rheumatic fever
View the document2. Secondary prophylaxis of rheumatic fever
View the documentTable 1. Treatment of Group a Streptococcal Pharyngitis (Primary Prevention of Rheumatic Fever).
View the documentTable 2. Prevention of Recurrences of Rheumatic Fever by Prevention of Group A Streptococcal Infections in Individuals who have had an initial attack of Rheumatic Fever (Secondary Prophylaxis).
Open this folder and view contentsDrug Data sheets

2. Secondary prophylaxis of rheumatic fever

For all individuals who have had an initial attack of rheumatic fever, whether or not they have rheumatic heart disease, continuous administration of an antibiotic is mandatory to prevent acquisition and infection of the upper respiratory tract by group A streptococci. Secondary prophylaxis has been documented to reduce significantly the risk of recurrent attacks with their attendant morbidity and mortality.

Antibiotic regimens for secondary prophylaxis differ. The regular intramuscular injection of repository penicillin (benzathine benzylpenicillin) is the most effective available treatment. Although classically given every four weeks, recent data indicate that 1,200,000 units of benzylbenzathine penicillin given every three weeks is more effective in preventing recurrences of rheumatic fever, especially in high-risk patients.

Several technical factors related to the benzathine benzylpenicillin injection can affect its bioavailability. For this reason it is recommended that health workers responsible for administering the injection are trained in the technique of giving injections. The injection should be deep into the muscle as recommended. More superficial injections allow the benzathine benzylpenicillin to remain in the subcutaneous tissue leading to decreased absorption and lower serum levels. Care should be taken, particularly in adults that the whole content of the vial is fully removed and injected..

Although the activity of benzathine benzylpenicillin remains stable in the vial for several years if adequately stored, the activity may be affected by the presence of preservatives, metal ions or bicarbonate in the vial. The physical properties of the solution, if not optimum, may also affect its degree of solubility and hence its absorption from the injection site. All of the above affects the biological activity of benzathine benzylpenicillin. Since different brands are produced in the market, continuous quality assurance is important to optimize not only its chemical activity but also its biological activity. This is needed to reduce variations between different brands and to assure effective serum penicillin levels.

For patients for whom the regular and repeated injections of benzathine benzylpenicillin are not given, an alternative but lesser effective method is the use of daily oral phenoxymethylpenicillin. The potential problems with oral prophylaxis that should be considered are:

Adherence is difficult;
Even when adherence can be assured, the rheumatic fever recurrence rates have been shown to be higher with this regimen than with intramuscular benzathine benzylpenicillin;

For patients known to be allergic to penicillin, an oral sulfonamide is recommended for secondary prophylaxis. It is not effective for treating established group A streptococcal infection. For individuals who cannot take either penicillin or sulfadiazine, erythromycin in a dose of 250 mg twice daily may be used. However, there are recent reports of group A streptococcal resistance to erythromycin.

Duration of secondary prophylaxis

There are several variables that affect the likelihood of recurrences of rheumatic fever, including the time since the most recent attack, the age of the patient and the risk posed by the environment. The duration of secondary prophylaxis should be adapted to the individual patient but some general principles can be stated. Patients without carditits in a previous attack should have prophylaxis for a minimum of five years after the last attack, and at least until age 18 and often longer if risk factors are high. Patients with cardiac involvement in the initial attack should continue prophylaxis at least until the age of 25 years, and longer if environmental conditions or other risk factors warrant it.

For patients with chronic valvular rheumatic heart disease, secondary prophylaxis for prolonged periods, even for life, has sometimes been recommended. It is prudent for the physician to consider each patient individually in determining the duration.

Antibiotic prophylaxis for secondary rheumatic fever should be continued through pregnancy. However, sulfonamides present a risk to the fetus and an alternative antibiotic (penicillin or erythromycin) should be substituted. The teenage years present a special problem, particularly with adherence. Special efforts must be made at this crucial period when the risk of recurrence is great.

*The general principles for secondary prophylaxis are:



No carditis/RHD

To 18 years and at least five years after the last attack

Documented carditis

At least to 25 years and often longer

Chronic carditis

For life

With artificial valves

For life

* see text for details


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