Stollerman GH, Rusoff JH, Hirschfeld I. Prophylaxis against group A streptococci in rheumatic fever. The use of single monthly injections of Benzathine Penicillin G. NEJM, 1955, 252, 787-92
In the 1930's, sulfonamide and sulfanilamide were introduced for the treatment of group A hemolytic streptococcus throat infection. These medications were, however, associated with significant toxicity and secondary effects. In the 1940's, penicillin was used with increasing frequency for the treatment of streptococcal infection and the prevention of rheumatic fever. Penicillin was recognized very rapidly as the treatment of choice for several reasons. First its action was bactericidal, second the streptococcal pharyngeal carrier state was eliminated with adequate dosages and third this medication was associated with rare serious secondary effects.
In 1952, Stollerman and Russoff described for the first time the use of intramuscular benzathine penicillin for the prevention of rheumatic fever. This new molecule, after single intramuscular injection, provided detectable levels of penicillin in the blood for prolonged period of time.
In this study, they administered three different dosages of benzathine penicillin (300,000 units once weekly, 600,000 units once every two weeks, and 1.2 million units once a month). They demonstrated that with a dosage of 600,000 units, they were able to obtain low bactericidal concentrations in the blood for a period of two weeks. This concentration was, however, adequate to treat efficiently group A streptococcal throat infections. The higher dose of 1,2 million units provided an optimal concentration level for a period of three to four weeks . The authors in their conclusion noted that "single injections of benzathine penicillin appeared to be effective in eliminating the streptococcus carrier state in most cases." They reported additional results confirming their preliminary findings in 1954, and 1955. Following these studies, benzathine penicillin was used in a large scale for the prevention of rheumatic fever and secondary prophylaxis in patients affected with this disease.
After the introduction of antibiotic treatment of throat infection, rheumatic fever was progressively eradicated in developed countries during the 20th century. Rheumatic fever, however, still remains the predominant cause of valvular heart disease worldwide.