streptococcal infection and consequently recurrent episodes, so as to avoid the appearance of new lesions, to limit valve disease progression, and to allow its resolution As a result, reduction in hospitalization, disability, intervention, and mortality rates is expected The institution of continuous prophylactic regimens is mandatory for all patients since they are particularly susceptible to developing subsequent attacks of the disease when faced with a GAS infection, symptomatic or not Prevention of colonization or streptococcal infections is markedly effective in reducing recurrences Secondary prophylaxis should be started soon after the diagnosis of an acute episode, or when well-documented rheumatic heart disease is established This preventative strategy is based on two premises First, there is also a causal relationship between the GAS pharyngotonsillitis and the subsequent attacks as it occurs in the primary episodes Second, an increased number of recurrences are usually associated with a poor prognosis as a consequence of the appearance of new valvar lesions or worsening of the preexisting ones In patients whose diagnosis of RF has not completely been elucidated, the need for secondary prophylaxis depends on the judgment of individual risks Its maintenance should be evaluated during the follow-up The regimens for secondary prevention are shown Table 54.5 Benzathine penicillin remains the drug of choice and the most effective to prevent recurrences Nonetheless, the current recommendations have shown controversy regarding intervals, dosages, and duration of the secondary prophylaxis.27,209,224–226 The use of 4-weekly benzathine penicillin has been considered the standard regimen; however, in populations with a high prevalence of RF, shorter intervals have been recommended This measure is supported by observations of higher rates of recurrent episodes related to monthly prophylactic regimens when compared to 3-weekly intervals In addition, pharmacokinetic studies have demonstrated inadequate or undetectable serum levels of penicillin 28 days after injection.227–230 Prevention with 2-weekly regimens has shown high serum levels of penicillin and lower rates of recurrences, but there is the inconvenience of the poor adherence to treatment because of the frequent use of medication.227,231 The choice of either a 3- or 4weekly interval therefore must be tailored to the epidemiologic context The administration of benzathine penicillin every 3 weeks is justified and recommended in areas where the risk of exposure to the GAS and the incidence of RF are particularly high This antibiotic regimen has also been recommended in special circumstances for patients considered to be at high risk, as for those who have shown recurrence in spite of complete adherence to 4-weekly regimen.100,209 For effective prevention, it is necessary to ensure that protective levels are maintained in the serum during the interval between the doses For effective prevention, it is necessary to ensure that protective levels will be reached and maintained in the serum during the interval between the doses, besides considering adverse factors such as lack of compliance with continuous medication, bioavailability, and absorption of the drug The use of the repository presentation has been considered more effective than oral penicillin Adequate levels are less predictable with the use of oral medication, contributing to higher risks of recurrences In this setting, bioavailability, absorption of the drug, and lack of compliance with a twice-daily oral regimen over long periods of time should be considered Oral erythromycin has been recommended for patients allergic to penicillin Table 54.5 Secondary Prevention of Rheumatic Fever: Prophylaxis of Recurrent Attacksa Agent Benzathine penicillin (benzathine penicillin G) Dose 600,000 U for patients