RESUMO
BACKGROUND: The optimal regimen of benzathine penicillin G for secondary prevention of rheumatic fever is controversial. Data from serum pharmacokinetic studies do not fully agree on the period of protection after drug administration. Data from concentration of penicillin in tonsils may provide additional information. METHODS: To evaluate penicillin concentrations in palatine tonsils and in sera 1, 10, 14 and 21 days after intramuscular injection of benzathine penicillin G 40,000 IU/kg, 58 children between 4 and 12 years of age with chronic tonsillitis and indication for tonsillectomy were given the study drug 1, 10, 14 or 21 days before surgery. Blood and tonsil samples were obtained during surgery, and penicillin concentrations were determined microbiologically by the agar well diffusion technique. RESULTS: Mean serum penicillin concentrations 1, 10, 14 and 21 days after drug administration were, respectively, 0.080, 0.031, 0.023 and 0.014 microg/ml. Mean penicillin concentrations in tonsils at 1, 10, 14 and 21 days were 0.023, 0.010, 0.007 and 0.002 microg/g, respectively. Detectable penicillin concentration in tonsils (method sensitivity, 0.006 microg/g) was obtained in all patients on Day 1 and in 91% and 83.3% of patients on Days 10 and 14, respectively. By Day 21 this proportion was reduced to 30%. CONCLUSIONS: The results of this study suggest that penicillin values may be inadequate for prevention of rheumatic fever by Week 3 of administration in a majority of children.
Assuntos
Penicilina G Benzatina/administração & dosagem , Penicilina G Benzatina/farmacocinética , Febre Reumática/prevenção & controle , Tonsilite/tratamento farmacológico , Análise de Variância , Disponibilidade Biológica , Criança , Pré-Escolar , Doença Crônica , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Humanos , Injeções Intramusculares , Masculino , Penicilina G Benzatina/sangue , Probabilidade , Estudos Prospectivos , Sensibilidade e Especificidade , Tonsilite/sangue , Tonsilite/diagnóstico , Resultado do TratamentoRESUMO
OBJECTIVE: To compare the efficacy of injections of 1.2 million units of benzathine penicillin G given every 3 weeks versus every 4 weeks for secondary prevention of rheumatic fever, based on the long-term outcome of patients receiving such prophylaxis. METHODS: A total of 249 consecutive patients with rheumatic fever, randomly assigned to either a 3-week or a 4-week regimen, were examined every 3 to 6 months, and followed for 794 and 775 patient-years, respectively. RESULTS: Compliance with each regimen was comparable: 83 (66.9%) of 124 patients in the 3-week group versus 92 (73.6%) of 125 patients in the 4-week group stayed in the program (p > 0.05). Streptococcal infections occurred less frequently in those receiving the 3-week regimen: 7.5 versus 12.6 per 100 patient-years (p < 0.01). Prophylaxis failed in 2 patients receiving the 3-week regimen and in 10 receiving the 4-week regimen (0.25 and 1.29 per 100 patient-years respectively; p = 0.015). Serum penicillin levels were adequate (> or = 0.02 micrograms/ml) in 100 (56%) of 179 samples obtained 21 days after penicillin injection in the 3-week regimen, and in 51 (33%) of 155 samples obtained 28 days after injection in the 4-week regimen (p < 0.01). Of 71 patients with mitral regurgitation in the 3-week regimen, 47 (66%) no longer had the murmur; of 87 patients in the 4-week regimen, 40 (46%) no longer had the murmur (p < 0.05). CONCLUSIONS: This 12-year controlled study indicates that the outcome of patients with rheumatic fever is better with a 3-week than with a 4-week penicillin prophylaxis regimen. Greater emphasis and more widespread use of the 3-week regimen should be recommended.
Assuntos
Penicilina G Benzatina/uso terapêutico , Febre Reumática/prevenção & controle , Cardiopatia Reumática/prevenção & controle , Adolescente , Adulto , Insuficiência da Valva Aórtica/complicações , Insuficiência da Valva Aórtica/epidemiologia , Insuficiência da Valva Aórtica/prevenção & controle , Criança , Pré-Escolar , Esquema de Medicação , Feminino , Seguimentos , Sopros Cardíacos/epidemiologia , Sopros Cardíacos/etiologia , Sopros Cardíacos/prevenção & controle , Humanos , Masculino , Insuficiência da Valva Mitral/complicações , Insuficiência da Valva Mitral/epidemiologia , Insuficiência da Valva Mitral/prevenção & controle , Cooperação do Paciente , Penicilina G Benzatina/sangue , Estudos Prospectivos , Recidiva , Indução de Remissão , Febre Reumática/complicações , Febre Reumática/epidemiologia , Cardiopatia Reumática/complicações , Cardiopatia Reumática/epidemiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
Serum concentrations of penicillin were measured in children with rheumatic fever. The adequacy of the values after administration of 1.2 million units of benzathine penicillin G every 2 or 3 weeks was confirmed; the adequacy of a 4-week regimen was questionable. The administration of 0.6 million units every 3 weeks was found to be inadequate to maintain serum levels high enough for the secondary prophylaxis of rheumatic fever.
Assuntos
Penicilina G Benzatina/administração & dosagem , Febre Reumática/tratamento farmacológico , Adolescente , Brasil , Criança , Humanos , Penicilina G Benzatina/sangue , Febre Reumática/sangue , Fatores de TempoRESUMO
Serum and urine penicillin levels were determined in 11 children with rheumatic fever (RF) who were receiving benzathine penicillin G (BPG) prophylactically every 3 weeks and in 10 children without RF who received the drug for the treatment of other infections. The dose given was 600,000 units for children weighing less than 25 kg and 1,200,000 units for those with a weight above 25 kg. Blood and urine samples were collected from both groups before and on days 7, 14 and 21 after BPG administration. Our results showed that: minimum inhibitory concentrations (MICs) of BPG for group A beta-hemolytic streptococci were 0.02 IU/ml or 0.0125 microgram/ml; intramuscular BPG did not give adequate serum levels to block the growth of group A beta-hemolytic streptococci in approximately 24 and 62% of children included in the study on days 14 and 21 after its administration, respectively; BPG metabolism was similar in both groups and did not depend on the underlying disease; serum and urine levels did not vary according to sex and weight; and there was a small correlation between serum and urine levels.
Assuntos
Penicilina G Benzatina/administração & dosagem , Penicilina G Benzatina/sangue , Febre Reumática/sangue , Febre Reumática/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Injeções Intramusculares , Masculino , Testes de Sensibilidade Microbiana , Penicilina G Benzatina/urina , Febre Reumática/urina , Streptococcus pyogenes/efeitos dos fármacosRESUMO
Because of published data suggesting the inadequacy of once-every-4-weeks intramuscular injections of benzathine penicillin G for secondary rheumatic fever prevention, serum penicillin levels were determined at 1, 3, 10, 21, and 28 days after administration of 1,200,000 units of this repository penicillin. A total of 193 samples were studied. Mean serum penicillin levels remained greater than or equal to 0.02 micrograms/ml for 21 days, but by 28 days only 44% of the serum samples had detectable levels of penicillin and only 36% had levels greater than or equal to 0.02 micrograms/ml. Patients weighing more than 45 kg had significantly lower serum penicillin levels than did those who weighed less. There were similar correlations with body surface area and with age. These data indicate that a significant percentage of patients receiving benzathine penicillin G prophylaxis for prevention of recurrent attacks of rheumatic fever are not protected during the fourth week. More frequent administration of benzathine penicillin G should be considered in instances of high risk of recurrence of rheumatic fever.