Preliminary consultation on preferred product characteristics of benzathine penicillin G for secondary prophylaxis of rheumatic fever

Objective. To review the literature on dose and regimens of intramuscular benzathine penicillin G (BPG) for secondary prophylaxis of recurrent rheumatic fever. Setting. For over 40 years BPG has been the gold standard for secondary prophylaxis, usually as a dose of 1 200 000 U (900 mg). Although studies have suggested that BPG injections every 3 weeks are superior to injections every 4 weeks, implementation of an every 3 weeks regimen can be problematic with regards to both patient compliance (adherence) and an increased burden on health resources. Findings. Some of the earliest studies of BPG suggested that larger doses resulted in prolongation of detectable penicillin levels. A recent study assessing plasma penicillin levels after BPG doses of 1 200 000 U, 1 800 000 U, and 2 400 000 U suggested there may be benefits in a BPG regimen every 4 weeks with doses higher than the standard 1 200 000 U. Conclusions. Further studies of higher dose BPG regimens seem justified. In addition, further work is needed on quality and storage options for different BPG preparations; location and method of BPG injections; the importance of weight differences between individuals; and ways of improving access to and compliance with BPG regimens.

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Non adherence to secondary prophylaxis for rheumatic fever

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20204536 ◽

2020 ◽

Vol 7 (11) ◽

pp. 2101

Author(s):

Santosh K. Saha ◽

Kamrun N. Choudhury ◽

Nihar R. Sarker ◽

Gias U. Ahmed ◽

Nazmul Hoque

Keyword(s):

Rheumatic Fever ◽

Previous History ◽

Cost Effective ◽

Secondary Prophylaxis ◽

Penicillin G ◽

P Value ◽

Benzathine Penicillin ◽

Female Ratio ◽

Benzathine Penicillin G ◽

One Year

Background: Secondary prophylaxis with benzathine penicillin G (BPG) is a cost-effective intervention for preventing morbidity and mortality related to rheumatic fever (RF). There is no reliable data available with regards to adherence to secondary prophylaxis and rates of recurrent RF in many developing countries, including Bangladesh. So, aim of this study was to estimate rate of non-adherence and find out risk of non-adherence to secondary prophylaxis for rheumatic fever.Methods: Total 230, 5-30 years patients of both sexes with definite previous history of RF taking secondary prophylaxis with injection benzathine penicillin G (BPG) were enrolled by simple random fashion. Last one-year injection profile of the patient was collected from the injection card. Patients were then classified as “non-adherent” when the rate of adherence was <80% of the expected injections and as “adherent” when it was ≥80%. After collection of data selective patients were invited for blood tests and echocardiography to identify recurrence of rheumatic fever. Results: Out of 230 patients, male were 96 (41.7%) and female were 134 (58.3%). Male and female ratio were 0.7. 173 (75.2%) were adherent with benzathine penicillin and 57 (24.8%) patients not adherent with benzathine penicillin. In adherent group only 5 (2.2%) and in non-adherent group 19 (8.3%) patients develop rheumatic recurrence and this finding was statistically significant (p-value 0.001). Conclusions: Non adherence to secondary prophylaxis with BPG was found a major risk factor for recurrent rheumatic fever. The main reasons of non-adherence were lack of counselling, fare of pain and fail to remember.

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Three-Versus Four-week Administration of Benzathine Penicillin G: Effects on Incidence of Streptococcal Infections and Recurrences of Rheumatic Fever

PEDIATRICS ◽

10.1542/peds.97.6.984 ◽

1996 ◽

Vol 97 (6) ◽

pp. 984-988

Author(s):

Hung-Chi Lue ◽

Mei-Hwan Wu ◽

Jou-Kou Wang ◽

Fen-Fen Wu ◽

Yu-Nian Wu

Keyword(s):

Rheumatic Fever ◽

Color Doppler ◽

Clinic Visit ◽

Penicillin G ◽

Controlled Study ◽

Streptococcal Infections ◽

Benzathine Penicillin ◽

Acute Phase Reactants ◽

Weight Percentage ◽

Benzathine Penicillin G

Objective. To investigate the effects of 3-week versus 4-week administration of benzathine penicillin G (BPG) on the incidence of Group A streptococcal infections and the recurrences of rheumatic fever (RF). Study Design. We started, in 1979, randomly allocating all patients with RF to a 3-week or 4-week BPG prophylaxis program. They were examined at the RF clinic, every 3 to 6 months, and at any time they did not feel well. During 1979 to 1989, throat cultures and sera for antistreptolysin O and streptozyme titers were obtained at each clinic visit. Chest radiographs, electrocardiogram, color Doppler echocardiograms, and acute phase reactants were obtained. Subjects. Two hundred forty-nine patients fulfilled the revised Jones criteria and were followed until December 1991: 124 in the 3-week and 125 in the 4-week program. Their age, sex, weight, percentage with history of RF, severity of cardiac involvement, follow-up duration, and compliance to program were comparable. Eight hundred eighty throat cultures were collected in the 3-week program and 770 were collected in the 4-week program. Six hundred sixteen and 627 sera were determined in each program for antistreptolysin O, and 582 and 592 sera for streptozyme titers. Results. True streptococcal infections occurred in both programs: 39 infections in the 3-week program, and 59 infections in the 4-week program (7.5 vs 12.7 per 100 patient-years). Four infections with no antibody response occurred in the 3-week program, and three such infections in the 4-week program. Nine RF recurrences occurred in 8 patients in the 3-week program, and 16 recurrences in 16 patients in the 4-week program. Prophylaxis failure occurred in 2 of 124 patients in the 3-week program, and in 10 of 125 patients in the 4-week program (0.25 vs 1.29 per 100 patient-years). The overall recurrences/infections rate in each program was comparable, 13.6% vs 15.5%, but the recurrences/infections rate due to prophylaxis failure was higher in the 4-week program than in the 3-week program, 3.0% versus 9.7%. Conclusions. This 12-year prospective and controlled study documented that streptococcal infections and RF recurrences occurred more often in the 4-week program than in the 3-week program. The risk of prophylaxis failure was fivefold greater in the 4-week program than in the 3-week program.

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Rheumatic Fever Article Questioned

PEDIATRICS ◽

10.1542/peds.74.6.1133a ◽

1984 ◽

Vol 74 (6) ◽

pp. 1133-1134

Author(s):

SYLVIA P. GRIFFITHS

Keyword(s):

Rheumatic Fever ◽

Intramuscular Injection ◽

Group A Streptococcus ◽

Penicillin G ◽

Benzathine Penicillin ◽

Benzathine Penicillin G ◽

Group A

To the Editor.— The suggestion of Nordin1 that there may be a need to re-evaluate the current recommended prophylaxis for children with rheumatic fever is valid, particularly if carefully planned and controlled studies could be carried out. However, the author's contention that "It has been assumed that the levels of penicillin [following monthly intramuscular injection of 1.2 million units of benzathine penicillin G] are adequate to prevent reinfection with group A streptococcus, and hence to prevent recurrences of rheumatic fever" has always been qualified by others.

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Recurrence of Rheumatic Fever During Prophylaxis with Monthly Benzathine Penicillin G

PEDIATRICS ◽

10.1542/peds.73.4.530 ◽

1984 ◽

Vol 73 (4) ◽

pp. 530-531

Author(s):

James D. Nordin

Keyword(s):

Rheumatic Fever ◽

Penicillin G ◽

Benzathine Penicillin ◽

Real Risk ◽

Benzathine Penicillin G ◽

The Subject

A 9-year-old girl had apparent recurrence of rheumatic fever while receiving monthly benzathine penicillin injections. A review of pharmacokinetc studies on the subject suggests that this is a real risk. A need for review of the current recommendations for rheumatic fever prophylaxis is suggested.

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Rheumatic Fever Prophylaxis Using Benzathine Penicillin G (BPG): Two-week Versus Four-week Regimens: Comparison of Two Brands of BPG

PEDIATRICS ◽

10.1542/peds.97.6.992 ◽

1996 ◽

Vol 97 (6) ◽

pp. 992-995

Author(s):

Ahmed Samir Kassem ◽

Salah R. Zaher ◽

Hamida Abou Shleib ◽

Abdel Ghany El-Kholy ◽

Ahmed A. Madkour ◽

...

Keyword(s):

Rheumatic Fever ◽

Recurrence Rate ◽

Penicillin G ◽

Diffusion Method ◽

High Recurrence Rate ◽

Benzathine Penicillin ◽

Benzathine Penicillin G ◽

Group A ◽

Upper Respiratory ◽

The Difference

Objective. This prospective study was aimed at answering two important questions: 1) Is a biweekly schedule of 1.2 million U intramuscular benzathine penicillin G (BPG) superior to a 4-week one in the prevention of upper respiratory Group A beta-hemolytic streptococcal (GABHS) infections and rheumatic fever (RF) recurrences? 2) Is there a difference in the bioavailability of BPG obtained from different manufacturers? Methodology. Three hundred sixty rheumatic patients aged 4 to 20 years were randomly assigned to either a biweekly (190 patients) or 4-week (160 patients) BPG prophylactic schedule and were followed-up monthly for 2 years by clinical examination, throat swab culture for GABHS and measurement of antistreptolysin O titer to detect GABHS infection and/or recurrences of RF (according to revised Jones' Criteria). Thereafter, 34 rheumatic subjects, aged 8 to 16 years were randomly assigned to receive a 4-week injection of 1.2 million U of either a locally manufactured BPG brand (22 patients) or an imported one (12 patients). Sera of all patients were tested for penicillin level by plate diffusion method on days 1, 2, 3, 4, 5, 6, 7, 14, 21, and 28 after the intramuscular injection of BPG. Results. The GABHS infection rate was found to be 0.2% and 0.3% for patients on the biweekly and 4-week BPG schedules, respectively, with no significant differences between them. However, the RF recurrence rate/patient/year for the 4-week schedule patients (0.12) was double that for the biweekly schedule ones (0.06). Estimation of the bioavailability of the two different brands of BPG demonstrated a difference in their pharmacokinetics and a decrease in the serum penicillin concentration below the minimum inhibitory concentration 3 weeks after the injection of either brand. Conclusion. Although a biweekly schedule may not be superior in preventing upper respiratory GABHS infection, it may play a role in preventing the sequelae of such infections. The short duration of penicillinemia explains the superiority of the 2-week schedule in RF prophylais. The difference in the pharmacokinetics of penicillin brands might contribute to the high recurrence rate of RF reported in Egypt.

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Allergic Reactions in Rheumatic Fever Patients on Long-term Benzathine Penicillin G: The Role of Skin Testing for Penicillin Allergy

PEDIATRICS ◽

10.1542/peds.97.6.981 ◽

1996 ◽

Vol 97 (6) ◽

pp. 981-983

Author(s):

Milton Markowitz ◽

Hung-Chi Lue

Keyword(s):

Developing Countries ◽

Rheumatic Fever ◽

The United States ◽

World Health ◽

Penicillin G ◽

Allergic Reactions ◽

Benzathine Penicillin ◽

Benzathine Penicillin G ◽

The Impact

An injection of 1.2 million U benzathine penicillin G (BPG) every 3 or 4 weeks has proven by far to be the most effective method to prevent recurrences of acute rheumatic fever.1-3 The efficacy of this method of prophylaxis was first demonstrated more than 40 years ago, and since its introduction, it has played a major role in reducing the morbidity and mortality from rheumatic fever.4 Rheumatic fever causes 25% to 40% of all cardiovascular diseases in developing countries.5 Because of the impact of this disease on public health, the World Health Organization (WHO) has helped establish programs for prevention of recurrent attacks of rheumatic fever in many developing countries.6 WHO recommends BPG as the prophylactic drug of choice. One of the problems encountered has been the high drop-out rates among patients enrolled in these programs. Among the reasons for discontinuing prophylaxis is the fear of an allergic reaction.7 The initial study using BPG for the prevention of recurrences of rheumatic fever in children and adolescents reported only 5 (1.2%) mild allergic reactions among 410 patients receiving monthly injections.1 Since then, although rheumatic fever prevention in the United States (U.S.) has consisted almost exclusively of using BPG, there been very few documented reports of serious allergic reactions in rheumatic fever patients on long-term prophylaxis. The only fatalities reported in the American literature occurred in four adults with advanced rheumatic heart disease.8,9 The salutary experience with BPG in the U.S. contrasts sharply with the numerous anecdotal reports of fatal allergic reactions to BPG in many developing countries.

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