scholarly journals ACCESS TO ESSENTIAL MEDICINES: ILLUMINATING DISPARITIES IN THE GLOBAL SUPPLY OF BENZATHINE PENICILLIN G IN THE CONTEXT OF RHEUMATIC FEVER/RHEUMATIC HEART DISEASE PREVENTION

2013 ◽  
Vol 61 (10) ◽  
pp. E2004 ◽  
Author(s):  
Kathryn Taubert ◽  
Stephen B. Marko
Heart Asia ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. e011191 ◽  
Author(s):  
Shannon Marantelli ◽  
Robert Hand ◽  
Jonathan Carapetis ◽  
Andrea Beaton ◽  
Rosemary Wyber

ObjectiveSecondary prophylaxis through long-term antibiotic administration is essential to prevent the progression of acute rheumatic fever to rheumatic heart disease (RHD). Benzathine penicillin G (BPG) has been shown to be the most efficacious antibiotic for this purpose; however, adverse events associated with BPG administration have been anecdotally reported. This study therefore aimed to collate case reports of adverse events associated with BPG administration for RHD prophylaxis.Study designA literature review was used to explore reported adverse reactions to BPG and inform development of a case report questionnaire. This questionnaire was circulated through professional networks to solicit retrospective reports of adverse events from treating physicians. Returned surveys were tabulated and thematically analysed. Reactions were assessed using the Brighton Collaboration case definition to identity potential anaphylaxis.ResultsWe obtained 10 case reports from various locations, with patients ranging in age from early-teens to adults. All patients had clinical or echocardiogram-obtained evidence of valvular disease. The majority of patients (80%) had received BPG prior to the event with no previous adverse reaction. In eight cases, the reaction was fatal; in one case resuscitation was successful and in one case treatment was not required. Only three cases met Level 1 Brighton criteria consistent with anaphylaxis.ConclusionThese results indicate that anaphylaxis is not a major cause of adverse reactions to BPG. An alternative mechanism for sudden death following BPG administration in people with severe RHD is proposed.


IDCases ◽  
2016 ◽  
Vol 4 ◽  
pp. 6-7 ◽  
Author(s):  
Joshua R. Francis ◽  
Rosemary Wyber ◽  
Bo Remenyi ◽  
David Croser ◽  
Jonathan Carapetis

2020 ◽  
Vol 75 (10) ◽  
pp. 2951-2959
Author(s):  
Joseph H Kado ◽  
Sam Salman ◽  
Robert Henderson ◽  
Robert Hand ◽  
Rosemary Wyber ◽  
...  

Abstract Background Benzathine penicillin G has been used as monthly deep intramuscular (IM) injections since the 1950s for secondary prevention of acute rheumatic fever and rheumatic heart disease (RHD). Injection frequency and pain are major programmatic barriers for adherence, prompting calls for development of better long-acting penicillin preparations to prevent RHD. We hypothesized that subcutaneous (SC) administration of benzathine penicillin G could delay penicillin absorption when compared with IM injections. Methods To compare the pharmacokinetic profile and tolerability of benzathine penicillin G according to different routes of administration, 15 healthy males participated in a randomized crossover study to receive benzathine penicillin G by either SC or IM routes, with a 10 week washout period before the second dose by the alternative route. Ultrasound guidance confirmed injection location. Penicillin concentrations and pain scores were measured for 6 weeks following injections. Results SC administration was well tolerated with no significant differences in pain scores. Following SC injection, the principal absorption half-life (95% CI) was 20.1 (16.3–29.5) days and 89.6% (87.1%–92.0%) of the drug was directed via this pathway compared with 10.2 (8.6–12.5) days and 71.3% (64.9%–77.4%) following IM administration. Lower peak and higher trough penicillin concentrations resulted following SC injection. Simulations demonstrated that SC infusion of higher doses of benzathine penicillin G could provide therapeutic penicillin concentrations for 3 months. Conclusions SC administration of benzathine penicillin G is safe and significantly delays penicillin absorption. High-dose benzathine penicillin G via the SC route would fulfil many product characteristics required for the next generation of longer-acting penicillins for use in RHD.


2021 ◽  
Vol 15 (6) ◽  
pp. e0009399
Author(s):  
Ezra B. Ketema ◽  
Nigus Z. Gishen ◽  
Abraha Hailu ◽  
Abadi Leul ◽  
Abera Hadgu ◽  
...  

Introduction Intramuscular benzathine penicillin G (BPG) injections are a cornerstone of secondary prophylaxis to prevent acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Uncertainties regarding inter-ethnic and preparation variability, and target exposure profiles of BPG injection are key knowledge gaps for RHD control. Methods To evaluate BPG pharmacokinetics (PK) in patients receiving 4-weekly doses in Ethiopia, we conducted a prospective cohort study of ARF/RHD patients attending cardiology outpatient clinics. Serum samples were collected weekly for one month after injection and assayed with a liquid chromatography-mass spectroscopy assay. Concentration-time datasets for BPG were analyzed by nonlinear mixed effects modelling using NONMEM. Results A total of 190 penicillin concentration samples from 74 patients were included in the final PK model. The median age, weight, BMI was 21 years, 47 kg and 18 kg/m2, respectively. When compared with estimates derived from Indigenous Australian patients, the estimate for median (95% confidence interval) volume of distribution (V/F) was lower (54.8 [43.9–66.3] l.70kg-1) whilst the absorption half-life (t1/2-abs2) was longer (12.0 [8.75–17.7] days). The median (IQR) percentage of time where the concentrations remained above 20 ng/mL and 10 ng/mL within the 28-day treatment cycle was 42.5% (27.5–60) and 73% (58.5–99), respectively. Conclusions The majority of Ethiopian patients receiving BPG as secondary prophylaxis to prevent RHD do not attain target concentrations for more than two weeks during each 4-weekly injection cycle, highlighting the limitations of current BPG strategies. Between-population variation, together with PK differences between different preparations may be important considerations for ARF/RHD control programs.


2016 ◽  
Vol 13 (2) ◽  
pp. 25-27 ◽  
Author(s):  
Rabi Malla ◽  
Suman Thapaliya ◽  
Prakash Gurung ◽  
Amit Bogati ◽  
Sunita Khadka ◽  
...  

Background and Aims: Acute rheumatic fever and rheumatic heart disease constitute an important public health problem in the developing countries. The disease results from an abnormal autoimmune response to a group A streptococcal infection in a susceptible host. We aim to describe the pattern of valvular involvement in patients taking Injection Benzathine Penicillin.Methods: All the patients, who were taking injection Benzathine penicillin during 15th April to 14th July, 2013 at our Centre, were included in this study. Demographic features like age, sex, echocardiographic diagnosis along with any adverse effects of Benzathine penicillin were collected.Results: A total of 661 patients were included in our study, out of which female predominated in numbers. Rheumatic heart disease rather than rheumatic fever was the cause for Penicillin injection. Mitral valve was the most common valve involved and it was more common in female.Pure mitral stenosis was the most common valvular involvement. Forty two percent patients underwent intervention; among them Percutaneous transluminal mitral commisuorotomy was the most common. There was no adverse event during the study time following penicillin injection.Conclusions: Women are more commonly affected than male. Mitral valve is the most common valve involved. Nepalese Heart Journal 2016; 13(2): 25-27


PEDIATRICS ◽  
1982 ◽  
Vol 70 (3) ◽  
pp. 506-507
Author(s):  
Bernard Boxerbaum

Introduction of secondary prophylaxis for patients with rheumatic fever is felt to be a major reason for improved prognosis of rheumatic heart disease.1,2(p163) The article by Ginsburg et al,3 raising questions concerning the efficacy of this practice, has prompted me to report our experience in the Rainbow Rheumatic Fever Clinic, Rainbow Babies and Childrens Hospital, where more than 80% of the patients receive 1,200,000 units of benzathine penicillin intramuscularly every 28 days. Seventy percent of the patients with rheumatic mitral regurgitation have lost their murmur, and no patient receiving regular intramuscular prophylaxis has developed stenosis.4


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