scholarly journals Severe adverse events following benzathine penicillin G injection for rheumatic heart disease prophylaxis: cardiac compromise more likely than anaphylaxis

Heart Asia ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. e011191 ◽  
Author(s):  
Shannon Marantelli ◽  
Robert Hand ◽  
Jonathan Carapetis ◽  
Andrea Beaton ◽  
Rosemary Wyber
Keyword(s):  
Heart Disease ◽  
Adverse Events ◽  
Rheumatic Heart Disease ◽  
Adverse Reactions ◽  
Case Reports ◽  
Penicillin G ◽  
Alternative Mechanism ◽  
Benzathine Penicillin ◽  
Benzathine Penicillin G ◽  
Rheumatic Heart

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.

scholarly journals Myositis complicating benzathine penicillin-G injection in a case of rheumatic heart disease

IDCases ◽  
2016 ◽  
Vol 4 ◽  
pp. 6-7 ◽  
Author(s):  
Joshua R. Francis ◽  
Rosemary Wyber ◽  
Bo Remenyi ◽  
David Croser ◽  
Jonathan Carapetis
Keyword(s):  
Heart Disease ◽  
Rheumatic Heart Disease ◽  
Penicillin G ◽  
Benzathine Penicillin ◽  
Benzathine Penicillin G ◽  
Rheumatic Heart

Subcutaneous administration of benzathine benzylpenicillin G has favourable pharmacokinetic characteristics for the prevention of rheumatic heart disease compared with intramuscular injection: a randomized, crossover, population pharmacokinetic study in healthy adult volunteers

2020 ◽  
Vol 75 (10) ◽  
pp. 2951-2959
Author(s):  
Joseph H Kado ◽  
Sam Salman ◽  
Robert Henderson ◽  
Robert Hand ◽  
Rosemary Wyber ◽  
...  
Keyword(s):  
Heart Disease ◽  
Rheumatic Heart Disease ◽  
Subcutaneous Administration ◽  
Penicillin G ◽  
Population Pharmacokinetic ◽  
High Dose ◽  
Benzathine Penicillin ◽  
Pain Scores ◽  
Benzathine Penicillin G ◽  
Rheumatic Heart

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.

scholarly journals High risk of early sub-therapeutic penicillin concentrations after intramuscular benzathine penicillin G injections in Ethiopian children and adults with rheumatic heart disease

2021 ◽  
Vol 15 (6) ◽  
pp. e0009399
Author(s):  
Ezra B. Ketema ◽  
Nigus Z. Gishen ◽  
Abraha Hailu ◽  
Abadi Leul ◽  
Abera Hadgu ◽  
...  
Keyword(s):  
Heart Disease ◽  
Rheumatic Heart Disease ◽  
Day Treatment ◽  
Secondary Prophylaxis ◽  
Population Variation ◽  
Penicillin G ◽  
Benzathine Penicillin ◽  
Indigenous Australian ◽  
Benzathine Penicillin G ◽  
Rheumatic Heart

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.

225 Rheumatic heart disease in Timor Leste school students (RHD-TL) follow-up study: assessment of secondary prophylaxis and outcomes in Timor Leste

2020 ◽  
Vol 41 (Supplement_1) ◽  
Author(s):  
A Horton ◽  
B Remenyi ◽  
K Davis ◽  
N Mock ◽  
E Paratz ◽  
...  
Keyword(s):  
Heart Disease ◽  
Rheumatic Heart Disease ◽  
Secondary Prophylaxis ◽  
Penicillin G ◽  
School Students ◽  
Borderline Cases ◽  
Follow Up Study ◽  
Timor Leste ◽  
Rheumatic Heart

Abstract Background The Rheumatic Heart disease in Timor Leste school students (RHD-TL) study identified Timor Leste as having some of the highest rates of definite rheumatic heart disease (RHD) in the world. The RHD-TL follow-up study aimed to assess the delivery and outcomes of the secondary prophylaxis program in known patients with echocardiographic screen detected definite and borderline RHD. Methods School-students in Timor Leste where reassessed over a 3-year period since the initial study in 2016. Prospective assessments included adherence to secondary prophylaxis, complications of prophylaxis, follow-up clinical assessment and serial echocardiography. Of the 48 patients, 25 Definite and 23 Borderline, 38 (79%) of all patients, and 92% of definite RHD cases have had one or more follow-up assessments including full datasets for adherence, recurrence rates and progression of disease. Follow-up is provided by the volunteer paediatric cardiology team and rheumatic heart disease team of two NGOs in collaboration with local clinics. Results The median duration of follow-up of the 38 patients was of 1.6 years. The median age was 13 years (range 8-22) and 75% were female. Adherence rates in patients with definite RHD was on average greater than 95% during the follow-up period. Of the 23 patients with mild or moderate RHD one case with documented acute rheumatic fever (ARF) recurrence progressed whilst 8 cases improved on benzathine-penicillin G (BPG) therapy. There was no progression of the 6 borderline cases who were not prescribed BPG. Out of the 9 borderline cases in whom BPG was prescribed, one, with 67% adherence, had a documented episode of ARF leading to echocardiographic progression and moderate definite RHD. Conclusion This was the first follow-up study to look at disease natural history, both in treated and untreated groups, in Timor-Leste and brought practical insights into the efficacy of the Timor Leste RHD monitoring and prophylaxis programs. Its ongoing project will enable advocacy and quality assessment for the program as it expands. Abstract 225 Figure 1.

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