Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Ketema EB

PROVIDER: S-EPMC8195421 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Ketema Ezra B EB Gishen Nigus Z NZ Hailu Abraha A Leul Abadi A Hadgu Abera A Hagos Kiflom K Berhane Samual S Tsega Temesgen T Page-Sharp Madhu M Davis Timothy Me TM Moore Brioni B Batty Kevin T KT Carapetis Jonathan J Salman Sam S Manning Laurens L

PLoS neglected tropical diseases 20210611 6

<h4>Introduction</h4>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.<h4>Methods</h4>To evaluate BPG pharmacokinetics (PK) in patients receiving 4-weekly doses in Ethiopia, we conducted a prospective cohort study of ARF/RHD p ...[more]

PMID: 34115748

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Project description:BackgroundMonthly intramuscular injections of benzathine penicillin G (BPG) remain the cornerstone of secondary prophylaxis for acute rheumatic fever and rheumatic heart disease (RHD). The barriers to successful delivery of BPG may be patient- or service-delivery-dependent.ObjectiveThe aim of the present study was to explore the perceived acceptability and implementation challenges of BPG treatment for RHD, from the perspective of healthcare providers (HCPs).MethodologyA descriptive qualitative study using semi-structured interview guides was conducted in four public hospitals in Ethiopia. Physicians and nurses who had at least 1 year of experience in delivering RHD secondary prophylaxis were recruited. The interviews were audio recorded, transcribed verbatim, and translated into English for analysis using framework method thematic analysis. Identified behavioral factors were mapped onto a theoretical framework of acceptability (TFA), and the Capability, Opportunity, Motivation-Behavior (COM-B) model.ResultTwenty-two interviews were conducted with HCPs (mean age 39 years, 55% nurses). Insights into BPG use and acceptability were categorized into four major themes related to: (1) individual factors (e.g., fear of anaphylactic reaction), (2) health system barriers (e.g., BPG shortage), (3) patient/caregiver perceptions (e.g., reliance on injectables, over expectation of treatment outcomes), and (4) product (e.g., injection pain, needle blockage).ConclusionsHCPs identified facilitators and barriers which highlight the complexities associated with BPG as secondary prophylaxis for RHD in Ethiopia. Based on these data, we suggest RHD control programs should (1) provide cross-disciplinary training and education programs to support safe and context-appropriate delivery of BPG (2) improve resourcing of health facilities to facilitate safe drug delivery, (3) establish a comprehensive system for auditing severe adverse reactions post-BPG injection to generate robust pharmacovigilance data, and consider alternative approaches to BPG delivery including access to improved formulations (e.g., BPG suspension formulations in pre-filled syringes).Highlights- Key barriers included (a) resistance from healthcare providers to administer benzathine penicillin G (BPG) due to their concerns about injection-related severe adverse events, and potential repercussions should an event occur, (b) poor community and healthcare provider awareness of the disease and its treatment, (c) lack of resources to manage adverse events, and (d) injection pain.- Key enablers included (a) perceived superior treatment benefits of BPG and (b) co-administration of lidocaine/analgesics to reduce injection pain.- Recommendations to address identified challenges include (a) improved training/education on RHD diagnosis, disease progression, and treatment, (b) improved access to supportive resources, (c) active adverse reaction monitoring and reporting, and (d) encouraging the provision/access of globally subsidized BPG suspension formulations in pre-filled syringes.

Project description:BackgroundYaws is a treponemal infection that was almost eradicated fifty years ago; however, the disease has re-emerged in a number of countries including Ghana. A single-dose of intramuscular benzathine penicillin has been the mainstay of treatment for yaws. However, intramuscular injections are painful and pose safety and logistical constraints in the poor areas where yaws occurs. A single center randomized control trial (RCT) carried out in Papua New Guinea in 2012 demonstrated the efficacy of a single-dose of oral azithromycin for the treatment of yaws. In this study, we also compared the efficacy of a single oral dose of azithromycin as an alternative to intramuscular benzathine penicillin for the treatment of the disease in another geographic setting.MethodologyWe conducted an open-label, randomized non-inferiority trial in three neighboring yaws-endemic districts in Southern Ghana. Children aged 1-15 years with yaws lesions were assigned to receive either 30mg/kg of oral azithromycin or 50,000 units/kg of intramuscular benzathine penicillin. The primary end point was clinical cure rate, defined as a complete or partial resolution of lesions 3 weeks after treatment. The secondary endpoint was serological cure, defined as at least a 4-fold decline in baseline RPR titre 6 months after treatment. Non- inferiority of azithromycin treatment was determined if the upper bound limit of a 2 sided 95% CI was less than 10%.FindingsThe mean age of participants was 9.5 years (S.D.3.1, range: 1-15 years), 247(70%) were males. The clinical cure rates were 98.2% (95% CI: 96.2-100) in the azithromycin group and 96.9% (95% CI: 94.1-99.6) in the benzathine penicillin group. The serological cure rates at 6 months were 57.4% (95% CI: 49.9-64.9) in the azithromycin group and 49.1% (95% CI: 41.2-56.9) in the benzathine penicillin group, thus achieving the specified criteria for non-inferiority.ConclusionsA single oral dose of azithromycin, at a dosage of 30mg/kg, was non-inferior to a single dose of intramuscular benzathine penicillin for the treatment of early yaws among Ghanaian patients, and provides additional support for the WHO policy for use of oral azithromycin for the eradication of yaws in resource-poor settings.Trial registrationPan African Clinical Trials Registry PACTR2013030005181 http://www.pactr.org/.

Project description:BackgroundBenzathine penicillin G (BPG) is a proven preventive agent for preventing the progression of rheumatic heart disease (RHD) and is recognized as a standard of care. However, ensuring adherence to BPG remains a global challenge. The objective of this review was to synthesize the available evidence on the barriers to and facilitators of BPG adherence among RHD patients.MethodsThis systematic review included both qualitative and quantitative studies on RHD patients published in the English language. This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The search strategy involved PubMed, Embase, CINAHL, Global Health, Scopus, and Web of Sciences databases to identify keywords and terms contained in the title and abstract and the index terms used to describe articles. The review included papers published from January 1, 2000, to March 30, 2024. Two independent reviewers screened, appraised, and extracted the data. The data analysis was carried out deductively to fit onto the components of the COM-B (Capability, Opportunity, Motivation-Behaviour) model.ResultsIn this review, 1067 records were screened, and 22 studies with 7338 participants were included. Thirty-five barriers and twenty facilitators were identified and mapped onto COM-B components. Physical capability (e.g., felt healthy), psychological capability (e.g., lack of knowledge), reflective motivation (e.g., poor patient handling), automatic motivation (e.g., BPG injection pain), physical opportunity (e.g., BPG unavailability) and social opportunity (e.g., inadequate counseling) were identified as barriers. The most discussed barrier was automatic motivation, followed by psychological capability and physical opportunity.ConclusionsOur review revealed variable levels of BPG adherence across studies and identified significant barriers and facilitators. Further research is recommended to identify contextual interventions to address barriers and capitalize on facilitators.Systematic review registrationPROSPERO CRD42024535398.

Project description:ObjectiveTo estimate the risk of serious adverse reactions to benzathine penicillin in pregnant women for preventing congenital syphilis.MethodsWe searched for clinical trials or cohorts that assessed the incidence of serious adverse reactions to benzathine penicillin in pregnant women and the general population (indirect evidence). MEDLINE, EMBASE, Scopus and other databases were searched up to December 2012. The GRADE approach was used to assess quality of evidence. Absolute risks of each study were calculated along with their 95% confidence intervals (95% CI). We employed the DerSimonian and Laird random effects model in the meta-analyses.ResultsFrom 2,765 retrieved studies we included 13, representing 3,466,780 patients. The studies that included pregnant women were conducted to demonstrate the effectiveness of benzathine penicillin: no serious adverse reactions were reported among the 1,244 pregnant women included. In the general population, among 2,028,982 patients treated, 4 died from an adverse reaction. The pooled risk of death was virtually zero. Fifty-four cases of anaphylaxis were reported (pooled absolute risk = 0.002%; 95% CI: 0%-0.003% I(2) = 12%). From that estimate, penicillin treatment would be expected to result in an incidence of 0 to 3 cases of anaphylaxis per 100,000 treated. Any adverse reactions were reported in 6,377 patients among 3,465,322 treated with penicillin (pooled absolute risk = 0.169%; 95% CI: 0.073%-0.265% I(2) = 97%). The quality of evidence was very low.ConclusionStudies that assessed the risk of serious adverse events due to benzathine penicillin treatment in pregnant women were scarce, but no reports of adverse reactions were found. The incidence of severe adverse outcomes was very low in the general population. The risk of treating pregnant women with benzathine penicillin to prevent congenital syphilis appears very low and does not outweigh its benefits. Further research is needed to improve the quality of evidence.

Project description:BackgroundThe shortage of benzathine penicillin G (BPG) worldwide presents a major challenge in the treatment of syphilis. Its availability for syphilis treatment has not been adequately evaluated in China.MethodsTwo surveys were conducted among hospitals providing sexually transmitted infection clinical services in Shandong Province in 2012 and 2018. Data on the basic information and BPG availability of the surveyed hospitals and related factors were collected and analyzed using SPSS 17.0.ResultsA total of 433 and 515 hospitals were surveyed in 2012 and 2018, respectively. A significant difference in BPG availability was observed among different levels and types of hospitals both in 2012 (X2 = 9.747, p = 0.008; X2 = 37.167, p = 0.000) and 2018 (X2 = 11.775, p = 0.003; X2 = 28.331, p = 0.000). The BPG availability among surveyed hospitals increased from 45.0% in 2012 to 56.4% in 2018 (X2 = 11.131, p = 0.001). The BPG availability was higher in 2018 than in 2012 among county-level hospitals (52.0% vs. 40.8%, X2 = 7.783, p = 0.005), general western medicine hospitals (62.1% vs. 50.0%, X2 = 6.742, p = 0.009), maternal and child health hospitals (57.1% vs. 26.9%, X2 = 13.906, p = 0.000), and public hospitals (56.8% vs. 45.0%, X2 = 11.361, p = 0.001). However, the county-level availability of BPG (at least one hospital has BPG in a county-level unit) has not improved between 2012 and 2018 (65.93% vs. 70.34%; X2 = 0.563, p = 0.453). The absences of clinical needs, restriction of clinical antibacterial drugs, and lack of qualifications for providing syphilis treatment were the major reasons for the low BPG availability of hospitals.ConclusionsBPG availability for syphilis treatment in Shandong Province remains low and presents disparities among different levels and types of hospitals, although it has been improved in recent years. The low availability of BPG for syphilis treatment in China is related to its clinical use by doctors rather than the market supply. Health care reforms should further improve the availability and accessibility of health services.

Dataset Information

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

Introduction

Methods

Results

Conclusions

Publications

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

Similar Datasets

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