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Background: Benzathine 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. Methods: This 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. Results: In 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. Conclusions: Our 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 registration: PROSPERO CRD42024535398. [ABSTRACT FROM AUTHOR]

Abstract Background Benzathine 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. Methods This 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. Results In 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. Conclusions Our 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 registration PROSPERO CRD42024535398.

Background: Syphilis is an infection of the Treponema pallidum bacteria that often occurs along with conditions such as Human Immunodeficiency Virus (HIV) infection, tuberculosis (TB), and oral candidiasis. A weakened immune system affects the complex interactions between these conditions and the clinical presentation as well as the therapeutic management provided to patients. Case: A 19-year-old male with a history of HIV complained of lesions on the skin and mouth. Anamnesis, physical examination, and serological test results establish the diagnosis of secondary syphilis and pulmonary tuberculosis, characterized by a one-month history of phlegm coughing and weight loss, was confirmed via sputum testing. Additionally, oral candidiasis was identified based on clinical examination. Discussion: The patient exhibited complex complications from secondary syphilis, HIV infection, TB, and oral candidiasis. In cases of syphilis with HIV, the appropriate treatment is three doses of Benzathine Penicillin G. Anti-Tuberculosis Drugs administration for TB was adjusted based on HIV status and therapy response, and antifungal fluconazole for oral candidiasis. Conclusions: This case highlights the importance of proper management and close monitoring of patients with multiple infectious conditions, including treatment of syphilis patients that has a higher incidence in men who have MSM, HIV, TB, and oral candidiasis. Timely and appropriate therapy strategies are essential to minimize complications and improve clinical outcomes.

An intramuscular (IM) suspension of benzathine penicillin G (BPG) has been used as first‐line therapy for the treatment of syphilis worldwide since its approval in the 1950s. However, there are limited reports about the pharmacokinetics of BPG. A Phase 1 study was conducted on eight Japanese healthy participants to investigate the pharmacokinetics (samples collected predose to 648 h post‐dose) and safety of 2.4 million units of BPG after a single IM injection. Following administration, penicillin G, the active moiety of BPG, was absorbed slowly from the injection site with a median time to Cmax (tmax) of 48 h post‐dose. After the achievement of Cmax, concentrations of penicillin G declined slowly in a monophasic fashion with a mean apparent terminal half‐life of 189 h. Geometric mean AUCinf and Cmax were 50770 ng•h/mL and 259 ng/mL, respectively. Median time (range) above the well‐accepted therapeutic concentration (18 ng/mL) for syphilis treatment was 561 h (439‐608 h [18‐25 days]), which reached and exceeded the necessary duration of 7‐10 days for syphilis treatment. Two participants were underdosed with residual drug left in the syringe due to the high viscosity of the drug product. Only one (12.5%) participant reported a mild adverse event of nasopharyngitis, which was considered not related to the study treatment. The study results supported BPG approval in Japan as an option for syphilis treatment. [ABSTRACT FROM AUTHOR]

In this study, we aimed to assess the prevalence of syphilis among people with human immunodeficiency virus (HIV; PWH) engaging in high-risk sexual behavior, determine the stage of syphilis, and evaluate treatment efficacy. A retrospective single-center cohort study was conducted at the AHEPA University General Hospital of Thessaloniki, focusing on PWH at high risk for sexually transmitted infections (STIs) attending outpatient care from January 2019 to December 2022. Sociodemographic and clinical data were collected, incident syphilis rates were identified, associations with HIV-related characteristics were explored, and the treatment response was assessed. Among 991 participants, 94 PWH were diagnosed with syphilis, representing 9.4% of the cohort. Incident syphilis cases experienced a decrease in the early COVID-19 era compared to 2019, followed by a gradual increase leading up to 2022. The majority of syphilis cases were asymptomatic latent syphilis (71.1%). Men who have sex with men (MSM) and younger individuals exhibited higher rates of co-infection during the study period. No significant association was found between incident syphilis and HIV-related factors. Most syphilis cases (86%) were treated with benzathine penicillin G (BPG). Treatment with BPG and doxycycline showed an increased success rate (96.7% vs. 92.9%), with no statistically significant difference observed between them (p = 0.438). This study highlights the alarming incidence of syphilis among PWH engaging in high-risk sexual behavior, particularly among younger MSM. BPG remains effective, and alternative regimens like doxycycline show promise, especially in settings with penicillin shortages or patient allergies. [ABSTRACT FROM AUTHOR]

Yu-Fen Huang,1 Hung-Jen Tang,2 Hung-Lin Hsu3 1Department of Pharmacy, Chi Mei Medical Center, Tainan, Taiwan; 2Division of Infectious Disease, Department of Medicine, Chi Mei Medical Center, Tainan, Taiwan; 3Department of Emergency Medicine, Chi Mei Medical Center, Tainan, TaiwanCorrespondence: Hung-Lin Hsu, Chi Mei Medical Center, No. 901, Zhonghua Road, Yongkang District, Tainan, 710, Taiwan, Tel +886-6-2812811, Email crystalarcx@gmail.comPurpose: The vicious cycle of recurrent cellulitis ultimately results in a high risk of relapse, which facilitates the use of antibiotic prophylaxis with monthly intramuscular benzathine penicillin G (BPG) to prevent recurrence. However, several clinical situations hinder the guideline recommendations in daily practice. Therefore, intramuscular clindamycin has been used as an alternative in our institution for years. This study aims to elucidate the effectiveness of monthly intramuscular antibiotics in preventing further cellulitis recurrence and evaluate the applicability of intramuscular clindamycin as an alternative to BPG.Patients and Methods: A retrospective cohort study was conducted at a medical center in Taiwan from January 2000 to October 2020. Adult patients with recurrent cellulitis were enrolled to receive monthly intramuscular antibiotic prophylaxis (including 1.2– 2.4MU BPG or 300– 600mg intramuscular clindamycin) or to be observed without prophylaxis. The decision to administer prophylaxis or observe was made at the discretion of the examining infectious disease specialists. Cox proportional-hazards regressions were performed to estimate hazard ratios (HR) and adjust for variables between groups. The Kaplan–Meier method was used to estimate survival curves.Results: Enrollment in the study consisted of 426 patients, with 222 receiving BPG, 106 receiving intramuscular clindamycin, and 98 being observed without prophylaxis. Both types of antibiotics resulted in a significantly lower recurrence rate than observation alone (27.9% for BPG, 32.1% for intramuscular clindamycin, and 82.7% for observation, P < 0.001). After adjusting for multiple variables, antibiotic prophylaxis continued to significantly reduce the risk of cellulitis recurrence by 82% (HR 0.18, 95% CI 0.13 to 0.26), by 86% (HR 0.14, 95% CI 0.09 to 0.20) with BPG, and by 77% (HR 0.23, 95% CI 0.14 to 0.38) with intramuscular clindamycin.Conclusion: Monthly intramuscular antibiotic prophylaxis was demonstrated to be effective in reducing cellulitis recurrence. Moreover, in the real-world practice, intramuscular clindamycin may serve as a reasonable alternative option to BPG.Keywords: recurrent cellulitis, prophylactic antibiotic, intramuscular clindamycin, benzathine penicillin G

In this study, we aimed to assess the prevalence of syphilis among people with human immunodeficiency virus (HIV; PWH) engaging in high-risk sexual behavior, determine the stage of syphilis, and evaluate treatment efficacy. A retrospective single-center cohort study was conducted at the AHEPA University General Hospital of Thessaloniki, focusing on PWH at high risk for sexually transmitted infections (STIs) attending outpatient care from January 2019 to December 2022. Sociodemographic and clinical data were collected, incident syphilis rates were identified, associations with HIV-related characteristics were explored, and the treatment response was assessed. Among 991 participants, 94 PWH were diagnosed with syphilis, representing 9.4% of the cohort. Incident syphilis cases experienced a decrease in the early COVID-19 era compared to 2019, followed by a gradual increase leading up to 2022. The majority of syphilis cases were asymptomatic latent syphilis (71.1%). Men who have sex with men (MSM) and younger individuals exhibited higher rates of co-infection during the study period. No significant association was found between incident syphilis and HIV-related factors. Most syphilis cases (86%) were treated with benzathine penicillin G (BPG). Treatment with BPG and doxycycline showed an increased success rate (96.7% vs. 92.9%), with no statistically significant difference observed between them (p = 0.438). This study highlights the alarming incidence of syphilis among PWH engaging in high-risk sexual behavior, particularly among younger MSM. BPG remains effective, and alternative regimens like doxycycline show promise, especially in settings with penicillin shortages or patient allergies.

[Display omitted] Regular intramuscular (i.m.) benzathine penicillin G (BPG) injections have been the cornerstone of rheumatic heart disease (RHD) secondary prophylaxis since the 1950s. Patient adherence to IM BPG is poor, largely due to pain, the need for regular injections every 3–4 weeks and health sector delivery challenges in resource-limited settings. There is an urgent need for new approaches for secondary prophylaxis, such as an implant which could provide sustained penicillin concentrations for more than 6 months. In this study we developed and evaluated a slow release implant with potential for substantially extended treatment. The side wall of a solid drug rich core was coated with polycaprolactone which acts as an impermeable barrier. The exposed surfaces at the ends of the implant defined the release surface area, and the in vitro release rate of drug was proportional to the exposed surface area across implants of differing diameter. The in vivo pharmacokinetics and tolerability of the implants were evaluated in a sheep model over 9 weeks after subcutaneous implantation. The absolute release rates obtained for the poorly water-soluble benzathine salt were dependent on the exposed surface area demonstrating the impermeability of the wall of the implant. The implants were well-tolerated after subcutaneous implantation in a sheep model, without adverse effects at the implantation site. Gross structural integrity was maintained over the course of the study, with erosion limited to the dual-exposed ends. Steady release of penicillin G was observed over the 9 weeks and resulted in approximately constant plasma concentrations close to accepted target concentrations. In principle , a long acting BPG implant is feasible as an alternative to i.m. injections for secondary prophylaxis of RHD. However, large implant size is currently a significant impediment to clinical utility and acceptability. [ABSTRACT FROM AUTHOR]

Background: World Health Organization (WHO) reported that there are 6 million new cases of syphilis worldwide per year. The incidence of syphilis in Indonesia has increased over the past few years, particularly among men who have sex with men (MSM). Purpose: To report a case of secondary syphilis with Human Immunodeficiency Virus (HIV) coinfection in MSM, thereby increasing understanding of high-risk sexual behavior among MSM. Case: A 26-year-old man with a chief complaint of rashes on both palms, soles of the feet, and face. The rashes spread with no itching, heat, or pain, which occurred two weeks ago. The patient was diagnosed with HIV in 2019. Physical examination found multiple violaceus macules with clear boundaries, 0.5–1 cm in size, covered with scales. Venereal Disease Research Laboratory (VDRL) serology titer was 1:16 and Treponema Pallidum Haemagglutination Assay (TPHA) was 1:20.480. The recent CD4 count was 440 with an undetectable HIV RNA viral load. Benzathine penicillin G 2.4 million units was given intramuscularly 3 times at 1-week intervals. The patient experienced clinical improvement and decreased VDRL and TPHA titers. Discussion: Syphilis patients with or without HIV would have similar clinical symptoms. However, syphilis patients with HIV tend to have more extensive lesions. The treatment option with three doses of benzathine penicillin G is still very effective in cases of syphilis with HIV. Conclusion: Syphilis has a higher incidence in MSM patients with extensive clinical manifestations of skin lesions. It can be observed in syphilis patients with HIV; therefore, close monitoring is needed.

Latar belakang. Infeksi Streptococcus yang memicu demam rematik dapat mendasari terjadinya penyakit jantung didapat pada anak. Demam rematik dapat dicegah baik dari pencegahan primordial, primer, dan sekunder. Anak dengan penyakit jantung rematik dapat dicegah keparahan penyakitnya dengan mencegah terjadinya infeksi Streptococcus berulang atau pencegahan sekunder. Pencegahan sekunder dianjurkan oleh World Health Organization (WHO) adalah dengan pemberian Benzathine Penicillin G (BPG) setiap 3 – 4 minggu. Tujuan. Mengetahui apakah pemberian BPG setiap 3 minggu dapat mengurangi peristiwa infeksi Streptococcus pada anak dengan penyakit jantung rematik dibanding pemberian setiap 4 minggu. Metode. Penelusuran pustaka database elektronik, yaitu Pubmed, ScienceDirect, Cochrane, dan Google Scholar dengan kata kunci “rheumatic heart disease”, “AND” “benzathine penicillin g”, “AND”, “streptococcal infection”, “AND”, “children”. Hasil. Diperoleh satu studi systematic review dan satu studi kohort yang sesuai. Kedua studi menunjukkan bahwa pemberian BPG setiap 3 minggu mengurangi kejadian infeksi Streptococcus daripada pemberian setiap 4 minggu dengan nilai NNT berturut-turut 6 dan 8. Kesimpulan. Pemberian BPG setiap 3 minggu terbukti dapat menurunkan kejadian infeksi Streptococcus pada pasien dengan penyakit jantung rematik.

Introduction: The incidence of syphilis is increasing in Japan. A new treatment, penicillin intramuscular injection, was launched in January 2022. This study aimed to determine syphilis treatments in Japan and investigate the impact of the new intramuscular penicillin formulation., Materials and Methods: Data from the Japanese Administrative Claims Database from January 2016 to September 2023 were used to identify patients diagnosed with syphilis, and the types and annual trends of antimicrobials prescribed were investigated. Furthermore, the characteristics of patients prescribed an intramuscular injection of benzathine penicillin G were compared with those of patients who were not., Results: Overall, 7867 patients were included in the analysis ( 81%, male; 5.4% positive for human immunodeficiency virus). Seventy-five percent of patients were diagnosed with syphilis in facilities with 0-19 beds. Annual trends showed oral amoxicillin as the most prescribed drug to 80% of patients throughout the study period. In 2023, 10.6% of patients received a prescription for an intramuscular penicillin formulation. Compared with those who did not receive this treatment, those who received it tended to have fewer clinic visits over 1 month (p = 0.0256)., Conclusions: Oral amoxicillin is the primary treatment for syphilis in Japan; however, the number of patients receiving intramuscular injection of benzathine penicillin G is increasing. Prescribed mainly by clinics, an intramuscular injection of benzathine penicillin G may contribute to a decreased number of office visits., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Rheumatic Fever (RF) and Rheumatic heart disease (RHD) are common cardiovascular diseases in developing countries. Long-term Benzathine Penicillin G (BPG) injection is being used for secondary prophylaxis of RF/RHD. Although allergic reactions to BPG are rare, there is a lot of fear and hesitancy in administering it. Objective: The objective of this study is to assess the safety of injection BPG used for secondary prophylaxis of RHD. Methods: Patients who had received secondary prophylaxis to RHD at our institute's outpatient department from January 1, 2015 to December 31, 2020, were analysed retrospectively. Results: Among 25,819 injections of BPG given to 2878 patients, eight patients had adverse events. Five patients had anaphylaxis, two had urticaria, and one had vasovagal syncope. Incidence of adverse events was 0.03% of injections and 0.28% of patients. Majority of adverse events were seen in patients more than 18 years (7 out of 8). All were treated successfully and there was no mortality. Conclusions: Life-threatening allergic reactions are very rare in patients on long-term intramuscular BPG for secondary prevention of RHD.

Kajela Kibirat Mekonen, Malede Berihun Yismaw, Alfoalem Araba Abiye, Tamrat Assefa Tadesse Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, EthiopiaCorrespondence: Tamrat Assefa Tadesse P.O. Box: 9086, Addis Ababa, EthiopiaEmail tamrat.assefa@aau.edu.etPurpose: Benzathine penicillin G (BPG) monthly administration is the most effective method for secondary prophylaxis against acute rheumatic fever (ARF). BPG’s efficacy largely depends on adherence to treatment. This study was aimed at assessing adherence to BPG prophylaxis and its determinants among adult patients with rheumatic heart disease.Patients and Methods: An institutional cross-sectional study design was used. One hundred and forty-five patients receiving monthly BPG at the Adult Cardiac Clinic of Tikur Anbessa Specialized Hospital (TASH) were interviewed. Their 1-year BPG prophylaxis administration record was also reviewed. The rate of adherence to BPG injection was determined by calculating the percentage of the administered drug from the total expected doses. Data were entered and analyzed using Statistical Package for Social Sciences (SPSS) software version 25. Both descriptive and logistic regression analyses were computed to describe different variables and assess factors associated with adherence, respectively. A p-value < 0.05 was used to declare association.Results: Among a total of 145 study participants involved, the majority (76.6%) of them had been receiving BPG for the last 10 years. The average adherence rate to monthly BPG injection was 80.60% with a range of 0% to 100%. However, only 101 (69.7%) of participants were taking ≥ 80% of their prescribed monthly BPG prophylaxis doses. Study participants with informal education 1.10 (0.023– 46.96) and secondary school education 0.89 (0.10– 8.11) were more and less likely to adhere to BPG injection, respectively, when compared with those who attended higher education programs. The regression analysis showed patients who were not admitted to the hospital (AOR: 26.22; CI: 2.55– 269.70; p=0.006) and once admitted patients (AOR: 50.08; CI: 2.87– 873.77; p=0.007) were more likely to adhere to their BPG injections than those admitted twice or more. The study participants who waited until the next appointment were also less adherent (AOR: 0.02; CI: 0.00– 0.13; p=0.000) than those who went a few days later for receiving the missed/late dose.Conclusion: The adherence rate to BPG injection among RHD patients was found to be high (80.60%). Patients’ admission status and their action on missed and/or late doses were found to be important determinants of adherence in this study.Keywords: rheumatic heart disease, benzathine penicillin G, adherence rate, Tikur Anbessa Specialized Hospital, Ethiopia

Syphilis is an important global health threat and little has changed in its treatment since the mid-20th century. For late-latent or syphilis infection of unknown duration, the standard treatment of multiple intramuscular injections of benzathine penicillin G (BPG) are associated with significant pain and distress to clients and caregivers, negatively impacting on treatment completion. Based on pharmacokinetic modelling from a Phase I study of subcutaneous infusion of high dose BPG (SCIP), we present its feasibility, safety and tolerability for treatment of syphilis in a single infusion. SCIP leads to more sustained penicillin concentrations above the desired target with less reported pain and reduced clinic visits. Painful intramuscular injections of long-acting penicillin remain the mainstay of treatment for syphilis. They are distressing to clients and caregivers and are thought to interfere with treatment acceptance, especially if more than one dose is required. We present a novel method of delivering the same penicillin treatment into the fat, which obviate the need for multiple doses and is associated with less reported pain – a potential gamechanger to improve syphilis treatment adherence and care cascade. [ABSTRACT FROM AUTHOR]

Introduction: Poorer serologic responses of early syphilis to treatment have been inconsistently reported in HIV-positive patients compared with HIV-negative patients, but the interpretation of previous studies is limited by discrepant study designs. The present study aimed to evaluate the effect of HIV infection on the treatment response to a single dose of benzathine penicillin G (BPG) for early syphilis. Methods: From January 2015 to March 2020, adult patients with early syphilis who received a single dose of BPG were enrolled and rapid plasma reagin (RPR) titers were periodically determined. The primary outcome was serologic response, defined as at least a fourfold decline of RPR titer at 12 months of BPG treatment compared with that at baseline, which was examined in the intention-to-treat (ITT) and per-protocol analyses. Treatment failure included lack of at least a fourfold decline in RPR titers and at least a fourfold increase in RPR titers. Results: We prospectively enrolled 184 HIV-positive and 68 HIV-negative participants with early syphilis, who were all men who have sex with men, with a higher proportion of previous syphilis (70.1%) and early latent syphilis (64.1%) among HIV-positive participants. In the ITT with last-observation-carried-forward analysis, HIV-positive participants had a significantly lower serologic response rate at 12 months of treatment than HIV-negative participants (73.4% vs. 91.2%). Of HIV-positive participants, 12.5% failed to achieve at least fourfold decline in RPR titers and 14.1% had at least a fourfold increase in RPR titers. The factors associated with 12-month serologic response were HIV infection (adjusted odds ratio [AOR] 0.33; 95% confidence interval [CI] 0.13–0.81) and RPR titer (per 1-log2 increase, AOR 1.36; 95% CI 1.23–1.51). Conclusion: HIV-positive patients with early syphilis had poorer serologic responses to BPG treatment than HIV-negative patients during a 12-month follow-up period. [ABSTRACT FROM AUTHOR]

Abstract Background The 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. Methods Two 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. Results A 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. Conclusions BPG 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.

Secondary prophylaxis of rheumatic heart diseases is efficient in reducing disease recurrence, heart damage, and cardiac impairment. We aimed to monitor the clinical evolution of a large Brazilian cohort of rheumatic patients under prolonged secondary prophylaxis. From 1986 to 2018, a cohort of 593 patients with rheumatic fever was followed every 6 months by the Reference Center for the Control and Prevention of Rheumatic Fever and Rheumatic Cardiopathy (CPCFR), Paraná, Brazil. In this cohort, 243 (41%) patients did not present cardiac damage (group I), while 350 (59%) were diagnosed with rheumatic heart disease (RHD) (group II) using the latest case definition. Among group II, 233 and 15 patients had impairment of the mitral and aortic valves, respectively, while 102 patients had impairment of both valves. Lesions on the mitral and aortic valves presented a regression in 69.9 and 48.7% of the patients, respectively. Active patient recruitment in the reference center and early detection of oropharyngeal GAS were important factors for optimal adherence to the prophylactic treatment. Patients with disease progression were associated with noncompliance to secondary prophylaxis. No patients undergoing regular prophylaxis presented progression of the rheumatic cardiac disease. Eighteen valvular surgeries were performed, and four (0.7%) patients died. This study confirmed that tailored and active efforts invested in rheumatic heart disease secondary prevention allowed for significant clinical improvement.

Abstract Benzathine penicillin G (BPG) is used as first‐line treatment for most forms of syphilis and as secondary prophylaxis against rheumatic heart disease (RHD). Perceptions that poor quality of BPG is linked to reported adverse effects and therapeutic failure may impact syphilis and RHD control programs. Clinical networks and web‐based advertising were used to obtain vials of BPG from a wide range of countries. The quality of BPG was assessed using a high performance liquid chromatography assay capable of detecting relevant impurities and degradation products. Tests for water content, presence of heavy metals and physical characteristics of BPG, including particle size analysis and optical microscopy, also were conducted. Thirty‐five batches of BPG were sourced from 16 countries across 4 WHO regions. All batches passed the US Pharmacopeia requirements for BPG injection (content), with no evidence of breakdown products or other detected contaminants. Water content and heavy metal analysis (n = 11) indicated adherence to regulatory standards and Good Manufacturing Practice. Particle size analysis (n = 20) found two batches with aggregated particles (>400 µm) that were dispersed following sonication. Current batches of BPG were of satisfactory pharmaceutical quality but aggregated particles were found in a modest proportion of samples. Future studies should focus on the physical characteristics of BPG which may contribute to variations in plasma penicillin concentrations an observed needle blockages in clinical practice. Pharmacopeial monographs could be revised to include standards on particle size and crystal morphology of BPG.

Benzathine penicillin G (BPG) is used as first-line treatment for most forms of syphilis and as secondary prophylaxis against rheumatic heart disease (RHD). Perceptions that poor quality of BPG is linked to reported adverse effects and therapeutic failure may impact syphilis and RHD control programs. Clinical networks and web-based advertising were used to obtain vials of BPG from a wide range of countries. The quality of BPG was assessed using a high performance liquid chromatography assay capable of detecting relevant impurities and degradation products. Tests for water content, presence of heavy metals and physical characteristics of BPG, including particle size analysis and optical microscopy, also were conducted. Thirty-five batches of BPG were sourced from 16 countries across 4 WHO regions. All batches passed the US Pharmacopeia requirements for BPG injection (content), with no evidence of breakdown products or other detected contaminants. Water content and heavy metal analysis (n = 11) indicated adherence to regulatory standards and Good Manufacturing Practice. Particle size analysis (n = 20) found two batches with aggregated particles (>400 ^m) that were dispersed following sonication. Current batches of BPG were of satisfactory pharmaceutical quality but aggregated particles were found in a modest proportion of samples. Future studies should focus on the physical characteristics of BPG which may contribute to variations in plasma penicillin concentrations an observed needle blockages in clinical practice. Pharmacopeial monographs could be revised to include standards on particle size and crystal morphology of BPG. [ABSTRACT FROM AUTHOR]

Rheumatic heart disease, as a result of a single or recurrent episode of acute rheumatic fever (ARF), remains a significant cause of morbidity and mortality in northern and remote Australia; ARF has a peak incidence among 5-14-year-old Aboriginal and Torres Strait Islander children. Long-term regular benzathine penicillin G injections are the only currently successful secondary prevention strategy; however, rates of adherence remain critically low. In contrast, rates of adherence to immunisations on the National Immunisation Program (NIP) Schedule are high, even among this target population. This article compares strategies used to implement and improve ARF secondary prophylaxis with those used in the NIP. Some successful NIP strategies, such as Service Incentive Payment for health providers, home-visiting delivery models and integration into the National Immunisation Register, if applied to ARF secondary prophylaxis have the potential to improve benzathine penicillin G adherence. [ABSTRACT FROM AUTHOR]

Since 1955, the recommended strategy for rheumatic heart disease (RHD) secondary prophylaxis has been benzathine penicillin G [BPG; 1.2 MU (900 mg)] injections administered intramuscularly every 4 weeks. Due to dosing frequency, pain, and programmatic challenges, adherence is suboptimal. It has previously been demonstrated that BPG delivered subcutaneously at a standard dose is safe and tolerable and has favorable pharmacokinetics, setting the scene for improved regimens with less frequent administration. The safety, tolerability, and pharmacokinetics of subcutaneous infusions of high-dose BPG were assessed in 24 healthy adult volunteers assigned to receive either 3.6, 7.2, or 10.8 MU (three, six, and nine times the standard dose, respectively) as a single subcutaneous infusion. The delivery of the BPG to the subcutaneous tissue was confirmed with ultrasonography. Safety assessments, pain scores, and penicillin concentrations were measured for 16 weeks post-dose. Subcutaneous infusion of penicillin (SCIP) was generally well tolerated with all participants experiencing transient, mild infusion-site reactions. Prolonged elevated penicillin concentrations were described using a combined zero-order (44 days) and first-order ( t 1/2 = 12 days) absorption pharmacokinetic model. In simulations, time above the conventionally accepted target concentration of 20 ng/mL (0.02 µg/mL) was 57 days for 10.8 MU delivered by subcutaneous infusion every 13 weeks compared with 9 days of every 4-weekly dosing interval for the standard 1.2 MU intramuscular dose (i.e., 63% and 32% of the dosing interval, respectively). High-dose SCIP (BPG) is safe, has acceptable tolerability, and may be suitable for up to 3 monthly dosing intervals for secondary prophylaxis of RHD., Competing Interests: The authors declare no conflict of interest.

The association between group A streptococcal infection and rheumatic fever (RF) was established in the early 20 th century. At the time, RF and subsequent rheumatic heart disease (RHD) were an untreatable scourge of young people in developed and developing countries. Resultingly, research efforts to understand, treat and prevent the disease were widepread. The development of antibiotics in the 1930s offered therapeutic promise, although antibotic treatment of acute RF had little impact. Improved understanding of the post-infectious nature of RF prompted attempts to use antibiotics prophylactically. Regular doses of sulphonamide antibiotics following RF appeared to reduce disease progression to RHD. Development of penicillin and later, benzathine penicillin G, was a further thereputic advance in the 1950s. No new prophylactic options against RF have emerged in the intervening 60 years, and delivery of regularly scheduled BPG injections remains a world wide challenge.

Background: Secondary prevention is an effective treatment for rheumatic heart disease (RHD), but ensuring high adherence to prophylaxis over many years is challenging and requires understanding of local factors. Methods: Participants were young people diagnosed with RHD through echocardiographic screening in Fiji. We used a structured interview to evaluate the following: health seeking behaviours; attitudes, practice, barriers and potential improvement strategies for adherence to antibiotic prophylaxis; and adolescent-friendly qualities of the health service. Results: One hundred and one participants were interviewed (median age, 17.2 years). Adherence was very low overall (adequate in 6%). Sore throat and fever with sore joints were experienced in the preceding year by 42% and 28%, respectively. Barriers to receiving treatment included taking alternate treatments and the perception that symptoms were benign and self-limiting. Reasons for missing prophylaxis injections included lack of awareness, feeling well, transport cost and access, and medication unavailability (>40% of participants each). The injection health service had many perceived strengths, but inclusion of adolescents in decision making, and quality of educational materials were deficiencies. Reminder strategies, particularly phone-based reminders, were considered helpful by 94%. Conclusions: We identified several factors influencing secondary prevention that may be used to develop interventions to improve adherence. [ABSTRACT FROM AUTHOR]

In this work, a micellar system of benzathine penicillin G (BPG) in sodium deoxycholate (NaDC) was developed and evaluated physicochemically. The solubility profile of the drug in water and buffer solutions at various pH was determined, as well as its n-octanol/water partition coefficient. The Critical Micellar Concentration of NaDC and its ability to incorporate BPG were also assessed. The study was carried out at low and high ionic strength which was adjusted by the addition of sodium chloride. The results demonstrated the ability of the micellar system to incorporate BPG, as well as to increase its apparent solubility in water. The enhancement of the solubility of BPG by the presence of NaDC micelles could be analyzed quantitatively within the framework of the pseudo-phase model. Concentration analysis showed that the micellar system could attain up to 90% incorporation of BPG. The incorporated drug is expected to exhibit improved stability, since the antibiotic enclosed in the hydrophobic core of micelles is rather shielded from the aqueous external environment. Keywords: Benzathine Penicillin G; micellar solubilization; micelles; pre-formulation; sodium deoxycholate.

In the ever-growing demand for drug nanocomplexes (DNCs), the need for smart systems or processes is indispensable to circumvent the demerits imposed by the conventional methods for the synthesis of DNCs. The demerits include prolonged hours of the synthesis, minimal loading and poor conjugation. Herein, we proposed a simplistic approach for the synthesis of DNCs through a magnetically active Polydimethylsiloxane micromixer which can render maximal loading in an unprecedented time. The UV–Vis, FTIR, and XRD analysis corroborate the proposed mechanism of conjugation of the drug and nanoparticles. The XPS, contact angle and zeta potential measurements revealed the composition, hydrophilicity and surface charges of the synthesized DNCs, respectively. Further, the microscopy images exemplify the encapsulation of the drug. In the antibacterial activity studies, the DNCs substantially inhibited the growth of the Staphylococcus aureus bacteria. FESEM images proved preferential accumulation of DNCs around bacterial cells effectively annihilating them. [ABSTRACT FROM AUTHOR]

Benzathine penicillin G (BPG) in powder form was exposed to a range of different doses of Co gamma radiation to investigate the effects of ionizing radiation using electron paramagnetic resonance (EPR) technique. Dependence of EPR signals with absorbed dose, time, temperature and microwave power were studied. In the light of the findings on all EPR experimental data, it can be suggested the radiosterilization of BPG in solid dry state could be technically feasible by EPR method. [ABSTRACT FROM AUTHOR]

Kounis syndrome is a life-threatening medical condition that causes severe allergic reaction and acute coronary syndrome. Benzathine penicillin G is one of the most widely used antibiotics in clinical practice, but it can enhance both allergic and hypersensitivity complications. In this report, we describe the case of a 42-year-old man admitted to our hospital who presented with cryptic tonsillitis accompanied by angioneurotic edema, chest pain, and electrocardiographic variations. The patient was diagnosed with Kounis syndrome and treated with oral antihistamines and prednisolone. He was discharged following a complete recovery and regression of electrocardiographic abnormalities within 72 hours.

Background. Treatment guidelines recommend the use of a single dose of benzathine penicillin G (BPG) for treating early syphilis in human immunodeficiency virus (HIV)-infected persons. However, data supporting this recommendation are limited. We examined the efficacy of single-dose BPG in the US Military HIV Natural History Study. Methods. Subjects were included if they met serologic criteria for syphilis (ie, a positive nontreponemal test [NTr] confirmed by treponemal testing). Response to treatment was assessed at 13 months and was defined by a ≥4-fold decline in NTr titer. Multivariate Cox proportional hazard regression models were utilized to examine factors associated with treatment response. Results. Three hundred fifty subjects (99% male) contributed 478 cases. Three hundred ninety-three cases were treated exclusively with BPG (141 with 1 dose of BPG). Treatment response was the same among those receiving 1 or >1 dose of BPG (92%). In a multivariate analysis, older age (hazard ratio [HR], 0.82 per 10-year increase; 95% confidence interval [CI], .73–.93) was associated with delayed response to treatment. Higher pretreatment titers (reference NTr titer <1:64; HR, 1.94 [95% CI, 1.58–2.39]) and CD4 counts (HR, 1.07 for every 100-cell increase [95% CI, 1.01–1.12]) were associated with a faster response to treatment. Response was not affected by the number of BPG doses received (reference, 1 dose of BPG; HR, 1.11 [95% CI, .89–1.4]). Conclusions. In this cohort, additional BPG doses did not affect treatment response. Our data support the current recommendations for the use of a single dose of BPG to treat HIV-infected persons with early syphilis. [ABSTRACT FROM AUTHOR]

For the treatment of early infectious syphilis, enhanced therapy with three dosages of benzathine penicillin G has been under consideration, particularly in the human immunodeficiency virus type 1 infected population (HIV-1). The serological outcome of 249 patients with primary and secondary syphilis treated with standard or enhanced therapy was analyzed retrospectively; 98% (139/142) achieved serological cure with a single dosage and 92% with enhanced therapy (P = 0.033). In HIV-1 infected individuals, cure rates were 88% after a single dosage compared to 97% after three dosages (P = 0.18). A fourfold decrease of Venereal Disease Research Laboratory (VDRL) titres was achieved within a median of 102 days after treatment initiation (SD = 2; 95% CI = 98–106). Patients aged over 40 years were 5.5 times (OR = 5.52; 95% CI = 1.43–21.32; P = 0.013) and patients with low baseline VDRL titres (≤1 : 32) were 4 times (OR = 4.25; 95% CI = 1.21–14.87; P = 0.024) more likely to experience serological failure. [ABSTRACT FROM AUTHOR]