Benzathine Penicillin G Research Articles

Osteomyelitis by Proteus spp after snake bite – Account of a still neglected tropical illness

Background: Serum therapy is used in accidents intervention. After the bite, the proposed treatment is based on the snake's type and size, on symptomatology for light, moderate or grave ones. Despite serum therapy's beneficial evidence, there is the need for monitoring and systematic follow-up on the first seven days after the accident. Aim: To report the case intervention with emergence of osteomyelitis by Proteus spp. occurred five weeks immediately after the snake bite. Methods: Case report of an adolescent individual aged 17, male, bitten at the proximal third of the lower left limb (LLL) living at rural zone at Mato Grosso (MT) countryside, Brazil. Immediate intervention was made with antiphospholipid serum 20 minutes after the bite. A single dose of Benzetacil® (Benzathine benzylpenicillin) was prescribed 48 hours after the accident, associated with anti-inflammatory and corticosteroid. The patient's re-internment with antibiotic therapy after the fifth day could not prevent the osteomyelitis at the tibia bone. To solve the case, two surgical interventions were required. For data analysis, initial and final moments of exams' values were compared, concurring to the assessment by MRI imaging. Results: It was found osteomyelitis in 3,5 cm of the tibia at nuclear MRI, in the result of anterior and fibular tibial muscle culture, and on the bone fragment of the tibia, by Proteus spp bacteria. Conclusions: It is possible to conclude that, in ophidic accidents, one must take into account the possibility the immune system may not respond to the bacterian microorganisms infected on the patient, being needed administration of antibiotics for either positive and negative gram. Such measures would avoid systemic wounds, longer internments and installation of physical deficiencies with increase of health costs.

The Impact of Monthly Prophylactic Antibiotics Use in Patients with Recurrent Cellulitis: A 20-Year Population-Based Cohort Study in a Medical Center.

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. 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. 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. 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.

Syphilis screening coverage and positivity by HIV treatment status among South African pregnant women enrolled in the 2019 antenatal HIV sentinel survey

We describe coverage of maternal syphilis screening, syphilis positivity, coverage of treatment and their association with maternal HIV infection and antiretroviral treatment (ART) status among pregnant women attending South African antenatal clinics. The 2019 antenatal care sentinel survey was a cross-sectional survey conducted from 1 October to 15 November 2019 at 1589 sentinel sites in all nine provinces of the country and aimed to enrol 36,000 pregnant women ages 15–49 years regardless of HIV, ART or syphilis status. Data collection procedures included obtaining written informed consent, a brief interview, medical record review and blood specimen collection. Completed data collection forms and specimens were sent to designated regional laboratories for data capture and HIV serology testing. Data analysis determined four outcomes i) syphilis screening coverage ii) syphilis positivity iii) coverage of any treatment and iv) with Benzathine penicillin G (BPG). Multivariable logistic regression models with or without interaction between HIV infection and ART status with province were used to determine factors associated with syphilis positivity. Of the 41 598 women enrolled, 35 900 were included in the analysis for syphilis screening coverage. The weighted syphilis screening coverage was 96.4% [95% Confidence Interval (CI) 95.9–96.7%] nationally and was lowest among HIV positive women not on ART at 93.5% (95% CI 92.2–94.5%). Syphilis positivity was 2.6% (95% CI 2.4–2.9%) nationally. Among those who were syphilis positive, 91.9% (95% CI 89.8–93.7%) had documentation of syphilis treatment status, of whom 92.0% (95% CI 89.8–93.9%) were treated, with the majority treated with one or more doses of BPG [92.2% (95% CI 89.8–94.3%)]. HIV-positive women, not on ART [adjusted odd ratio (aOR) 2.24 (95% 1.71–2.93)] and those on ART [aOR 2.25 (95% CI 1.91–2.64)] were more likely to be syphilis positive compared to those who were HIV negative. The national syphilis screening coverage met the global screening target of 95%. Syphilis positivity was higher among HIV positive women compared to negative women. Introduction of rapid syphilis testing and ensuring a universal supply of appropriate treatment for syphilis will reduce the likelihood of mother-to-child transmission of syphilis.

Utilization of Injectable Drugs for Communicable and Non-communicable Diseases in Primary Healthcare: A Retrospective Study in Turkey

Objective: Primary care, which is often the first level of contact for patients with various communicable diseases (CDs) and noncommunicable diseases (NCDs), might exhibit patterns of injectable drug utilization different from hospitals. We aimed to examine injection prescribing to adults with CD or NCD in primary care. Methods: In this retrospective study, single-diagnosis injectable drug-containing prescription data from Family Medicine Information System comprising 32 provinces of Turkey were analysed. The prescriptions were grouped by diagnosis as “CD” (n=3848) and “NCD” (n=9338). Injectable drug utilization patterns in these groups were analysed by demographics, diagnoses, and drug subgroups. Results: Out of 13186 prescriptions, 70.8% were issued for NCDs. NCD prescriptions were mostly generated for women and elderly (p&lt;0.05 for both). About 63.3% (n=2948) of injectable drugs in CD prescriptions were antibiotics and 12.6% were analgesics. Cefazolin (15.2%) was the most commonly prescribed antibiotic for acute pharyngitis and acute sinusitis, and benzathine benzylpenicillin (12.8%) was the top-choice for acute tonsillitis and rheumatic fever. In NCD prescriptions, 34.0% (n=4214) of injectable agents were analgesics and 16.9% were muscle relaxants. The most frequently encountered drug in NCD prescriptions was thiocolchicoside (16.3%), which was the top-choice in all seven common musculoskeletal diagnoses. Conclusion: Muscle relaxants and analgesics were the most commonly prescribed injectable drugs for NCDs, musculoskeletal diseases in particular. Antibiotics were frequently encountered in CD prescriptions, mostly as broad-spectrum for lower respiratory tract infections (RTIs) and narrow-spectrum for upper RTIs. These findings may elucidate the issues to especially focus on regarding excessive use of injections.

Treatment Completion With Three-Dose Series of Benzathine Penicillin Among People Diagnosed With Late Latent and Unknown Duration Syphilis, Maricopa County, Arizona.

Syphilis is a public health concern as cases are rising each year. If untreated, syphilis is associated with significant morbidity and risk of vertical transmission during pregnancy. For people with late latent and unknown duration stages, 3 injections of benzathine penicillin G (BPG) at 1-week intervals are recommended. Our study quantified treatment for people diagnosed with late latent and unknown duration syphilis in Maricopa County, Arizona with a secondary analysis of pregnant women to assess completion of 3 injections of BPG in multiple time intervals. Maricopa County syphilis case data were extracted from the state-run database (PRISM). Records were reviewed for people with late latent and unknown duration syphilis during January 1, 2016, to December 31, 2021. Treatment types and time intervals between treatments were analyzed. Of a total of 14,924 people with syphilis reported in Maricopa County, 5372 (36.0%) were staged as late latent or unknown duration syphilis. Completion of 3 BPG injections in the time frame of 7 to 9 days was 42.9% (n = 2302). Completion among pregnant women (n = 406) with 3 injections was 68.7% (n = 279). The completion rate of 3 BPG injections for people with late latent or unknown duration syphilis is low. An unmet need exists to identify barriers to treatment including access to BPG and public health follow-up after the first injection. Prioritized effort is needed to identify and classify patients as having earlier stages of syphilis that require only 1 BPG injection.

Syphilis in pregnancy at Public Health Centre III North Denpasar

Introduction: Syphilis is a sexually transmitted infection (STI) caused by the bacterium Treponema pallidum. Syphilis in pregnancy is often asymptomatic, so early detection of syphilis is needed to prevent a poor pregnancy outcome and transmission of infection to the baby.&#x0D; Case: A 25-year-old woman, pregnant with her second child at 24 weeks of gestation, came without any health complaint for a routine prenatal check-up. On syphilis screening, reactive TPHA and RPR titer of 1:2 were found. The patient was diagnosed with syphilis infection in pregnancy. The patient has been treated with Benzathine Benzylpenicillin 2.4 million IU intramuscular injection once a week for 3 consecutive weeks.&#x0D; Conclusion: Syphilis is a sexually transmitted infection that infects pregnant women. Treponemal transmission in pregnant women was detected early in the ninth week of pregnancy. The diagnosis of syphilis was made by dark-field microscopy, treponemal antibody tests (TPHA, FTA-ABS), and non-treponemal antibody tests (VDRL, RPR). Penicillin is the gold standard therapy for syphilis in pregnant women.

Challenges and outcomes of implementing a national syphilis follow-up system for the elimination of congenital syphilis in Cambodia: a mixed-methods study

ObjectivesWe aimed to describe the challenges and outcomes of implementing a national syphilis follow-up system to improve syphilis management in maternal and child health (MCH) services in Cambodia.DesignOperational study; quantitative...

Congenital syphilis in a preterm newborn with gastrointestinal disorders and postnatal growth restriction

BackgroundCongenital syphilis (CS) depends on the placental transmission of Treponema pallidum (TP) spirochetes from an infected mother to fetus during pregnancy. It shows a wide clinical variability with cutaneous and visceral manifestations, including stillbirths, neonatal death, and asymptomatic cases. Preterm infants with CS may have more severe features of disease than the term ones, due to the combined pathogenic effect of both CS and prematurity.Case presentationWe report on a female preterm (32+6 weeks of gestation) newborn showing most of the typical CS manifestations, in addition to gastrointestinal disorders including feeding difficulties, colon stenosis and malabsorption leading to postnatal growth restriction. The mother resulted positive at the syphilis screening test of the first trimester of pregnancy, but she did not undergo any treatment. At birth, our newborn was VDRL positive (antibody titer four times higher compared to the mother), and she was treated with intravenous benzathine benzylpenicillin G for 10 days (50,000 IU/Kg three times per day). Poor tolerance to enteral nutrition (abdominal distension, increased biliary type gastric secretions) was observed. A barium enema X-Ray identified a colon stenosis within the descending tract. However, the poor general conditions due to a concurrent fungal sepsis did not allow to perform any surgical procedure, and a conservative approach with total parenteral nutrition was started. The following evolution was marked by difficulties in enteral feeding including refusal of food and vomiting, to which also contributed the neurological abnormalities related to a perinatal asphyxia, and the affective deprivation for the physical absence of the mother during hospitalization. At 5 months of age, after the introduction of an amino acid-based formula (Neocate LCP Nutricia ®), an improvement of enteral feeding was observed, with no further and significantly decreased episodes of abdominal distension and vomiting respectively, and regular stool emission. A psychological support offered to the family allowed a more stable bond between the mother and her baby, thus providing a significant additional benefit to food tolerance and growth. She was discharged at 5 months of age, and included in a multidisciplinary follow-up. She at present shows global growth delay, and normal development apart from mildly increased tone of lower limbs.ConclusionsOur report highlights less common clinical CS manifestations like gastrointestinal disorders including feeding difficulties, colon stenosis and malabsorption leading to postnatal growth delay. Moreover, it underlines how prematurity may worsen the clinical evolution of such congenital infection, due to the additional pathogenic effect of possible associated diseases and/or conditions like sepsis, hypoxic/ischemic injury, or use of drugs. CS may be observed also in high-income countries, with high rates of antenatal screening and availability of prenatal treatment. A multidisciplinary network must be guaranteed to the affected subjects, to ensure adequate care and improve the quality of life for patients and their families.

Adherence to secondary prevention of rheumatic fever and rheumatic heart disease in young people: an 11‐year retrospective study

Objectives:To evaluate the secondary prevention of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) in the Townsville region, Australia. Methods:Adherence to benzathine benzylpenicillin G (BPG) was determined for 196 children and young adults aged under 22 years between January 2009 and December 2019, and factors associated with BPG adherence were analysed. Secondary outcomes included attendance at specialist reviews and echocardiograms. Results:Adequate adherence (80%) to regular BPG injections was met by 51.1% of the cohort. Adequate BPG adherence more likely occurred for those that attended the Paediatric Outreach Clinic (OR4.15, 95%CI:2.13‐8.05) or a school delivery program (OR1.87, 95%CI:1.11‐3.45). People with moderate/severe RHD had greater BPG adherence (OR1.76,95%CI:1.00‐3.10). People in rural/remote areas were less likely to have adequate BPG adherence compared to urban counterparts (OR0.31, 95%CI:0.15‐0.65). Adherence to echocardiography was 66% and specialist review attendance was 12.5–50%. Conclusion:Half of the cohort in the Townsville region received adequate BPG prophylaxis to prevent ARF/RHD. Although rates were relatively higher than those reported in other Australian regions, health delivery goals should be close to 100%. Low attendance at specialist services was reported. Implication for public health:Delivery models with dedicated services, case management and family support could improve BPG adherence in individuals with ARF/RHD. Further resources in rural and remote areas are needed.

Congenital Infections: Priorities and Possibilities for Resource-limited Settings.

Congenital Infections: Priorities and Possibilities for Resource-limited Settings.

Roadmap to incorporating group A Streptococcus molecular point-of-care testing for remote Australia: a key activity to eliminate rheumatic heart disease.

Roadmap to incorporating group A Streptococcus molecular point-of-care testing for remote Australia: a key activity to eliminate rheumatic heart disease.

A Review on the Diagnosis and Treatment of Syphilis

Syphilis is a multi-phase sexually transmitted disease through contacting with a partner infected by syphilis or from a gravida to her newborn congenitally. The reappearance of syphilis is a severe public health concern, particularly because syphilis lesions would boost the chance of acquiring and spreading human immunodeficiency virus (HIV) infection. A dose of benzathine penicillin G (BPG) through intramuscular injection is the current treatment for syphilis, which is the optimal treatment for all stages of syphilis. Although some alternatives such as doxycycline and ceftriaxone are also evidently effective, the optimal therapy is still BPG, especially in latent syphilis and pregnancy. Because of the clinically significant azithromycin resistance, this second-line medication is no longer used routinely. Currently, macrolide resistance is the only antibiotic resistance with clinical evidence. Even though still no vaccine is published for syphilis, syphilis is a promising disease for vaccine development. The vaccine for syphilis is currently under research. This paper contained information about the pathological process, symptoms, diagnosis of syphilis, and effective treatment using antibiotics. The review also discussed future vaccine directions.

Therapeutics for rheumatic fever and rheumatic heart disease.

SUMMARYThe goals of acute rheumatic fever therapy are to relieve symptoms, mitigate cardiac valve damage and eradicate streptococcal infection. Preventing future recurrences requires long-term secondary antibiotic prophylaxis and ongoing prevention of Streptococcus pyogenes (group A streptococcus) infectionsThe recommended regimen for secondary prophylaxis comprises benzathine benzylpenicillin G intramuscular injections every four weeks. For patients with non-severe or immediate penicillin hypersensitivity, use erythromycin orally twice dailyThe goals of therapy for rheumatic heart disease are to prevent progression and optimise cardiac function. Secondary antibiotic prophylaxis can reduce the long-term severity of rheumatic heart diseasePatients with rheumatic heart disease, including those receiving benzathine benzylpenicillin G prophylaxis, should receive amoxicillin prophylaxis before undergoing high-risk dental or surgical procedures. If they have recently been treated with a course of penicillin or amoxicillin, or have immediate penicillin hypersensitivity, clindamycin is recommended

Population pharmacokinetic study of benzathine penicillin G administration in Indigenous children and young adults with rheumatic heart disease in the Northern Territory, Australia.

Benzathine penicillin G (BPG) is the cornerstone of secondary prophylaxis to prevent Streptococcus pyogenes infections, which precede acute rheumatic fever (ARF). The paucity of pharmacokinetic (PK) data from children and adolescents from populations at the highest risk of ARF and rheumatic heart disease (RHD) poses a challenge for determining the optimal dosing and frequency of injections and undermines efforts to develop improved regimens. We conducted a 6 month longitudinal PK study of young people receiving BPG for secondary prophylaxis. Throat and skin swabs were collected for microbiological culture along with dried blood spot (DBS) samples for penicillin concentrations. DBSs were assayed using LC-MS/MS. Penicillin concentration datasets were analysed using non-linear mixed-effects modelling and simulations performed using published BMI-for-age and weight-for-age data. Nineteen participants provided 75 throat swabs, 3 skin swabs and 216 penicillin samples. Throat cultures grew group C and G Streptococcus. Despite no participant maintaining penicillin concentration &gt;20 ng/mL between doses, there were no S. pyogenes throat infections and no ARF. The median (range) observed durations &gt;20 ng/mL for the low- and high-BMI groups were 14.5 (11.0-24.25) and 15.0 (7.5-18.25) days, respectively. Few patients at highest risk of ARF/RHD receiving BPG for secondary prophylaxis maintain penicillin concentrations above the target of 20 ng/mL beyond 2 weeks during each monthly dosing interval. These PK data suggest that some high-risk individuals may get inadequate protection from every 4 week dosing. Future research should explore this gap in knowledge and PK differences between different populations to inform future dosing schedules.

Investigating latent syphilis in HIV treatment-experienced Ethiopians and response to therapy.

We investigated people with HIV (PWH) receiving combination antiretroviral therapy (cART) for latent syphilis infection prevalence, risk factors, treatment response, and neurosyphilis. A prospective follow-up study was conducted on PWH and latent syphilis. The cases were randomly assigned to receive either benzathine penicillin G (BPG) or doxycycline (DOXY), and the posttreatment response was evaluated after 12 and 24 months. The traditional algorithm was used for serodiagnosis, and a semi-quantitative rapid plasma reagin (RPR) test monitored disease activity and treatment effectiveness. Of the 823 participants, 64.8% were women, and the mean age was 41.7±10 years. Thirty-one (3.8%) of the participants (22 males and nine females) had latent syphilis. The risk factors were male sex (aOR = 3.14), increasing age (aOR = 1.04 per year), and cART duration (aOR = 1.01 per month). Baseline RPR titers were: ≤1:4 in 19 (61.3%), between 1:8 and 1:32 in 10 (32.2%), and >1:32 in 2 (6.4%). None of the seven cerebrospinal fluid analyses supported a neurosyphilis diagnosis. In the 12th month of treatment, 27 (87.1%) had adequate serological responses, three (9.7%) had serological nonresponse, and one (3.2%) had treatment failure. Syphilis treatment was repeated in the last four cases with the alternative drug. In terms of adequate serologic response, both therapies were comparable at the 12th month, p = 0.37. All cases responded to treatment in the 24th month. In PWH receiving cART, latent syphilis occurred more in men than women, suggesting an investigation of sexual practices and the impact of antenatal syphilis screening. Syphilis disease activity reduces in the latent stage. Therefore, the routine cerebrospinal fluid analysis contributes little to the diagnosis of asymptomatic neurosyphilis and the treatment success of latent syphilis. DOXY is an alternative to BPG, and cART improves serologic response to latent syphilis treatment.

Evaluation of different bacterial honey isolates as probiotics and their efficient roles in cholesterol reduction

Continue to hypothesize that honey is a storehouse of beneficial bacteria, and the majority of these isolates are levansucrase producers. Accordingly, ten bacterial strains were isolated from different honey sources. Four honey isolates that had the highest levansucrase production and levan yield were identified by the partial sequencing of the 16S rRNA gene as Achromobacter sp. (10A), Bacillus paralicheniformis (2M), Bacillus subtilis (9A), and Bacillus paranthracis (13M). The cytotoxicity of the selected isolates showed negative blood hemolysis. Also, they are sensitive to the tested antibiotics (Amoxicillin + Flucloxacillin, Ampicillin, Gentamicin, Benzathine benzylpenicillin, Epicephin, Vancomycin, Amikacin, and Zinol). The isolates had strong alkaline stability (pHs 9, 11) and were resistant to severe acidic conditions (29–100 percent). The tested isolates recorded complete tolerance to both H2O2 and the bile salt (0.3% Oxgall powder) after 24 h incubation. The cell-free supernatant of the examined strains had antifungal activities against C. Albicans with varying degrees. Also, isolates 2M and 13M showed strong activities against S. aureus. The isolates showed strong adhesion and auto-aggregation capacity. Isolate 10A showed the highest antioxidant activity (91.45%) followed by 2M (47.37%). The isolates recorded different catalase and protease activity. All isolates produced cholesterol oxidase and lipase with different levels. Besides, the four isolates reduced LDL (low-density lipoprotein) to different significant values. The cholesterol-reducing ability varied not only for strains but also for the time of incubation. The previous results recommended these isolates be used safely in solving the LDL problem.

The treatment outcome and predictors of serological response in syphilis in a sexually transmitted infections center, China.

Serology is the mainstay for syphilis treatment monitoring. Baseline rapid plasma reagin (RPR) titre, HIV status, and syphilis stage have been found to be associated with the time to serological response among syphilis patients. This study mainly aims to evaluate the time to serological response, and to identify factors affecting the serological outcome. Medical records of syphilis cases diagnosed in Peking Union Medical College Hospital (PUMCH) between 2008 and 2018 were retrospectively reviewed. Kaplan-Meier analysis was performed to evaluate the median time to serologic response and cumulative probability of serologic response over time according to different variables. Cox regression model was conducted to find factors associated with serological response. There were 984 patients diagnosed with primary, secondary, or latent syphilis cases and receiving injections of benzathine penicillin G (BPG) as initial treatment at the Peking Union Medical College Hospital (PUMCH) between 2008 and 2018. Finally, data on 571 patients, including 49 (8.6%) primary syphilis, 261 (45.7%) secondary syphilis, and 261 (45.7%) latent syphilis, were used for analysis. It took longer time to achieve serological response for subjects aged ≥45years than younger individuals (89days versus 58days; p=0.008). Males achieved serological response more quickly than females (71days versus 83days; p = 0.011). There was a significant difference in the time to serological response according to different syphilis stages (p < 0.001), with 55days (95% CI, 43-67days) for primary, 57days (95% CI, 51-63days) for secondary, and 117days for latent syphilis. In addition, patients with lower baseline RPR titre had longer period to achieve serological response (252days [95% CI, 129-375days] for RPR titre ≤1:8, 78days [95% CI, 63-93days] for RPR titres from 1:16 to 1:32, and 53days [95% CI, 49-57days] for RPR titres ≥1:64, respectively; p<0.001). However, no significant difference in time to serological response to treatment was found according to HIV coinfection status. The result of multivariate Cox regression analysis showed that being older than 45years with latent syphilis, HIV coinfection, or with baseline RPR titre ≤1:8 was associated with slow response. Among patients followed for at least 1year or seroreverted, 128 (36.9%) had seroreverted within a year, and 219 (63.1%) still had a positive RPR after 1year. For multiple logistical regression, being female and HIV coinfection were significantly associated with the failure of seroreversion (OR, 0.42 [95% CI, 0.26-0.68]; p <0.001). This study revealed that younger age, higher initial RPR titre, early syphilis stage, and HIV-negative status were associated with faster serological cure. Female sex, individuals with HIV coinfection, and latent syphilis were significantly associated with the failure of seroreversion.

Penicillin Reactions in Patients With Severe Rheumatic Heart Disease: A Presidential Advisory From the American Heart Association.

Secondary antibiotic prophylaxis with regular intramuscular benzathine penicillin G (BPG) is the cornerstone of rheumatic heart disease management. However, there is a growing body of evidence that patients with rheumatic heart disease who have severe valvular heart disease with or without reduced ventricular function may be dying from cardiovascular compromise following BPG injections. This advisory responds to these concerns and is intended to: (1) raise awareness, (2) provide risk stratification, and (3) provide strategies for risk reduction. Based on available evidence and expert opinion, we have divided patients into low‐ and elevated‐risk groups, based on symptoms and the severity of underlying heart disease. Patients with elevated risk include those with severe mitral stenosis, aortic stenosis, and aortic insuffiency; those with decreased left ventricular systolic dysfunction; and those with no symptoms. For these patients, we believe the risk of adverse reaction to BPG, specifically cardiovascular compromise, may outweigh its theoretical benefit. For patients with elevated risk, we newly advise that oral prophylaxis should be strongly considered. In addition, we advocate for a multifaceted strategy for vasovagal risk reduction in all patients with rheumatic heart disease receiving BPG. As current guidelines recommend, all low‐risk patients without a history of penicillin allergy or anaphylaxis should continue to be prescribed BPG for secondary antibiotic prophylaxis. We publish this advisory in the hopes of saving lives and avoiding events that can have devastating effects on patient and clinician confidence in BPG.

Secondary Antibiotic Prophylaxis for Latent Rheumatic Heart Disease

BackgroundRheumatic heart disease affects more than 40.5 million people worldwide and results in 306,000 deaths annually. Echocardiographic screening detects rheumatic heart disease at an early, latent stage. Whether secondary antibiotic prophylaxis is effective in preventing progression of latent rheumatic heart disease is unknown.MethodsWe conducted a randomized, controlled trial of secondary antibiotic prophylaxis in Ugandan children and adolescents 5 to 17 years of age with latent rheumatic heart disease. Participants were randomly assigned to receive either injections of penicillin G benzathine (also known as benzathine benzylpenicillin) every 4 weeks for 2 years or no prophylaxis. All the participants underwent echocardiography at baseline and at 2 years after randomization. Changes from baseline were adjudicated by a panel whose members were unaware of the trial-group assignments. The primary outcome was echocardiographic progression of latent rheumatic heart disease at 2 years.ResultsAmong 102,200 children and adolescents who had screening echocardiograms, 3327 were initially assessed as having latent rheumatic heart disease, and 926 of the 3327 subsequently received a definitive diagnosis on the basis of confirmatory echocardiography and were determined to be eligible for the trial. Consent or assent for participation was provided for 916 persons, and all underwent randomization; 818 participants were included in the modified intention-to-treat analysis, and 799 (97.7%) completed the trial. A total of 3 participants (0.8%) in the prophylaxis group had echocardiographic progression at 2 years, as compared with 33 (8.2%) in the control group (risk difference, −7.5 percentage points; 95% confidence interval, −10.2 to −4.7; P<0.001). Two participants in the prophylaxis group had serious adverse events that were attributable to receipt of prophylaxis, including one episode of a mild anaphylactic reaction (representing <0.1% of all administered doses of prophylaxis).ConclusionsAmong children and adolescents 5 to 17 years of age with latent rheumatic heart disease, secondary antibiotic prophylaxis reduced the risk of disease progression at 2 years. Further research is needed before the implementation of population-level screening can be recommended. (Funded by the Thrasher Research Fund and others; GOAL ClinicalTrials.gov number, NCT03346525.)

Population Pharmacokinetic Study of Benzathine Penicillin G Administration in Indigenous Children and Young Adults With Rheumatic Heart Disease in the Northern Territory, Australia

Benzathine penicillin G (BPG) is the cornerstone of secondary prophylaxis to prevent Streptococcus pyogenes infections which precede acute rheumatic fever (ARF). The paucity of pharmacokinetic (PK) data from children and adolescents from populations at the highest risk of ARF and rheumatic heart disease poses a challenge for determining the optimal dosing and frequency of injections and undermines efforts to develop improved regimens.