Effects of crystalline penicillin G sodium on human T-cells differentiation.

BACKGROUND: Although antibiotics are well-known for their anti-bacterial effects, their inaugurated immunomodulatory roles in chronic inflammatory diseases have not elucidated yet. Anecdotal reports support the beneficial effects of parenteral penicillin in arthritis suggesting an immunomodulatory other than antibacterial effects for penicillin. The present study was designed to address the possible effects of penicillin G sodium (PCN-G) on different T-helper cells differentiation. MATERIALS AND METHODS: In this experimental study, peripheral blood mononuclear cells (PBMCs) of 10 healthy donors were isolated using Ficoll density gradient. The stimulated PBMCs by anti-CD3, anti-CD28, and anti-CD69 were cultured in the presence of 120 µg/ml of PCN-G. Foxp3, T-bet, RORγT, GATA3 as well as interferon-gamma (IFN-γ) and interleukin (IL)-17A mRNA in stimulated cells were measured by the real-time polymerase chain reaction. Mann-Whitney U-test was used for determining differences between the medium of gene expression levels of stimulated cell population and unstimulated cells by PCN. Correlations between the related genes were determined using the Spearman test. RESULTS: Based on the results, T-bet gene expression levels were similar in stimulated cells by PCN G after 24 and 48 h while significant reduction was observed after 72 incubation with PCN G (difference = 3; 0.09-0.34; P = 0.031). Meanwhile, treated cells with PCN G expressed decreased levels of IFN-γ (difference = 8.0; 0.49-1.07; P = 0.001) and IL-17A (difference = 2.2; 0.05-0.75; P ≤ 0.05) genes comparing to unstimulated cell by PCN-G. GATA3 genes expression levels downregulated by PCN G after 72 h of incubation by PBMCs (difference = 1.1; 0.77-0.88; P = 0.035). CONCLUSION: Our results confirmed the immunomodulatory role of PCN G by affecting the expression of different cytokines genes in PBMCs.

Azithromycin vs penicillin G benzathine for early syphilis: A meta-analysis of randomized controlled trials.

Syphilis is a very serious infection that causes acute cutaneous manifestations. Penicillin is the gold standard for treating syphilis. This meta-analysis was conducted based on self-published randomized controlled trials (RCTs) data to compare the efficacy of azithromycin with penicillin for treating syphilis. RCTs on azithromycin vs penicillin for the treatment of syphilis were retrieved from the Cochrane Library, MEDLINE, EBSCO, Embase, Ovid, and other databases, and the estimated risk ratio (RR) and 95% confidence interval (CI) were used to study the following outcome indicators: 3-month response rate, 6-month response rate, 12-month response rate, recurrence rate, serum fixation rate, and failure rate. This meta-analysis included seven RCTs involving 639 subjects (of whom 335 were treated with azithromycin and 304 were treated with penicillin). There was no significant difference in the 3-month response rate (RR = 0.97, 95% CI: 0.79-1.19), 6-month response rate (RR = 1.01, 95% CI: 0.85-1.20), 12-month response rate (RR = 1.02, 95% CI: 0.97-1.09), serum fixation rate (RR = 0.71, 95% CI: 0.24-2.12), and failure rate (RR = 0.62, 95% CI: 0.33-1.16). In summary, there is no evidence in the literature that azithromycin is less effective than penicillin for treating syphilis.

Availability of Injectable Antimicrobial Drugs for Gonorrhea and Syphilis, United States, 2016.

We estimated the availability of the injectable antimicrobial drugs recommended for point-of-care treatment of gonorrhea and syphilis among US physicians who evaluated patients with sexually transmitted infections in 2016. Most physicians did not have these drugs available on-site. Further research is needed to determine the reasons for the unavailability of these drugs.

Chemoprophylaxis against group A streptococcus during military training.

Chemoprophylaxis with intramuscular benzathine penicillin G has been used widely by the U.S. military to prevent epidemics of group A streptococcus infections during basic training. The recent global shortage of benzathine penicillin prompted a detailed analysis of this issue in 2017 by military preventive medicine and infectious disease authorities in San Antonio, Texas, and San Diego, California, USA. This paper explores the history of group A streptococcus and chemoprophylaxis in the U.S. military training environment, current policy and practice, and challenges associated with widespread chemoprophylaxis. In light of the history presented, preventive medicine authorities at basic training centers should be extremely cautious about discontinuing benzathine penicillin chemoprophylaxis.

Tolerability of IM penicillin G benzathine diluted or not with local anesthetics, or different gauge needles for syphilis treatment: a randomized clinical trial.

BACKGROUND: Penicillin G Benzathine (PGB) is the cornerstone of syphilis treatment. However, its intramuscular (IM) administration is associated with pain at the site of injection. The dilution of PGB with local anesthetics is recommended in some guidelines, but the evidence that supports it, particularly in adults and in HIV infection, is scarce. Preliminary clinical experience also suggests that the IM administration of PGB through increased needle gauges might improve its tolerability. The aim of the study to identify less painful ways of administering IM PGB in the treatment of syphilis in adults. METHODS: Multicenter, randomized, double-blinded clinical trial in patients diagnosed with primary syphilis that required a single IM injection of PGB 2400,00 IU. Patients were randomized to receive PGB diluted with 0.5 mL mepivacaine 1% (MV) or PGB alone, and both groups either with a long 19G or short 21G IM needle. The primary objective was the effect on local pain immediately after the administration through a visual scale questionnaire on pain (0 to 10). RESULTS: One hundred eight patients were included, 27 in each group. Ninety-four (94.4%) were male, and 41.7% were also HIV-infected. Mean age 36.6 years (SD 11). Significant differences in immediate pain intensity were observed when comparing the long 19G group with anesthesia (mean pain intensity, [MPI] 2.92 [CI 95% 1.08-4.07]) vs long 19G without anesthesia (MPI 5.56 [CI 95% 4.39-6.73), p < 0.001; and also between short 21G group with anesthesia (MPI 3.36 [CI 95% 2.22-4.50]) vs short 21G without anesthesia (MPI 5.06 [CI 95% 3.93-6.19]), p = 0.015). No significant differences in immediate pain were observed between 19G and 21G in the presence or absence of anesthesia (p = 1.0 in both cases). No differences were found between study arms after 6 and 24 h. CONCLUSIONS: The IM administration of 1% mepivacaine-diluted PGB induces significantly less immediate local pain as compared to PGB alone. The needle gauge did not have any effect on the pain. Based on these results, we suggest anesthetic-diluted IM PGB as the standard treatment for primary syphilis. TRIAL REGISTRATION: EudraCT 2014-003969-24 (Date of registration 18/09/2014).

[Supply disruptions and drug shortages: the example of benzathine benzylpenicillin]. / Tensions d'approvisionnement et ruptures de stock des médicaments : l'exemple de la benzathine benzylpénicilline.

Supply disruptions and drug shortages : the example of benzathine benzylpenicillin. Despite collective mobilisation, drug shortages have increased in recent years, creating a strong impact on public health. Anti-infective drugs, mainly injectable antibiotics, are particularly affected by these shortages. Although the causes of these ruptures are multiple, they are mainly related to the effects of globalisation and industrial strategies of rationalisation of production costs. The shortage of benzathine benzylpenicillin illustrates the action of the French Medicines Agency (ANSM), and the various actors to guarantee access to care and limit the consequences for the patient. Beyond measures taken at national level by the regulatory authorities in connection with the pharmaceutical companies, it is necessary to set up a concerted action at European level to fight effectively against drug shortages.

Tensions d'approvisionnement et ruptures de stock des médicaments : l'exemple de la benzathine benzylpénicilline. Malgré une mobilisation collective, les ruptures de stock des médicaments se sont multipliées ces dernières années, créant un fort retentissement en matière de santé publique. Les médicaments anti-infectieux, principalement les antibiotiques injectables, sont particulièrement impactés par ces pénuries. Bien que les causes de ces ruptures soient multiples, elles sont principalement liées aux effets de la mondialisation et des stratégies industrielles de rationalisation des coûts de production. La rupture de la benzathine benzylpénicilline illustre l'action de l'Agence nationale de sécurité du médicament et des produits de santé et des différents acteurs pour garantir l'accès aux soins et limiter les conséquences pour le patient. Au-delà des mesures prises au plan national par les autorités sanitaires en lien avec les laboratoires pharmaceutiques, il est nécessaire de mettre en place une action concertée au niveau européen pour lutter efficacement contre les pénuries de médicaments.

Evaluation of Combined Strategy to Reduce the Pain of Penicillin G Benzathine Injection in Primary Syphilis.

Background: Intramuscular (IM) injection of penicillin G Benzathine (PGB) is widely recognized as the primary treatment for patients at all stages of syphilis. However, the discomfort and induration associated with PGB injections are often a challenge for patients. While lidocaine is already known to reduce injection pain and is standard practice in some countries, the added value of combining lidocaine with the z-track technique has not been thoroughly investigated. This study aims to observe the use of combining lidocaine with the Z-track technique in the treatment of syphilis, and to explore less painful methods of administering IM PGB for the treatment of syphilis in adult patients. Methods: 32 syphilis patients requiring penicillin treatment were injected with 1.2 million units of penicillin on both sides of the buttocks. The left side was injected using the traditional method with 0.9% saline as the solvent (control Group), while the right side was injected using a "z" injection method with 0.2% lidocaine as the solvent (experimental Group). The success rate of the single injection, the intensity and duration of the post-injection pain and the induration reaction were observed and recorded. Results: There was no statistically significant difference in single injection success rate and immediate post injection pain score between the two sides (P>0.05). However, the right side had a lower pain score at 30 minutes post injection and fewer induration reactions, showing a statistically significant difference between the two sides (P<0.05). Chi-squared analysis showed that age, gender and BMI had no significant effect on pain scores 30 minutes after injection in either the control or intervention groups. (P>0.05). Conclusion: The lidocaine + Z-track penicillin method can reduce delayed pain and induration reactions in patients with syphilis, and provides an additional approach to improving patient comfort beyond the standard use of lidocaine alone. This method merits clinical promotion.

The effect of benzylpenicillin prohylaxis after birth on length and weight of syphilis-exposed infants in eastern China.

BACKGROUND: We conducted this study to assess the impact of an intervention to interrupt mother-to-child transmission on the height and weight of syphilis-exposed infants after receiving penicillin prophylaxis after birth and to provide a scientific basis for further elimination of mother-to-child transmission. METHODS: We recruited 419 infants born to syphilis-infected mothers from 2015 to 2020 in Changzhou, and performed 1:1 matching to infants born to syphilis-free mothers during the same period. All infants were followed up to 18 months of age. We collected height and weight data and compared them. RESULTS: At 18 months of age, the height and weight of the syphilis-exposed infants were almost greater than the WHO reference standards. However, when compared with local unexposed infants, there were almost no differences. The boys born to mothers who received two courses of treatment had longer body lengths at 18 months of age than did those born to mothers who did not receive two courses of treatment, and the girls born to mothers who did not receive treatment had lower body weights at 3 months of age than did both treated groups. CONCLUSION: The growth trajectory of infants without congenital syphilis born to syphilis-infected mothers is virtually indistinguishable from that of the general local population. Syphilis-exposed newborns can receive preventive treatment as a public health intervention.

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.

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.

Adherence to Secondary Prophylaxis for Acute Rheumatic Fever and Rheumatic Heart Disease: A Systematic Review.

BACKGROUND: Optimal delivery of regular benzathine penicillin G (BPG) injections prescribed as secondary prophylaxis for acute rheumatic fever (ARF) and rheumatic heart disease (RHD) is vital to preventing disease morbidity and cardiac sequelae in affected pediatric and young adult populations. However, poor uptake of secondary prophylaxis remains a significant challenge to ARF/RHD control programs. OBJECTIVE: In order to facilitate better understanding of this challenge and thereby identify means to improve service delivery, this systematic literature review explored rates of adherence and factors associated with adherence to secondary prophylaxis for ARF and RHD worldwide. METHODS: MEDLINE was searched for relevant primary studies published in the English language from 1994-2014, and a search of reference lists of eligible articles was performed. The methodological quality of included studies was evaluated using a modified assessment tool. RESULTS: Twenty studies were included in the review. There was a range of adherence to varying regimens of secondary prophylaxis reported globally, and a number of patient demographic, clinical, socio-cultural and health care service delivery factors associated with adherence to secondary prophylaxis were identified. CONCLUSION: Insights into factors associated with lower and higher adherence to secondary prophylaxis may be utilized to facilitate improved delivery of secondary prophylaxis for ARF and RHD. Strategies may include ensuring an effective active recall system, providing holistic care, involving community health workers and delivering ARF/RHD health education.

Congenital syphilis confirmed by pcr as a result of treatment failure for syphilis in pregnancy. case report

ABSTRACT Introduction: Congenital syphilis is a major public health problem, and early diagnosis and treatment are necessary to prevent it. Penicillin G benzathine is the treatment of choice in pregnant women; however, it may fail to prevent fetal infection, as in the present case. Case presentation: Male newborn, son of an HIV negative mother with gestational syphilis (venereal disease research laboratory (VDRL) 1:4 dilution, positive treponemal test) diagnosed at week 21 of gestation and treated with three doses of 2 400 000 IU of penicillin G benzathine. At delivery, the mother presented VDRL 1:1 dilution. The newborn was diagnosed with congenital syphilis due to VDRL 1:4 dilution, positive treponemal test, elevated aspartate aminotransferases, hypos-thenuria, proteinuria, hematuria, and leukocyturia that resolved after treatment with crystalline penicillin for 10 days. The molecular testing in blood showed a high treponemal load. The VDRL test at 3 months was non-reactive. Conclusions: Preventing congenital syphilis with the recommended treatment for gestational syphilis may fail. Moreover, diagnosing this condition in an asymptomatic newborn is difficult. Therefore, clinical and serological tests are recommended to confirm whether maternal treatment was effective in the fetus.

RESUMEN Introducción. La sífilis congénita es un importante problema de salud pública y para prevenirla es necesario diagnosticar y tratar la sífilis gestacional de forma temprana. En el presente caso la gestante recibió el tratamiento de elección (penicilina benzatínica), pero este no previno la infección fetal. Presentación del caso. Recién nacido masculino, hijo de una madre con serología negativa para el virus de la inmunodeficiencia humana y positiva para sífilis gestacional diagnosticada en la semana 21 (prueba VDRL con dilución 1:4 y prueba treponémica rápida positiva) y tratada con tres dosis de 2 400 000 UI de penicilina benzatínica. En el parto, la madre presentó VDRL con dilución 1:1 y el recién nacido fue diagnosticado con sífilis congénita por presentar VDRL con dilución 1:4, prueba treponémica rápida positiva, niveles de aspartato aminotransferasa elevados, hipostenuria, proteinuria, hematuria y leucocituria, condiciones que se resolvieron luego de recibir tratamiento con penicilina cristalina durante 10 días. El estudio molecular en sangre realizado al momento del nacimiento evidenció una alta presencia de Treponema pallidum. La prueba VDRL a los 3 meses fue no reactiva. Conclusiones. Prevenir la sífilis congénita con el tratamiento recomendado para sífilis gestacional puede fallar, además, diagnosticar sífilis congénita en un recién nacido asintomático es difícil, por lo cual se recomienda hacer un seguimiento clínico y serológico para confirmar si el tratamiento materno fue efectivo en el feto.

Who was affected by the shortage of penicillin for syphilis in Rio de Janeiro, 2013-2017? / A quem afetou o desabastecimento de penicilina para sífilis no Rio de Janeiro, 2013-2017?

ABSTRACT OBJECTIVE To analyze the shortage of benzathine penicillin G (BPG), characterizing its temporal evolution and spatial distribution in the city of Rio de Janeiro from 2013 to 2017. METHODS This ecological study used gestational and congenital syphilis notifications, BPG distribution records, and sociodemographic data from the population of Rio de Janeiro. To quantify the shortage, a BPG supply indicator was estimated per quarter for each neighborhood between 2013 and 2017. Thematic maps were created to identify areas and periods with greater BPG shortage, described according to sociodemographic factors, health services network, and epidemiological features in the incidence of syphilis. RESULTS BPG shortage in Rio de Janeiro from 2013 to 2017 was not homogeneous in space nor in time. The temporal evolution and spatial distribution of BPG scarcity shows that the shortage affected the inhabitants of the municipality in different ways. Shortage was lower in 2013 and 2016 and more severe in 2014, 2015, and 2017, particularly in neighborhoods within the programmatic areas PA3 and PA5, poorer and with higher prevalence rates of gestational and congenital syphilis. CONCLUSIONS Analyzing BPG shortage and its temporal evolution and spatial distribution in Rio de Janeiro allowed us to realize that the inhabitants are affected in different ways. Understanding this process contributes to the planning of actions to face shortage crises, minimizing possible impacts on the management of syphilis and reducing inequality in access to treatment.

RESUMO OBJETIVO Analisar o desabastecimento da penicilina benzatina (PB), caracterizando sua evolução temporal e distribuição espacial no município do Rio de Janeiro de 2013 a 2017. MÉTODOS Trata-se de estudo ecológico misto realizado com notificações de sífilis gestacional e congênita, registros de distribuição de PB e de dados sociodemográficos da população dos bairros do município do Rio de Janeiro. Para mensurar o desabastecimento foi calculado por trimestre um indicador de abastecimento de PB para cada bairro, entre 2013 e 2017. Mapas temáticos foram produzidos para identificar áreas e períodos com maior desabastecimento de PB, o qual foi descrito segundo condições sociodemográficas, rede de serviços de saúde e aspectos epidemiológicos da incidência de sífilis por bairro. RESULTADOS O desabastecimento de PB no município do Rio de Janeiro, no período de 2013 a 2017, não foi homogêneo no espaço ou no tempo. A evolução temporal e a distribuição espacial da escassez de PB revelam que o desabastecimento afetou de formas distintas os habitantes do município, sendo menor em 2013 e 2016 e mais intenso em 2014, 2015 e 2017, principalmente nos bairros das áreas programáticas AP3 e AP5, mais pobres e com maiores taxas de sífilis gestacional e congênita. CONCLUSÕES Analisar o desabastecimento de PB e sua evolução temporal e distribuição espacial no município do Rio de Janeiro permitiu reconhecer que os habitantes do município são afetados de diferentes modos. Compreender esse processo ajuda a planejar ações para enfrentar crises de desabastecimento, minimizando possíveis impactos no controle da sífilis, além de reduzir a desigualdade no acesso ao tratamento.