Penicilina: da descoberta ao patenteamento do processo de produção em larga escala / Penicillin: from discovery to patenting the large-scale production process

Resumo A partir de pesquisa sobre a descoberta, a invenção e a inovação relacionadas à penicilina, por amostra de atividades de resolução de problemas tecnológicos rastreada pela distribuição, no período de 1929 a 1945, de trabalhos científicos, relatórios de governo, inovações e patentes, o artigo propõe uma reflexão sobre a importância do progresso científico para a segurança nacional. A análise destaca a trajetória tecnológica e os resultados na área de propriedade intelectual, considerando um fator importante a política implementada nos EUA para catalisar processos de inovação e oferecer condições institucionais para atender às demandas de defesa nacional, o que não significa necessariamente unicidade de solução em outros contextos.

Abstract This article examines discoveries, inventions, and innovations related to penicillin by sampling activities to solve technological problems which can be traced by the distribution of scientific articles, government reports, innovations, and patents between 1929 and 1945, and proposes reflection on the importance of scientific progress for national security. The analysis highlights the technological trajectory and outcomes in the area of intellectual property, considering US policy implemented to catalyze innovation and provide institutional conditions to meet national defense needs as an important factor, although this did not necessarily imply a unique solution in other contexts.

Antimicrobial resistance of Streptococcus uberis isolated from bovine mastitis: Systematic review and meta-analysis.

Streptococcus uberis is one of the most common pathogens associated with bovine mastitis, commonly treated with antimicrobials (AM), favoring the appearance of antimicrobial resistance (AMR). The objective of this work was to determine the proportion of phenotypic AMR among S. uberis isolated worldwide from bovine intramammary infections between the years 1983-2022, and to assess the variables associated by means of a systematic review and metanalysis. Sixty articles were eligible for quantitative review. Ninety-four independent studies were obtained. The antimicrobials evaluated in more S. uberis strains were penicillin (21,987 strains), oxacillin (21,727 strains), erythromycin (20,013 strains), and ampicillin (19,354 strains). Most of the studies included in this meta-analysis were from Europe (44), followed by America (25), Africa (10), Asia (10), and Oceania (5). Among the included articles, 22 were published from 1983 to 2006, 23 from 2007 to 2012, 25 from 2013 to 2015, and the remaining 24 after 2016. Penicillin, erythromycin, and tetracycline were the antimicrobials with >25 studies. Therefore, the following analyses were performed only for these antimicrobials, presenting a high heterogeneity index (I2). The variability observed for penicillin and tetracycline was only explained, partially, by continent of origin. The variability observed for erythromycin was not explained by any of the potential explanatory variables included in this study. The S. uberis proportion of resistance to antimicrobials is highly variable and probably influenced by many factors other than those studied in this meta-analysis, where it was not possible to inform a unique average proportion of resistance.

Evaluación de hábitos de medicación sistémica de odontólogos especialistas y no especialistas en endodoncia ante patologías pulpares en Argentina / Evaluation of systemic medication habits of specialists and non-specialists dentists in endodontists in relation to different pulp pathologies in Argentina

Objetivo: Determinar los hábitos de medicación sistémica de odontólogos especialistas y no especialistas en endodoncia ante diferentes patologías pulpares previos al tratamiento en- dodóntico en Argentina. Materiales y métodos: Se diseñó una encuesta para evaluar la prescripción de antibióticos, tipo de antibióticos, tiempo de prescripción, indicación de antinflamatorios no es- teroides y esteroides ante diferentes patologías pulpares. Se envió a 635 odontólogos especialistas y no especialistas en endodoncia a través de SurveyMonkey. Por medio de la prue- ba de Chi cuadrado se evaluaron las diferencias de medica- ción entre los grupos estudiados. Resultados: En pulpitis se medicó con antibióticos en el 3,48% de los casos y con antinflamatorios en un 62,60%. En necrosis pulpar sin fístula no se indicó ninguna medica- ción en un 64,47% de los casos, seguido de antibióticos en un 24,56%. En necrosis con fístula, el 52,38% no indicó nin- guna medicación, seguido de medicación con antibióticos en un 35,49%. En periodontitis apical aguda la principal medica- ción fue con antinflamatorios (52,79%), seguido de antibió- ticos (32,87%); y en el absceso alveolar agudo, un 57,10% indicó antibióticos seguido de antinflamatorios. El antibiótico de elección fue la penicilina en un 65,23% de los casos, y en caso de alergia a la misma, el antibiótico elegido fue azitromi- cina (30,12%). El tiempo de prescripción fue de 7 días. En la comparación entre especialistas y no especialistas hubo dife- rencias estadísticamente significativas para pulpitis y necrosis con fístula (p<0,01) y no las hubo entre necrosis sin fístula, periodontitis apical aguda y absceso alveolar agudo (p> 0,05). Conclusiones: La penicilina fue el antibiótico de elec- ción de la mayoría de los odontólogos argentinos encuestados junto al ibuprofeno como anti-inflamatorio. Existiría una so- bremedicación en patologías endodónticas que podría contri- buir a la resistencia microbiana a los antibióticos (AU)

Aim: Determine the systemic medication habits of den- tists specialists and non-specialists in endodontists in differ- ent pulp pathologies prior to root canal treatment in Argen- tina. Materials and methods: A survey was designed to evaluate the prescription of antibiotics, the type of antibiotics, prescription time, indication of non-steroidal anti-inflamma- tory drugs in different pulp pathologies. It was sent to 635 general dentists and endodontic specialists via SurveyMon- key. A Chi-square test was made to evaluate the differences in medication between the studied groups. Results: In pulpitis, antibiotics were prescribed in 3.48% of cases and anti-inflammatories in 62.60%. In pul- pal necrosis without fistula, no medication was indicated in 64.47% of cases, followed by antibiotics in 24.56%. In ne- crosis with fistula, 52.38% did not indicate any medication, followed by medication with antibiotics in 35.49%. In acute apical periodontitis the main medication was anti-inflamma-tories (52.79%), followed by antibiotics (32.87%); and for acute alveolar abscess, 57.10% indicated antibiotics, fol- lowed by anti-inflammatories. The antibiotic of choice was penicillin in 65.23% of the cases, and in case of allergy to it, the chosen antibiotic was azithromycin (30.12%). The prescription time was 7 days. In the comparison between specialists and non-specialists, there were significant dif- ferences for pulpitis and necrosis with fistula (p<0.01) and there were no significant differences between necrosis without fistula, acute apical periodontitis and acute alveo- lar abscess (p>0.05). Conclusions: Penicillin was the antibiotic of choice for the majority of the surveyed Argentine dentists, as well as ibuprofen as an anti-inflammatory drug. These could reflect an overmedication in endodontics pathologies that could con- tribute to microbial resistance to antibiotics (AU)

Antiangiogenic activity of the penicillin derivative TAP7f in melanoma.

Previously , we demonstrated that the non-antibiotic penicillin derivative TAP7f inhibited melanoma metastasis in vitro and in vivo through the downregulation of ß-catenin and integrin αVß3. As angiogenesis is required for tumor growth and metastasis, we decided to explore the possible antiangiogenic effect of TAP7f. We found that TAP7f inhibited proliferation, migration, tube formation, and actin cytoskeleton organization of human endothelial cells. In a gel plug assay, an in vivo model for angiogenesis, TAP7f also blocked vascular formation induced by fibroblast growth factor 2. Furthermore, when murine B16-F10 melanoma cells pre-treated with TAP7f were injected intradermally in mice, we observed a decrease in the number and thickness of the capillaries surrounding the tumor. Additionally, TAP7f downregulated vascular endothelial growth factor (VEGF) and platelet-derived growth factor-B (PDGF-B) expression in B16-F10 cells and VEGF receptor expression in HMEC-1 endothelial cells. When the antitumor effect of TAP7f was studied in C57BL/6 J mice challenged with B16-F10 melanoma cells, a significant reduction of tumor growth was observed. Furthermore, a decreased expression of VEGF, PDGF-B, and the endothelial cell marker CD34 was observed in tumors from TAP7f-treated mice. Together, our results suggest that the antiangiogenic activity of TAP7f contributes to its antitumor and antimetastatic action and positions this penicillin derivative as an alternative or complementary agent for the treatment of melanoma. KEY MESSAGES: • TAP7f inhibits proliferation, migration, tube formation, and actin cytoskeleton organization of endothelial cells. • TAP7f downregulates VEGF receptor expression in endothelial cells. • TAP7f downregulates VEGF and PDGF expression in melanoma cells. • TAP7f inhibits angiogenesis in vivo.

Evaluation of the follow-up of children treated for congenital syphilis in a municipality in the state of Espírito Santo, when it lacked crystalline penicillin / valiação do acompanhamento de crianças tratadas para sífilis congênita em município do estado do espírito santo em época de falta de penicilina cristalina

Introduction: Syphilis is a sexually transmitted infection caused by the bacterium Treponema pallidum. In Brazil, its incidence has increased, along with the lack of penicillin, the antibiotic of choice for congenital syphilis, from 2014 to 2017. During this period, children were treated with alternative drugs, but to date, data from the scientific literature do not recommend another antibiotic. Objective: To compare the progression, according to the established treatment, and evaluate the follow-up in health care facilities in Vila Velha (Espírito Santo) of children with congenital syphilis aged up to two years, born in Hospital Infantil e Maternidade Alzir Bernardino Alves ­ a reference in neonatology and low-risk pregnancy in the state at the time ­ from 2015 to 2016, when the hospital experienced a greater lack of penicillin. Methods: This is a retrospective cross-sectional observational study based on data from medical records of the hospital and other healthcare facilities in the city. We performed statistical analyses, per health district, of epidemiological and sociodemographic data, as well as those related to visits, their frequency, and clinical profile, according to the follow-up parameters proposed by the Ministry of Health at the time. Results: Medical records of 121 children were evaluated, presenting as the main findings: only 35% of the children completed the follow-up; among those treated with ceftriaxone, 55.2% completed the follow-up, and 100% of the children whose venereal disease research laboratory was greater than that of their mother at birth completed the follow-up. Of the symptomatic children at birth who remained or became symptomatic at follow-up, 58.8% used ceftriaxone. Conclusion: Among symptomatic children at birth, most of those treated with ceftriaxone remained symptomatic at follow-up. The Counseling and Testing Center was the most successful facility in the follow-up of these children. District 5 had the lowest success rate in the follow-up of these patients, and districts 1 and 2 showed the lowest rates of appropriate approach to congenital syphilis during follow-up. (AU)

Introdução: A sífilis é uma infecção sexualmente transmissível causada pela bactéria Treponema pallidum. No Brasil, sua incidência vem aumentando, acompanhada da falta de penicilina, antibiótico de escolha para a sífilis congênita, no período de 2014­2017. Nesse período, as crianças foram tratadas com medicamentos alternativos, porém dados da literatura científica até o momento não recomendam outro antibiótico. Objetivo: Comparar a evolução, de acordo com o tratamento instituído, e avaliar o acompanhamento nas unidades de saúde em Vila Velha (ES), até os dois anos de idade, das crianças com sífilis congênita nascidas no Hospital Infantil e Maternidade Alzir Bernardino Alves ­ referência em neonatologia e gravidez de baixo risco no estado na época ­ de 2015 a 2016, período em que houve maior falta de penicilina no hospital. Métodos: Estudo observacional do tipo transversal, retrospectivo, baseado em dados dos prontuários do hospital e outras Unidades de Saúde do município. Foram analisados estatisticamente, por região de saúde, dados epidemiológicos, sociodemográficos, bem como relativos às consultas, sua periodicidade e ao perfil clínico, de acordo com os parâmetros de seguimento propostos pelo Ministério da Saúde na época. Resultados: Avaliaram-se os prontuários de 121 crianças, obtendo-se como principais achados: somente 35% das crianças tiveram seguimento completo; das crianças tratadas com ceftriaxona, 55,2% tiveram seguimento completo, e 100% das crianças que tiveram VDRL maior que o da mãe no parto completaram o seguimento. Das crianças sintomáticas ao nascimento e que permaneceram ou ficaram sintomáticas no seguimento, 58,8% fizeram uso de ceftriaxona. Conclusão: Das crianças sintomáticas ao nascimento, as tratadas com ceftriaxona, em sua maioria, mantiveram-se sintomáticas no seguimento. O Centro de Testagem e Aconselhamento teve maior êxito no acompanhamento dessas crianças. A região 5 teve a menor taxa de êxito no seguimento desses pacientes, e as regiões 1 e 2 menor taxa de abordagem correta para sífilis congênita durante o seguimento. (AU)

Follow-up of infants with congenital syphilis during the penicillin shortage period.

OBJECTIVE: To analyze the follow-up, in specialized outpatient clinics, of infants reported with congenital syphilis during the penicillin shortage. METHOD: A cross-sectional study was carried out in ten public maternity hospitals affiliated with the Brazilian Unified Health System in the city of Fortaleza, state of Ceará. Clinical records of infants reported with congenital syphilis who were born alive in 2015 were used to describe correlates of attendance at recommended clinical follow-up appointments. RESULTS: A total of 469 infants reported with CS from January 1/2015 to December 31/2015 were included in the analysis. The results show that most infants did not attend the follow-up visits (368/469, 78.5%) and the main associated factors are that the follow-up clinic is located in a different hospital from that where the infant was born (OR: 3.7; CI: 2.20-6.22; p < 0.001) and the use of illicit drugs by the mother (OR: 3.2; CI: 1.57-6.87; p = 0.002). Only 33.7% (34/101) were followed until discharge. CONCLUSION: The majority of infants with reported congenital syphilis during this period did not attend the follow-up visits. Public health efforts aimed at reaching the parents of infants with CS should be a priority to ensure appropriate clinical identification and management of the associated outcomes of this vertically transmitted infection.

Pulmonary and thoracic infection by Fusobacterium nucleatum. / Infección pulmonar y torácica por Fusobacterium nucleatum.

INTRODUCTION: Fusobacterium nucleatum is an anaerobic bacillus that is part of the oral microbiota and dental pla que. This can cause local and potentially remote infections, which are exceptional in pediatrics. Ob jective: To present the case of a patient with lung injury with chest wall invasion by Fusobacterium nucleatum. CLINICAL CASE: An 11-year-old female immunocompetent patient who consulted due to a two-week history of cough, night sweats, without fever or weight loss, and increased volume at the left spleen thoracic level. There was no history of chest wall trauma or travel outside the country. Two weeks before the onset of symptoms, she was treated for dental caries. Imaging studies and CT scan showed left spleen pneumonia, which invades the pleura and the chest wall. A minimal thoracotomy was performed, releasing a thick, foul-smelling liquid. The studies for common germs and tubercu losis were negative. Hematology ruled out tumor lesions. The anaerobic study reported the develo pment of Fusobacterium nucleatum. The patient was treated with penicillin followed by amoxicillin presenting good clinical and radiological responses. The dental procedure was suspected as the cause of infection. CONCLUSIONS: Fusobacterium nucleatum can occasionally cause remote or extra-oral in fections in immunocompetent patients, such as pneumonia with chest wall invasion, therefore it is necessary to bear it in mind.

Treatment administered to newborns with congenital syphilis during a penicillin shortage in 2015, Fortaleza, Brazil.

BACKGROUND: Between 2014 and 2016, Brazil experienced a severe shortage in penicillin supply, resulting in a lack of treatment among some pregnant women and newborns with syphilis and the use of non-evidence-based regimens. This study evaluated all live births in Fortaleza reported with CS in 2015 in order to identify the different therapeutic regimens used in newborns during this period of penicillin shortage. METHODS: A retrospective cross-sectional study design was conducted using manually extracted data from medical chart review of maternal and infant cases delivered in 2015 from all public maternity hospitals in the city of Fortaleza. Data collection occurred from June 2017 to July 2018. RESULTS: A total of 575 congenital syphilis cases were reported to the municipality of Fortaleza during 2015 and 469 (81.5%) were analyzed. Of these, only 210 (44.8%) were treated with a nationally-recommended treatment. As alternative therapeutic options, ceftriaxone was used in 65 (13.8%), Cefazolin in 15 (3.2%) and the combination of more than one drug in 179 (38.2%). Newborns with serum VDRL titers ≥1:16 (p = 0.021), who had some clinical manifestation at birth (p = 0.003), who were born premature (p <  0.001), with low birth weight (p = 0.010), with jaundice indicative of the need for phototherapy (p = 0.019) and with hepatomegaly (p = 0.045) were more likely to be treated with penicillin according to national treatment guidelines compared to newborns treated with other regimens. CONCLUSION: During the period of shortage of penicillin in Fortaleza, less than half of the infants reported with CS were treated with a nationally-recommended regimen, the remaining received treatment with medications available in the hospital of birth including drugs that are not part of nationally or internationally-recommended treatment recommendations.

Prophylactic antibiotics for preventing pneumococcal infection in children with sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) is a group of inherited disorders that result in haemoglobin abnormalities and other complications. Injury to the spleen, among other factors, contribute to persons with SCD being particularly susceptible to infection. Infants and very young children are especially vulnerable. The 'Co-operative Study of Sickle Cell Disease' observed an incidence rate for pneumococcal septicaemia of 10 per 100 person-years in children under the age of three years. Vaccines, including customary pneumococcal vaccines, may be of limited use in this age group. Therefore, prophylactic penicillin regimens may be advisable for this population. This is an update of a Cochrane Review which was first published in 2002, and previously updated, most recently in 2017.  OBJECTIVES: To compare the effects of antibiotic prophylaxis against pneumococcus in children with SCD receiving antibiotic prophylaxis compared to those without in relation to: 1. incidence of Streptococcus pneumoniae infection; 2. mortality (as reported in the included studies); 3. drug-related adverse events (as reported in the included studies) to the individual and the community; 4. the impact of discontinuing at various ages on incidence of infection and mortality. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which is comprised of references identified from comprehensive electronic database searches and also two clinical trials registries: ClinicalTrials.gov and the WHO International Registry Platform (not in 2020 given access issues relating to Covid-19 pandemic). Additionally, we carried out hand searching of relevant journals and abstract books of conference proceedings. Date of the most recent search: 25 January 2021. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing prophylactic antibiotics to prevent pneumococcal infection in children with SCD with placebo, no treatment or a comparator drug. DATA COLLECTION AND ANALYSIS: The standard methodological procedures expected by Cochrane were used. Both authors independently extracted data and assessed trial quality. The authors used the GRADE criteria to assess the certainty of the evidence. MAIN RESULTS: Six trials were identified by the searches, of which three trials were eligible for inclusion. A total of 880 children, who were between three months to five years of age at randomization were included. The included studies were conducted in centres in the USA and in Kingston, Jamaica. In trials that investigated initiation of penicillin on risk of pneumococcal infection, the odds ratio was 0.37 (95% confidence interval 0.16 to 0.86) (two trials, 457 children) (low-certainty evidence), while for withdrawal the odds ratio was 0.49 (95% confidence interval 0.09 to 2.71) (one trial, 400 children) (low-certainty evidence). Adverse drug effects were rare and minor. Rates of pneumococcal infection were found to be relatively low in children over the age of five years. Overall, the certainty of the evidence for all outcomes was judged to be low. The results from the risk of bias assessment undertaken identified two domains in which the risk of bias was considered to be high, these were incomplete outcome data (attrition bias) (two trials) and allocation concealment (selection bias) (one trial). Domains considered to have a low risk of bias for all three trials were selective reporting (reporting bias) and blinding (performance and detection bias). AUTHORS' CONCLUSIONS: The evidence examined was determined to be of low certainty and suggests that prophylactic penicillin significantly reduces risk of pneumococcal infection in children with homozygous SCD, and is associated with minimal adverse reactions. Further research may help to determine the ideal age to safely withdraw penicillin.

Failure to recognize Low non-treponemal titer syphilis infections in pregnancy May lead to widespread under-treatment.

OBJECTIVES: Rates of maternal syphilis have increased five-fold in Brazil in the past decade. While penicillin remains the only appropriate treatment for maternal syphilis, we hypothesized that low non-treponemal titers (<1:16) may lead to reduced penicillin treatment in Brazil. METHODS: Using Brazilian Ministry of Health data on women diagnosed with maternal syphilis between January 1, 2010, and December 31, 2018, we conducted a random-effects logistic regression model with a cluster correction at the state level to evaluate predictive factors of penicillin treatment. RESULTS: We observed yearly increases in cases of pregnant women with syphilis from 2010 to 2018. There was significant variation by state: 52,451 cases were reported in São Paulo, followed by 26,838 in Rio de Janeiro. Among 215,937 cases of maternal syphilis, 91·3% received penicillin. In the random-effects model, a non-treponemal titer ≥1:16 was associated with 1·44 higher odds of receiving penicillin (95% confidence interval [CI]: 1·391·48), and prenatal care was associated with a 2·12 increased odds of receiving penicillin (95% CI: 2·022·21). Although there is an association between the absence of prenatal care and inadequate treatment for syphilis, 83·2% of women in this cohort who did not receive penicillin were engaged in prenatal care. CONCLUSIONS: Providers may inappropriately exclude low non-treponemal titers and thereby fail to use penicillin treatment in maternal syphilis. While the cause of the maternal syphilis epidemic in Brazil is multifactorial, we believe our findings can be used to develop targeted interventions throughout Brazil as well as shape public health initiatives globally.

A realidade da sífilis em gestantes: análise epidemiológica entre 2014 e 2018 / The reality of syphilis in pregnant women: epidemiological analysis between 2014 and 2018 / La realidad de la sífilis en gestantes: análisis epidemiológico entre 2014 y 2018

Objetivo: conhecer as gestantes com sífilis no estado de São Paulo, últimos cinco anos disponíveis. Método: estudo epidemiológico, quantitativo descritivo transversal, com dados secundários, com diagnósticos notificados (Sistema de Informação de Agravos de Notificação) - banco de dados do Departamento de Informática do Sistema Único de Saúde, das gestantes com sífilis, período 2014-2018. Resultados: encontrado 44.894 gestantes com sífilis no estado de SP, com crescimento importante nos dois últimos anos, maior prevalência (53,1%) na idade de 20-29 anos, raças brancas (43,1%), ensino fundamental completo (27,9%) e médio completo (26,1%). Maior percentual de diagnósticos realizado no primeiro trimestre (49,4%) e, 3,9% das gestantes não realizaram tratamento. Conclusão: é um agravo crescente, com baixa qualidade no preenchimento das fichas de notificação, prejudicando a assistência/qualidade do pré-natal, interferindo nas análises adequadas, afetando a tomada de decisão para tratamento correto. Resultados podem auxiliar em ações de educação em saúde e prevenção dos grupos vulneráveis.

Objective: to get to know pregnant women with syphilis in the state of São Paulo, the last five years available. Method: epidemiological, quantitative, descriptive cross-sectional study, with secondary data, with notified diagnoses (Information System for Notifiable Diseases) - database of the Department of Informatics of the Unified Health System, of pregnant women with syphilis, period 2014-2018. Results: found 44,894 pregnant women with syphilis in the state of SP, with significant growth in the last two years, higher prevalence (53.1%) at the age of 20-29 years, white races (43.1%), complete elementary school (27,9%) and complete high school (26.1%). Higher percentage of diagnoses performed in the first trimester (49.4%) and 3.9% of pregnant women did not undergo treatment. Conclusion: it is a growing problem, with low quality in filling out the notification forms, impairing the prenatal care / quality, interfering in the appropriate analyzes, affecting the decision-making for correct treatment. Results can assist in health education and prevention of vulnerable groups.

Objetivo: conocer mujeres embarazadas con sífilis en el estado de São Paulo, los últimos cinco años disponibles. Método: estudio epidemiológico, cuantitativo, descriptivo transversal, con datos secundarios, con diagnósticos notificados (Sistema de Información de Enfermedades Notificables) - base de datos del Departamento de Informática del Sistema Único de Salud, de gestantes con sífilis, período 2014-2018. Resultados: se encontraron 44.894 gestantes con sífilis en el estado de SP, con crecimiento significativo en los últimos dos años, mayor prevalencia (53,1%) en la edad de 20-29 años, razas blancas (43,1%), primaria completa (27 , 9%) y bachillerato completo (26,1%). Mayor porcentaje de diagnósticos realizados en el primer trimestre (49,4%) y 3,9% de gestantes no recibieron tratamiento. Conclusión: es un problema creciente, con baja calidad en el llenado de los formularios de notificación, perjudicando la calidad / atención prenatal, interfiriendo en los análisis adecuados, afectando la toma de decisiones para el correcto tratamiento. Los resultados pueden ayudar en la educación sanitaria y la prevención de grupos vulnerables.

Parâmetros morfofuncionais dos espermatozoides de catetos criopreservados com diferentes antimicrobianos / Morphofunctional parameters of collared peccary sperm frozen with different antimicrobials

The aim was to evaluate the effects of the addition of antimicrobials to the diluent for the cryopreservation of the semen of collectors, especially on the morphofunctional parameters. Ten ejaculates from adult males were obtained by electroejaculation. The samples were evaluated for volume, concentration, motility, morphology, membrane functionality, sperm viability, mitochondrial activity and binding capacity. Subsequently, they were cryopreserved in Tris with egg yolk (20%) and glycerol (3%) added or not (control) with gentamicin (70µg/mL), or with the penicillin (1000 IU/mL) + streptomycin (1mgE/mL). After one week, the samples were thawed and evaluated according to the fresh semen. As for the results, no significant differences were observed between the control treatment and those added with antimicrobials, emphasizing that these do not damage the sperm morphofunctional parameters during cryopreservation. In this sense, it is suggested that both gentamicin and the penicillin/streptomycin combination could be added to the extender for the cryopreservation of the collared peccary semen.

Sífilis materna no Sul do Brasil: epidemiologia e estratégias para melhorar / Maternal syphilis in Southern Brazil: epidemiology and improvement strategies

Objetivo: Este estudo teve como principal objetivo estimar a prevalência de sífilis gestacional e fatores associados à infecção em uma Maternidade no Sul do Brasil no ano de 2018. Métodos: Trata-se de estudo descritivo, transversal, retrospectivo, no qual foram avaliados os testes rápidos para sífilis de todas as gestantes internadas para atenção ao parto ou ao abortamento na Maternidade Carmela Dutra no ano de 2018. Nos casos confirmados de sífilis, foram obtidos dados epidemiológicos, adequação do tratamento, coinfecção pelo HIV e resultados gestacionais. Resultados: Entre os prontuários analisados, 161 (3,6%) foram considerados casos de sífilis materna. A média de idade das gestantes foi de 27,98 (±6,65), 54 (33,5%) eram primigestas, 114 (70,8%) se declararam brancas, 125 (77,5%) estavam em uma união estável e 85 (52,7%) tinham escolaridade até o ensino médio. Quanto ao tratamento, 71 (44%) trataram de maneira adequada e 90 (56%), de maneira inadequada, e 44 (27,3%) delas realizaram o diagnóstico apenas no momento da internação hospitalar. Entre as pacientes que realizaram tratamento inadequado de sífilis, 28 (53,4%) apresentaram títulos iguais ou superiores a 1:8. Entre as pacientes que realizaram teste rápido para HIV na internação, 5 (3,7%) apresentaram coinfecção com a doença. Com relação ao tratamento dos parceiros no pré-natal, 11,8% não realizaram nenhum tipo de tratamento, porém em 66 (41%) prontuários não constava essa informação. Com relação ao desfecho neonatal, 5 (7,4%) pacientes com tratamento inadequado para sífilis tiveram parto prematuro, 5 (7,4%) recém- -nascidos foram de baixo peso e 22 (24,5%) pacientes apresentaram abortamento da gestação. Conclusão: A alta taxa de tratamentos inadequados sugere falhas na assistência pré-natal e indica serem necessárias novas estratégias para reduzir a transmissão de sífilis na gestação.(AU)

Objective: The aim of this study is to estimate the prevalence of maternal syphilis and factors associated with the infection in Carmela Dutra Maternity in 2018. Methods: This is a descriptive, cross-sectional and retrospective study. All of the syphilis rapid- tests on pregnant women admitted for childbirth or miscarriage assistance at Carmela Dutra Maternity in 2018 were avaluated. In the cases of confirmed syphilis infection, the variables were epidemiological data, adequacy of treatment, HIV coinfection and gestational outcomes. Results: Out of all the medical records analyzed, 161 (3.6%) were considered maternal syphilis (MS). The average age of the pregnant women was 27.98 (± 6.65), 54 (33.5%) were primigestae, 114 (70.8%) declared themselves white, 125 (77.5%) were in a stable relationship and 85 (52.7%) had a high school education. Regarding treatment, 71 (44%) were treated adequately and 90 (56%) inadequately. Forty-four (27.3%) were diagnosed only at the time of hospitalization. Amongst patients who had inadequate syphilis treatment, 28 (53.4%) had titers equal to or greater than 1:8. Amongst patients who underwent rapid HIV testing during hospitalization, 5 (3.7%) had HIV coinfection. Regarding the partners treatment during prenatal, 11.8% did not receive any treatment, but 66 (41%) of the medical records did not contain this information. Regarding neonatal outcome, 5 (7.4%) of patients with inadequate treatment for syphilis had premature birth, 5 (7.4%) of newborns were underweight and 22 (24.5%) had miscarriages. Conclusion: The high rate of inadequate treatment suggests failure in prenatal care and indicates that new strategies are necessary to reduce syphilis transmission during pregnancy.(AU)

Neurosyphilis in Brazilian newborns: a health problem that could be avoided.

Syphilis is a public health problem, especially in pregnant women, due to the risk of transmission to the fetus and the involvement of the central nervous system, causing neurosyphilis. A case-control study was carried out to analyze the variables associated with neurosyphilis in Brazilian newborns of pregnant women with syphilis admitted for childbirth. Newborns were submitted to treponemal and non-treponemal tests, cerebrospinal fluid analysis, and long bone radiography. Newborns diagnosed with neurosyphilis and congenital syphilis were defined as cases and controls, respectively. The length of hospitalization and mean cost of neurosyphilis treatment were also evaluated. Twenty-one cases of newborns with neurosyphilis and 42 controls with congenital syphilis were included in the study. Out of 63 pregnant women with syphilis, 95.2% (60/63) received prenatal care, 74.6% (47/63) were diagnosed with syphilis during this period, 31.9% (15/47) underwent treponemic tests, 80.8% (38/47) were treated with penicillin and only 46.8% (22/47) of the partners received the treatment. Clinical complications such as low birth weight were observed in 12.7% (8/63) of the newborns. About 50.8% (32/63) of the newborns were hospitalized due to syphilis complications and each case of neurosyphilis spent at least US$ 881.48 on treatment and hospitalization. The results showed that the prenatal coverage is not sufficient to prevent neurosyphilis. The late diagnosis of syphilis in pregnant women and inadequate follow-up of sexual partners may favor the vertical transmission of T. pallidum in pregnant Brazilian women. Thus, improving the quality of health services is important for a more effective control of neurosyphilis.

Double Trouble: Challenges in the Diagnosis and Management of Ocular Syphilis in HIV-infected Individuals.

Syphilis and HIV infection may coexist in the same individual. Ocular syphilis and/or neurosyphilis may develop at any stage of coinfection, with a stronger association between ocular and neurosyphilis in individuals living with HIV, than in HIV-uninfected individuals. The diagnosis of ocular syphilis in HIV-infected and -uninfected patients remains with some controversy due to unspecific clinical manifestations and limited diagnostic tests. Penicillin is the mainstay of treatment of ocular syphilis, but alternative options are warranted. This review describes the epidemiology, pathophysiology, and clinical manifestations, as well as the diagnostic and therapeutic challenges posed by ocular syphilis against the background of HIV coinfection.

Sífilis, la gran simuladora / 8 SYPHILIS, THE GREAT SIMULATOR. Case report of a patient with syphilitic uveitis

La sífilis desde hace siglos desafía a la humanidad, es transmitida por vía sexual y verticalmente durante la gestación.9 Esta enfermedad se hizo conocida en Europa a finales del siglo XV,13 y su rápida propagación por todo el continente la transformó en una de las principales plagas mundiales.Era preocupante el crecimiento de la endemia sifilítica en el siglo XIX 13.1. En contrapartida la medicina se desarrollaba, y la síntesis de las primeras drogas se hacía realidad. El mayor impacto tal vez fue la introducción de la penicilina en 1946, la cual por su eficacia hizo a muchos pensar que la enfermedad estaba controlada. En un estudio de revisión de literatura se dice que a raíz de la introducción de la penicilina la incidencia de sífilis (y de uveítis sifilítica) fue disminuyendo constantemente hasta finales de los años 90.3 resultando en la disminución del interés por su estudio y control. Con la aparición del síndrome de inmunodeficiencia adquirida (SIDA).2 se incrementó dramáticamente la evolución de esta enfermedad.En la literatura oftalmológica se comenzaron a documentar cada vez más casos e incluso se ha llegado a hablar de la «nueva epidemia de sífilis ocular¼1 Se estima que, anualmente, unos 357 millones de personas contraen alguna de las cuatro infecciones de transmisión sexual (ITS) siguientes: clamidias, gonorrea, sífilis o tricomoniasis.7 En el mundo hay una incidencia anual de aproximadamente 12 millones de pacientes con sífilis el 90% ocurre en países en desarrollo (OMS).

Syphilis has defied humanity for centuries, is transmitted sexually and vertically during pregnancy. This disease became known in Europe at the end of the 15th century,13 and its rapid spread throughout the continent transformed it into one of the main world plagues. The growth of the syphilitic endemic in the 19th century was worrisome.13.1 In contrast, medicine developed, and the synthesis of the first drugs became a reality. Perhaps the biggest impact was the introduction of penicillin in 1946, which, due to its effectiveness, led many to believe that the disease was controlled. In a literature review study, it is said that following the introduction of penicillin the incidence of syphilis (and syphilitic uveitis) was steadily decreasing until the end of the 90s.3 resultando in the decrease of interest in its study and control. With the onset of acquired immunodeficiency syndrome (AIDS). the evolution of this disease increased dramatically. In the ophthalmological literature, more and more cases have been documented and there has even been talk of the "new epidemic of ocular syphilis".1.1 It is estimated that some 357 million people each year get one of the four sexually transmitted infections (STIs) following: chlamydia, gonorrhea, syphilis or trichomonas's. In the world there is an annual incidence of approximately 12 million patients with syphilis 90% occurs in developing countries (WHO)

A comparison of different antibiotic regimens for the treatment of infective endocarditis.

BACKGROUND: Infective endocarditis is a microbial infection of the endocardial surface of the heart. Antibiotics are the cornerstone of treatment, but due to the differences in presentation, populations affected, and the wide variety of micro-organisms that can be responsible, their use is not standardised. This is an update of a review previously published in 2016. OBJECTIVES: To assess the existing evidence about the clinical benefits and harms of different antibiotics regimens used to treat people with infective endocarditis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase Classic and Embase, LILACS, CINAHL, and the Conference Proceedings Citation Index - Science on 6 January 2020. We also searched three trials registers and handsearched the reference lists of included papers. We applied no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) assessing the effects of antibiotic regimens for treating definitive infective endocarditis diagnosed according to modified Duke's criteria. We considered all-cause mortality, cure rates, and adverse events as the primary outcomes. We excluded people with possible infective endocarditis and pregnant women. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, 'Risk of bias' assessment, and data extraction in duplicate. We constructed 'Summary of findings' tables and used GRADE methodology to assess the quality of the evidence. We described the included studies narratively. MAIN RESULTS: Six small RCTs involving 1143 allocated/632 analysed participants met the inclusion criteria of this first update. The included trials had a high risk of bias. Three trials were sponsored by drug companies. Due to heterogeneity in outcome definitions and different antibiotics used data could not be pooled. The included trials compared miscellaneous antibiotic schedules having uncertain effects for all of the prespecified outcomes in this review. Evidence was either low or very low quality due to high risk of bias and very low number of events and small sample size. The results for all-cause mortality were as follows: one trial compared quinolone (levofloxacin) plus standard treatment (antistaphylococcal penicillin (cloxacillin or dicloxacillin), aminoglycoside (tobramycin or netilmicin), and rifampicin) versus standard treatment alone and reported 8/31 (26%) with levofloxacin plus standard treatment versus 9/39 (23%) with standard treatment alone; risk ratio (RR) 1.12, 95% confidence interval (CI) 0.49 to 2.56. One trial compared fosfomycin plus imipenem 3/4 (75%) versus vancomycin 0/4 (0%) (RR 7.00, 95% CI 0.47 to 103.27), and one trial compared partial oral treatment 7/201 (3.5%) versus conventional intravenous treatment 13/199 (6.53%) (RR 0.53, 95% CI 0.22 to 1.31). The results for rates of cure with or without surgery were as follows: one trial compared daptomycin versus low-dose gentamicin plus an antistaphylococcal penicillin (nafcillin, oxacillin, or flucloxacillin) or vancomycin and reported 9/28 (32.1%) with daptomycin versus 9/25 (36%) with low-dose gentamicin plus antistaphylococcal penicillin or vancomycin; RR 0.89, 95% CI 0.42 to 1.89. One trial compared glycopeptide (vancomycin or teicoplanin) plus gentamicin with cloxacillin plus gentamicin (13/23 (56%) versus 11/11 (100%); RR 0.59, 95% CI 0.40 to 0.85). One trial compared ceftriaxone plus gentamicin versus ceftriaxone alone (15/34 (44%) versus 21/33 (64%); RR 0.69, 95% CI 0.44 to 1.10), and one trial compared fosfomycin plus imipenem versus vancomycin (1/4 (25%) versus 2/4 (50%); RR 0.50, 95% CI 0.07 to 3.55). The included trials reported adverse events, the need for cardiac surgical interventions, and rates of uncontrolled infection, congestive heart failure, relapse of endocarditis, and septic emboli, and found no conclusive differences between groups (very low-quality evidence). No trials assessed quality of life. AUTHORS' CONCLUSIONS: This first update confirms the findings of the original version of the review. Limited and low to very low-quality evidence suggests that the comparative effects of different antibiotic regimens in terms of cure rates or other relevant clinical outcomes are uncertain. The conclusions of this updated Cochrane Review were based on few RCTs with a high risk of bias. Accordingly, current evidence does not support or reject any regimen of antibiotic therapy for the treatment of infective endocarditis.

Importancia del dentista y del equipo auxiliar de salud bucal en el proceso de diagnóstico de sífilis / Importance of the dentist and the auxiliary oral health team in the diagnosis of syphilis

ABSTRACT Introduction: Syphilis is classified as a sexually transmitted infectious-contagious disease with the causative agent Treponema pallidum (Tp). It presents distinct stages of evolution: The primary phase is characterized by the appearance of the hard chancre, the secondary phase by the spread of Tp through the bloodstream and systemic involvement, and the tertiary phase by organ infection and nervous system impairment. In congenital syphilis, the Tp is transmitted vertically from mother to child. Objective: Report a case in which the dental team participated in the diagnosis of syphilis. Case presentation: A male 26-year-old patient with leukoderma, HIV-positive and under regular antiretroviral treatment, with no other chronic systemic changes and no previous history of Tp infection, was referred for evaluation by the oral health team. The patient reported having had bisexual relations in recent months with a condom and orogenital contact without a condom. He had not noticed any type of "wound" on the body. Intraoral examination found multiple reddish macules scattered on the lingual dorsum, with a slight detachment and little pain. The quick test was a reagent for syphilis. The patient was referred for evaluation at the medical clinic. Treatment started by two applications of benzyl penicillin with a 7 days' separation between them. Complementary blood tests were also indicated, with special attention to VDRL, which eventually confirmed the Tp infection. Conclusions: Participation of the oral health team in the diagnosis of syphilis constitutes a complementary force for the improvement of health care processes(AU)

RESUMEN Introducción: La sífilis se clasifica como una enfermedad contagiosa infecciosa de transmisión sexual, con el agente causal Treponema pallidum (Tp). Presenta distintos estadios de evolución: la fase primaria caracterizada por la aparición del chancre duro; la fase secundaria, la diseminación de la Tp a través del torrente sanguíneo y la afectación sistémica; y la fase terciaria, en que hay infección de órganos y deterioro del sistema nervioso, además de sífilis congénita, forma esta en la que Tp es transmitida verticalmente por la mujer embarazada. Objetivo: Informar sobre un caso en el que la participación del equipo dental colaboró ​​en el proceso de diagnóstico de la sífilis. Presentación del caso: Paciente con 26 años de edad, leucodermia, VIH positivo y en tratamiento antirretroviral regular, sin otros cambios crónicos a nivel sistémico y sin antecedentes de infección por Tp. Se remitió para evaluación con el equipo de salud oral. Informó haber tenido relaciones bisexuales en los últimos meses con un condón y contacto orogenital sin condón. No notó ningún tipo de "herida" en el cuerpo. En el examen intrabucal, se encontraron múltiples máculas rojizas dispersas en el dorso lingual, con un ligero desprendimiento y con poco dolor. La prueba rápida fue un reactivo para sífilis. El paciente fue remitido para su evaluación a clínica médica. Comenzó el tratamiento con dos aplicaciones de penicilina bencilo, con un intervalo de 7 días y se solicitó análisis de sangre complementarios, con especial atención al VDRL, que posteriormente confirmó la infección por Tp. Conclusiones: La participación del equipo de salud bucal frente al diagnóstico de la sífilis, se constituye como una fuerza complementaria para la mejora de los procesos en salud(AU)