The antiinflammatory and electrophysiological effects of fingolimod on penicillin-induced rats / Os efeitos antiinflamatórios e eletrofisiológicos do fingolimode em ratos induzidos pela penicilina

Abstract Background The fact that inflammation triggers epileptic seizures brings to mind the antiepileptic properties of anti-inflammatory drugs. Objective To investigate the electrophysiological and anti-inflammatory effects of fingolimod on an experimental penicillin-induced acute epileptic seizure model in rats. Methods Thirty-two male Wistar rats were divided into four groups: control (penicillin), positive control (penicillin + diazepam [5 mg/kg]), drug (penicillin + fingolimod [0.3 mg/kg]) and synergy group (penicillin + diazepam + fingolimod). The animals were anesthetized with urethane, and epileptiform activity was induced by intracortical injection of penicillin (500,000 IU). After electrophysiological recording for 125 minutes, IL-1β, TNF-α, and IL-6 were evaluated by ELISA in the serum of sacrificed animals. Results During the experiment, animal deaths occurred in the synergy group due to the synergistic negative chronotropic effect of diazepam and fingolimod. Although not statistically significant, fingolimod caused a slight decrease in spike-wave activity and spike amplitudes in the acute seizure model induced by penicillin (p > 0.05). Fingolimod decreased serum IL-1β (p < 0.05); fingolimod and diazepam together reduced IL-6 (p < 0.05), but no change was observed in serum TNF-α values. Conclusion Even in acute use, the spike-wave and amplitude values of fingolimod decrease with diazepam, anticonvulsant and anti-inflammatory effects of fingolimod will be more prominent in chronic applications and central tissue evaluations. In addition, concomitant use of fingolimod and diazepam is considered to be contraindicated due to the synergistic negative inotropic effect.

Resumo Antecedentes O fato de a inflamação desencadear crises epilépticas traz à mente as propriedades antiepilépticas dos anti-inflamatórios. Objetivo Investigar os efeitos eletrofisiológicos e anti-inflamatórios do fingolimode em um modelo experimental de crise epiléptica aguda induzida por penicilina em ratos. Métodos Trinta e dois ratos Wistar machos foram divididos em quatro grupos: controle (penicilina), controle positivo (penicilina + diazepam [5 mg/kg]), droga (penicilina + fingolimode [0,3 mg/kg]) e grupo sinergia (penicilina + diazepam + fingolimode). Os animais foram anestesiados com uretano, e a atividade epileptiforme foi induzida por injeção intracortical de penicilina (500.000 UI). Após registro eletrofisiológico por 125 minutos, IL-1β, TNF-α e IL-6 foram avaliados por ELISA no soro dos animais sacrificados. Resultados Durante o experimento, ocorreram mortes de animais no grupo sinérgico devido ao efeito cronotrópico negativo sinérgico do diazepam e do fingolimode. Embora não seja estatisticamente significativo, o fingolimode causou uma ligeira diminuição na atividade pico-onda e nas amplitudes pico no modelo de convulsão aguda induzida pela penicilina (p > 0,05). O fingolimode diminuiu a IL-1β sérica (p < 0,05); fingolimode e diazepam juntos reduziram a IL-6 (p < 0,05), mas não foi observada alteração nos valores séricos de TNF-α. Conclusão Pensa-se que o efeito anticonvulsivante leve de uma dose única de fingolimode será mais proeminente em aplicações crônicas e em avaliações de tecidos centrais. Além disso, o uso concomitante de fingolimode e diazepam é considerado contraindicado devido ao efeito inotrópico negativo sinérgico.

Cost utility of penicillin use in primary care for the prevention of complications associated with syphilis / Custo-utilidade do uso da penicilina na atenção primária para a prevenção de complicações associadas à sífilis congênita

Introduction: Despite penicillin being the drug of choice for the treatment of syphilis, many pregnant women who test positive for syphilis do not receive the drug as recommended by the Ministry of Health, contributing to the increase in costs associated with congenital syphilis. Objective: This study aims to estimate the incremental cost-effectiveness ratio of administering at least one dose of 2.4 million IU of benzathine penicillin in the first trimester of pregnancy as soon as the result of a positive rapid treponemal test performed during antenatal care in primary care units of the Brazilian National Health System. Methods: An analytical model was proposed based on a decision tree. The perspective of the analysis was the one used in The Brazilian National Health System. The clinical outcomes were abortion, prematurity, neonatal death, stillbirth, and congenital syphilis, estimated in terms of disability-adjusted life-years. Only direct costs were considered. Deterministic and probabilistic sensitivity analyses were performed. Results: The model predicted that the most efficient strategy is the one that includes the administration of penicillin in primary care for cases of gestational syphilis. This strategy is more effective, although more costly. The cost per disability-adjusted life-years averted with the use of this strategy was estimated at R$49.79 (US$ 10.67). Conclusion: The prenatal strategy in primary care units that includes the administration of penicillin to pregnant women with syphilis during the first trimester of pregnancy has the greatest potential to be cost-effective.

Introdução: A despeito de a penicilina ser o medicamento de escolha para o tratamento da sífilis, muitas gestantes com teste positivo para sífilis não recebem o medicamento como recomendado pelo Ministério da Saúde, concorrendo para o aumento dos custos associados à sífilis congênita. Objetivo: Estimar a razão de custo-efetividade incremental da administração de pelo menos uma dose de 2,4 milhões de Unidades Internacionais de penicilina benzatina no primeiro trimestre de gravidez, tão logo se tenha o resultado de um teste rápido treponêmico positivo realizado na consulta pré-natal em unidades de atenção primária do Sistema Único de Saúde. Métodos: Um modelo analítico foi proposto a partir de uma árvore de decisão. A perspectiva da análise foi a do Sistema Único de Saúde. Os desfechos em saúde foram aborto, prematuridade, morte neonatal, natimorto e sífilis congênita, estimados em termos de anos de vida ajustados a incapacidades (disability-adjusted life-years). Apenas os custos diretos foram considerados. Análises de sensibilidade determinística e probabilística foram realizadas. Resultados: O modelo previu que a estratégia mais eficiente é aquela que inclui a administração da penicilina na atenção primária aos casos de sífilis gestacional. Embora essa estratégia possa representar maior custo, apresenta maior efetividade. O custo por disability-adjusted life-years evitado com o uso dessa estratégia foi estimado em R$49,79. Conclusão: A estratégia de pré-natal nas unidades de atenção primária que inclui a administração da penicilina em gestantes com sífilis ainda no primeiro trimestre de gestação é a que apresenta o maior potencial para ser custo-efetiva.

Discussion on the dimerization reaction of penicillin antibiotics / 药物分析学报

Penicillins are one type of the most important antibiotics used in the clinic.Control of drug impurity profiles is an important part of ensuring drug safety.This is particularly important in penicillins where polymerization can lead to polymers as elicitors of passive cutaneous anaphylaxis.The current under-standing of penicillin polymerization is based on reactions with amino groups,but no comprehensive mechanistic understanding has been reported.Here,we used theoretical calculations and column switching-LC/MS techniques to study penicillin dimerization.Ampicillin and benzylpenicillin were selected as representative penicillins with or without amino groups in the side chain,respectively.We identified four pathways by which this may occur and the energy barrier graphs of each reaction process were given.For benzylpenicillin without an amino group in the 6-side chain,dimerization mode A is the dominant mode,where the 2-carboxyl group of one molecule reacts with the β-lactam of another molecule.However,ampicillin with an amino group in the 6-side chain favors dimerization mode C,where the amino group of one molecule attacks the β-lactam of another molecule.These findings can lead to a polymer control approach to maintaining penicillin antibiotics in an active formulation.

Reatividade cruzada entre betalactâmicos: uma abordagem prática / Cross-reactivity among beta-lactams: a practical approach

Os betalactâmicos são a classe de drogas que mais causam reações de hipersensibilidade envolvendo um mecanismo imunológico específico, e são os principais desencadeantes entre os antimicrobianos. São representados pelas penicilinas, cefalosporinas, carbapenêmicos, monobactâmicos e inibidores da betalactamase. A estrutura química básica destes fármacos consiste na presença dos seguintes componentes: anel betalactâmico, anel adjacente e cadeias laterais, sendo todos potenciais epítopos. Os anticorpos da classe IgE e linfócitos T estão frequentemente envolvidos no reconhecimento desses epítopos. A reatividade cruzada depende da estabilidade dos produtos intermediários (determinantes antigênicos) derivados da degradação dos anéis betalactâmicos, anéis adicionais e da semelhança estrutural das cadeias laterais entre as drogas. Classicamente acreditava-se num grande potencial de reatividade cruzada dentro de cada classe e até entre as classes, mas estudos da última década mostraram que indivíduos alérgicos à penicilina (com testes cutâneos positivos) reagiam às cefalosporinas em aproximadamente 3% dos casos, aos carbapenêmicos em cerca de 1%, e praticamente não reagiam aos monobactâmicos. Essa reatividade ou tolerância parece estar vinculada ao grau de similaridade entre as cadeias laterais desses antibióticos. Nesta revisão, ressaltamos a importância da investigação sistematizada na confirmação ou exclusão de alergia aos betalactâmicos, descrevemos a prevalência da reatividade cruzada entre estes fármacos e sugerimos um algoritmo de abordagem desses pacientes baseados em sua estrutura química e nos dados publicados na literatura.

Beta-lactams are the drugs most commonly involved in hypersensitivity reactions mediated by a specific immune mechanism and are the main triggers among antibiotics. They include penicillins, cephalosporins, carbapenems, monobactams and beta-lactam inhibitors. The basic chemical structure of these drugs consist on the presence of the following components: betalactam ring, an adjacent ring and side chains, all of which are potential epitopes. IgE antibodies and T lymphocytes are often involved in recognizing those epitopes. Cross-reactivity depends on the stability of intermediate products (antigenic determinants) derived from the degradation of the beta-lactam ring, on the adjacent rings, and on the structural similarity of the side chains between drugs. Classically, it was believed that there was a great potential for cross-reactivity within each class and even between classes, but studies from the last decade showed that individuals allergic to penicillin (with positive skin tests) reacted to cephalosporins in approximately 3% of cases, to carbapenems in about 1%, and rarely reacted to monobactams. This reactivity or tolerance seems to be linked to the degree of similarity between the side chains of these antibiotics. In this review, we emphasize the importance of systematic investigation to confirm or exclude allergy to beta-lactams, we describe the prevalence of crossreactivity between these drugs and we suggest an algorithm for approaching these patients based on their chemical structure and on data published in the literature.

Historia de la penicilina: más allá de los héroes, una construcción social / History of penicillin: Beyond heroes, a social construction

RESUMEN El hecho científico conocido como "penicilina" se ha considerado tradicionalmente como el producto del ingenio de Alexander Fleming, ganador del Premio Nobel por descubrir esta "droga milagrosa". Apartándose de esta idea popular, se hace necesario resaltar el desarrollo de la penicilina como un constructo social, producto del trabajo invaluable de varios científicos, sumado a un contexto social excepcional que motivó la voluntad política y el apoyo de la industria farmacéutica; en ausencia de cualquiera de estos, la penicilina no sería lo que significa hoy para nosotros o, simplemente, no existiría en el arsenal terapéutico. Los conceptos epistemológicos de "estilo de pensamiento" y "colectivo de pensamiento" como fundamentos en la construcción del conocimiento, presentes en la obra epistemológica de Ludwick Fleck, apoyan la conclusión, a partir del recuento histórico, de la necesidad de apartarnos de la penicilina como el producto de un descubrimiento de un único héroe, para verla como una construcción social, que además es un ejemplo clásico de serendipia. La penicilina, además, tiene otras facetas menos conocidas históricamente como el uso de ella de manera cruda, producida y usada por médicos generales, o la búsqueda de información para su producción durante la segunda guerra mundial; estas se abordan en este breve recuento histórico.

SUMMARY The scientific breakthroug we know as "penicillin", has been traditionally considered as the result of the genius of Alexander Fleming, awarded with the Nobel Prize for the discovery of the "miracle drug". Standing aside from this popular idea, it is important to highlight the development of penicillin as a social construct and the product of the invaluable work of several scientists, in addition to an exceptional social framework that raised the political desire and the pharmaceutical industry support; without any of these, penicillin wouldn't even have the meaning it has today, or it wouldn't even exist. The epistemological concepts of "style of thinking" and "collectivity of thought" as basis in the construction of knowledge, present in Ludwick Fleck's epistemological work, support the conclusion, based the historical account, about the need of standing aside from the idea of penicillin as the discovery of a single hero, and considering it a social construction instead, and a classical example of serendipity. Other aspects less known about penicillin history, such as the use of crude penicillin by general practitioners, or the seeking of information about how to produce it during World War II, which are addressed in this brief historical account.

Allergy to penicillin and betalactam antibiotics / Alergia a penicilina e antibióticos beta-lactâmicos

ABSTRACT Betalactams are the most frequent cause of hypersensitivity reactions to drugs mediated by a specific immune mechanism. Immediate reactions occur within 1 to 6 hours after betalactam administration, and are generally IgE-mediated. They clinically translate into urticaria, angioedema and anaphylaxis. Non-immediate or delayed reactions occur after 1 hour of administration. These are the most common reactions and are usually mediated by T cells. The most frequent type is the maculopapular or morbilliform exanthematous eruption. Most individuals who report allergies to penicillin and betalactams can tolerate this group of antibiotics. To make diagnosis, a detailed medical history is essential to verify whether it was an immediate or non-immediate reaction. Thereafter, in vivo and/or in vitro tests for investigation may be performed. The challenging test is considered the gold standard method for diagnosis of betalactam hypersensitivity. The first approach when suspecting a reaction to betalactam is to discontinue exposure to the drug, and the only specific treatment is desensitization, which has very precise indications. The misdiagnosis of penicillin allergy affects the health system, since the "penicillin allergy" label is associated with increased bacterial resistance, higher rate of therapeutic failure, prolonged hospitalizations, readmissions, and increased costs. Thus, it is essential to develop strategies to assist the prescription of antibiotics in patients identified with a label of "betalactam allergy" at hospitals, and to enhance education of patients and their caregivers, as well as of non-specialist physicians.

RESUMO Os beta-lactâmicos constituem a causa mais frequente de reações de hipersensibilidade a fármacos mediadas por mecanismo imunológico específico. As reações imediatas ocorrem em 1 até 6 horas após a administração do beta-lactâmico, sendo geralmente IgE-mediadas. Elas se traduzem clinicamente por urticária, angioedema e anafilaxia. As reações não imediatas ou tardias ocorrem após 1 hora da administração. São as reações mais comuns, sendo geralmente mediadas por células T. O tipo mais frequente é o exantema maculopapular ou morbiliforme. A maioria dos indivíduos que refere alergia aos beta-lactâmicos pode tolerar esse grupo de antibióticos. No diagnóstico, uma história clínica detalhada é fundamental para verificar se a reação foi do tipo imediato ou não imediato. A partir daí, podem ser realizados testes in vivo e/ou in vitro para investigação. O teste de provocação é considerado o método padrão-ouro no diagnóstico de hipersensibilidade aos beta-lactâmicos. A primeira conduta diante da suspeita de uma reação ao beta-lactâmico é suspender a exposição ao medicamento, e o único tratamento específico é a dessensibilização, que possui indicações bem precisas. O diagnóstico equivocado de alergia à penicilina afeta o sistema de saúde, pois o rótulo de "alergia à penicilina" está associado a aumento da resistência bacteriana, maior índice de falha terapêutica, hospitalizações prolongadas, readmissões e aumento dos custos. Assim, torna-se fundamental elaborar estratégias com o objetivo de auxiliar na prescrição de antibióticos em pacientes com rótulo de "alergia aos beta-lactâmicos" nos hospitais e melhorar a educação dos pacientes e seus responsáveis, além de médicos não especialistas.

Penicillin desensitization in allergic pregnant women with syphilis. Report of two cases / Desensibilización a penicilina en mujeres embarazadas alérgicas. Informe de dos casos

ABSTRACT Syphilis during pregnancy has a high risk of congenital transmission with disastrous fetal consequences. Penicillin (PNC) is the only effective antimicrobial for the treatment of pregnant women with syphilis. Chilean guidelines do not consider desensitization to PNC in these women. We report two cases of pregnant women aged 32 and 23 years, with immediate allergy to PNC and syphilis who were safely and successfully desensitized using a four-hour intravenous protocol in the critical care unit and who subsequently received benzathine G PNC. An electronic survey was conducted among approximately 100 Clinical Pharmacists (CP) in the country. Of these, 16 answered and 13 reported having experience in drug desensitization, in at least five cases with PNC and none reported deaths or cardiorespiratory arrest. Desensitization to PNC can be carried out safely and in Chile, this alternative should be incorporated to the management of pregnant women with syphilis and immediate allergy to PNC, instead of using erythromycin.

La sífilis durante el embarazo tiene un alto riesgo de transmisión congénita con consecuencias desastrosas para el feto. La penicilina (PNC) es el único compuesto efectivo para el tratamiento de sífilis en una mujer embarazada.. En Chile, ante alergias de tipo inmediata, no se considera la desensibilización a la PNC en mujeres embarazadas por norma ministerial. Se comunican dos casos de mujeres embarazadas con alergia tipo inmediata y sífilis durante la gestación que fueron desensibilizadas a este compuesto con un protocolo endovenoso de 4 horas en la unidad de pacientes críticos, sin observar complicaciones, recibiendo posteriormente PNC G Benzatina. Se efectuó una encuesta electrónica a farmacéuticos clínicos del país que incluyó más de 100 profesionales. De ellos, 16 contestaron y 13 declararon poseer experiencia en desensibilización de fármacos, en al menos cinco casos con PNC y ninguno reportó muertes o paro cardiorrespiratorio. La desensibilización a PNC puede ser efectuada en forma segura en embarazadas con alergia de tipo inmediata a PNC que cursan con sífilis. En Chile se debería incorporar esta alternativa en el manejo de mujeres embarazadas con sífilis y alergia inmediata a PNC en lugar de solo considerar por norma el uso de eritromicina.

Diagnóstico e tratamento da síndrome do choque tóxico estreptocócico em unidade de terapia intensiva pediátrica: relato de caso / Diagnosis and treatment of streptococcal toxic shock syndrome in the pediatric intensive care unit: a case report

RESUMO Dentre as infecções causadas por Streptococcus β hemolyticus do grupo A de Lancefield, talvez a síndrome do choque tóxico seja a mais grave, com alto índice de mortalidade. A semelhança clínica com outras formas de choque, principalmente séptico, pode, muitas vezes, confundir o avaliador e interferir na escolha da terapêutica mais adequada. Esse relato tem o objetivo de auxiliar seus leitores quanto à necessidade de adicionar tal síndrome como diagnóstico diferencial, frente a quadros de choque, principalmente aqueles que não apresentam manifestações clínicas bem definidas. Para isso, apresentamos o quadro de um lactente com sintomas gripais comuns, que evoluiu rapidamente com exantema, rebaixamento do nível de consciência, sinais clínicos e laboratoriais de choque, com necessidade de suporte intensivo. Além de culturas indicando o agente etiológico, o aparecimento de exantema e fasciíte necrosante levou ao diagnóstico, mas, em menos de 50% dos casos temos sinais clínicos clássicos dessa entidade. As penicilinas em terapia combinada com aminoglicosídeos ainda são a terapia de escolha e possuem alto nível de evidência. Apesar da gravidade a evolução foi satisfatória.

ABSTRACT Among the infections caused by Streptococcus β hemolyticus from the Lancefield serogroup A, toxic shock syndrome is perhaps the most severe, and its mortality rate is high. Its clinical similarity to other forms of shock, especially septic shock, can often confuse the evaluator and interfere with the selection of the most appropriate therapy. This report aims to inform readers of the need to add this syndrome as a differential diagnosis in cases of shock, especially those with no well-defined clinical manifestations. For this purpose, we present the case of an infant with common flu-like symptoms who progressed rapidly with a rash, a reduced level of consciousness and clinical and laboratory signs of shock that required intensive support. In addition to cultures indicating the etiological agent, the appearance of exanthema and necrotizing fasciitis led to the diagnosis. However, less than 50% of cases present classic clinical signs of this entity. Penicillins combined with aminoglycosides are still the therapy of choice and are supported by a high level of evidence. Despite the severity of this patient's presentation, the progression was satisfactory.

The effect of vortioxetine on penicillin-induced epileptiform activity in rats / O efeito da vortioxetina sobre a atividade epileptiforme induzida pela penicilina em ratos

ABSTRACT Vortioxetine is a multimodal antidepressant agent that modulates 5-HT receptors and inhibits the serotonin transporter. It is indicated especially in cases of major depressive disorder related to cognitive dysfunction. There are many studies investigating the effects of antidepressants on the seizure threshold and short-term epileptic activity. However, the effect of vortioxetine on epileptic seizures is not exactly known. Our aim was to investigate the effects of vortioxetine on penicillin-induced epileptiform activity. Twenty-seven Wistar rats were divided into three groups: sham-control group, positive control group (diazepam), and vortioxetine group. After a penicillin-induced epilepsy model was formed in each of the three groups of animals, 0.1 ml of saline was administered to the control group, 0.1 ml (10 mg/kg) vortioxetine was administered in the vortioxetine group, and 0.1 mL (5 mg/kg) of diazepam was administered in the positive control group, intraperitoneally. The epileptic activity records were obtained for 120 minutes after the onset of seizure. There was no significant difference in spike wave activity between the vortioxetine and diazepam groups, whereas this was significantly reduced in the vortioxetine group compared with the controls. The administration of vortioxetine at a dose of 10 mg/kg immediately after the seizure induction significantly decreased the spike frequencies of epileptiform activity compared with the control group. No significant difference was found between the vortioxetine and positive controls. This study showed that vortioxetine reduces the number of acutely-induced epileptic discharges. Vortioxetine may be an important alternative for epileptic patients with major depressive disorder-related cognitive dysfunction.

RESUMO A vortioxetina é um agente antidepressivo multimodal que modula os receptores 5HT e inibe o transportador de serotonina. Está indicada, principalmente nos casos de transtorno depressivo maior (TDM), relacionado à disfunção cognitiva. Existem muitos estudos que investigam os efeitos dos antidepressivos no limiar convulsivo e na atividade epiléptica de curto prazo. No entanto, o efeito da vortioxetina nas crises epilépticas não é exatamente conhecido. Nosso objetivo é investigar os efeitos da vortioxetina sobre a atividade epileptiforme induzida pela penicilina. Vinte e sete ratos Wistar foram divididos em três grupos, grupo controle-sham, grupo controle positivo (Diazepam) e grupo vortioxetina. Depois, 0,1 mg (10 mg / kg) de vortioxetina foi administrado no grupo vortioxetina, e 0,1 ml (5 mg / kg) / kg) de diazepam foi administrado no grupo de controle positivo intraperitonealmente. Os registros de atividade epiléptica foram obtidos durante 120 minutos após o início da convulsão. Não houve diferença significativa na atividade de pico entre o grupo de voritoxetina e diazepam, embora tenha sido significativamente reduzida no grupo de vortioxetina em comparação com os controles. A administração de vortioxetina na dose de 10 mg / kg imediatamente após a indução das convulsões diminuiu significativamente as frequências de espícula da atividade epileptiforme em comparação com o grupo controle. Nenhuma diferença significativa foi encontrada entre a vortioxetina e controles positivos. Este estudo mostrou que a vortioxetina reduz o número de descargas epilépticas agudamente induzidas. A vortioxetina pode ser uma alternativa importante para pacientes epilépticos com disfunção cognitiva relacionada à TDM.

Drug utilization patterns of antibiotics in outpatient department of educare dental hospital at Malappuram, Kerala, India

Background: Drug utilization studies aims to evaluate factors related to the prescribing, dispensing, administering and taking of medication, and its associated events. Antibiotic prescription by dental practitioners has an important impact on the rate of general antibiotic prescription use, and an attempt has been made to establish a surveillance system for the monitoring and control of the use of these drugs.Methods: Retrospective record-based study was conducted at outpatient department at Educare Dental College and Hospital, Chattipparamba, Malappuram, Kerala. About 2802 prescriptions were screened, drugs prescribed were noted, tabulated and analysed.Results: Total no. of prescriptions 2802, total no. of antibiotics prescribed 2916, average no of antibiotics per prescription 1.04. Out of antibiotics prescribed 72% were monotherapy and 28% were fixed dose combination. Among antibiotics beta lactam antibiotics were commonly prescribed followed by nitroimidazoles and macrolides.Conclusions: The study was conducted to analyze the drug utilization pattern in outpatient department at dental hospital. Most of prescription were rational, both monotherapy and polypharmacy were practiced. Safer drug with less adverse effect profile were considered. Among the antibiotic amoxicillin was the commonest.

Sífilis ocular en una población Colombiana: manifestaciones clínicas y resultados del tratamiento / Ocular syphilis in a Colombian population: clinical manifestations and treatment outcomes

Diseño de estudio: Retrospectivo observacional descriptivo. Método: Se recolectaron datos de pacientes con sífilis ocular evaluados en un centro de referencia de oftalmología en Colombia desde marzo de 2015 hasta febrero de 2017. Resultados: Dieciséis pacientes fueron diagnosticados con sífilis ocular durante el período estudiado. Cuatro (25%) pacientes tuvieron afectación de ambos ojos, para un total de 20 ojos. Hubo 11 (68.8%) hombres y 5 (31.3%) mujeres. La edad media de presentación fue de 51.1 años (23-86 años). Cuatro pacientes masculinos estaban coinfectados con VIH. La manifestación más frecuente fue la panuveítis en ocho ojos (40%). Seis pacientes (37.5%) presentaron hallazgos dermatológicos sistémicos. El tratamiento incluyó penicilina cristalina y esteroides sistémicos. El seguimiento medio fue de 16.2 meses (12-21 meses). La agudeza visual media mejoró de 1,01 ± 0,71 logMAR a 0,58 ± 0,64 logMAR después del tratamiento. Conclusión: La sífilis es una causa poco común de infl amación intraocular. Sin embargo, la incidencia ha venido en aumento en los últimos años tanto en pacientes VIH positivo como VIH negativo. La panuveítis es el hallazgo ocular más frecuente. El pronóstico visual es bueno si hay un diagnóstico y tratamiento temprano.

Background: Syphilis is a sexually transmitted disease caused by Treponema pallidum. It can remain dormant in the individual throughout life. The manifestations of ocular involvement are similar to other infl ammatory eye conditions. It is crucial to make an early diagnosis and management in order to avoid complication. Objective: to describe the clinical characteristics and the results of the treatment of patients with ocular syphilis. Study design: observational retrospective study. Method: Retrospective cohort of patients with ocular syphilis evaluated in an ophthalmology reference center in Colombia from March 2015 to February 2017. Results: Sixteen patients were diagnosed with ocular syphilis during the studied period. Four (25%) patients had involvement of both eyes, for a total of 20 eyes. There were 11 (68.8%) men and 5 (31.3%) women. The mean age of presentation was 51.1 years (23-86 years). Four male patients were coinfected with HIV. Th e most frequent manifestation was panuveitis in eight eyes (40%). Six patients (37.5%) presented systemic dermatological fi ndings. Treatment included crystalline penicillin and systemic steroids. The mean follow-up was 16.2 months (12-21 months). The mean visual acuity improved from 1.01 ± 0.71 logMAR to 0.58 ± 0.64 logMAR after treatment. Conclusion: Syphilis is a rare cause of intraocular inflammation. However, the incidence has been increasing in recent years in both HIV positive and HIV negative patients. Panuveitis is the most frequent ocular finding. The visual prognosis is good if there is an early diagnosis and treatment.

Oral desensitization to penicillin for the treatment of pregnant women with syphilis: A successful program / Dessensibilização oral à penicilina para o tratamento da sífilis na gestação: um exemplo de experiência bem-sucedida

Abstract Gestational syphilis is a prevalent disease in Brazil and other low and medium income countries. Desensitization to penicillin is recommended for pregnant women with syphilis who are allergic to β-lactams. This is a descriptive study utilizing outpatient medical records from 2011 to 2015 from a mother and child hospital that is part of the national healthcare system in the South of Brazil, which performs an average of 3,600 birth assistances per year. All cases of pregnant women with syphilis and presumptive diagnosis of β-lactam allergy during the study period were included. The patients referred for desensitization originated from the hospital prenatal care service, as well as from municipal/state antenatal care services. Oral desensitization was performed in the obstetric emergency room, and adult and pediatric intensive care units were available at all times. Ten patients underwent desensitization during the period of study. Personal history of urticaria was the most common reaction that demanded desensitization. All patients tolerated the procedure well, and showed no adverse reactions.We report a successful program of oral desensitization. None of the patients presented adverse reactions or complications, a fact that corroborates the feasibility and safety of the desensitization protocol. Oral administration of penicillin comes at a low cost, and optimizes the use of time and resources.

Resumo A sífilis gestacional é uma doença prevalente no Brasil e em outros países de baixa e média renda. A dessensibilização à penicilina é recomendada para mulheres grávidas com sífilis que são alérgicas a β-lactâmicos. Este é um estudo descritivo que utiliza registros médicos de 2011 a 2015 de um hospital público materno-fetal do Sul do Brasil com média de 3.600 partos anuais. Foram incluídos todos os casos de gestantes com sífilis e diagnóstico presuntivo de alergia a β-lactâmicos durante o período de estudo. As pacientes encaminhadas para dessensibilização originaram-se do serviço pré-natal hospitalar internamente, bem como dos serviços municipais e estaduais de atendimento pré-natal. A dessensibilização oral foi realizada na sala de emergência obstétrica, e a unidade de terapia intensiva estava disponível em todos os momentos para o atendimento de possíveis intercorrências. Dez pacientes foram submetidas à dessensibilização durante o período estudado. História pessoal de urticária foi a reação mais comum que exigiu dessensibilização à penicilina. Todas as pacientes toleraram bem o procedimento, e não mostraram reações adversas. Relatamos no presente manuscrito um programa bem-sucedido de dessensibilização oral à penicilina. Nenhuma das pacientes apresentou reações adversas ou complicações, corroborando a viabilidade e segurança do protocolo de dessensibilização. A administração oral de penicilina tem baixo custo, e otimiza o uso de tempo e recursos para o tratamento adequado de sífilis gestacional no cenário apresentado.

Non-human Immunodeficiency Virus-related Ocular Syphilis in a Korean Population: Clinical Manifestations and Treatment Outcomes

PURPOSE: To describe the clinical manifestations and treatment outcomes of ocular syphilis in patients without human immunodeficiency virus (HIV) infection. METHODS: A total of 45 eyes from 39 patients with ocular syphilis confirmed by serologic tests were reviewed retrospectively. The included cases were all non-HIV-infected patients presenting with intraocular inflammation from 2002 to 2014 at Kyung Hee University Hospital. Medical records of 45 eyes were analyzed and included best-corrected visual acuity and ophthalmologic examination findings of the anterior and posterior segments to determine the focus of inflammation. Optical coherence tomography and fluorescein angiography findings as well as both medical and surgical management were also analyzed. RESULTS: The mean patient age was 61.0 years (range, 37 to 89 years). Bilateral ocular involvement occurred in 6 patients (15.4%), and diagnoses at presentation were most frequently related to posterior uveitis (38%), followed by panuveitis (29%) and optic neuritis (11%). Isolated interstitial keratitis and intermediate uveitis were uncommon (4%, both). Twenty-eight eyes (62.2%) were treated with penicillin, and 11 eyes (24.4%) underwent surgical treatment. The mean baseline best corrected visual acuity was 0.79 ± 0.59 (mean ± standard deviation, logarithm of the minimum angle of resolution) and significantly improved to 0.60 ± 0.63 at the final follow-up after treatment (p = 0.019). Mean visual improvement was significantly greater in the penicillin-treated group (p = 0.001). Visual impairment at the final visit occurred in 11 eyes (24.4%). Among the visual impairment group, 10 eyes (90.1%) had posterior segment-involving uveitis. CONCLUSIONS: Visual outcomes of treated, non-HIV-related ocular syphilis were favorable regardless of time to presentation. Posterior segment-involving uveitis at presentation was associated with poor visual outcome.

Goma sifilítica intracraneal en un paciente adolescente VIH seronegativo: reporte de un caso / Intracranial syphilitic gummain an HIV negative adolescent patient: a case report

La sífilis es una enfermedad sistémica causada por la espiroqueta Treponema pallidum que compromete al sistema nervioso central en cualquier etapa y cuyas presentaciones clínicas se modificaron en las últimas décadas. Se presenta el caso de un varón de 16 años con antecedentes de conducta sexual de riesgo y sífilis hace 3 años, sin recibir tratamiento. Acude por cefalea y disminución de visión hace 4 meses. Evaluación inicial objetiva hemianopsia homónima derecha, edema papilar bilateral y retinopatía exudativa izquierda. Pruebas serológicas de sífilis reactivas, VIH: no reactivo. Resonancia magnética de encéfalo: proceso expansivo en lóbulo occipital izquierdo captador de contraste. Recibió tratamiento para sífilis por 3 días y por sospecha inicial de proceso neoproliferativo se realizó biopsia que evidenció proceso granulomatosocrónico sifilítico. En su reingreso, mostró mayor compromiso de agudeza y defecto del campo visual. Potenciales evocados visuales: ausente en ambos ojos. Se inició Penicilina G sódica por 4 semanas (por evidencia de mejoría imagenológica) asociado a corticoides, encontrando disminución serológica y discreta mejoría clínica al término del tratamiento. La neurosífilis gomatosa esuna presentación infrecuente de la sífilis terciaria debiéndose considerar como diagnóstico diferencial en lesiones expansivas intracraneales en individuos VIHseronegativos con serología de sífilis reactiva.

Syphilis is a systemic disease caused by the spirochete Treponema pallidum which can compromise the central nervous system at any stage and whose clinical presentations have been modified in recent decades. Were port the case of a 16 years old male with a 3-years history of sexual risk behavior and syphilis with no treatment who experienced headache and decreased vision for four months. Initial assessment showed right homonymous hemianopia, bilateral papilledema and left exudative retinopathy. Serological tests for syphilis: reactive HIV: non-reactive. Brain MRI revealed a single irregularly enhancing lesion in the left occipital lobe. He received treatment for syphilis for three days, and stereotactic biopsies were performed by the initial suspicion of brain tumour. Histological examination showed a chronic granulomatous consistent with neurosyphilis. In his read mission, greater affectation of acuity and visual field defect was evident. Visual evoked potentials: absent in both eyes. Penicillin G sodium was initiated for 4weeks (for evidence of improvement imagenological)associated with corticosteroids, showing serological and discrete clinical improvement at the end of treatment decreased. The gummatous neurosyphilisis a rare form of tertiary syphilis which ever considered as differential expansive intracranial lesions in HIV-seronegative individuals with reactive syphilis serology.

Penicillin allergy evaluation: experience from a drug allergy clinic in an Arabian Gulf Country, Kuwait

BACKGROUND: Hypersensitivity to penicillin has been studied worldwide, but data regarding patterns of sensitization in Arabian Gulf countries are scarce. OBJECTIVE: To describe the patterns of penicillin hypersensitivity during a 6-year study in Kuwait in terms of demographics, type of the culprit drug, in vivo and in vitro allergy testing. METHODS: One hundred and twenty-four patients referred to the drug allergy clinic for penicillin allergy were fully evaluated by skin prick and intradermal testing. Drug provocation test was done on patients with negative results. RESULTS: A total of 124 patients were evaluated for penicillin allergy. Mean age was 37.8 (standard deviation, 12.7) years, range from 8 to 74 years. Thirty-nine male (31.5%) and 85 female patients (68.5%) were included. Diagnosis of penicillin allergy was confirmed in 46 patients (37.1%). Among the 44 confirmed allergic patients by skin evaluation we had 15 (34.1%) positive skin prick test, and 29 (65.9%) positive intradermal testing. Among patients with positive skin testing, 47.7% were positive to major determinant benzylpenicilloyl poly-L-lysine, 20.4% to minor determinant mixture, 50.0% to penicillin G and 40.9% to ampicillin; 13.6% of patients were positive to amoxicillin by skin prick test. One patient had a positive radioallergosorbent test and one had a positive challenge test. CONCLUSION: Penicillin allergy is a common problem with an incidence of about one third in our study subjects.

Analysis of the distribution of age and sex and the resistance of penicillin and levofloxacin among 672 Streptococcus pneumoniae that were isolated from sputum / 中国医师杂志

Objective To investigate the distribution of age and sex and the resistance of penicillin (p) and levofloxacin (LEV) among Streptococcus pneumoniae that were isolated from sputum.Methods The sputum specimens of our hospital from 2011 to 2013 were collected with the requirements of the third edition of National Clinical Laboratory Procedures,and 672 Streptococcus pneumoniae bacteria were isolated.Gram-Positive (GP) identification card was used to identify any doubt bacteria.LEV sensitivity was tested with Kirby-Bauer (KB) assay,and minimum inhibitory concentration (MIC) of P was tested with reagent strips (P-E test).Results A total of 672 Streptococcus pneumoniae bacteria was isolated in sputum.The number of age 0 to 6 years was 267 (39.73％),＞6 to 14 years was 62 (9.23％),＞ 14 to 60 years was 85 (12.65％),and ＞60 years was 258(38.39％) ; and isolating rates of age 0 to 6 years and ＞60 years were higher than other groups with statistically significant difference (P ＜0.01).The isolating rate of male (59.23％) was higher than female (40.77％) with a statistically significant difference (P ＜0.01).The sensitive rate of penicillin (p) to isolated strain was 73.78％ in 2011,71.32％ in 2012,and 53.50％ in 2013,respectively.MIC of isolated strain penicillin was increased year by year; however,LEV treated the isolated strain remain had a high sensitivity in first three years,the sensitivity of Streptococcus pneumoniae had no significant correlation between penicillin and LEV.Conclusions The resistance of penicillin was increased to streptococcus pneumoniae,patients who were infected by streptococcus pneumoniae and were allergic or resistant to penicillin can be considered to use an alternative therapy with LEV.

Type 1 Ig-E mediated allergy to human insulin, insulin analogues and beta-lactam antibiotics / Hipersensibilidade imediata a insulina humana, análogos de insulina e a antibióticos beta-lactâmicos

Insulin, a crucial therapeutic agent for diabetes mellitus, has been rarely associated with hypersensitivity events. We present a 69-year-old type-2 diabetic patient with urticariform lesions on the sites of subcutaneous injection of insulin. The patient denied any known allergies, except for an unspecific cutaneous reaction after intramuscular penicillin administration in childhood. Prick tests revealed positive reactions to all tested human insulins and insulin analogues. Serum IgE levels were above normal range and RAST tests were positive for human, bovine and porcine insulins, as well as beta-lactams. Type 1 IgEmediated allergy to insulin analogues demands a prompt diagnosis and represents a significant therapeutic challenge in diabetic patients.

A insulina é um agente indispensável para o controlo da diabetes mellitus. Os efeitos adversos da sua administração, em particular fenómenos de hipersensibilidade, são raros. Apresentamos um doente de 69 anos, diabético do tipo 2, com episódios recorrentes de lesões urticariformes nos locais de administração subcutânea de insulina. Negava alergias medicamentosas, à excepção de reacção não especificada na infância após penicilina intramuscular. Foram realizados testes cutâneos por puntura (prick tests) com diversos tipos de insulina humana e análogos, todos com reacções positivas, associando elevação dos níveis de IgE sérica e provas RAST positivas para as insulinas humana, bovina e porcina e para os antibióticos beta-lactâmicos. A alergia a análogos de insulina exige um diagnóstico precoce, originando um desafio terapêutico importante no doente diabético.

Challenge Test Results in Patients With Suspected Penicillin Allergy, but No Specific IgE

PURPOSE: Patients with a history of allergic reaction to penicillin, but with no detectable specific IgE, are common and pose a dilemma. Challenge tests are considered to be the diagnostic gold standard. The aim of this study was to identify subgroups of patients with very low risk for reactions who could be safely tested using a more rapid and simple procedure. METHODS: A total of 580 consecutively referred adult patients with a history of non-serious cutaneous allergic reactions to penicillin, but with no IgE, were challenged with therapeutic doses of penicillin V (phenoxymethylpenicillin), penicillin G (benzylpenicillin), or both. RESULTS: Only 14 of 580 patients had a positive challenge test. In 11 of the 14, a reaction to challenge occurred within 2 hours, and none were anaphylactic. The year of the original reaction was known for 555 patients; a positive challenge was seen in only 0.4% of those with an original reaction >15 years before challenge, but in 4.6% of those with a more recent original reaction (P=0.001). Onset of a reaction within the first day of the original exposure was a predictive factor for a positive challenge (P=0.001) in patients challenged within 15 years of the original reaction. CONCLUSIONS: Among suspected penicillin-allergic patients with non-severe skin reactions and no detectable specific IgE, the subgroup of patients who originally reacted more than 15 years previously had very low risk for reacting to a challenge. The risk was higher in patients with a more recent original reaction, especially if the symptoms had occurred within the first day of exposure.

IgE-Mediated Hypersensitivity Reactions to Cephalosporins

Cephalosporins are commonly prescribed either orally or parenterally for the treatment of bacterial infections because of wide safety margin compared with penicillins. Skin testing with a parent cephalosporin antibiotic has routinely been performed in Korea in the fear of developing anaphylaxis after the administration of a cephalosporin although penicillins are antibiotics that most commonly induce severe or life-threatening IgE-mediated reactions (anaphylaxis). In this review, we will discuss IgE-mediated hypersensitivity reactions to cephalosporins. Immunopathogenesis of IgE-mediated hypersensitivity reaction to cephalosporins, limitations of skin testing with parent cephalosporin antibiotics, and prescription strategy of cephalosporins for patients with a history of cephalosporin or penicillin hypersensitivity was described.

Successful outpatient management of pelvic actinomycosis by ceftriaxone: a report of three cases

Pelvic actinomycosis is a chronic granulomatous suppurative disease caused by actinomyces israeli. Intravenous penicillin is the preferred antimicrobial but it requires hospitalization up to one month. An outpatient treatment strategy would be cost effective and a good choice for patients. Here we present three cases in which intramuscular ceftriaxone was successfully used in the outpatient settings following surgery and IV penicillin treatment in the hospital.