Condução da toxoplasmose gestacional / Management of gestational toxoplasmosis

A toxoplasmose é uma doença proveniente do Toxoplasma gondii, um protozoário que tem os felinos como seu hospedeiro definitivo e os mamíferos e aves como seu hospedeiro intermediário. Tem um curso benigno e autolimitado quando acomete um indivíduo imunocompetente, no entanto a infecção durante a gestação acarreta até 50% de chance de toxoplasmose congênita, podendo causar danos severos ao feto. A virulência dos genótipos encontrados nas Américas Central e do Sul é a mais alta, comparada a Europa e América do Norte, tendo a doença um comportamento mais agressivo. Os estudos relatam a diminuição da infecção fetal em até 60% com o uso da espiramicina, usada ainda na profilaxia. Este artigo discute sobre a triagem materna pré-natal e sua necessidade, a profilaxia e o tratamento da infecção fetal ainda intraútero, com o objetivo de diminuir a transmissão vertical e as sequelas neonatais com suas implicações ao longo da vida.(AU)

Toxoplasmosis it is a disease originating from Toxoplasma gondii, a protozoan that has felines at as ultimate host and mammals and birds at as intermediate host. Has a benign and self-limiting course when affects immunocompetent individual, however, infection during pregnancy leads 50% chance of congenital toxoplasmosis and can cause severe damage to the fetus. The virulence of genotypes found in Central and South America is the highest compared to Europe and North America, having the disease a more aggressive behavior. Studies report a reduction in fetal infection 60% with the use spiramycin still used for prophylaxis. This article discusses prenatal maternal screening, prophylaxis and treatment of fetal infection still in utero with the objective of decreasing vertical transmission and neonatal sequelae with their lifelong implications.(AU)

Toxoplasmosis congénita, una mirada en la actualidad del tratamiento; revisión de la literatura / Congenital toxoplasmosis, a look at contemporary treatment; literature review / Toxoplasmose congênita, um olhar atual no tratamento; revisão de literatura

Introducción. La Toxoplasmosis congénita constituye una causa significativa de morbi-mortalidad neonatal en países de bajos ingresos como Colombia. Puede originar prematuridad, secuelas patológicas y pérdida fetal. El tamizaje en las gestantes y, a su vez, un tratamiento oportuno y adecuado disminuye la transmisión vertical y sus nefastas secuelas. El objetivo es presentar evidencia científica actualizada sobre el tratamiento farmacológico de la Toxoplasmosis Congénita. Metodología. Se realizó una búsqueda no sistemática en bases de datos: Pubmed, Medline, Clinical Key y Springer. Se incluyeron artículos originales y de revisión de tema publicados desde enero de 2014 hasta abril de 2019. División de los temas tratados. se abordan la fisiopatología y clínica, el abordaje diagnóstico, alternativas de prevención y tratamiento. Conclusiones. En la actualidad la terapia farmacológica es limitada, los esquemas de manejos se basan en espiramicina o la combinación de sulfadiazina/pirimetamina y ácido folínico; estas moléculas no son del todo bien toleradas y presentan un amplio espectro de reacciones adversas secundario a sus efectos tóxicos; resulta necesario la ejecución de estudios aleatorizados para evaluar su efectividad. Cómo citar: Rueda-Paez YS, Valbuena-Ruiz L, Quintero-Pimiento N, Pinilla-Plata A, Sayago-Silva J. Toxoplasmosis congénita, una mirada en la actualidad del tratamiento; revisión de la literatura. MedUNAB. 2019;22(1):51-63. doi: 10.29375/01237047.2612

Introduction. Congenital Toxoplasmosis constitutes a significant cause of neonatal morbimortality in underdeveloped countries like Colombia. It can cause prematurity, pathological after-effects and fetal loss. Screening expectant mothers and in turn, a timely and adequate treatment, reduce vertical transmission and its devastating effects. The objective is to present up-to-date scientific evidence about the pharmacological treatment of Congenital Toxoplasmosis. Methodology. A non-systematic search of databases was conducted: Pubmed, Medline, Clinical Key and Springer. Original and topic review articles were included dating from January 2014 to April 2019. Division of topics covered. Physiopathology and clinical pathology, diagnostic approach, prevention and treatment alternatives were addressed. Conclusions. At this time, pharmacological therapy is limited, management schemes are based on spiramycin or a combination of sulfadiazine/pyrimethamine and folinic acid; these molecules are not very well tolerated and exhibit a wide spectrum of adverse reactions apart from their toxic effects, thus it is necessary to conduct randomized studies to evaluate its effectiveness. Cómo citar: Rueda-Paez YS, Valbuena-Ruiz L, Quintero-Pimiento N, Pinilla-Plata A, Sayago-Silva J. Toxoplasmosis congénita, una mirada en la actualidad del tratamiento; revisión de la literatura. MedUNAB. 2019;22(1):51-63. doi: 10.29375/01237047.2612

Introdução. A toxoplasmose congênita é uma causa significativa de morbidade e mortalidade neonatal em países de baixa renda, como a Colômbia. Pode causar prematuridade, sequelas patológicas e perda fetal. A triagem em gestantes e, por sua vez, um tratamento oportuno e adequado diminui a transmissão vertical e suas consequências desastrosas. O objetivo é apresentar evidências científicas atualizadas sobre o tratamento farmacológico da Toxoplasmose Congênita. Metodologia. Foi realizada uma revisão não sistemática nas bases de dados: Pubmed, Medline, Clinical Key e Springer. Foram incluídos tanto artigos originais, quanto revisões de tópicos publicados de janeiro de 2014 até abril de 2019. Divisão dos tópicos discutidos. foram abordadas a fisiopatologia e a clínica, a abordagem diagnóstica, alternativas para prevenção e tratamento. Conclusões. Atualmente, a terapia farmacológica é limitada, os esquemas terapéuticos baseiam-se na espiramicina ou na combinação de sulfadiazina/pirimetamina e ácido folínico; estas moléculas não são totalmente toleradas e apresentam um amplo espectro de reações adversas secundárias aos seus efeitos tóxicos. É necessário realizar estudos randomizados para avaliar sua eficácia. Cómo citar: Rueda-Paez YS, Valbuena-Ruiz L, Quintero-Pimiento N, Pinilla-Plata A, Sayago-Silva J. Toxoplasmosis congénita, una mirada en la actualidad del tratamiento; revisión de la literatura. MedUNAB. 2019;22(1):51-63. doi: 10.29375/01237047.2612

Efecto del tratamiento prenatal con espiramicina en la frecuencia de retinocoroiditis por toxoplasmosis congénita en una cohorte colombiana / Effect of antenatal spiramycin treatment on the frequency of retinochoroiditis due to congenital toxoplasmosis in a Colombian cohort

Resumen Introducción. La toxoplasmosis de la gestación es frecuente y grave. Hasta ahora no hay consenso sobre la utilidad del tratamiento para prevenir complicaciones oculares en el neonato. En la actualidad, uno de los medicamentos utilizados en las madres diagnosticadas es la espiramicina oral. Infortunadamente, en algunas mujeres gestantes no se hace el diagnóstico prenatal y, por esta u otras razones, no reciben el tratamiento. Objetivo. Describir la relación entre el tratamiento con espiramicina durante el embarazo en madres con toxoplasmosis de la gestación y la presentación de toxoplasmosis ocular en los recién nacidos. Materiales y métodos. Se llevó a cabo un estudio observacional descriptivo de serie de casos. Se evaluó una serie prospectiva de pacientes con toxoplasmosis de la gestación durante tres años de seguimiento en el Servicio de Retinología de la Clínica Universitaria Bolivariana de Medellín. Resultados. Se registraron 23 madres con diagnóstico de toxoplasmosis de la gestación. Quince de ellas (65 %) recibieron durante la gestación tratamiento con espiramicina en dosis de 3 g al día; uno de los neonatos (6,6 %) presentó toxoplasmosis ocular. De las ocho (35 %) pacientes que no recibieron tratamiento, cinco (62,5 %) tuvieron hijos con compromiso ocular por toxoplasma. La razón de momios (odds ratio, OR) del efecto protector contra dicho compromiso en los pacientes cuyas madres recibieron tratamiento fue de 0,04 (IC95% 0,00-0,67), con valor de p menor de 0,01 en la prueba exacta de Fisher. Solo se evidenció compromiso del sistema nervioso central por toxoplasmosis mediante las imágenes de tomografía o ecografía cerebral en dos (14 %) pacientes de las 14 en quienes se hicieron estos estudios. Los dos pacientes presentaron, además, compromiso ocular; ambos fueron diagnosticados en el momento del nacimiento y sus madres no habían recibido tratamiento prenatal. Conclusiones. Estos resultados evidencian que el tratamiento con espiramicina durante el embarazo en la toxoplasmosis de la gestación redujo en 96 % (IC95% 33-100 %) el riesgo relativo de presentar la enfermedad en el recién nacido.

Abstrat Introduction: Gestational toxoplasmosis is frequent and severe. There is still debate about the benefits of treatment against ocular manifestations in the newborn. Spiramycin treatment is used for this purpose, unfortunately prenatal diagnosis is sometimes delayed and pregnant women are not treated. Objective: To describe the relationship between treatment with spiramycin during pregnancy in mothers with gestational toxoplasmosis and development of ocular toxoplasmosis in newborns. Materials and methods: We conducted a descriptive study of a case series. We evaluated a prospective cohort of patients diagnosed with gestational toxoplasmosis during three years at the Retinology Service at the Clínica Universitaria Bolivariana in Medellín. Results: Gestational toxoplasmosis was found in 23 mothers; 15 (65%) were treated during pregnancy with 3 g per day of spiramycin, eight (35%) patients were untreated. In the treated group just one newborn developed ocular toxoplasmosis (6.6%), in contrast with five (62.5%) of the eight patients who did not receive treatment. These results suggest that pregnancy treatment reduces the relative risk of ocular toxoplasmosis in the newborn by 96% (95% CI: 33 - 100%). Only two (14%) of the patients who were evaluated, had nervous system involvement related to toxoplasmosis in CT scan or cerebral ultrasound. These two patients also developed ocular pathology and were diagnosed at the time of birth, so they did not received antenatal treatment. Conclusions: A protective effect was found against the ocular involvement in patients whose mother received treatment with spiramycin (OR=0.04;95% CI: 0.00-0.67), p<0.01 (Fisher's Exact Test).

Transcriptomic analysis of a spiramycin Ⅰ-resistant Staphylococcus aureus mutant / 中国药科大学学报

The clinical utility of macrolide antibiotics has declined due to the appearance of resistant isolates.A spiramycin Ⅰ-resistant Staphylococcus aureus ATCC29213-R was induced and isolated with increasing the concentration of spiramycin Ⅰ,which exhibits an A→C transversion at position 2089 in the 23S rRNA gene,which is first reported in the S.aureus.A RNA-seq based transcriptomic analysis was performed to understand the overall response of resistant bacteria to spiramycin Ⅰ treatment with subinhibitory dosage.Inn this study,There are a total of 322 up-regulated and 82 down-regulated genes in spiramycin Ⅰ-treated S.aureus ATCC29213-R and 426 up regulated,838 down-regulated in spiramycin Ⅰ-treated S.aureus ATCC29213,which were identified differentially expressed compared to their control with a minimum 2-fold change (Q ＜ 0.05).Interestingly,The data showed that argH and argG transcripts,in the arginine biosynthetic pathway,were decreased by 13.51-fold and 21.45-fold,respectively,compared to the control,while the expression level of three genes involved in arginine catabolism,arcA,arcC,and argF,increased by 35-fold,18.05-fold and 30.84-fold,respectively.The results revealed that spiramycin Ⅰ could trigger the up-regulation of the genes of ACME-Arc system which allows S.aureus to survive in acidic environments of human skin.This suggesed the arginine-deiminase pathway may be a potential target for treatment of the resistant S.aureus.

Fermentation, isolation, purification and characterization of an antitubercular antibiotic from Streptomyces luridus MTCC 4402.

Tuberculosis, caused by Mycobacterium tuberculosis, continues to be a serious public health problem around the world, and it urges the need for development of new antitubercular drugs. An antibiotic producing strain, Streptomyces luridus (MTCC 4402) was earlier isolated from soil by our group. In this work, the phylogenic status was established by 16S rRNA gene sequence analysis. The strain was found to be active against clinically resistant strains. The culture was grown in shake flasks in a medium containing cornsteep liquor, glucose, CaCO3, soyabean meal and starch. Antibiotic production reached maximum at the end of 72 h. and fermentation profile was obtained. The active compound was extracted into ethyl acetate and was subjected to activity guided purification by column chromatography using silica gel, TLC and HPLC methods. The pure compound eluted at 16.7 min. by gradient elution was subjected to 1H, 13C NMR and mass spectral analyses. The acquired data was compared with that of natural products’ data base and found to be a known antibiotic, spiramycin. The purified compound was studied for mutagenic, cytotoxicity, antitubercular activities. It was non mutagenic at the concentration of 1000 mg/mL, non cytotoxic and active as antitubercular agent at a concentration of 64 mg/mL and was comparable to rifampicin.

The prevalence of genotypes that determine resistance to macrolides, lincosamides, and streptogramins B compared with spiramycin susceptibility among erythromycin-resistant Staphylococcus epidermidis

Coagulase-negative staphylococci, particularly Staphylococcus epidermidis, can be regarded as potential reservoirs of resistance genes for pathogenic strains, e.g., Staphylococcus aureus. The aim of this study was to assess the prevalence of different resistance phenotypes to macrolide, lincosamide, and streptogramins B (MLSB) antibiotics among erythromycin-resistant S. epidermidis, together with the evaluation of genes promoting the following different types of MLSB resistance:ermA, ermB, ermC,msrA, mphC, and linA/A’. Susceptibility to spiramycin was also examined. Among 75 erythromycin-resistantS. epidermidis isolates, the most frequent phenotypes were macrolides and streptogramins B (MSB) and constitutive MLSB (cMLSB). Moreover, all strains with the cMLSB phenotype and the majority of inducible MLSB (iMLSB) isolates were resistant to spiramycin, whereas strains with the MSB phenotype were sensitive to this antibiotic. The D-shape zone of inhibition around the clindamycin disc near the spiramycin disc was found for some spiramycin-resistant strains with the iMLSB phenotype, suggesting an induction of resistance to clindamycin by this 16-membered macrolide. The most frequently isolated gene was ermC, irrespective of the MLSB resistance phenotype, whereas the most often noted gene combination wasermC, mphC, linA/A’. The results obtained showed that the genes responsible for different mechanisms of MLSB resistance in S. epidermidis generally coexist, often without the phenotypic expression of each of them.