Mutaciones asociadas a resistencia a rifampicina e isoniacida en aislamientos clínicos del complejo Mycobacterium tuberculosis de pacientes del Hospital Roosevelt / Mutations associated with resistance to rifampin and isoniazid in clinical isolates of the Mycobacterium tuberculosis complex from patients at Roosevelt Hospital

El aumento de tuberculosis y la multidrogo resistencia de cepas de micobacterias es un problema de los sistemas de salud, en 2009, en el Hospital Roosevelt Gordillo y cols, determinaron la TB-MDR en pacientes con tuberculosis diagnosticada microbiológicamente, la tasa de resistencia fue de 4.3%. Objetivo: Determinar los patrones de resistencia y perfiles genéticos de cepas con monoresistencia y cepas TB-MDR del Complejo M. tuberculosis. Métodos: Se utilizaron dos métodos para evaluar las cepas de M. tuberculosis, un método fenotípico, MGIT, y un método Genotípico, Genotype HAIN LifeScience para determinar el perfil genético de las cepas. Resultados: Se evaluaron 846 cepas de micobacterias de los años 2008 al 2013, encontrándose un 2.2% de TB-MDR. Las cepas evaluadas genotípicamente fueron 761, a las cuales se determinó los genes de resistencia, encontrándose monoresistencia a Isoniacida en 58 cepas, 7.6%, monoresistencia a Rifampicina en 18 cepas, 2.4% y 15 cepas MDR, 2.0%. Las mutaciones más frecuentes en monoresistencia fueron inhA MUT1 y katG MUT1 y la combinación de ambos genes 3.2%, 3.0% y 1.3%, para cepas TB-MDR la combinación rpoB Mutación silenciosa + katG MUT1 + inhA MUT1. Se encontró que en pacientes con cepas MDR el 3.1% son HIV+ y el 1.5% son HIV-...(AU)

Introduction: The increase of tuberculosis and multidrug resistance in mycobacteria strains is a problem for health systems, in 2009, in Hospital Roosevelt, Gordillo and cols, determined the TB-MDR in patients diagnosed with tuberculosis microbiologically, the resistance rate was 4.3%. Objective: To determine the resistance patterns and genetic profiles of monoresistant strains and MDR-TB strains of M. tuberculosis complex. Methods: Two methods for evaluating M. tuberculosis strains were used, a phenotypic method, MGIT, and a genotypic method, Genotype HAIN LifeScience to determine the genetic profile of the strains. Results: 846 strains of mycobacteria of the years 2008 to 2013 were evaluated, finding 2.2% of MDR-TB. The strains genotypically evaluated were 761, of wich, resistance genes were determined, finding isoniazid monoresistance in 58 strains, 7.6%, Rifampicin monoresistance in 18 strains, 2.4% and 15 MDR strains, 2.0%. The most frequent mutations for monoresistant strains were inhA MUT1 and katG MUT1 and the combination of both genes 3.2%, 3.0% and 1.3%, respectively, and the most frequent mutations for TB-MDR strains was the combination rpoB silent mutation + katG MUT1 + inhA MUT1. There was found that in patients with MDR strains 3.1% are HIV+ and 1.5% are HIV-. Conclusions: The percentage of TB-MDR strains was 2.3%, and the most common genes were rpoB silent mutation, inhA MUT1 y katG MUT1. There was found a higher percentage of monoresistance in isoniazid than rifampicin, being the HIV+ patient population the one that presented higher percentages in both monoresistance to RIF and INH and TB-MDR strains.

Antimicrobial activity of different filling pastes for deciduous tooth treatment

Guedes-Pinto paste is the filling material most employed in Brazil for endodontic treatment of deciduous teeth; however, the Rifocort® ointment has been removed. Thus, the aim of this study was to investigate the antimicrobial potential of filling pastes, by proposing three new pharmacological associations to replace Rifocort® ointment with drugs of already established antimicrobial power: Nebacetin® ointment, 2% Chlorhexidine Gluconate gel, and Maxitrol® ointment. A paste composed of Iodoform, Rifocort® ointment and Camphorated Paramonochlorophenol (CPC) was employed as the gold standard (G1). The other associations were: Iodoform, Nebacetin® ointment and CPC (G2); Iodoform, 2% Chlorhexidine Digluconate gel and CPC (G3); Iodoform, Maxitrol® ointment and CPC (G4). The associations were tested for Staphylococcus aureus (S. aureus), Streptococcus mutans (S. mutans), Streptococcus oralis (S. oralis), Enterococcus faecalis (E. faecalis), Escherichia coli (E. coli), and Bacillus subtilis (B. subtilis), using the methods of dilution on solid medium – orifice agar – and broth dilution. The results were tested using statistical analysis ANOVA and Kruskal-Wallis. They showed that all the pastes had a bacteriostatic effect on all the microorganisms, without any statistically significant difference, compared with G1. S. aureus was statistically significant (multiple comparison test of Tukey), insofar as G2 and G3 presented the worst and the best performance, respectively. All associations were bactericidal for E. coli, S. aureus, S. mutans and S. oralis. Only G3 and G4 were bactericidal for E. faecalis, whereas no product was bactericidal for B. subtilis. Thus, the tested pastes have antimicrobial potential and have proved acceptable for endodontic treatment of primary teeth.

Histological evaluation of bone response to pediatric endodontic pastes: an experimental study in guinea pig

This study aimed to evaluate by the intra-osseous implant technique the most commonly used materials for pulp therapy in pediatric dentistry: calcium hydroxide (CH), Guedes Pinto paste and CTZ paste, according to FDI (1980) and ANSI/ADA (1982) recommendations. Thirty guinea pigs, 10 for each material, divided into experimental periods of 4 and 12 weeks received one implant on each side of the lower jaw symphysis. The external lateral tube wall served as control for the technique. At the end of the observation periods, the animals were euthanized and specimens were prepared for routine histological examination. It was observed that CH and CTZ paste induced severe inflammation, a large amount of necrotic tissue, lymphocytes, foreign body cells and bone resorption, while Guedes Pinto Paste induced little or no inflammation in the 4-week observation period. After 12 weeks, the reactions to CH and Guedes Pinto paste were also absent/mild, presenting a general pattern of replacement by recently formed bone tissue while a moderate to severe inflammatory response was observed with CTZ paste. Guedes Pinto paste presented acceptable biocompatibility levels in both analyzed periods; CH only showed acceptable biocompatibility in the 12-week period while CTZ paste showed no biocompatibility in both periods. Among the tested materials, only Guedes Pinto paste presented an acceptable biocompatibility.

A pesquisa teve como objetivo avaliar a biocompatibilidade através da técnica de implantes intra-ósseos dos materiais utilizados em odontopediatria para tratamento pulpar: hidróxido de cálcio, pastas Guedes Pinto e CTZ, de acordo com as recomendações da FDI (1980) e ANSI/ADA(1982). Trinta guinea pigs, dez para cada material, divididos em períodos experimentais de 4 e 12 semanas receberam um implante em cada lado da sínfise mandibular. A parede lateral externa do copo serviu como controle para a técnica. No final dos períodos experimentais, os animais foram sacrificados e os espécimes preparados para o exame histológico de rotina. Observou-se que o hidróxido de cálcio e a pasta CTZ mostraram reação inflamatória severa, grande quantidade de tecido necrosado, linfócitos, células de corpo estranho e reabsorção óssea; enquanto a pasta Guedes Pinto induziu pouca ou nenhuma inflamação no período de 4 semanas. Após 12 semanas as reações para o hidróxido de cálcio e pasta Guedes Pinto foram ausentes/suaves apresentando um padrão geral de substituição por tecido ósseo neoformado, enquanto uma resposta inflamatória de moderada a severa foi observada para a pasta CTZ. A pasta Guedes Pinto apresentou níveis aceitáveis de biocompatibilidade nos dois períodos analisados; hidróxido de cálcio apresentou biocompatibilidade aceitável somente no período de 12 semanas e a pasta CTZ não mostrou biocompatibilidade em ambos os períodos. Entre estes, apenas a pasta Guedes Pinto apresentou níveis de biocompatibilidade nos dois períodos analisados.

Inhibition of multiplication of leprosy bacilli in nude mice by intermittent dosed new rifamycin derivative krm-1648 combined with sparfloxacin

The inhibition of multiplication of mycobacterium leprae inoculated into footpads of nude mice by the oral administration of new rifamycin derivative KRM-1648 and a new quinolone, sparfloxacin [SPFX]; was examined. When these two drugs were administered alternately at intervals of 3 or 4 days [thus once weekly for each drug] between 3 and 5 months after infection, the use of 0.6 mg/kg of KRM-1648 and 10mg/kg of sparfloxacin were found to be sufficient to prevent entirely multiplication of M.leprae. However with the alternate administration of 0.3 kg of KRM-1648 and 5 mg/kg sparfloxacin the inhibition of multiplication of M.leprae was partial as it was also examined with the administration of 1 mg/kg of KRM-1648 alone or 20 mg/kg/ of sparfloxacin alone once a weekly. However the simultaneous administration of 0.6 mg/kg of KRM-1648 with 10 mg/kg of sparfloxacin once per week entirely prevented the multiplication of M. leprae. Taking these findings into consideration there is possible future use of these type multi drug regimens was discussed

Inhibition of multiplication of leprosy bacilli in nude mice by simultaneous adminstration of new rifamycin derivative krm-1648 and sparfloxacin combined with dapsone

The inhibition of multiplication of mycobacterium leprae inculated in to foot pads of nude mice by oral administration of new rifamycin derivative KRM-1648 and a new quinoline, sparfloxacin [SPFX] combined with dapsone [DDS]: was examined. When these drugs administered simultaneously once weekly, the use of 0.6 mg/Kg of KRM, 10 mg/kg of sparfloxacin and 0.001/ Dapsone, entirely prevented the multiplication of M. leprae even the number of non solid bacilli detected was less than that inoculated into each foot pad. This study revealed the possible future use of this multi-drug regimen in the chemotherapy of leprosy patient

Agentes antituberculosos. Nuevas alternativas farmacológicas / Antituberculous drugs. New alternatives

La principal indicación de los fármacos antituberculosos de segunda línea es la presencia de tuberculosis resistente a drogas primarias. Comparados con los antituberculosos de primera línea, estos fármacos tienen una menor actividad antimicrobiana, más efectos colaterales, algunos son más caros y varios regímenes en los que se incluyen estas drogas son administradas por un mayor tiempo. Los principales fármacos son: ácido paraaminosalicílico (PAS), tiacetazona, clofazimina, etionamida, cicloserina, capreomicina, amikacina y kanamicina. Sus mecanismos de acción y de resistencia, así como su absorción, eliminación y efectos colaterales son diferentes para cada droga. Para el PAS y la tiacetazona los efectos colaterales más importantes son a nivel gastrointestinal; la clofazimina puede producir hiperpigmentación de la piel; la ciloserina puede originar síntomas neurológicos; los aminoglucósidos y la capreomicina generalmente causan trastornos vestibulococleares. Las contraindicaciones y las dosis de cada fármaco, de acuerdo a las posibles enfermedades concomitantes, son quizás de los aspectos a considerar más importantes cuando estas drogas son administradas

In vivo activities of novel benzoxazinorifamycins against Mycobacterium leprae.

Among the four newly synthesized benzoxazinorifamycin derivatives, KRM-1648 and KRM-2312 completely inhibited the multiplication of rifampicin-sensitive as well as rifampicin-resistant strains of M. leprae in the foot-pads of mice. Both were found to be more potent than rifampicin and were bactericidal. In combination with ofloxacin, another potent bactericidal drug against M. leprae, both KRM-1648 and KRM-2312 exhibited synergism. Thus, combination of one of these benzoxazinorifamycin derivatives and ofloxacin in multidrug regimens is worth evaluating in clinical trials.

In vitro and in vivo interactions of drugs used in multidrug therapy in leprosy.

Interactions of different drugs commonly used in multiple drug therapy were evaluated using both in vitro culture (cell-free as well as macrophage) system and mouse footpad. No additive effects were obtained in the in vitro system when dapsone was combined with either rifampicin or clofazimine, while a strong antagonism was observed when clofazimine was combined with rifampicin but not with rifabutin. In the mouse footpad system, a strong synergism was obtained when clofazimine was combined with either rifampicin or rifabutin, but significant antagonism was observed with the combination of clofazimine and dapsone.