Tyrimų tikslas – išsiaiškinti DVAsiurblių aktyvumą dar neištirtose E. typographi bakterijose, esančiose žievėgraužio tipografo žarnyno mikrofloroje, jas veikiant eterinių aliejų sudedamąją dalimimircenu (MC). Tyrimai atlikti VDU Biochemijos katedroje vykdant potenciometrinius universalaus daugiavaisčio atsparumo siurblių substrato TPP+ jonų srautų per ląstelės apvalkalėlį matavimus.E. typographiląsteliųreakcijas į mirceną lyginome su šios medžiagos poveikiu gramneigiamosiomsE. coli ir S. enterica, ir gramteigiamosiomsS. aureus ir B. subtilis ląstelėms. MC poveikįE. typographiląstelėms stebėjome ir lyginome su pokyčiais, paveikus jas rezerpinu (RZ) ir RND šeimos siurblių slopikliufenilalanil-arginil-β-naftilamidu(PAβN).Tyrėme laukinio tipo ir mutantines E. coliirS. entericaląsteles, o taip pat ląsteles su pralaidinta išorine membrana bei pažeistais DVA siurbliais. Lygindami E. typographiląsteles su gramteigiamosiomis ląstelėmis, išsiaiškinome, kadPAβN panašiai slopina TPP+ kaupimąsi S. aureus, B. subtilis ir E. typographi ląstelėse, bet gramteigiamosioms ląstelėms reikia didesnės MC koncentracijos iki pilnos ląstelių plazminės membranos depoliarizacijos. Alkaloidas rezerpinas EDTA dorotose E. typographi ląstelėse skatino substrato TPP+ jonų sugertį, o ląstelėse su intaktine išorine membrana depoliarizavo plazminę membraną. / The aim of the study was to determine activity of MDR pumps in yet uninvestigated E. typography cells discovered in bark beetle gut microflora. The cells were exposed to myrcene anintegral part essential oils. The Investigations were carried out at department of Biochemistry of VMU using potentiometric analysis of a flow through the cell envelope of an universal substrate of multidrug resistant pumps substrate TPP+ions. Reactions of E. typography cells to myrcene were compared with effects of this compound on Gram-negative E. coli and S. entericaas well as Gram-positive S. aureus and B. subtiliscells. Effects of myrcene on E. typography cell were compared with the cell responses to alkaloid reserpine (RZ) and RND-type efflux pump inhibitor phenylalanyl – arginine – β – naphthylamide ( PAβN ). We investigated also wild type and mutant E. coli and S. enterica cells, including the cells with EDTA-permeabilized outer membrane. Comparing E. typographycells with Gram-positive bacteria we found that inhibition of S. aureus, B. subtilis and E. typography pumpsusing PAβN was similar, but Gram-positive bacteria required higher concentrations of MC to depolarize the cells. Alkaloid reserpine stimulated the accumulation of TPP+ions by EDTA-treated E. typographycells but in the case of cells with the intact outer membrane this inhibitor depolarized the cells.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 4 uppsatser.

Thesis (M.P.H.)--University of Texas Health Science Center at Houston, School of Public Health, 2008. / Source: Masters Abstracts International, Volume: 46-05, page: 2665. Adviser: Tommy C. Douglas. Includes bibliographical references.

Magister Pharmaceuticae - Mpharm / Many studies have investigated the pharmacokinetics (PK) of anti-tuberculosis drugs in tuberculosis patients. However, currently in South Africa, no studies have been done on ethionamide (ETH) PK in adult MDR-TB patients that are infected with HIV and those without HIV infection. Therefore, the objective of this current study was firstly, to find out ethionamide plasma concentration using the LC-MS method; secondly, to evaluate and compare the pharmacokinetics of ethionamide in MDR-TB patients infected with and without HIV infection; thirdly, to examine the effects of ARVs and kidney impairment on the PK of ethionamide and fourthly, to find out the consequence of sex and age on ETH PK parameters.

nÃo hà / Baixos nÃveis sangÃÃneos de drogas antituberculose podem ser causa de resistÃncia do Mycobacterium tuberculosis. Este estudo objetivou avaliar a absorÃÃo intestinal transcelular e paracelular e verificar possÃvel repercussÃo nas concentra-ÃÃes sÃricas de de rifampicina (RMP) e isoniazida (INH) em pacientes com tuberculose multirresistente (TBMR). Realizou-se estudo caso-controle no AmbulatÃrio de Tisiologia do Hospital de Messejana, em Fortaleza-CearÃ, entre agosto de 2006 e abril de 2007. TBMR foi definida como o caso de portador de bacilo resistente a pelo menos RMP+INH, de acordo com o teste de sensibilidade realizado pelo mÃtodo das proporÃÃes. Foram formados dois grupos para controle, o dos portadores de tuberculose sensÃvel (TBS) e o dos voluntÃrios sÃos (VS). Realizaram-se exames hematolÃgicos e bioquÃmicos, o teste da lactulose / manitol (L/M) (para avaliar a absorÃÃo intestinal) e coleta de dados clÃnicos e sociais de todos os voluntÃrios. Para a avaliaÃÃo das concentraÃÃes sÃricas foi coletado sangue duas e seis horas apÃs a ingestÃo observada da RMP+INH. A tÃcnica utilizada para a quantificaÃÃo da L e M na urina e dosagem sÃrica de RMP e INH foi a cromatografia lÃquida de alta pressÃo. O total de componentes dos grupos com TBMR, TBS e de sadios foi, respectivamente, 41, 33 e 41, emparelhados por gÃnero e idade. Na anÃlise univariada, encontrou-se mediana / variaÃÃo do percentual de excreÃÃo urinÃria da L e M menor no grupo com TBMR em relaÃÃo aos sadios (p<0,05). Ao se corrigir para a associaÃÃo alcoolismo + tabagismo ou Ãndice de massa corporal (IMC), desapareceu a significÃncia da menor excreÃÃo de lactulose nos portadores de TBMR. ApÃs a anÃlise multivariada, a mÃdiaÂdesvio-padrÃo (dv) do percentual de excreÃÃo urinÃria do M foi menor no grupo com TBMR em relaÃÃo ao grupo de VS (p=0,0291) e em relaÃÃo ao de TBS (p=0,0369). A relaÃÃo L/M foi semelhante entre os grupos (p=0,4747). A concentraÃÃo sÃrica mÃxima de INH (CHX) mÃdiaÂdesvio-padrÃo foi maior no grupo com TBMR (3,82Â1,18) em relaÃÃo ao VS (2,79Â1,19), p<0,01, nÃo havendo diferenÃa entre TBS e VS nem entre TBMR e TBS. ApÃs a anÃlise multivariada, a CHX aumentou no grupo VS (3,07Â0,24), mas continuou a ser maior no grupo com TBMR e, agora, com diferenÃa significante em relaÃÃo apenas à TBS. Houve CHX < 3 Âg/ml em 18,8% (6/32) dos casos e 56,7% (17/30) dos sadios (p<0,05), nÃo havendo diferenÃa entre TBS, 39,3% (11/28) e sadios. ApÃs a anÃlise multivariada, a mediaÂdp da concentraÃÃo sÃrica mÃxima de RMP (CRX) foi menor no grupo com TBMR do que nos sadios (p<0,05) e no grupo com TBS do que nos sadios (p<0,001), nÃo havendo diferenÃa entre TBMR e TBS. Houve (CRX) < 8 Âg/ml em 90,6% (29/32) dos portadores de TBMR e 66,7% (20/30) dos sadios (p<0,05) e em 82,1% (23/28) do grupo com TBS (em relaÃÃo aos sadios, p<0,05). Em conclusÃo, observou-se reduÃÃo na absorÃÃo transcelular intestinal em pacientes com TBMR versus TBS ou sadios, e os dados sugerem significante participaÃÃo do alcoolismo+tabagismo e IMC na reduÃÃo do transporte paracelular em portadores de TBMR. A CRX foi mais baixa em portadores de TBMR e TBS do que em sadios, com altas proporÃÃes de nÃveis subterapÃuticos de RMP e INH nos trÃs grupos, principalmente para CRX, mas, tambÃm preocupante para CHX. / Reduced antituberculosis drugs concentrations are associated with Mycobacterium tuberculosis resistance. This study aims to evaluate intestinal permeability and serum concentrations of rifampin (RIF) and isoniazid (INH) in patients with multidrug-resistant tuberculosis (MDR-TB). A case-control was conducted with outpatients who attended Messejanaâs Hospital in Fortaleza-Cearà from August 2006 to April 2007. MDR-TB (case) was defined as resistance to at least RIF+INH according to the susceptibility test by the proportion method. Two control groups were formed. The drug sensible TB (DS-TB) group defined so when the isolate was sensible to RIF, INHH, streptomycin and ethambutol and the healthy control group (HC). The final MDR-TB, DS-TB and health control groups composition was 41, 33 and 41 respectively, matched by sex and age. Biochemical and haematological examinatios, lactulose:mannitol (L/M) test (to access intestinal absorption) were performed as well as social and clinical interview in all volunteers. To access the serum concentrations two blood samples were collect at two and six hours after RIF and INH ingestion in 32 MDR-TB and 28 DS-TB patients and 30 HC. The drug serum concentrations and L/M test in urine were performed by HPLC. After univariate analysis the median/range of the L and M urinary excretion percentage was significantly lower in MDR-TB patients comparing to HC (p<0.05). Adjusting for alcoholism+tabagism association or Body Mass Index (BMI), this difference disappeared for lactulose. After multivariate analysis the mean  standard (sd) deviation M urinary excretion percentage was lower in MDR-TB than in HC (p=0.0291) group or DS-TB (p=0.0369) group. The L:M ratio did not differ between the groups (p=0.4747). The meanÂsd of the INH maximum serum concentration (HCmax) was higher in MDR-TB (3.82Â1.18) than in HC (2.79Â1.19) group, p<0.01 and there was no difference between DS-TB and HC nor between MDR-TB and DS-TB groups. After multivariate analysis the HCmax increased in HC (3.07Â0.24), but, remained to be higher in MDR-TB group, and now, significantly higher only than DS-TB group. There was HCmax < 3 Âg/ml in 18.8% (6/32) of the cases and 56.7% (17/30) of the HC (p<0.05) and no difference between DS-TB (39.3%, 11/28) and HC. After multivariate analysis the meanÂsd RIF maximum serum concentration (RCmax) was lower in MDR-TB than in HC(p,0.05) and in DS-TB than in HC (p<0.001), with no difference between MDR-TB and DS-TB groups. The RCmax was < 8 Âg/ml in 90.6% (29/32) of the cases and 66.7% (20/30) of HC (p<0.05) and in 82.1% (23/28) of the DS-TB patients (comparing to HC, p<0.05). In conclusion there was reduction in transcellular intestinal absorption in MDR-TB versus DS-TB or HC and the data suggest that alcoholism+tabagism association and BMI have an important role in the reduction of paracellular transport in MDR-TB patients. The RCmax was low in MDR-TB and DS-TB patients with high proportions of subtherapeutic levels in theses groups, mainly for RCmax, but also worrying for HCmax.

A tuberculose multirresistente (TBMR) - resistência simultânea a rifampicina e isoniazida, principais fármacos do esquema de tratamento da tuberculose (TB), gera mais ônus aos doentes e aos Serviços de Saúde, pois acarreta maiores custos, aumenta o tempo de tratamento e relaciona-se a prognósticos desfavoráveis. A TBMR ocorre devido à falha em algum princípio do tratamento, seja por parte dos profissionais e serviços de saúde, seja por questões ligadas ao doente. Frente a isso, o presente estudo objetivou identificar e analisar as condições de produção da TBMR relacionadas ao doente e seu entorno. Esta investigação foi realizada junto aos sujeitos em seguimento em um hospital de referência do interior paulista, entre janeiro de 2010 a janeiro de 2012. Foi utilizada a abordagem qualitativa. Por meio da análise dos prontuários médicos do serviço terciário, caracterizamos o universo do estudo - composto por todos os doentes já seguidos pela instituição, descrevendo e analisando dados sociodemográficos e clínicos correspondentes. Caracterizamos, também, a amostra estudada, formada por oito doentes de TBMR em seguimento, detalhando seu contexto de vida e trajetória com a doença, assim como a estruturação municipal para seu acompanhamento. A segunda etapa do trabalho constituiu na análise das percepções dos sujeitos a cerca do adoecimento por TB e pela forma MR. Os dados foram coletados por meio de entrevistas semi-estruturadas, gravadas e transcritas na íntegra. Os textos resultantes constituíram o corpus do estudo, organizado com recurso do software Atlas. Ti versão 7.0 e analisado sob o referencial teórico da Análise de Discurso, de matriz francesa. Os resultados da investigação baseiam-se na análise de três aspectos: percurso diagnóstico - em que é apontadas a percepção da doença e dos sintomas, as histórias pessoais e familiares do adoecimento por TB, o desenvolver até a obtenção do diagnóstico e as histórias de fracasso dos tratamentos convencionais; tratamento e acompanhamento dos casos MR - momento em que são discutidas questões ligadas a percepção do tratamento pelos doentes, as modalidades de supervisão empreendidas, os instrumentos e insumos fornecidos, além do apoio da rede familiar; coordenação da assistência - em que são analisadas as nuances da relação entre os diferentes serviços envolvidos na atenção ao doente, tanto dentro do mesmo nível assistencial quanto em sua intersecção com a atenção terciária, a fim de compreender suas fragilidades e promover as potencialidades para o tratamento dos sujeitos. Essas condições de produção mostraram-se complexas, ao passo que sofrem influência das peculiaridades da forma como os serviços locais de atenção organizando-se para atender esses doentes, além de questões relacionadas à trajetória de vida e doença desses sujeitos, apontando para a necessidade de ampliação do espaço de negociação dentro do sistema de saúde. / Multidrug-resistant tuberculosis - simultaneous resistance to rifampicin and isoniazid, the main drugs in the treatment for tuberculosis (TB), generates more onuses to patients and Health Services because it involves higher costs, increases the treatment time and relates to the unfavorable outcomes. MDR-TB occurs due to failure in some treatment principles, either by professionals and health services, or by patient issues. Concerning this, the present study aimed to identify and analyze the conditions of MDR-TB production related to the patients and their surroundings. This investigation was conducted with the subjects followed up in a referral hospital in São Paulo State, between January 2010 and January 2012. It was used a qualitative approach. By analyzing the medical records of the tertiary service, we characterized the universe of the study - consisting of all patients who were already followed by the institution, describing and analyzing the demographic and clinical data matching. We also characterized the sample, formed by eight MDR-TB patients in follow-up, detailing the context of their lives and the disease trajectory, as well as the municipal structure to monitor them. The second stage of the work consisted of analyzing the subjects\' perceptions about TB development and MR strain. Data was collected through semi-structured interviews which were recorded and fully transcribed. The resulting texts constituted the corpus of the study, organized using the Atlas.Ti software version 7.0 and analyzed from the theoretical framework of Discourse Analysis of French matrix. The results are based on analysis of three aspects: The first is diagnosis route - which shows the disease and symptoms perception of the patient, personal and family histories of TB development, the disease development until the diagnosis, and the failed conventional treatment stories. The second aspect was treatment and monitoring of MDR cases - when cases are discussed we focused on the following aspects: perceptions of treatment by patients, undertaken methods of supervision, instruments and inputs provided, and the familiar support network. The third is assistance coordination - where the nuances of the relationship between several departments involved in the patient care are analyzed, within the same care level as well as its intersection with tertiary care in order to understand their weaknesses and promote the potential treatments for the subjects. These production conditions proved to be complex whereas the local care services peculiarities influence the way they are organized to assist these patients, as well as aspects related to life and illness trajectory of these subjects, indicating the need of expanding the negotiation space within the health system

PURPOSE: The purpose of this study was to assess factors associated with the development of drug resistant tuberculosis in Ethiopia. DESIGN: A quantitative case-control study was conducted to determine if there were any significant differences in prevalence of pre-defined factors between cases and controls. METHODS: Cases were patients with drug resistant tuberculosis who had a confirmed diagnosis by culture drug-susceptibility or gene expert tests. Successfully treated, tuberculosis symptom free patients who had been on first-line tuberculosis treatment and who were registered as cured or treatment completed were taken as controls. An equal number of cases (N=181) and controls (N=181) was selected using a systematic random sampling method and was used in the study. A structured questionnaire developed by the researcher was used to collect data. Odds ratio and multiple logistic regression were used to quantify the strength of association between dependent and independent variables. RESULTS: The development of drug resistant tuberculosis was significantly associated with two or more previous episodes of tuberculosis illness (adjusted odds ratio (AOR): 14.84; 95% CI 8.90 –24.75), previous first-line tuberculosis treatment not directly observed by a health worker for 7 to 8 weeks (AOR: 13.41; 95% CI 8.06 – 22.29) and previous first-line tuberculosis treatment outcome of failure (AOR: 39.19; 95% CI 12.05 -127.46). Interruption of first-line tuberculosis treatment for one day or more (AOR = 4.28; 95% CI 2.76 – 6.64) and history of treatment in the first-line tuberculosis treatment category for previously treated patients (AOR: 3.70; 95% CI 2.40 – 5.72) were also significantly associated with the development of drug resistant tuberculosis in the current study. CONCLUSION: Patients with a history of previous first-line tuberculosis treatment, patients who interrupted previous first-line tuberculosis treatment and patients with previous first-line tuberculosis treatment outcome of failure were at high risk of developing drug resistant tuberculosis. Therefore, the full course of first-line tuberculosis treatment should be given, following the Directly Observed Treatment (DOT) guide. Patients with recurrent tuberculosis and unfavourable first-line tuberculosis treatment outcome should be tested for drug susceptibility. / Health Studies / D. Litt. et Phil. (Health Studies)

The purpose of this study was to explore and describe the personal experiences of enrolled nurses while caring for patients infected with multidrug-resistant tuberculosis (MDR-TB) in an urban tuberculosis hospital in KwaZulu-Natal province, South Africa. Generic qualitative research was conducted with a sample of purposively selected enrolled nurses who cared for MDR-TB patients. Data was collected through in-depth individual interviews and analysed using Colaizzi’s (1978) method of data analysis. The research findings revealed six major themes: the working context, fear of contracting the disease, problems that have an impact on the quality of nursing care, nurses' perceptions of the patients, support structures and nurses' expressed needs. The findings of this study indicate that the nurses work in a challenging environment and need to be supported, as they experience more negative than positive feelings while caring for these patients. / Health Studies / (M.A. (Health Studies))

Thesis (PhD)--Stellenbosch University, 2012. / ENGLISH ABSTRACT: The prevalence of multi-drug resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis has been increasing to alarming levels globally. This has been exacerbated by tuberculosis (TB) co-infection with HIV where the epidemic is endemic. South Africa as a developing country is hit hard by TB and efforts to develop TB drugs that are compatible with anti-retroviral medication and also effective against MDR/XDR, could help shorten the treatment duration of the current TB treatment regimens. This thesis presents the identification and characterisation of a novel furanone based compound (F1082) and its derivatives as leads for anti-TB drug development. Furanones are generally known for an array of biological activities ranging from antibacterial, antifungal and antitumor. F1082 has an aromatic benzene structure and was identified from screening synthetic compounds against M. tuberculosis. It is potent against M. tuberculosis at minimum inhibitory concentration (MIC) of 8 μg/ml. It is selective for mycobacteria since it did not inhibit the growth of Gram-positive and Gram-negative bacteria at concentrations five times the MIC for M. tuberculosis. F1082 is generally bacteriostatic around MIC concentrations in its effects against M. tuberculosis however; it may be bactericidal at higher concentrations. It is as effective against MDR, XDR and clinical isolates of M. tuberculosis at the same concentration as the M. tuberculosis H37Rv reference strain. This suggests that F1082 may have a different mechanism of action compared to current TB drugs. It has been shown to have no antagonistic effect with the first-line anti-TB drugs and it has been shown to synergize with rifampicin by reducing the MIC of rifampicin. A drawback of F1082 is that it is cytotoxic to human cell lines, but this is presently being addressed through the synthesis of analogues that have shown improved activity and less cytotoxicity. The synthesis of more than 40 analogues has led to identification of 4 compounds that have more than five times higher activity and more than 100 times less cytotoxicity against human cell-lines. Microarray analyses have identified possible metabolic pathway/s in M. tuberculosis that is/are affected by F1082. One subset of genes which showed the most prominent alteration encodes the siderophores, which are involved with iron homeostasis in the M. tuberculosis bacillus. Of these genes, 7 were of interest (mbtB, mbtC, mbtD, mbtE, mbtF, mbtH and bfrB) as they all fall in the same cluster and are involved in iron acquisition. Due to the involvement of iron we also show that F1082 generates oxidative stress that is metal (iron) dependent. From the results we conclude that F1082 is a promising antituberculosis lead compound with unique target properties and also specificity against mycobacteria. / AFRIKAANSE OPSOMMING: Die voorkoms van veelvuldige middelweerstandige M.tuberculosis (MDR) en uiters middelweerstandige M.tuberculosis (XDR) is besig om toe te neem teen ‘n kommerwekkende tempo wêreldwyd. Hierdie situasie word vererger met die ko-infektering van M.tuberculosis en HIV. Suid- Afrika, as ontwikkelende land, word sleg benadeel met tuberkulose siekte. Antituberkulose middels wat kan saamwerk met bestaande antiretrovirale middels en ook effektief is teen MDR en XDR stamme, kan alles meewerk om die behandelingstyd van tuberkulose te verkort. In hierdie tesis identifiseer en karakteriseer ons ‘n furanoon-gebaseerde verbinding (F1082) en derivate daarvan as voorloper-middels vir anti-tuberkulose middelontwikkeling. Furanone is algemeen bekend vir ‘n verskeidenheid van biologiese aktiwiteite insluitende antibakteriële-, antifungale- en antitumor aktiwiteite. F1082 bevat ‘n aromatiese benseenstruktuur en is oorspronklik geïdentifiseer gedurende die skandering van sintetiese middels teen M.tuberculosis. Dit het ‘n sterk werking teen M.tuberculosis met ‘n minimum inhibitoriese konsentrasie (MIC) van 8ug/ml. Dit is baie selektief vir mikobakterieë aangesien dit nie gram-positiewe of gram-negatiewe bakterieë teen 5 maal die MIC, soos vir M.tuberculosis, geïnhibeer het nie. F1082 is bevind om, by laer konsentrasies, bakteriostaties te wees in sy aktiwiteit teen M.tuberculosis maar by hoër konsentrasies word ‘n meer bakteriosidiese effek waargeneem. F1082 is effektief teen MDR, XDR en kliniese isolate van M.tuberculosis en teen dieselfde konsentrasie soos vir die M. tuberculosis H37Rv verwysingstam waargeneem is. Dit impliseer dat F1082 dalk ‘n alternatiewe meganisme van werking het in vergelyking met die van die huidige TB teenmiddels. F1082 toon geen antagonistiese werking in kombinasie met die voorste anti- TB middels nie, maar toon wel sinergistiese werking in kombinasie met rifampisien. F1082 toon nog sitotoksiese aktiwiteit teenoor menslike sellyne, maar die sintese van derivate van F1082 toon tot dusvêr groter anti-TB aktiwiteit en verminderde sitotoksisiteit. Die sintese van meer as 40 homoloë het gelei tot die identifisering van vier verbindings met vyf keer hoër anti-TB aktiwiteit en honderd keer verminderde sitotoksisiteit teen menslike sellyne as F1082 self. “Microarray” ontledings het ‘n aantal metabolise paaie geïdentifiseer waar F1082 ‘n effek kan uitoefen. Een stel gene wat die mees uitstaande effek toon kodeer vir siderofore wat betrokke is by yster homeostase in M.tuberculosis. Van hierdie gene was daar sewe van belang omdat hulle in dieselfde groep voorkom en almal betrokke is by ysteropname (mbtB, mbtC, mbtD, mbtE, mbtF, mbtH, bfrB). Weens die rol wat F1082 in ysterhomeostase speel, toon ons ook dat F1082 intrasellulêre oksidatiewe stres bevorder wat yster afhanklik is. Al ons resultate dui daarop dat F1082 ‘n belowende ant-TB voorloper verbinding is met spesifisiteit teen M.tb en unieke teikeneienskappe in M. tuberculosis.

Nas últimas décadas, a incidência de infecções hospitalares causadas por bactérias Gramnegativas multidrogarresistentes (MDR) vem crescendo de maneira vertiginosa em todo o mundo, de modo que a Organização Mundial de Saúde (OMS) recentemente reconheceu essas infecções como uma preocupação mundial devido ao seu impacto negativo sobre as taxas de mortalidade intra-hospitalar e dos custos da assistência à saúde, afetando tanto os países desenvolvidos quanto os em desenvolvimento. Atualmente considera-se que a higienização das mãos, o uso racional de antimicrobianos e o isolamento de contato são as principais medidas disponíveis para contenção desse avanço. Porém, elas são apenas parcialmente efetivas e de implementação trabalhosa e onerosa. Assim, considera-se necessário o desenvolvimento de formas mais simples e eficientes paralidar com esse problema. No presente estudo, nos propusemos a avaliar o impacto da administração de um produto simbiótico a pacientes colonizados e/ou infectados por bactérias Gram-negativas MDR sobre as taxas de descolonização desses patógenos no trato digestivo. Trata-se de um ensaio clínico randomizado, duplamente cego, controlado com placebo, envolvendo 101 pacientes hospitalizados com colonização prévia por bactérias Gram-negativas MDR, demonstrada por meio de cultura seletiva de swab retal, cuja intervenção consistiu na administração oral ou enteral diária de 1010 unidades de Lactobacillus bulgaricus e 1010 unidades de Lactobacillus rhamnosus associados a fruto-oligossacarídeos durante (FOS) 7 dias. O desfecho primário do estudo foi a descolonização completa do trato digestivo posterior à intervenção, que, na análise do tipo \"intenção de tratar modificada\" foi de 16,7% (8/48) no grupo experimental e 20,7% (11/53) no grupo controle (p=0,600). Na análise \"per protocol\", a descolonização completa do trato observada foi de 18,9% (7/37) no grupo experimental e 23,3% (7/30) no grupo controle (p=0,659). Em uma análise multivariada por meio de modelo de regressão logística o uso do simbiótico não influenciou significativamente o risco de descolonização completa do trato digestivo (OR= 0,80, IC 95%= 0,28-2,27, p= 0,678). A ocorrência de eventos adversos de natureza leve a moderada foi semelhante entre os grupos: 7,55% no grupo que utilizou placebo e 6,25% no grupo sob intervenção (p= 1,000). Nenhum evento adverso grave potencialmente relacionado às medicações de estudo foi observado. Nas condições estudadas, os dados obtidos pelo estudo nos levam à conclusão de que o simbiótico estudado demonstrou-se inefetivo na descolonização do trato digestivo de pacientes previamente colonizados por bactérias Gram-negativas MDR. / In recent decades the incidence of multidrug resistant (MDR) Gram-negative nosocomial infections has been dramatically raising in the whole world. The World Health Organization (WHO) recently recognized nosocomial infections due to MDR pathogens as a global concern due to its negative impact on patients, health-care workers and health-care institutions, affecting developed countries as well as developing ones. They negatively impact in-hospital mortality and health-care related costs. Hand hygiene promotion, antibiotic stewardship and contact precautions are the main available measures to control such MDR Gram-negative organisms in hospitals. However, they are only partially effective as well as difficult to be implemented and expensive. Therefore, simpler and more effective actions are thought to be helpful and urgent. In the present study, we analyzed the impact of the administration of a symbiotic product on patients harboring Gram-negative multidrug-resistant bacteria upon the subsequent rates of decolonization of these pathogens from the gastro-intestinal tract.This is a double-blinded and placebo controlled randomized clinical trial evaluating the oral/enteral daily administration of 1010 units of Lactobacillus bulgaricusplus 1010 units of Lactobacillus rhamnosus associated with fructo-oligosacharide (FOS), or placebo, for 7 days, to 101 patients previously colonized by MDR Gram-negative bacteria, identified through selective culture of rectal swab. The primary study outcome was the rate of complete decolonization of the MDR microorganism from the gastro-intestinal tract following the intervention. In the \"modified intention to treat\" analysis, decolonization rates observed were 16.7% (8/48) in the experimental group and 20.7% (11/53) in the placebo group (p=0,600). In the \"per protocol\" analysis, decolonization rates were 18.9% (7/37) in the experimental group and 23.3% (7/30) in the placebo group (p=0,659). In a logistic regression model, symbiotic use did not produce any impact on the chance of decolonization (OR=0.80, CI95%=0.28-2.27, p=0.678). Mild to moderate adverse events occured similarly in both the placebo (7.55%) and the experimental group (6.25%), (p=1,000). No severe adverse event potentially related to the medications was detected during the study period. In the present study conditions, the results obtained lead to the conclusion that the studied symbiotic proved to be ineffective to decolonize patients harboring multidrug resistant Gram-negative bacilli.