Use of a symbiotic product to decolonize patients harboring multidrug-resistant Gram-negative bacilli

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

A randomized clinical trial on the effectiveness of a symbiotic product to decolonize patients harboring multidrug-resistant Gram-negative bacilli

Abstract INTRODUCTION: We aimed to evaluate the effectiveness of a symbiotic product to decolonize the intestinal tract of patients harboring multidrug-resistant (MDR) Gram-negative bacilli and to prevent nosocomial infections. METHODS: This was a randomized, double blind, placebo-controlled clinical trial, conducted in a tertiary-care university hospital. All adult hospitalized patients with a positive clinical culture and a positive rectal swab for any MDR Gram-negative bacilli were potentially eligible. Exclusion criteria were pregnancy, immunosuppression, and bowel obstruction/perforation. The intervention consisted of administering a symbiotic product (Lactobacillus bulgaricus, Lactobacillus rhamnosus, and fructo-oligosaccharides) twice a day for seven days via the oral/enteral route. RESULTS: Between August 1, 2012 and December 22, 2013, 116 of 275 eligible patients were allocated to treatment (n=57) and placebo (n=59). Overall, 101 patients received at least four doses of the study products and were included in the modified intention-to-treat analysis. The primary study outcome, a negative rectal swab for MDR Gram-negative bacilli after treatment, was identified in 16.7% (8/48) and 20.7% (11/53) of patients in the experimental and placebo group, respectively (p=0.60). The secondary outcome, the combined incidence of nosocomial respiratory and urinary tract infections, was 37.5% (18/48) in the experimental group versus 22.6% (12/53) in the control group (adjusted odds ratio: 1.95, 95% confidence interval: 0.69-5.50, p=0.21). Length of stay after the beginning of the intervention, incidence of adverse events, and in-hospital mortality rates were similar in both study groups. CONCLUSIONS: Under the present study conditions, symbiotic administration was not effective for decolonizing hospitalized patients harboring MDR Gram-negative bacilli