Impact of Lactobacillus plantarum use on colonization, infection by multiresistant bacteria and the microbioma of patients submitted to Hematopoietic Stem Cell Transplant

• Grant number: 18/13147-3
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2018
• End date: February 28, 2021
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Silvia Figueiredo Costa
• Grantee: Silvia Figueiredo Costa
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Ester Cerdeira Sabino

Abstract

The prevention and treatment of infections have improved the results of hematopoietic stem cell transplantation (HSCT) in recent decades. However, infection still represent a major cause of morbidity and mortality in HSCT. A proposal to reduce infections with multidrug-resistant (MDR) pathogens is the handling of the microbiome of the gastrointestinal tract. In HSCT the diversity and stability of intestinal microbiome are heavily modified by increasing the risk of infections and graft-versus-host disease (GVHD). The use of probiotics is one of the alternatives to modulate the microbiome. Objective: to evaluate the use of L. plantarum in the contribution of intestinal microbiome equilibrium and consequently the impact on the rate of colonization and infection by MDR in HSCT patients,Methodology: two studies will be carry out, a pilot study of decolonisation of patients colonized by MDR with the use of L. plantarum and a prospective double-blind randomized controlled trial with intention-based analysis treat, the use of L. plantarum in the prevention of colonization and infection by MDR. The study will be conducted at the Central Institute of the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (ICHCFMUSP), in the unit cell therapy clinic (UCTC). The sample size was calculated based on historical rate of hospital infection control Committee with 80% power to detect a reduction of incidence rate of 50% in the primary outcome in the intervention group, being estimated 266 participants (130 patients in each arm). The following MDR will be evaluated: vancomycin-resistant Enterococci, carbapenem or colistin-resistant Gram-negative bacteria (K. pneumoniae, P. aeruginosa and A. baumannii). In the study of decolonization are included patients colonized by MDR that receive the L. plantarum on the HSCT to neutropenia. Stool collection will be held (in particular with Guanidine bottle) and rectal swab for weekly searches of MDR and pre and microbiome characterization after decolonization. The prospective study will include all patients who perform HSCT ceasing the use of probiotic in the presence of mucositis, or GVHD in grafting. Laboratory testing shall be carried out in the laboratory of medical research LIM-54. The characterization of intestinal microbiome will be held by the amplification of the 16S ribosomal segment V4 domain bacteria, using the primers F515 (5 2-CACGGTCGKCGGCGCCATT-3 ') and R806 (5 2-GGACTACHVGGGTWTCTAAT-3 '). The sequencing step is performed with the PGMTM Ion Sequencing kit 400 (Life Technologies) and the Ion platform.The amount of L. plantarum offered will be of 5 x 109 colony forming units (CFU) twice daily in capsule form of gastric release produced in compounding pharmacy. The safety of the probiotic usage will be the absence of bacteremia caused by L. plantarum since the beginning of use until D + 60. Patients in the control group will receive placebo capsules and will be instructed to use them also to the intervention group patients. In a randomized, prospective study the primary outcome is the prevention of colonization and infection by multidrug-resistant bacteria in patients of HSCT and as secondary outcome: modulation of microbiome; diet and microbiome in HSCT patients; gastrointestinal toxicities; costs with antibiotic therapy. (AU)