Nosocomial Transmission of MDR-TB in Bucharest, Romania

Study Overview
=================
Brief Summary
-----------------
Single-center, observational, prospective cohort study including patients hospitalized on the multidrug-resistant tuberculosis ward at Marius Nasta Institute. The increasing rates of multidrug-resistant (MDR) tuberculosis (TB) are causing great concern. The current study that will be conducted at the Marius Nasta Institute, one of two nationwide excellence treatment centers for MDR-TB in Romania, is aiming to prospectively investigate the population structure of patients with MDR-TB admitted for treatment and the M. tuberculosis strains isolated from these patients. Transmission of MDR- strains of Mycobacterium tuberculosis among patients hospitalized there will be also ascertained. Additionally biomarkers for treatment response during the course of the tuberculosis therapy will be evaluated. The study will be conducted in a co-operation between the Marius Nasta Institute and the German Center for Infection Research (DZIF).

Detailed Description
-----------------
Single-center, observational, prospective cohort study including all patients hospitalized on the MDR-TB ward at Marius Nasta Institute. An estimated 100 patients with MDR-TB consecutively admitted for treatment at the MNI will be assessed for eligibility as study participants. All potential participants will be asked to provide information on demographic, epidemiological and clinical characteristics as well as prior treatment and disease history. Microbiological data, treatment and adverse events data will also be recorded. The data is expected to supplement the existing body of knowledge about patients with MDR-TB from the region. In order to characterize M. tuberculosis strains, sputum samples will be collected from the participants upon admission to the MDR-TB ward and after 3 months of therapy. Additionally, subsequent samples identified as being positive after prior culture conversion will also undergo testing. Key examinations on these samples include drug susceptibility testing on solid media and molecular typing. If samples originating from the same patient show discordance, whole genome sequencing will be performed to allow strain comparison between the actual patient strain and those isolated from other patients to identify potential nosocomial transmission. The location on ward of patients as well as their activities will also be recorded in the scope of identifying possible routes of transmission. Blood and urine samples will be collected at specific time points during the study and further assessed in order to identify candidate biomarkers that are potentially correlated with response to anti-tuberculosis therapy. All data generated from this study will be collected on standardized study forms and entered in a password-secured database.

Official Title
-----------------
Nosocomial Transmission of Multidrug-resistant Tuberculosis at the Marius Nasta Institute in Bucharest, Romania

Conditions
-----------------
Tuberculosis, Multidrug-resistant

Intervention / Treatment
-----------------
* Other: Routine management practices applied


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects with confirmed pulmonary MDR-TB Subject able and willing to give informed consent Exclusion Criteria: physical or mental inability preventing study participation at the discretion of the investigator member of a vulnerable or special population (prisoner, soldier, mentally ill, under guardianship, age <18 years.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with MDR-TB<br>Patients with multidrug-resistant tuberculosis admitted for treatment at the Marius Nasta Institute will be included | Other: Routine management practices applied<br>* all patients will be treated according to routine procedures, no intervention<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with nosocomially transmitted MDR-TB |  | until the end of treatment - ca. 20 months after enrolment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concordance between phenotypic drug susceptibility testing and detected resistance mutations |  | until the end of treatment - ca. 20 months after enrolment | 
| Proportion of patients with changes in drug susceptibility pattern during treatment |  | until the end of treatment - ca. 20 months after enrolment | 
| Proportion of patients with mixed infections |  | until the end of treatment - ca. 20 months after enrolment | 
| Clustering within the MDR-TB patient population |  | until the end of treatment - ca. 20 months after enrolment | 
| Number of patients with different TB genotypes (e.g. Beijing, LAM, EAI, etc.) |  | until the end of treatment - ca. 20 months after enrolment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
tuberculosis, MDR-TB