We propose to recruit 200 elderly hospitalized participants within 48 hours of admission to the study hospital. The potential patients shall be screened and shall be approached for informed consent. The eligible participants and/or their responsible adult family members (for those unable to consent themselves) shall be approached for consent using the participant information sheet (PIS) and consent form. They will be fully informed about the trial through the PIS supplemented with verbal explanations following the ethical principles. If a participant who himself/herself was not in a capacity to give consent (consent given by the responsible family member) regains capacity during the trial period, the participant will be fully informed about the trial and informed consent to remain in the trial will be obtained from him/her. A screening, eligibility, consenting and randomisation log will be kept at the study site. Randomisation: After obtaining informed consent, the participants will be randomized into one of the two arms in 1:1 ratio, using double-layered opaque envelopes with the allocation arms generated following computerized block randomization with variable blocks of 4 and 6 (by an independent biostatistician using a web-based random number generator). The envelopes will be kept centrally by an independent nurse (not involved in the study). The research staff obtaining consent from the participant will inform the independent nurse and the nurse shall assign the study ID as per the envelope sequentially. The independent nurse shall open the envelope, identify the arm (Arm A-TM-mix or Arm B-Placebo) allocation and inform the study team member. Once opened for a participant, the envelope will not be used for another participant even if the participant declines participation subsequently. The used envelopes shall be submitted to an independent statistician.

Product preparation and supply: After opening the sealed envelope and allocation of arm, the study team member will inform the product preparation team (PPT) about the study ID and randomization allocation arm for the appropriate supply of the study product. The study products shall be prepared daily and packed in similar bottles, labeled with the participant’s ID (not arm/product) and supplied individually to the participant’s bedside.

·       Intervention product arm (Arm A- Torani-Xylitol mix, TX-mix): The participants in the intervention product arm, the Torani product (Arm-A) shall be prepared centrally and supplied. The Torani product shall be supplied. The bottles shall be packed with 350 ml of the Torani and 5 gm of Xylitol added to the bottle and sealed/capped. The content of the Torani product shall be analysed for microbiota and SCFA content periodically. The study IDs of the participants shall be pasted on the bottles.

·       Comparison product arm (Amr B- plain water, placebo): The participants in the comparator arm (Arm B-Placebo) shall be provided plain mineral water. The bottled water available in the market shall be procured and packed into similar bottles with 350 ml for each participant. The study IDs of the participants shall be pasted on the bottles.

These packed bottles shall be supplied to the respective participant’s bedside daily. The participants shall be asked to consume these drinks within two hours of supply.

Blinding and masking: Due to the nature of the products, the participant and research staff cannot be blinded. The laboratory analysis team and outcome assessing team would be blinded to the study group allocation. The bottles shall be selected to minimize the visualization of the product and the products shall be masked. For any reason, if required, the intervention product may be stopped as per the instruction of the treating doctor.

Adherence and tolerance: The participant’s adherence to the study product will be collected from various sources: daily feedback collected by the research staff from each participant about consumption and the supply log with the PPT shall be checked. The tolerance to the product shall be captured using a structured CRF daily.

Withdrawal and loss to follow-up: Each participant has the right to withdraw from the trial at any time. The refusal to participate or withdraw will not affect the participant’s standard care in the hospital. Any patient discharged, referred, LAMA or died prior to the schedule shall be noted.

Adverse events: Any untoward medical occurrence in the participants irrespective of the causal relationship with the intervention product will be recorded. We will collect the information about the serious adverse events (SAEs). The SAEs shall be causality assigned into one of the categories; unrelated, unlikely, possible, probable, definite or not assessable.

Follow-up: The participants will be followed up monthly after the discharge through day 90 after completion of the 14-day consumption schedule for any infection, gastrointestinal disturbances or recurrence of CDI.

Data collection: The following data and samples will be collected from the participants using structured Case Record Forms (CRFs).

·       Baseline: socio-demography, occupation, anthropometry, household/occupational animal contact, illness and diagnosis, comorbidities, fresh stool sample/rectal swab (within 48 hours) for CD testing;

·    During intervention and hospital stay: clinical status, blood tests, study product intake and tolerance, medications, any feature of CD infection, stool/rectal swab (for toxin, NAAT or culture) and blood (for TLC, DLC) samples if CDI suspected;

·   On Day 7 or 15 or at discharge/death/referral/LAMA: stool sample for CD isolation and inflammatory markers (in selected participants), the clinical condition shall be documented on day 15 (one day after completion of the intervention product consumption). At discharge, the final diagnosis, outcome, clinical condition, drugs given, any isolated organisms (culture from other sites/body fluids) will be documented. For the patients discharged or referred or LAMA before the day 15 sample collection, stool sample/rectal swab shall be collected at discharge/referral/LAMA.

·       Follow up contacts on days 30(+7), days 60(+7) and days 90(+7) post-completion of therapy: health, any illness/infection (diagnosed, suspected), medication use, hospitalization, any blood tests, food practices for probiotics and fermented rice-water, and animal contact (household/occupational) over the telephone.

The study team members shall be trained for the counseling to obtain consent and data collection. For the clinical components, the team members shall seek assistance from the treating doctors and investigators.

The study data will be collected using a paper-based form which will then be entered into an electronic form. A copy of source documents will be maintained at the study site with the study records to recheck the validity of data as needed. Range and limits checks for data values, skip patterns and validation rules will be used to improve the accuracy of the data. Access to the data entry software will be password protected to ensure confidentiality. Data will be accessible only to the study investigators. Periodic de-identified reports will be submitted to IEC and DSMB. Raw data will be provided on request to the DSMB for interim analysis.

Sample processing and testing:

·       The stool samples will be subjected to GDH and toxin assay (EIA) tests. For the samples positive GDH and/or toxin shall be subjected for NAAT. In selected cases, culture for CD (using selective media and anaerobic Gas pack) shall be done. The sample aliquots shall be stored at -80⁰C for further analysis. The positive culture isolates shall be subjected to VITEK-2 for AST.

· The CD-positive isolates from 30 participants (8-10 each from, who acquired CD, who eliminated CD, who had confirmed/suspected CDI) shall be subjected to whole genome sequencing.

· The fecal cytokines CXCL-5, CXCL-8) and lactoferrin shall be estimated by ELISA kit in a sub-set of 25 participants per arm at baseline and after completion of product consumption (day 15).

·  The Torani samples (once a month) will be tested for microbiota (culture to detect the lactobacillus species); bacteria (16S rRNA gene sequencing to identify bacteria species) using molecular sequencing techniques, and SCFA (HPLC).