Evaluation of Early Antibiotic Discontinuation Versus Standard Management in Elderly Patients with Viral Pneumonia Using Amoxicillin, Clavulanic Acid, Piperacillin, Tazobactam, and Pristinamycin

The primary objective of this study is to demonstrate that **early cessation** of antibiotics in cases of viral pneumonia, whether presumed or confirmed, leads to a reduction in antibiotic consumption at one month. This is clinically relevant as it addresses the growing concern of antibiotic overuse and its contribution to antibiotic resistance, particularly in elderly patients hospitalized for viral infections.

Secondary objectives include:

• Showing that early cessation of antibiotics in the absence of microbiological confirmation reduces the occurrence of side effects.
• Reducing the duration and complications associated with hospitalization.
• Ensuring that early cessation does not modify mortality or autonomy at one month (M1) and three months (M3).
• Confirming that early cessation does not alter antibiotic consumption at three months (M3).

The clinical trial involves **elderly patients** hospitalized for viral infections, specifically focusing on those with viral pneumonia. The study population includes both male and female participants, with an age range categorized as elderly. The trial does not target a vulnerable population. Participants were selected based on hospitalization for a lower respiratory infection, characterized by specific clinical signs such as hyperthermia, hyperleukocytosis, purulent sputum, or rales on pulmonary auscultation, along with a pulmonary image. A microbiological diagnostic sample must have been taken within 48 hours of hospitalization. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed as a **cluster-randomized controlled study** to evaluate the benefits of early discontinuation of antibiotic therapy compared to standard management in elderly patients hospitalized for viral infections. The primary objective is to demonstrate that early cessation of antibiotics in cases of viral pneumonia, whether presumed or confirmed, reduces antibiotic consumption at one month. The trial is expected to commence recruitment on January 15, 2025, and conclude by April 15, 2027, with a total duration of approximately 27 months.

Participants will be randomly assigned to either the intervention group, receiving early discontinuation of antibiotics, or the control group, following standard antibiotic management. The study will be conducted in an open-label manner, meaning both participants and investigators will be aware of the treatment allocation. The trial will include several study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as hospitalization for a lower respiratory infection and microbiological diagnostic sampling within 48 hours. Follow-up visits will be scheduled to monitor the primary endpoint, which is the number of days without antibiotics at day 30, and secondary endpoints, including side effects of antibiotics, other complications, mortality, and duration of hospitalization.

The expected length of participant involvement is up to three months, with assessments at one month (M1) and three months (M3) post-enrollment. Conditions that may lead to early termination from the study include withdrawal of consent, adverse events, or any situation where continued participation is deemed not in the best interest of the participant. The trial will utilize antibiotics such as **amoxicillin sodium**, **clavulanic acid**, **piperacillin sodium**, **tazobactam sodium**, **pristinamycin**, and **ceftriaxone**, administered via injection, IV infusion, or orally, depending on the specific medication and treatment group. The maximum treatment period for these antibiotics is seven days, with dosage and administration routes tailored to each product's characteristics.

The clinical trial involves the administration of several **antibiotic** treatments, each with specific pharmaceutical forms, dosages, and routes of administration. The first experimental medication is a combination of **amoxicillin sodium** and **clavulanic acid**, classified under the ATC code J01CR02 as "Amoxicillin and Beta-lactamase Inhibitor." This medication is provided in a pharmaceutical form identified as PHF00231MIG and is administered via injection. The maximum daily dose is 3 grams, with a total maximum dose of 21 grams over a treatment period of up to 7 days.

The second experimental treatment is a combination of **piperacillin sodium** and **tazobactam sodium**, categorized under the ATC code J01CR05 as "Piperacillin and Beta-lactamase Inhibitor." This medication is available in the pharmaceutical form PHF00230MIG and can be administered either through intravenous injection or infusion. The maximum daily dose is 12 grams, with a total maximum dose of 84 grams over a 7-day treatment period.

The third treatment involves **pristinamycin**, marketed as PYOSTACINE 500 mg, in the form of a film-coated tablet. This medication is classified under the ATC code J01FG01. It is administered orally, with a maximum daily dose of 3 grams and a total maximum dose of 21 grams over a 7-day period.

The fourth treatment is **ceftriaxone**, provided as a powder for solution for injection. The maximum daily dose for ceftriaxone is 1 gram, with a total maximum dose of 7 grams over a treatment period of up to 7 days. This medication is administered via injection.

All treatments are non-paediatric formulations and are not classified as orphan drugs. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed treatment regimens. The trial aims to evaluate the benefits of early discontinuation of antibiotic therapy compared to standard management in elderly patients hospitalized for viral infections.

Efficacy in this clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is the "Number of days without antibiotics at D30," which will measure the reduction in antibiotic consumption at one month. Secondary endpoints include the evaluation of side effects of antibiotics, such as **Clostridial colitis**, venitis, diarrhea, nausea, vomiting, BMR germ colonization, allergy, and other attributable effects. Additionally, other complications will be monitored, including nosocomial infections, complications of decubitus, intra-hospital mortality from any cause, confusion, and other complications attributable to hospitalization. Mortality rates at M1 and M3, as well as autonomy scores (ADL and IADL) at these timepoints compared to those 15 days before hospitalization, will also be assessed. The duration of hospitalization in acute care and the number of days without antibiotics at M3 are further secondary endpoints.