Clinical Research Directory

The LalelaLung Study: Digital Stethoscope Clinical Evaluation

Pneumonia is the leading infectious cause of death in children under five years of age worldwide, and most of these deaths occur in low- and middle-income countries. In these settings, frontline health workers diagnose pneumonia using the World Health Organization's Integrated Management of Childhood Illness (IMCI) guidelines, which rely mainly on counting how fast a child is breathing and checking for chest indrawing. This approach has saved many lives, but it is not very specific. As a result, many children who actually have self-limiting viral illnesses that do not require antibiotics are nonetheless treated with antibiotics, contributing to the global rise of antimicrobial resistance. New digital stethoscopes paired with artificial intelligence (AI) can record a child's lung sounds and automatically detect abnormal sounds such as crackles and wheezes with accuracy comparable to physicians. The LaLeLa Lung Study will evaluate whether adding an AI-enabled digital stethoscope to standard IMCI assessment improves the accuracy of pneumonia diagnosis among children aged 2 to 59 months who present with cough and/or difficult breathing at a primary care clinic in Cape Town, South Africa. The main component (Objective 1) is a randomized, triple-blinded diagnostic accuracy study that will enroll 350 children, randomly assigned in a 1:1 ratio to either IMCI care enhanced by the AI-enabled digital stethoscope or standard IMCI care. An independent panel of physicians, blinded to the AI results and to study-arm assignment, will review each case and serve as the reference standard for determining whether pneumonia was truly present. The investigators hypothesize that IMCI enhanced by the AI stethoscope will diagnose pneumonia more accurately, and target antibiotics more appropriately, than standard IMCI alone. Nested sub-studies will additionally evaluate a second AI stethoscope for tuberculosis detection, a wearable lung-sound and respiratory-rate patch, an automated respiratory-rate monitor, and a smartphone-connected pulse oximeter. A separate component (Objective 2) is a mixed-methods implementation study at a second clinic that will assess how easily health workers can use these devices, how acceptable the devices are to health workers and caregivers, and how well the devices fit into routine clinic workflows. Throughout the study, all AI-generated results will remain concealed from clinic staff, study clinicians, and caregivers, so the AI-generated results will not influence the care any child receives. All children continue to receive standard IMCI care. Findings will help inform whether AI-enabled digital auscultation should be integrated into childhood pneumonia care in South Africa and similar low-resource settings, with the goal of improving diagnosis, strengthening antibiotic stewardship, and reducing antimicrobial resistance and child mortality.

Dynamics of AMR Spread, Persistence and Evolution Between Humans, Animals and Their Environment

Humans in contact with animals such as dog owners, may be at risk of antimicrobial resistance (AMR) acquisition. This is the central issue to be investigated in DYASPEO

Nasopharyngeal Carriage of S. Pneumoniae

This nasopharyngeal (NP) carriage surveillance study was requested by the European Agency for the Evaluation of Medicinal Products as a post-licensing commitment to determine whether the use of the pneumococcal conjugate vaccines (PCVs) including 7 then 13 valents (introduced in 2001 and 2010, respectively) caused a shift in the distribution of Streptococcus pneumoniae serotypes in children with acute otitis media and modified the resistance of this bacterial species to antibiotics.

Oritavancin for CIED Infections With MDR Gram-positive Cocci

The study aimed to conduct a randomized, non-inferiority controlled trial to compare the short- and medium-term efficacy and safety of two antibiotic dosage regimens in cardiac implantable electronic devices (CIED) infections with multidrug-resistant Gram-positive cocci: 1) single-dose therapy with a long-half-life antibiotic (oritavancin) vs. standard 7-14 days of therapy with a short-half-life antibiotic (vancomycin) for CIED surgical incision site or pocket infection; and 2) fractionated therapy with a long-half-life antibiotic (oritavancin) at seven-day intervals compared to standard therapy with a short-half-life antibiotic (vancomycin) fractionated in 2-3 daily doses in cases of lead-related infectious endocarditis.

Antimicrobial Therapeutic Drug Monitoring During Lung Transplant Perioperative Phase

Background: Post-LUTX pneumonia represents a leading cause of death along the first month after LUTX. Donor-derived transmission of pathogenic species occurs up to 25% of recipients receiving a graft with a positive BAL culture, despite in-vitro adequate antimicrobial prophylaxis. Hypothesis: LUTX recipients are either exposed to suboptimal antimicrobial doses or antimicrobial penetration into the lug parenchyma is altered either due to surgery (absence of bronchial anastomoses) or to the hyperinflammatory state. Methods: LUTX recipients admitted to the intensive care unit at the Fondazione IRCCS Ca' Granda Policlinico Hospital. According to the institutional perioperative prophylaxis protocol and the donor/recipient ecology the most frequent antimicrobial molecules administered will be: cefepime, vancomycin, and meropenem. Antimicrobial pharmacokinetics will be investigated at three timepoints. Plasma levels of the ongoing antimicrobial molecule will be assessed at ICU admission, on postoperative day 1 and on postoperative day 3. Bronchoalveolar lavage (BAL) samples for the measurement of BAL antimicrobial levels will be collected during the BAL performed for clinical indication on postoperative day 1 and on postoperative day 3. Absolute plasma and BAL antimicrobial levels will be assessed. The ratio of BAL to plasma dosage of antimicrobial will be assessed to evaluate antimicrobial penetration within the target tissue. Correlation between both plasma and BAL antimicrobial dosage and recipients' postoperative fluid balance, body weight, vasopressor requirement, renal function will be performed.