Bacterial Infection

This is a Phase 4, interventional, multi-center pharmacokinetics (PK) study in up to 200 adult patients who are residing in an ICU. This study will compare the abilities of Cystatin C (CysC) and CysC-based estimated Glomerular Filtration Rate (eGFR) equations to characterize the PK profiles of meropenem and cefepime relative to Serum Creatinine (SCR), Serum Creatinine based Equation (SCRE), and iohexol in critically ill patients with suspected or documented AMR Gram-negative infections. We hypothesize that CysC and CysC-based eGFR equations will characterize the PK profiles of meropenem and cefepime at the population and individual levels with greater accuracy and precision than SCR and SCREs. Iohexol will be administered to patients enrolled in the study and serve as the reference indicator of measured Glomerular Filtration Rate (mGFR), which is the gold standard assessment of kidney function. We further hypothesize that the predictive performances of CysC and CysC-based eGFR equations in estimating the PK profiles of meropenem and cefepime at the population and individual levels will be comparable to iohexol. Firstly, population PK (PopPK) modeling will be used to develop meropenem and cefepime PopPK models informed by CysC, CysC-based eGFR equations, SCR, and SCREs (renal function biomarkers), and iohexol clearance. Secondly, model diagnostics will then be used to compare the predictive performances of the renal function biomarkers PopPK models for each antibiotic relative to iohexol PopPK model. Lastly, Monte Carlo simulation (MCS) will be used to design PK/ pharmacodynamics (PD) optimized meropenem and cefepime dosing schemes based on the renal function biomarker PopPK model with the best predictive performance for use in the treatment of critically ill adult patients with suspected or documented AMR Gram-negative infections and varying degrees of renal function. The primary objective of this study is to compare the abilities of renal function biomarkers (CysC, CysC-based eGFR equations, SCR, SCREs) relative to iohexol to characterize the PK profiles of meropenem and cefepime in critically ill adult patients with suspected or documented AMR Gram-negative infections.

This study aims to evaluate whether microbiological testing of the perfusion fluid used to transport transplanted organs can help predict the development of infections in liver and kidney transplant recipients, including possible donor-derived infections (infections transmitted from the donor organ). The study will include all liver and kidney transplant recipients with available perfusion fluid culture results from 2021 until the start of the study (retrospective phase) and for two years after study initiation (prospective phase). The study will assess how often high-risk microorganisms are identified in perfusion fluid, whether these findings are associated with complications or infections in recipients, and whether they affect patient outcomes, including mortality.

The goal of this clinical trial is to learn how rifaximin 200 mg is processed in the body (pharmacokinetics) in children 6 to 11 years old with acute diarrhea that may be caused by bacteria. It will also learn about the safety and effectiveness of rifaximin when given with oral rehydration therapy (ORT) compared with ORT alone. The main questions it aims to answer are: How does rifaximin 200 mg move through and leave the body in children with acute diarrhea? Is rifaximin safe for children in this age group? Does rifaximin plus ORT help resolve diarrhea faster than ORT alone? Researchers will compare rifaximin plus ORT to ORT alone to see if adding rifaximin improves outcomes. Participants will: Take one rifaximin 200 mg tablet + ORT three times a day for 3 days or receive ORT alone Receive oral rehydration therapy according to the investigator's standard of care Attend up to 4 clinic visits over 5 days and receive 4 follow-up phone calls Provide blood samples on Day 1 and Day 3 for pharmacokinetic testing (rifaximin group only) Provide stool samples to identify bacterial pathogens Keep a diary of stool frequency and consistency to help determine when diarrhea resolves Be monitored for side effects, vital signs, and laboratory changes