Escherichia coli Infection (E. coli)

Researchers are studying the safety and effects of a medicine combining aztreonam and avibactam (ATM-AVI) for treating infections caused by gram-negative bacteria in newborns and infants under 9 months old admitted to hospitals. This Phase 2a study aims to understand how the medicine behaves in the body and how well it is tolerated. It includes hospitalized infants with suspected or confirmed bacterial infections requiring intravenous antibiotics. The study has two parts. In Part A, participants receive a single intravenous infusion of ATM-AVI over three hours to assess safety, tolerability, and drug levels without treating the infection. In Part B, participants receive multiple intravenous infusions every 6 to 8 hours for 3 to 14 days as treatment for their infection, with some also receiving metronidazole or other antibiotics as needed. Blood samples and clinical responses are monitored during and after treatment. Participants will undergo blood tests to measure ATM-AVI levels and safety assessments during treatment and up to 5 weeks after infusion. Clinical responses to treatment are evaluated at the end of intravenous therapy, oral antibiotic switch if applicable, and at a test-of-cure visit 7 to 14 days post-treatment. An independent committee will oversee safety, and the total participation lasts about 5 weeks for Part A and up to 7 weeks for Part B.

Researchers are evaluating the use of D-mannose supplementation to prevent recurrent urinary tract infections (rUTI) in post-menopausal women. This randomized, double-blind, placebo-controlled study aims to improve understanding of rUTI prevention in this population, which is disproportionately affected and understudied. The study tests whether daily D-mannose intake over 6 months and up to one year effectively reduces the occurrence of uncomplicated rUTIs compared to placebo. Participants will be randomly assigned in a 2:1 ratio to receive either D-mannose (2 grams daily, taken as four 500 mg capsules) or a placebo for 12 months. The study follows CONSORT guidelines and includes two groups: one receiving the active supplement and the other receiving a placebo. The study aims to enroll 90 women who are currently free of UTI but have a history of recurrent infections. During the study, participants will attend follow-up appointments to monitor urinary tract health through urine cultures and symptom assessments. Researchers will collect data on failure rates, number of antibiotic treatments for UTI, symptom severity, and any serious adverse events related to D-mannose over an average follow-up of five years. This allows long-term observation of the supplement's impact on rUTI prevention and safety.

Urinary tract infection (UTI) is a common bacterial infection affecting millions worldwide, with recurrent cases leading to high antibiotic use and health costs. This trial investigates alternative treatments by studying the ability of a non-pathogenic E.coli strain (ABU) to prevent recurrent UTIs by outcompeting the harmful bacteria. The study is a placebo-controlled, double-blind clinical trial aimed at strengthening evidence for this approach. Participants will be randomly assigned to one of two groups: one receiving bladder flushing with the non-pathogenic ABU bacterial strain as a preventive treatment, and the other receiving bladder flushing with a saline solution as a placebo. This study uses a quadruple-blind design to ensure unbiased results and focuses on evaluating the clinical effect of these interventions in preventing recurrent cystitis. During the 1½-year follow-up, participants will undergo various assessments including monitoring the number of UTI events, time to first UTI after intervention, quality of life questionnaires, symptom scoring, and microbiological and laboratory tests. Safety aspects such as complications and hospitalizations will also be tracked. The study includes patients with different bladder conditions and requires regular clinical and microbiological evaluations throughout the trial period.

Researchers are evaluating an investigational phage therapy for adults with spinal cord injury (SCI) who have neurogenic bladders colonized by Escherichia coli bacteria. This Phase 1b study aims to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of the therapy. Participants have bacteriuria and use either indwelling catheters or require intermittent catheterization for bladder drainage. The study is randomized, double-blind, placebo-controlled, and conducted at a single center. About 30 participants will be randomized to receive either the investigational phage therapy or a placebo. The phage therapy involves a personalized mixture of up to three phages targeting the participant's dominant E. coli strain. This sterile solution is instilled directly into the bladder via catheter twice daily for 7 days. The placebo group receives sterile saline solution administered the same way and schedule. Treatment includes 14 doses over 7 days, followed by a flush of sterile saline after each dose. Participants may be inpatients or outpatients and will undergo up to 30 days of screening before randomization. After treatment, follow-up visits occur on Days 14, 21, 28, and 35 to monitor safety and collect data. Assessments include adverse event monitoring, pharmacokinetic and pharmacodynamic evaluations, and bladder-related health checks. The total study duration per participant is up to 65 days. Safety and tolerability are the primary outcomes measured during and after treatment.

Researchers are evaluating new home-based methods to measure medication and chemical concentrations in sweat and saliva compared to standard blood tests in patients with chronic or infectious diseases who are receiving medications. The study aims to see if a smart wristband can accurately monitor substances like electrolytes and metabolites in sweat, which may help in health monitoring and disease diagnosis. This pilot observational study is focused on assessing the feasibility of these wearable sweat sensors. Participants provide sweat samples using a Macroduct Sweat Collection System, saliva samples, and blood samples within 24 hours after taking their medications. They also complete short questionnaires lasting 5 to 10 minutes and allow their medical records to be reviewed. The study collects samples and data to compare the new home-based methods against the standard liquid chromatography-mass spectrometry of plasma. During the study, patients are followed periodically after completing sample collection to monitor results and assess feasibility. Researchers measure how well the home-based sampling predicts medication levels and observe plasma concentrations within 4 hours. The study includes ongoing follow-up to evaluate the ease of obtaining home-based samples and to review medical data over time.

This research aims to evaluate the effects of a multi-component chlorination intervention on maternal and neonatal health in public healthcare facilities in western Kenya. The trial focuses on reducing bacterial contamination and antibiotic-resistant infections in neonates born at these facilities. The study is a cluster randomized controlled trial involving 36 health facilities, with a goal to provide evidence on how chlorinated water supply and reliable chlorine disinfectant use impact bacterial contamination and infection rates. Health facilities will be randomly assigned either to a control group or to an intervention group. Intervention facilities will receive passive inline chlorine dosers that automatically treat water used in maternity wards, along with a steady supply of chlorine disinfectant. Half of the intervention sites will produce chlorine on-site using electrochlorinators, while the other half will receive bulk chlorine deliveries. Both intervention and control facilities will receive infection prevention and control messaging. Facilities will also get equipment like mops and spray bottles for surface cleaning. Participants include pregnant adults or mature minors giving birth at enrolled facilities and their newborns. Researchers will collect data over 24 months, assessing bacterial contamination in water, on hands, and on surfaces, as well as gut colonization by pathogenic and antibiotic-resistant bacteria in mothers and neonates. Health outcomes like possible serious bacterial infection and sepsis symptoms will be monitored during the first week after birth. The study will also track neonatal and maternal mortality up to 28 days postpartum to understand the intervention's impact on infection and health.

Researchers are evaluating the clinical and antibacterial effects, safety, and pharmacokinetics of the drug Fluorothiazinone compared to a placebo for preventing hospital-acquired gram-negative bacterial infections in patients who are on mechanical ventilation. The study is a randomized, double-blind, placebo-controlled clinical trial conducted by the Gamaleya Research Institute of Epidemiology and Microbiology. Participants are randomly assigned to receive either Fluorothiazinone tablets or a matching placebo. Those in the treatment group take 2400 mg per day (4 tablets twice daily) for the first two days, then 1800 mg per day (3 tablets twice daily) from day three onward for up to 14 days or until ventilator-associated pneumonia caused by gram-negative bacteria develops. Tablets are taken twice daily, 12 hours apart, 30 minutes after meals. The placebo group follows the same dosing schedule with inactive tablets. During the study, participants are monitored for the development of pneumonia, bloodstream infections, and urinary tract infections associated with mechanical ventilation over a 14-day therapy period. Researchers track the time to infection onset, the proportion of patients affected by infections or septic complications, and any fatal outcomes. Safety, tolerability, and blood levels of Fluorothiazinone are also evaluated. The study includes adult patients in intensive care units who have been on mechanical ventilation for no more than 12 hours and are at high risk of requiring ventilation within 72 hours.

Access to safe drinking water remains a major challenge in rural households of developing countries, leading to millions of deaths annually due to unsafe water sources. This research evaluates a program that provides coupons for free dilute chlorine solution to improve child health by reducing diarrhea, fever, and cough incidents. The study is a large-scale randomized controlled trial conducted at health clinics, assessing the sustained health impacts and behavior related to chlorine use and health clinic visits. Participants are randomly assigned to receive coupons redeemable for a monthly supply of a 150ml bottle of dilute chlorine solution at registered health facilities for 12 months or to a control group that receives no coupons after enrollment. The intervention is delivered via SMS with an ID for coupon redemption after enrollment over a phone call. The study is conducted in collaboration with the Kenya Medical Research Institute at Health and Demographic Surveillance Systems sites. Participants are monitored for chlorine use in drinking water at 6-month intervals up to 36 months, along with assessments of child illness occurrences like diarrhea and fever. Data collection also includes child mortality and verbal autopsies for deceased children, providing valuable information for future studies on the mortality impact of chlorine distribution. The study involves ongoing data collection on self-reported health facility visits and objective measures of chlorine use over the study period.

Metallo-β-lactamase-producing carbapenem-resistant Gram-negative bacteria (MBL-CR-GNB) are a serious global health threat due to their ability to break down almost all β-lactam antibiotics. Current inhibitors like avibactam cannot stop metallo-β-lactamases, limiting treatment options. Researchers are studying the combination of ceftazidime-avibactam with aztreonam, which works together to fight these infections. This phase 4 clinical trial aims to compare different infusion methods for this combination in patients with complicated infections caused by MBL-CR-GNB. Participants will receive either a 3-hour simultaneous intravenous infusion of ceftazidime-avibactam 2.5g and aztreonam 2g every 8 hours, or a sequential infusion where ceftazidime-avibactam is given over 2 hours followed by aztreonam over 1 hour every 8 hours. The study is randomized and double-blinded, comparing the effects of these two dosing schedules. Both methods are being evaluated for their ability to reach effective drug levels and their impact on infection outcomes. During the trial, researchers will monitor patients for clinical cure rates within 14 days, microbiological eradication, and any adverse events. Assessments include genotypic testing to confirm bacterial resistance, clinical evaluations, and safety monitoring. The study will follow patients through their treatment period, with careful tracking of infection response and potential side effects to determine if one infusion method offers advantages over the other.

Researchers are evaluating a new approach for managing uncomplicated Gram-negative bacteraemia, a bloodstream infection caused by certain bacteria. The study aims to compare the effects and costs of switching early to oral antibiotics within 72 hours after the first positive blood culture versus continuing standard intravenous (IV) antibiotic therapy. This international, open-label, phase IV trial involves clinically stable adult inpatients who are not critically ill and seeks to determine if the oral treatment is not worse than the IV treatment by a small margin. Participants are randomly assigned to one of two groups. In one group, patients switch to oral antibiotics such as fluoroquinolones (commonly ciprofloxacin) or trimethoprim-sulfamethoxazole within 72 hours after blood culture collection. Dosages are adjusted based on patient weight and kidney function. If oral treatment fails, patients can return to IV antibiotics. The other group continues IV antibiotics, such as ceftriaxone or cefazolin, for at least another 24 hours after randomization. The recommended total antibiotic course is about seven days but can be longer if needed. Patients may be discharged home or receive outpatient IV therapy as appropriate. During the study, researchers will monitor participants for outcomes like survival up to 90 days after randomization, days on IV antibiotics, adverse events, hospital stay length, readmissions, and quality of life scores. Data on health economics will also be collected. Follow-up assessments include evaluating mortality at 30 days, antibiotic use, treatment changes, and health-related quality of life at screening, end of treatment, and day 90. The study continues until July 2026, with careful monitoring of safety and treatment effects throughout.