Clinical Research Directory

MP101 in Adults With Acute Pseudomonas Aeruginosa Pneumonia

The purpose of this study is to evaluate the safety and tolerability of a single intravenous dose of MP101 administered in addition to standard antibiotic therapy in adult patients with acute Pseudomonas aeruginosa pneumonia. The study will also assess the pharmacokinetic and pharmacodynamic characteristics of MP101 and its antibacterial activity, including changes in P. aeruginosa burden in sputum and changes in susceptibility to MP101 and concomitant antibiotics.

Urine Pneumococcal Antigen Project

Background:Pneumonia caused by the bacteria Streptococcus pneumoniae is a leading cause of death among children under five years of age, especially in sub-Saharan Africa. Accurate diagnosis remains challenging due to the need for invasive procedures to obtain samples for culture-based diagnostic tests, which are not very sensitive for detecting S.pneumoniae, particularly after antibiotic use. Serotype-specific urinary antigen detection (ssUAD) assays are a promising, non-invasive alternative for the surveillance and diagnosis of pneumococcal disease. Importantly, they can identify different serotypes of S.pneumoniae, which is crucial for monitoring vaccine impact. However, the ability of the ssUAD to identify invasive disease due to S.pneumoniae has not been studied in children in sub-Saharan Africa, where high rates of asymptomatic carriage may affect diagnostic accuracy. Aim: The overall aim of this study is to evaluate the performance of the ssUAD test to detect pneumococcal carriage, and distinguish it from invasive disease, among children under five years old in Blantyre, Malawi. Methods:This study will test 350 existing urine samples that have already been collected from children as part of the NP Resistome study (Protocol V 5.0, LSTM reference 24-076), including healthy children in the community, children with pneumonia in the community, and children hospitalised with pneumonia. Participants of the NP Resistome study will be recruited from Ndirande Health Centre (NHC), Gateway Primary Care Centre (GPCC) and Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi. Aliquots from each urine sample will be tested using the ssUAD in the UK, as the assay is not currently available in Malawi. Urinary detection of pneumococcal serotypes will be compared with both culture-based and metagenomic sequencing results from nasopharyngeal swab samples taken as part of the main study.

Different Methods of Aerosolized Polymyxin B Inhalation for Treating Carbapenem-Resistant Gram-Negative Bacterial Pneumonia.

Study Design: A randomized, open-label, parallel-group clinical trial comparing the efficacy and safety of jet nebulization versus vibrating mesh nebulization of sulfate polymyxin B in mechanically ventilated patients with carbapenem-resistant Gram-negative bacterial pneumonia. Participants: 144 patients (72 per group) will be enrolled from December 2023 to December 2025. Interventions: Group A: 25mg polymyxin B + 5ml sterile water via jet nebulizer (respirator-assisted). Group B: 25mg polymyxin B + 5ml sterile water via vibrating mesh nebulizer (respirator-assisted). Both groups receive additional intravenous polymyxin B (2.0mg/kg loading dose, followed by 1.25mg/kg every 12h) starting 12h after nebulization. Treatment duration: 14 days. Key Procedures: Nebulization parameters: Fixed ventilator settings (SIMV+PSV mode, tidal volume 8ml/kg, PEEP 6cmH₂O). Bronchoalveolar lavage (BAL) and blood sampling: BAL fluid (BALF) and blood collected pre-nebulization (baseline), 1h post-nebulization, and at steady-state (days 3-7). BALF analyzed for polymyxin B concentration, urea nitrogen, and inflammatory mediators (IL-6, TNF-α, etc.). Primary Outcomes: Clinical efficacy: Total response rate (cure + improvement). 28-day survival rate. Time to fever resolution and bacterial clearance. Drug exposure: Polymyxin B concentration in alveolar epithelial lining fluid (ELF) and blood. Secondary Outcomes: Inflammatory response: Changes in BALF and serum IL-6, TNF-α, CRP levels. Safety: Nephrotoxicity (changes in serum creatinine/urea nitrogen). Airway complications (bronchospasm incidence). Assessment Timeline: Clinical monitoring: Daily evaluation of vital signs, sputum volume, and ventilator parameters. Lab tests: Blood tests (hematology, renal function, inflammatory markers) at baseline, days 3/7/14. Microbiological evaluation: Sputum cultures on days 3/7/14. Statistical Analysis: Efficacy and safety endpoints compared between groups using t-tests or chi-square tests. A p-value \<0.05 will be considered statistically significant.

Novel Tools to Improve Management of Paediatric Community-Acquired Pneumonia - ToolCAP

The ToolCAP study aims to see if using ultrasound to look at the lungs when children have symptoms of a lung infection will safely allow doctors to improve how they treat those infections. The study will also look at if it's possible to improve how doctors decide which children need antibiotics. * Lung infections are the most common reason for children to go to the clinic/hospital. * Doctors usually give an antibiotic to every child with a lung infection. * Lung infections can be caused by 2 different types of germs - bacteria or viruses. * Antibiotics only work against bacteria and not against viruses. Lung infections caused by viruses don't need antibiotics as the body fights them by itself. * Lots of research now shows that only 1 in 4 children with a lung infection actually needs an antibiotic, as the rest only have a viral infection causing the symptoms. * This means that 3 in 4 children get an antibiotic when they don't need it. * Taking too many antibiotics can cause problems for children as it can cause diseases like diabetes or asthma. * Nowadays, due to too many people using too many antibiotics, experts are starting to worry that bacteria are starting to become resistant (stronger than the antibiotic). * Ultrasound of the lungs appears to be a way of safely looking at the lungs to see if there is an infection and may help doctors better decide who needs an antibiotic. This study includes children aged 2 months-12 years who come to the hospital with a lung infection. Children who are very unwell or who have already had 2 days of antibiotic treatment will not be allowed to be in the study.