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Gram-negative bacteria present a significant challenge to global health due to their resistance to multiple antibiotics, as reported by the National Institutes of Health (NIH). To address this issue, the NIH has granted $3.96 million to Vincent Tam, a professor at the University of Houston College of Pharmacy. Tam aims to develop more effective combination therapies that can overcome these bacteria's defenses.
Tam is working on creating an advanced monitoring device and data-processing algorithm designed to aid in the development of combination therapies. "The rate of new drug development is unlikely to keep pace with the increase in multidrug resistance, so a robust method to guide rational selection of combination therapy would be crucial to delay returning to the pre-antibiotic era," stated Tam. He emphasized that his long-term goal is optimizing antibiotic use in clinical settings.
The research will focus on bacteria such as Pseudomonas aeruginosa and Klebsiella pneumoniae. Gram-negative infections are particularly challenging and often occur in hospital settings, leading to various severe conditions like urinary tract infections and pneumonia.
These bacteria have protective capsules that make them difficult for white blood cells to ingest. When they die, they release toxins that can cause inflammation or septic shock. Tam explained that once their research concludes, clinicians could be better guided in selecting combination therapies without needing extensive knowledge about specific resistance mechanisms.
Tam's plan involves identifying effective antibiotic combinations against resistant strains and validating mathematical model predictions with clinical outcomes using strains like Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. "However, the proposed model-based system is not confined to a specific antimicrobial agent-pathogen combination," noted Tam.
Collaborating with Tam are Michael Nikolaou from UH's chemical and biomolecular engineering department, William Musick from Houston Methodist Hospital, and Truc Cecilia Tran from Houston Methodist Research Institute.