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NRX-101 (D-Cycloserine + Lurasidone) Is Active against Drug-Resistant Urinary Pathogens In Vitro
Michael T Sapko1, Michael Manyak2, Riccardo Panicucci1
1NRx Pharmaceuticals, 1201 N Market St, Suite 111, Wilmington, DE 19801, USA.
D-Cycloserine (DCS) shows antibacterial activity against urinary pathogens, including drug-resistant strains. The combination drug NRX-101, containing DCS, also demonstrated efficacy without lurasidone interfering with DCS
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- D-Cycloserine (DCS) is an FDA-approved antibiotic for tuberculosis (TB) and urinary tract infections (UTIs).
- DCS efficacy for UTIs declined due to side effects; however, NRX-101, a DCS and lurasidone combination, received FDA designations for infectious diseases.
- Multidrug-resistant (MDR) bacterial strains pose a significant challenge in treating complicated UTIs.
Purpose of the Study:
- To evaluate the in vitro antibacterial activity of NRX-101 against key urinary tract pathogens.
- To assess the impact of lurasidone on the antimicrobial efficacy of D-Cycloserine (DCS).
- To determine the Minimum Inhibitory Concentrations (MICs) of NRX-101 and DCS in relevant media.
Main Methods:
- Antibacterial activity testing of NRX-101 and DCS against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii.
- Testing was performed in cation-adjusted Mueller-Hinton broth (caMHB) and artificial urine media (AUM).
- Minimum Inhibitory Concentrations (MICs) were determined using serial dilutions for both reference and multidrug-resistant strains.
Main Results:
- D-Cycloserine (DCS) exhibited antibacterial activity against all tested urinary pathogens.
- Lurasidone did not significantly inhibit or enhance the antibacterial action of DCS in vitro.
- MICs for NRX-101 and DCS ranged from 8 to 1024 mcg/mL in caMHB and 128 to 512 mcg/mL in AUM.
Conclusions:
- D-Cycloserine (DCS) possesses significant antibacterial activity against common and drug-resistant urinary pathogens.
- Lurasidone does not interfere with the in vitro antimicrobial efficacy of DCS.
- These findings support the further clinical development of NRX-101 for treating complicated urinary tract infections.
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