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bioRxiv · 10.1101/2024.01.14.575572

NRX-101 (D-Cycloserine + Lurasidone) , a Qualified Infectious Disease Product, is Active Against Drug-Resistant Urinary Pathogens In Vitro

Sapko, M. T.·Manyak, M.·Panicucci, R.·Javitt, J. C.
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Abstract

BackgroundD-Cycloserine (DCS) is a broad-spectrum antibiotic that is currently FDA-approved to treat tuberculosis (TB) disease and urinary tract infection. Despite numerous reports showing good clinical efficacy, DCS fell out of favor as a UTI treatment because of its propensity to cause side effects. NRX-101, a fixed dose combination of DCS and lurasidone, has been awarded Qualified Infectious Disease Product and Fast Track Designation by the US Food and Drug Administration and is being developed for various CNS indications because of its unique synergistic effect; each component mitigates side effects of the other. MethodsIn this study, we tested NRX-101 against the urinary tract pathogens E. coli, P. aeruginosa, K. pneumoniae, and A. baumannii in Mueller Hinton broth (caMHB) and artificial urine media (AUM). Several strains were multidrug resistant. Test compounds were serially diluted in broth/media. Minimum inhibitory concentration (MIC) was defined as the lowest concentration of test compound at which no bacterial growth was observed. ResultsDCS exhibited antibacterial efficacy against all strains tested while lurasidone did not appreciably affect the antibacterial action of DCS in vitro. In AUM, the MICs ranged from 128 to 512 mcg/ml for both DCS and NRX-101. In caMHB, MICs ranged from 8 to 1024 mcg/ml for NRX-101 and 32 to 512 mcg/ml for DCS alone. ConclusionsOur data confirm that DCS as antibacterial activity against reference and drug-resistant urinary pathogens. Furthermore, lurasidone does not interfere with DCSs anti-microbial action in vitro. These results support the clinical development of NRX-101 as a treatment for complicated urinary tract infection.

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Sapko, M. T., Manyak, M., Panicucci, R., Javitt, J. C.. 2024-01-14. NRX-101 (D-Cycloserine + Lurasidone) , a Qualified Infectious Disease Product, is Active Against Drug-Resistant Urinary Pathogens In Vitro. https://doi.org/10.1101/2024.01.14.575572

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