Abstract
Background D-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.
Methods In 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.
Results DCS 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.
Conclusions Our data confirm that DCS as antibacterial activity against reference and drug-resistant urinary pathogens. Furthermore, lurasidone does not interfere with DCS’s anti-microbial action in vitro. These results support the clinical development of NRX-101 as a treatment for complicated urinary tract infection.
Competing Interest Statement
All authors have received compensation and hold equity in NRx Pharmaceuticals, Inc. The research presented was performed under contract by Charles River Laboratories, Inc.
Footnotes
Funding: This study was sponsored by NRx Pharmaceuticals and conducted independently by Charles River Laboratories, Portishead.
Transparency declarations: All authors received compensation from and/or own shares of NRx Pharmaceuticals. The studies described herein were independently conducted by Charles River Laboratories, Portishead.
