Turning the Tide against Antibiotic Resistance by Evaluating Novel, Halogenated Phenazine, Quinoline, and NH125 Compounds against Species Clinical Isolates and Type Strains.

Escalating levels of antibiotic resistance in mycoplasmas, particularly macrolide resistance in and , have narrowed our antibiotic arsenal. Further, mycoplasmas lack a cell wall and do not synthesize folic acid, rendering common antibiotics, such as beta-lactams, vancomycin, sulfonamides, and trimethoprim, of no value. To address this shortage, we screened nitroxoline, triclosan, and a library of 20 novel, halogenated phenazine, quinoline, and NH125 analogues against species and clinical isolates from urine. We tested a subset of these compounds ( = 9) against four mycoplasma type strains (, , , and ) using a validated broth microdilution or agar dilution method. Among 72 species clinical isolates, nitroxoline proved most effective (MIC, 6.25 µM), followed by an -arylated NH125 analogue (MIC, 12.5 µM). NH125 and its analogue had significantly higher MICs against isolates than against isolates, whereas nitroxoline did not. Nitroxoline exhibited bactericidal activity against isolates but bacteriostatic activity against the majority of isolates. Among the type strains, the compounds had the greatest activity against and , with 8 (80%) and 5 (71.4%) isolates demonstrating MICs of ≤12.5 µM, respectively. Triclosan also exhibited lower MICs against and Overall, we identified a promising range of quinoline, halogenated phenazine, and NH125 compounds that showed effectiveness against and and found that nitroxoline, approved for use outside the United States for the treatment of urinary tract infections, and an -arylated NH125 analogue demonstrated low MICs against species isolates.