Turning the Tide against Antibiotic Resistance by Evaluating Novel, Halogenated Phenazine, Quinoline, and NH125 Compounds against Ureaplasma spp. Clinical Isolates and Mycoplasma Type Strains [Susceptibility]

Escalating levels of antibiotic resistance in mycoplasmas, particularly macrolide resistance in Mycoplasma pneumoniae and M. genitalium, 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 Ureaplasma spp. and M. hominis clinical isolates from urine. We tested a subset of these compounds (n = 9) against four mycoplasma type strains (M. pneumoniae, M. genitalium, M. hominis and U. urealyticum) using a validated microbroth or agar dilution method. Among 72 Ureaplasma spp. clinical isolates, nitroxoline proved most effective (MIC₉₀: 6.25 µM), followed by an N-arylated NH125 analogue (MIC₉₀: 12.5 µM). NH125 and its analogue had significantly higher MICs against U. urealyticum versus U. parvum isolates, whereas nitroxoline did not. Nitroxoline exhibited bactericidal activity against U. parvum isolates, but bacteriostatic activity against the majority of U. urealyticum isolates. Among the type strains, the compounds had the greatest activity against M. pneumoniae and M. genitalium with 8 (80%) and 5 (71.4%) demonstrating MICs ≤12.5 µM, respectively. Triclosan also exhibited lower MICs against M. pneumoniae and M. genitalium. Overall, we identified a promising range of quinoline and NH125 compounds that showed effectiveness against M. pneumoniae and M. genitalium and found that nitroxoline, approved to treat urinary tract infections outside the US and an N-arylated NH125 analogue demonstrated low MICs against Ureaplasma spp. isolates.

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