Comparative efficacy of levofloxacin, azithromycin, and doxycycline prophylaxis and treatment in an experimental <i>Ureaplasma</i> murine lung infection model

Although lung transplant recipients who develop <i>Ureaplasma-</i>associated hyperammonemia syndrome are treated with <i>Ureaplasma</i>-targeted antibiotics, optimal therapy is incompletely defined, and typically not based on real-time antimicrobial susceptibility testing results. This study compared levofloxacin, azithromycin, and doxycycline prevention and treatment of <i>Ureaplasma urealyticum</i> (UU) and <i>Ureaplasma parvum</i> (UP) infections in an immunosuppressed murine lung infection model. For prophylaxis, mice received antibiotics before infection with UP-FS (susceptible to all study antibiotics), UP-AzmR (azithromycin-resistant), UP-LevR (levofloxacin-resistant), or UU-DoxR (doxycycline-resistant), with lung bacterial loads (color changing units [CCUs]) measured 18 hours following infection. For UP-FS, doxycycline was most active (Δ4.84 log₁₀ CCU/g; <i>P</i> = 0.0006), followed by levofloxacin (Δ2.45 log₁₀ CCU/g; <i>P</i> = 0.018), with azithromycin yielding a nonsignificant CCU reduction. Doxycycline (Δ1.9 log₁₀ CCU/g; <i>P</i> = 0.0025) and levofloxacin (Δ1.3 log₁₀ CCU/g; <i>P</i> = 0.004) showed activity against UP-AzmR. Only doxycycline showed activity against UP-LevR (Δ2.28 log₁₀ CCU/g; <i>P</i> = 0.0002), and only azithromycin showed activity against UU-DoxR (Δ0.67 log₁₀ CCU/g; <i>P</i> = 0.0175). For treatment, antibiotics were administered 24 hours following infection; doxycycline significantly reduced bacterial loads of all study isolates, except UU-DoxR. In addition, azithromycin was active against UP-LevR (Δ1.21 log₁₀ CCU/g reduction; <i>P</i> = 0.0003). In summary, except for doxycycline-resistant UU, doxycycline was active in preventing and treating <i>Ureaplasma</i> lung infection in immunosuppressed mice.