Comparative efficacy of levofloxacin, azithromycin, and doxycycline prophylaxis and treatment in an experimental Ureaplasma murine lung infection model.

Abstract

Although lung transplant recipients who develop Ureaplasma-associated hyperammonemia syndrome are treated with Ureaplasma-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 Ureaplasma urealyticum (UU) and Ureaplasma parvum (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; P = 0.0006), followed by levofloxacin (Δ2.45 log₁₀ CCU/g; P = 0.018), with azithromycin yielding a nonsignificant CCU reduction. Doxycycline (Δ1.9 log₁₀ CCU/g; P = 0.0025) and levofloxacin (Δ1.3 log₁₀ CCU/g; P = 0.004) showed activity against UP-AzmR. Only doxycycline showed activity against UP-LevR (Δ2.28 log₁₀ CCU/g; P = 0.0002), and only azithromycin showed activity against UU-DoxR (Δ0.67 log₁₀ CCU/g; P = 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; P = 0.0003). In summary, except for doxycycline-resistant UU, doxycycline was active in preventing and treating Ureaplasma lung infection in immunosuppressed mice.