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

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