Fleming Derek, Al-Jabri Maha Y, Patel Robin
Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Division of Public Health, Infectious Diseases, and Occupational Medicine, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Antimicrob Agents Chemother. 2025 May 7;69(5):e0172424. doi: 10.1128/aac.01724-24. Epub 2025 Apr 14.
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.
尽管针对发生相关高氨血症综合征的肺移植受者使用了靶向抗生素进行治疗，但最佳治疗方案尚未完全明确，且通常并非基于实时抗菌药敏试验结果。本研究在免疫抑制的小鼠肺部感染模型中比较了左氧氟沙星、阿奇霉素和多西环素对解脲脲原体（UU）和人型支原体（UP）感染的预防和治疗效果。对于预防，小鼠在感染UP-FS（对所有研究抗生素敏感）、UP-AzmR（阿奇霉素耐药）、UP-LevR（左氧氟沙星耐药）或UU-DoxR（多西环素耐药）之前接受抗生素治疗，并在感染后18小时测量肺部细菌载量（变色单位[CCUs]）。对于UP-FS，多西环素活性最高（Δ4.84 log CCU/g；P = 0.0006），其次是左氧氟沙星（Δ2.45 log CCU/g；P = 0.018），阿奇霉素使CCU降低不显著。多西环素（Δ1.9 log CCU/g；P = 0.0025）和左氧氟沙星（Δ1.3 log CCU/g；P = 0.004）对UP-AzmR有活性。只有多西环素对UP-LevR有活性（Δ2.28 log CCU/g；P = 0.0002），只有阿奇霉素对UU-DoxR有活性（Δ0.67 log CCU/g；P = 0.0175）。对于治疗，在感染后24小时给予抗生素；多西环素显著降低了所有研究分离株的细菌载量，但UU-DoxR除外。此外，阿奇霉素对UP-LevR有活性（降低Δ1.21 log CCU/g；P = 0.0003）。总之，除了对多西环素耐药的UU外，多西环素在预防和治疗免疫抑制小鼠的支原体肺部感染方面具有活性。
