Al-Jabri, Maha Y.

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 log 10 CCU/g; P = 0.0006), followed by levofloxacin (Δ2.45 log 10 CCU/g; P = 0.018), with azithromycin yielding a nonsignificant CCU reduction. Doxycycline (Δ1.9 log 10 CCU/g; P = 0.0025) and levofloxacin (Δ1.3 log 10 CCU/g; P = 0.004) showed activity against UP-AzmR. Only doxycycline showed activity against UP-LevR (Δ2.28 log 10 CCU/g; P = 0.0002), and only azithromycin showed activity against UU-DoxR (Δ0.67 log 10 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 log 10 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.

ABSTRACT Ureaplasma species can cause systemic infections in immunocompromised hosts, including lung transplant recipients. Here, we investigated the impact of prior exposure to Ureaplasma urealyticum on the risk of U. urealyticum and Ureaplasma parvum infection in mice subjected to an immunosuppression regimen similar to that administered to solid organ transplant recipients. Mice were immunized with three intramuscular injections of U. urealyticum , with control mice injected with adjuvant only. Following immunization, mice received tacrolimus, mycophenolate mofetil, and methylprednisolone, and then were challenged with U. urealyticum or U. parvum intraperitoneally and intratracheally over 6 days. Relative U. urealyticum antibody levels in plasma were assessed over time, and lungs were harvested at sacrifice for bacterial load quantification, assessed using a color-changing unit assay. U. urealyticum antibody levels were higher in immunized compared with control animals ( P < 0.0001), even when animals were immunosuppressed. U. urealyticum and U. parvum lung burden was reduced in immunized compared with control mice (~6 log 10 reduction for U. urealyticum and <1 log 10 reduction for U. parvum ; P = 0.008 and 0.046, respectively). In summary, this study shows that prior exposure to live U. urealyticum provides some protection against infection with U. urealyticum . IMPORTANCE Ureaplasma -induced hyperammonemia syndrome is a rare but potentially deadly complication of solid organ transplantation, especially lung transplantation. The pathophysiology of this relatively recently recognized condition is poorly understood, and it is unclear what factors may influence patient susceptibility. This study investigates the possible protective effects of prior exposure to Ureaplasma urealyticum in a mouse model subjected to an immunosuppression regimen similar to that given to lung transplant recipients. The findings show that prior exposure could provide protection against Ureaplasma lung infection.