tacrolimus and Hyperammonemia

A 58-year-old woman developed rapidly progressive neurological symptoms and finally loss of vigilance 5 weeks following primarily successful lung transplantation. A posterior reversible encephalopathy syndrome (PRES) under treatment with tacrolimus as well as hyperammonemia due to sepsis with Ureaplasma urealyticum could be identified as the causes. Infections with Ureaplasma, bacteria which produce ammonia as a product of metabolism, are increasingly being identified in immunocompromised people by specific PCR (polymerase chain reaction) procedures and should routinely be taken into consideration as the cause of unspecific neurological symptoms.

Topics: Brain Edema; Female; Humans; Hyperammonemia; Immunocompromised Host; Lung Transplantation; Middle Aged; Posterior Leukoencephalopathy Syndrome; Postoperative Complications; Status Epilepticus; Tacrolimus; Ureaplasma Infections; Ureaplasma urealyticum

Hyperammonemia syndrome is an often fatal complication of lung transplantation which has been recently associated with Ureaplasma infection. It has not been definitely established that Ureaplasma species can cause hyperammonemia. We established a novel immunocompromised murine model of Ureaplasma urealyticum infection and used it to confirm that U. urealyticum can cause hyperammonemia. Male C3H mice were pharmacologically immunosuppressed with mycophenolate mofetil, tacrolimus and oral prednisone for seven days, and then challenged intratracheally (IT) and/or intraperitoneally (IP) with 107 CFU U. urealyticum over six days, while continuing immunosuppression. Spent U. urealyticum-free U9 broth was used as a negative control, with uninfected immunocompetent mice, uninfected immunosuppressed mice, and infected immunocompetent mice serving as additional controls. Plasma ammonia concentrations were compared using Wilcoxon ranks sum tests. Plasma ammonia concentrations of immunosuppressed mice challenged IT/IP with spent U9 broth (n = 14) (range 155-330 μmol/L) were similar to those of normal mice (n = 5), uninfected immunosuppressed mice (n = 5), and U. urealyticum IT/IP challenged immunocompetent mice (n = 5) [range 99-340 μmol/L, p = 0.60]. However, immunosuppressed mice challenged with U. urealyticum IT/IP (n = 20) or IP (n = 15) had higher plasma ammonia concentrations (range 225-945 μmol/L and 276-687 μmol/L, respectively) than those challenged IT/IP with spent U9 broth (p<0.001). U. urealyticum administered IT/IP or IP causes hyperammonemia in mice pharmacologically immunosuppressed with a regimen similar to that administered to lung transplant recipients.

Topics: Ammonia; Animals; Disease Models, Animal; Hyperammonemia; Immunocompromised Host; Immunosuppressive Agents; Male; Mice; Mice, Inbred C3H; Mycophenolic Acid; Prednisone; Real-Time Polymerase Chain Reaction; Tacrolimus; Ureaplasma Infections; Ureaplasma urealyticum