Disseminated Ureaplasma infection as a cause of fatal hyperammonemia in humans

Ankit Bharat*, Scott A. Cunningham, G. R Scott Budinger, Daniel Kreisel, Charl J. DeWet, Andrew E. Gelman, Ken Waites, Donna Crabb, Li Xiao, Sangeeta Bhorade, Namasivayam Ambalavanan, Daniel F. Dilling, Erin M. Lowery, Todd Astor, Ramsey Hachem, Alexander S. Krupnick, Malcolm M. DeCamp, Michael G. Ison, Robin Patel

*Corresponding author for this work

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

Hyperammonemia syndrome is a fatal complication affecting immunosuppressed patients. Frequently refractory to treatment, it is characterized by progressive elevations in serum ammonia of unknown etiology, ultimately leading to cerebral edema and death. In mammals, ammonia produced during amino acid metabolism is primarily cleared through the hepatic production of urea, which is eliminated in the kidney. Ureaplasma species, commensals of the urogenital tract, are Mollicutes dependent on urea hydrolysis to ammonia and carbon dioxide for energy production. We hypothesized that systemic infection with Ureaplasma species might pose a unique challenge to human ammonia metabolism by liberating free ammonia resulting in the hyperammonemia syndrome. We used polymerase chain reaction, specialized culture, and molecular resistance profiling to identify systemic Ureaplasma infection in lung transplant recipients with hyperammonemia syndrome, but did not detect it in any lung transplant recipients with normal ammonia concentrations. Administration of Ureaplasmadirected antimicrobials to patients with hyperammonemia syndrome resulted in biochemical and clinical resolution of the disorder. Relapse in one patient was accompanied by recurrent Ureaplasma bacteremia with antimicrobial resistance. Our results provide evidence supporting a causal relationship between Ureaplasma infection and hyperammonemia, suggesting a need to test for this organism and provide empiric antimicrobial treatment while awaiting microbiological confirmation.

Original languageEnglish (US)
Pages (from-to)284ra59
JournalScience translational medicine
Volume7
Issue number284
DOIs
StatePublished - Apr 22 2015

ASJC Scopus subject areas

  • Medicine(all)

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    Bharat, A., Cunningham, S. A., Budinger, G. R. S., Kreisel, D., DeWet, C. J., Gelman, A. E., Waites, K., Crabb, D., Xiao, L., Bhorade, S., Ambalavanan, N., Dilling, D. F., Lowery, E. M., Astor, T., Hachem, R., Krupnick, A. S., DeCamp, M. M., Ison, M. G., & Patel, R. (2015). Disseminated Ureaplasma infection as a cause of fatal hyperammonemia in humans. Science translational medicine, 7(284), 284ra59. https://doi.org/10.1126/scitranslmed.aaa8419