Disseminated Ureaplasma infection as a cause of fatal hyperammonemia in humans.

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 Ureaplasma-directed 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.

• Authors: 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
• Journal: Science translational medicine (Sci Transl Med) Vol. 7 Issue 284 Pg. 284re3 (Apr 22 2015) ISSN: 1946-6242 [Electronic] United States
• PMID: 25904745 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2015, American Association for the Advancement of Science.

Chemical References

• Carbon Dioxide
• Ammonia

Topics

• Adult
• Ammonia (chemistry)
• Carbon Dioxide (chemistry)
• Cohort Studies
• Drug Resistance, Bacterial
• Female
• Humans
• Hyperammonemia (etiology, microbiology)
• Immunocompromised Host
• Immunosuppression Therapy (adverse effects)
• Kidney (microbiology, pathology)
• Lung Diseases (complications, surgery)
• Lung Transplantation (adverse effects)
• Male
• Microbial Sensitivity Tests
• Middle Aged
• Polymerase Chain Reaction
• Postoperative Complications
• Ureaplasma
• Ureaplasma Infections (complications, physiopathology)