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Citation
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HERO ID
2996598
Reference Type
Journal Article
Title
Disseminated Ureaplasma infection as a cause of fatal hyperammonemia in humans
Author(s)
Bharat, A; Cunningham, SA; Budinger, GRS; Kreisel, D; Dewet, CJ; Gelman, AE; Waites, Ken; Crabb, D; Xiao, Li; Bhorade, S; Ambalavanan, N; Dilling, DF; Lowery, EM; Astor, T; Hachem, R; Krupnick, AS; Decamp, MM; Ison, MG; Patel, R
Year
2015
Is Peer Reviewed?
1
Journal
Science Translational Medicine
ISSN:
1946-6242
Volume
7
Issue
284
Page Numbers
284re3
Language
English
PMID
25904745
DOI
10.1126/scitranslmed.aaa8419
Web of Science Id
WOS:000353377400012
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.
Tags
IRIS
•
Ammonia
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