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

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

Published In Sci Transl Med, (2015 Apr 22)

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.

PubMed ID: 25904745 Exiting the NIEHS site

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

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