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

39 Citations (Scopus)

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

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Ureaplasma Infections
Hyperammonemia
Ammonia
Ureaplasma
Urea
Tenericutes
Lung
Brain Edema
Bacteremia
Carbon Dioxide
Mammals
Hydrolysis
Kidney
Amino Acids
Recurrence
Polymerase Chain Reaction
Liver
Therapeutics
Serum

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Bharat, Ankit ; Cunningham, Scott A. ; Budinger, G. R Scott ; 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. / Disseminated Ureaplasma infection as a cause of fatal hyperammonemia in humans. In: Science translational medicine. 2015 ; Vol. 7, No. 284. pp. 284ra59.
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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.",
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Bharat, A, Cunningham, SA, Budinger, GRS, Kreisel, D, DeWet, CJ, Gelman, AE, Waites, K, Crabb, D, Xiao, L, Bhorade, S, Ambalavanan, N, Dilling, DF, Lowery, EM, Astor, T, Hachem, R, Krupnick, AS, DeCamp, MM, Ison, MG & Patel, R 2015, 'Disseminated Ureaplasma infection as a cause of fatal hyperammonemia in humans', Science translational medicine, vol. 7, no. 284, pp. 284ra59. https://doi.org/10.1126/scitranslmed.aaa8419

Disseminated Ureaplasma infection as a cause of fatal hyperammonemia in humans. / Bharat, Ankit; Cunningham, Scott A.; Budinger, G. R Scott; 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.

In: Science translational medicine, Vol. 7, No. 284, 22.04.2015, p. 284ra59.

Research output: Contribution to journalArticle

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T1 - Disseminated Ureaplasma infection as a cause of fatal hyperammonemia in humans

AU - Bharat, Ankit

AU - Cunningham, Scott A.

AU - Budinger, G. R Scott

AU - Kreisel, Daniel

AU - DeWet, Charl J.

AU - Gelman, Andrew E.

AU - Waites, Ken

AU - Crabb, Donna

AU - Xiao, Li

AU - Bhorade, Sangeeta

AU - Ambalavanan, Namasivayam

AU - Dilling, Daniel F.

AU - Lowery, Erin M.

AU - Astor, Todd

AU - Hachem, Ramsey

AU - Krupnick, Alexander S.

AU - DeCamp, Malcolm M.

AU - Ison, Michael G.

AU - Patel, Robin

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