title: 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.affiliation: Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. abharat@nm.org.
authors.forename: Ankit
authors.initials: A
authors.lastname: Bharat
authors.affiliation: Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Cunningham
authors.affiliation: Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: G R
authors.initials: GR
authors.lastname: Scott Budinger
authors.affiliation: Washington University, St. Louis, MO 63110, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kreisel
authors.affiliation: Washington University, St. Louis, MO 63110, USA.
authors.forename: Charl J
authors.initials: CJ
authors.lastname: DeWet
authors.affiliation: Washington University, St. Louis, MO 63110, USA.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Gelman
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL 35233, USA.
authors.forename: Ken
authors.initials: K
authors.lastname: Waites
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL 35233, USA.
authors.forename: Donna
authors.initials: D
authors.lastname: Crabb
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL 35233, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Bhorade
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL 35233, USA.
authors.forename: Namasivayam
authors.initials: N
authors.lastname: Ambalavanan
authors.affiliation: Loyola University Chicago Stritch School of Medicine, Chicago, IL 60153, USA. Hines VA Hospital, Hines, IL, USA. RML Specialty Hospital, Hinsdale, IL 60521, USA.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Dilling
authors.affiliation: Loyola University Chicago Stritch School of Medicine, Chicago, IL 60153, USA.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Lowery
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Todd
authors.initials: T
authors.lastname: Astor
authors.affiliation: Washington University, St. Louis, MO 63110, USA.
authors.forename: Ramsey
authors.initials: R
authors.lastname: Hachem
authors.affiliation: Washington University, St. Louis, MO 63110, USA.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Krupnick
authors.affiliation: Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Malcolm M
authors.initials: MM
authors.lastname: DeCamp
authors.affiliation: Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Ison
authors.affiliation: Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Robin
authors.initials: R
authors.lastname: Patel
mesh_terms: D000328:Adult; D000641:Ammonia / Q000737:chemistry; D002245:Carbon Dioxide / Q000737:chemistry; D015331:Cohort Studies; D024881:Drug Resistance, Bacterial; D005260:Female; D006801:Humans; D022124:Hyperammonemia / Q000209:etiology* / Q000382:microbiology*; D016867:Immunocompromised Host; D007165:Immunosuppression Therapy / Q000009:adverse effects; D007668:Kidney / Q000382:microbiology / Q000473:pathology; D008171:Lung Diseases / Q000150:complications / Q000601:surgery; D016040:Lung Transplantation / Q000009:adverse effects; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011183:Postoperative Complications; D014509:Ureaplasma; D016869:Ureaplasma Infections / Q000150:complications* / Q000503:physiopathology
chemical_list: D002245:Carbon Dioxide; D000641:Ammonia