Disseminated Ureaplasma infection as a cause of fatal hyperammonemia in humans.
Disseminated Ureaplasma infection as a cause of fatal hyperammonemia in humans.
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DOI：
10.1126/scitranslmed.aaa8419
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发表时间：
2015-04-22
影响因子：
17.1
通讯作者：
Patel R
中科院分区：
文献类型：
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作者：
Bharat A;Cunningham SA;Scott Budinger GR;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
高氨血症综合征是影响免疫抑制患者的致命并发症。通常难以治疗，其特点是病因不明的血清氨进行性升高，最终导致脑水肿和死亡。在哺乳动物中，氨基酸代谢过程中产生的氨主要通过肝脏产生的尿素来清除，尿素在肾脏中被消除。脲原体是泌尿生殖道的共生体，是依靠尿素水解为氨和二氧化碳来产生能量的Mollicutes。我们假设尿原体的全身性感染可能通过释放游离氨导致高氨血症综合征，从而对人体氨代谢造成独特的挑战。我们使用聚合酶链反应、专门培养和分子耐药性分析来鉴定高氨血症肺移植受者的全身性脲原体感染，但未在氨浓度正常的肺移植受者中检测到。对高氨血症患者应用脲原体定向抗菌剂可使该疾病的生化和临床解决。1例复发伴复发性脲原体菌血症伴抗菌药物耐药性。我们的结果为脲原体感染与高氨血症之间的因果关系提供了证据，表明需要对这种有机体进行检测，并在等待微生物学确认的同时提供经验性抗菌治疗。
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.