Case Report
Fatal hyperammonaemia caused by Mycoplasma hominis Mark E Wylam, Cassie C Kennedy, Nina M Hernandez, Steve G Peters, Joseph J Maleszewski, Stephen D Cassivi, John P Scott
Mycoplasma hominis Lancet 2013; 382: 1956 Division of Pulmonary and Critical Care Medicine (M E Wylam MD, Prof S G Peters MD, C C Kennedy MD, Prof J P Scott MD); Department of Anatomic Pathology (J J Maleszewski MD); Division of Thoracic Surgery (Prof S D Cassivi MD), Mayo Clinic College of Medicine, Rochester, MN, USA; and Purdue University, Lafayette, IN, USA (N M Hernandez BS) Correspondence to: Dr Mark E Wylam, Division of Pulmonary and Critical Care Internal Medicine, Mayo Clinic College of Medicine, 200 First Street, SW, Rochester, MN 55905, USA [email protected]
See Online for appendix
1956
A 64-year-old woman had bilateral-sequential lung transplantation for pulmonary fibrosis. The adolescent donor had a history of polysubstance abuse and massive head trauma. On postoperative day 4 the transplant recipient was extubated, developed fever to 38·4°C, and became less alert. CT of the head showed no specific findings. On postoperative day 6 neurological examination showed minimal eye movements and severe encephalopathy. MRI brain scan showed small foci of restricted diffusion consistent with posterior reversible encephalopathy syndrome, attributed to intravenous tacrolimus. On postoperative day 7, generalised status epilepticus prompted reintubation. Thin watery airway secretions showed no bacterial growth. Later that day ammonia was greater than 704 μmol/L (=15 cfu, confirmed by DNA sequencing). At autopsy, severe acute cerebral ischaemic necrosis with parenchymal autolysis and spinal cord infarction were noted. Findings of acute laryngitis and tracheitis were recorded, with mucosal ulceration probably due to M hominis. Acute left lower lobe bronchopneumonia was noted with fibrinous pleuritis and pericarditis, as well as infarcts of small bowel, spleen, liver, and lungs. Real-time PCR/FRET was positive with an M hominis DNA probe, and was seen on both tissue (trachea, lung, small bowel and colon) and whole blood specimens. These results were supported by immunofluorescent findings of M hominis colonising the surface of the trachea, heart, and bronchiolar epithelium and alveoli within areas of neutrophilic alveolar exudates (appendix) detected by in-situ hybridisation with a fluoresceinlabelled species-specific probe. In this lung transplant recipient, septicaemia and hyperammonaemia due to M hominis suggest these
factors were the proximate aetiology leading to encephalopathy and ultimately death. Acute idiopathic hyperammonaemia has been noted during treatment for acute leukaemia,1 stem cell transplantation, and organ transplantation, including lung.2 The cause of the disorder in each case remained undetermined, but premortem blood cultures grew M hominis in one reported patient.1 An acquired reduction in hepatic glutamine synthetase activity has been suggested. However, the absence of liver disease and normal plasma and urinary aminoacid profiles have suggested against underlying defects in the urea cycle. Schlesinger3 first described the rapid synthesis of ammonia from M hominis as an observation of the rapid depletion of arginine in mammalian cell culture medium because of contamination by M hominis. Schimke and Barile4 showed that the breakdown of arginine to ornithine occurs by arginine deiminase, an enzyme which is 10% of the mass volume of the bacterium. Until the recent use of PCR for M hominis, the static effects of sodium polyanethol sulphonate, the anticoagulant in automated liquid blood culture media systems has greatly reduced the sensitivity of detection of mycoplasma.5 We can reasonably conclude that acute hyperammonaemia in this lung transplant recipient was due to occult M hominis infection. We suggest that while conducting a thorough search for other causes of hyperammonaemia empiric treatment with fluoroquinolones should be initiated in any immunosuppressed patient with unexplained hyperammonaemia. In addition to traditional microbiological culture techniques we recommend RT-PCR be done as a sensitive test for detecting occult infection with M hominis. Contributors MEW provided insight into the relationship between M hominis and hyperammonaemia. MEW and SGP wrote the report. CCK, SDC, and JPS looked after the patient. NMH and JJM did the laboratory diagnosis. Written consent to publication was obtained from the patient’s family. Acknowledgments Funding source: Annenberg Foundation Pulmonary Research Award to MEW. References 1 Watson AJ, Chambers T, Karp JE, Risch VR, Walker WG, Brusilow SW. Transient idiopathic hyperammonaemia in adults. Lancet 1985; 2: 1271–74. 2 Lichtenstein GR, Kaiser LR, Tuchman M, et al. Fatal hyperammonemia following orthotopic lung transplantation. Gastroenterology 1997; 112: 236–40. 3 Rouse HC, Bonifas VH, Schlesinger RW. Dependence of adenovirus replication on arginine and inhibition of plaque formation by pleuropneumonia-like organisms. Virology 1963; 20: 357. 4 Schimke RT, Barile MF. Arginine metabolism in pleuropneumonia-like organisms isolated from mammalian cell culture. J Bacteriol 1963; 86: 195–206. 5 Waites KB, Canupp KC. Evaluation of BacT/ALERT system for detection of Mycoplasma hominis in simulated blood cultures. J Clin Microbiol 2001; 39: 4328–31.
www.thelancet.com Vol 382 December 7, 2013
Fatal hyperammonaemia caused by Mycoplasma hominis Mark E Wylam, Cassie C Kennedy, Nina M Hernandez, Steve G Peters, Joseph J Maleszewski, Stephen D Cassivi, John P Scott
Mycoplasma hominis Lancet 2013; 382: 1956 Division of Pulmonary and Critical Care Medicine (M E Wylam MD, Prof S G Peters MD, C C Kennedy MD, Prof J P Scott MD); Department of Anatomic Pathology (J J Maleszewski MD); Division of Thoracic Surgery (Prof S D Cassivi MD), Mayo Clinic College of Medicine, Rochester, MN, USA; and Purdue University, Lafayette, IN, USA (N M Hernandez BS) Correspondence to: Dr Mark E Wylam, Division of Pulmonary and Critical Care Internal Medicine, Mayo Clinic College of Medicine, 200 First Street, SW, Rochester, MN 55905, USA [email protected]
See Online for appendix
1956
A 64-year-old woman had bilateral-sequential lung transplantation for pulmonary fibrosis. The adolescent donor had a history of polysubstance abuse and massive head trauma. On postoperative day 4 the transplant recipient was extubated, developed fever to 38·4°C, and became less alert. CT of the head showed no specific findings. On postoperative day 6 neurological examination showed minimal eye movements and severe encephalopathy. MRI brain scan showed small foci of restricted diffusion consistent with posterior reversible encephalopathy syndrome, attributed to intravenous tacrolimus. On postoperative day 7, generalised status epilepticus prompted reintubation. Thin watery airway secretions showed no bacterial growth. Later that day ammonia was greater than 704 μmol/L (=15 cfu, confirmed by DNA sequencing). At autopsy, severe acute cerebral ischaemic necrosis with parenchymal autolysis and spinal cord infarction were noted. Findings of acute laryngitis and tracheitis were recorded, with mucosal ulceration probably due to M hominis. Acute left lower lobe bronchopneumonia was noted with fibrinous pleuritis and pericarditis, as well as infarcts of small bowel, spleen, liver, and lungs. Real-time PCR/FRET was positive with an M hominis DNA probe, and was seen on both tissue (trachea, lung, small bowel and colon) and whole blood specimens. These results were supported by immunofluorescent findings of M hominis colonising the surface of the trachea, heart, and bronchiolar epithelium and alveoli within areas of neutrophilic alveolar exudates (appendix) detected by in-situ hybridisation with a fluoresceinlabelled species-specific probe. In this lung transplant recipient, septicaemia and hyperammonaemia due to M hominis suggest these
factors were the proximate aetiology leading to encephalopathy and ultimately death. Acute idiopathic hyperammonaemia has been noted during treatment for acute leukaemia,1 stem cell transplantation, and organ transplantation, including lung.2 The cause of the disorder in each case remained undetermined, but premortem blood cultures grew M hominis in one reported patient.1 An acquired reduction in hepatic glutamine synthetase activity has been suggested. However, the absence of liver disease and normal plasma and urinary aminoacid profiles have suggested against underlying defects in the urea cycle. Schlesinger3 first described the rapid synthesis of ammonia from M hominis as an observation of the rapid depletion of arginine in mammalian cell culture medium because of contamination by M hominis. Schimke and Barile4 showed that the breakdown of arginine to ornithine occurs by arginine deiminase, an enzyme which is 10% of the mass volume of the bacterium. Until the recent use of PCR for M hominis, the static effects of sodium polyanethol sulphonate, the anticoagulant in automated liquid blood culture media systems has greatly reduced the sensitivity of detection of mycoplasma.5 We can reasonably conclude that acute hyperammonaemia in this lung transplant recipient was due to occult M hominis infection. We suggest that while conducting a thorough search for other causes of hyperammonaemia empiric treatment with fluoroquinolones should be initiated in any immunosuppressed patient with unexplained hyperammonaemia. In addition to traditional microbiological culture techniques we recommend RT-PCR be done as a sensitive test for detecting occult infection with M hominis. Contributors MEW provided insight into the relationship between M hominis and hyperammonaemia. MEW and SGP wrote the report. CCK, SDC, and JPS looked after the patient. NMH and JJM did the laboratory diagnosis. Written consent to publication was obtained from the patient’s family. Acknowledgments Funding source: Annenberg Foundation Pulmonary Research Award to MEW. References 1 Watson AJ, Chambers T, Karp JE, Risch VR, Walker WG, Brusilow SW. Transient idiopathic hyperammonaemia in adults. Lancet 1985; 2: 1271–74. 2 Lichtenstein GR, Kaiser LR, Tuchman M, et al. Fatal hyperammonemia following orthotopic lung transplantation. Gastroenterology 1997; 112: 236–40. 3 Rouse HC, Bonifas VH, Schlesinger RW. Dependence of adenovirus replication on arginine and inhibition of plaque formation by pleuropneumonia-like organisms. Virology 1963; 20: 357. 4 Schimke RT, Barile MF. Arginine metabolism in pleuropneumonia-like organisms isolated from mammalian cell culture. J Bacteriol 1963; 86: 195–206. 5 Waites KB, Canupp KC. Evaluation of BacT/ALERT system for detection of Mycoplasma hominis in simulated blood cultures. J Clin Microbiol 2001; 39: 4328–31.
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