scholarly journals Case Report: About a Case of Hyperammonemia Syndrome Following Lung Transplantation: Could Metagenomic Next-Generation Sequencing Improve the Clinical Management?

2021 ◽  
Vol 8 ◽  
Author(s):  
Charlotte Michel ◽  
Michela Raimo ◽  
Vladimir Lazarevic ◽  
Nadia Gaïa ◽  
Nina Leduc ◽  
...  

Background:Mycoplasma hominis and Ureaplasma spp. are responsible for opportunistic infections in transplant patients, sometimes causing a life-threatening hyperammonemia syndrome. Both pathogens are not identified with standard microbiology techniques, resulting in missed or delayed diagnosis. We present a clinical case that illustrates the added value that next-generation sequencing (NGS) may offer in the diagnosis of respiratory infections in immune-compromised patients.Results: A 55 years-old man with idiopathic pulmonary fibrosis underwent double lung transplantation. He received antibiotic prophylaxis with piperacillin-tazobactam and azythromycin. At day 4 post-transplantation (PTx), the patient presented an acute respiratory distress. A broncho-alveolar lavage (BAL) was performed. At day 5 PTx, the patient presented a status epilepticus due to diffuse cerebral oedema. Serum ammonia concentration was 661 μg/dL. BAL bacterial culture was negative. Because of the clinical presentation, special cultures were performed and identified 100.000 CFU/mL of M. hominis and Ureaplasma spp. and specific PCRs were positive for M. hominis and Ureaplasma parvum. Antibiotic therapy was shifted to therapeutic dose of azithromycin and doxycycline; within 48 h ammonia serum concentrations returned to normal but the coma persisted several weeks, followed by a persistent frontal lobe syndrome. A follow-up BAL was performed on day 11 Ptx. The Mycoplasma/Ureaplasma culture was negative, yet the specific PCRs remained positive. Bacterial culture found 100 CFU/mL of Staphylococcus aureus and viral culture was positive for Herpes Simplex Virus-1. These results were confirmed by metagenomic next-generation sequencing (mNGS). In the bacterial fraction, the majority of reads belonged to Corynebacterium propinquum (34.7%), S. aureus (24.1%) and Staphylococcus epidermidis (17.1%). Reads assigned to M. hominis, Ureaplasma urealyticum and parvum represented 0.71, 0.13, and 0.04% of the bacterial fraction and corresponded to 6.9 × 103, 9.7 × 102, and 3.7 × 102 genome equivalents per mL of BAL fluid, respectively. These results are in favor of a cure of the atypical infection.Conclusions: mNGS offered added diagnostic and quantitative values compared to PCR tests, which can remain positive after resolved infections. The initiation of appropriate antibiotic therapy would have occurred earlier on, possibly resulting in a better clinical outcome if mNGS had been performed in a routine fashion.

2020 ◽  
Author(s):  
Dong Liu ◽  
Ji Zhang ◽  
Bo Wu ◽  
Feng Liu ◽  
Shugao Ye ◽  
...  

Abstract Background: The effect of donor lung pathogenic bacteria on the prognosis of lung transplantation is not clear. We used the technique of next-generation sequencing (NGS) to detect the pathogenic bacteria from the lower respiratory tract and analyzed whether the colonized bacteria of donor lung could affect the outcomes of lung transplantation.Methods: All patients who underwent lung transplantation from March 2018 to June 2018 at Wuxi People's Hospital affiliated to Nanjing Medical University were included in this study. Twelve cases of donor lung were obtained, and 17 lung transplants were performed, including 12 single lung transplantation and 5 bilateral lung transplantation. The colonized bacteria in the lower lobe tissue of donor lung were detected by NGS, and the bacteria culture method was used to detect the bacteria in the airway secretion before and after the operation. The information of length of extracorporeal membrane oxygenation (ECMO) support, mechanical ventilation time, length of intensive care unit (ICU) stay, duration of fever and length of hospital stay were collected for prognostic analysis.Results: Compared with bacterial culture methods, the positive rate by using NGS in the lungs were higher (52.9% vs 41.2%). Among the patients who had detected bacteria by NGS in donor lungs before surgery, only one patient (1/9) developed the same bacteria after lung transplantation. Based on results of NGS and bacterial culture, there is no association between the colonized bacteria in donor lungs and the patient outcomes of immediate posttransplant period. Conclusion: NGS showed more sensitive than bacterial culture for detection of bacteria. The colonized bacteria in different parts of the lung are inconsistent. There is no association between the colonized bacteria in donor lungs and short-term outcome of lung transplantation patients.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Dong Liu ◽  
Ji Zhang ◽  
Bo Wu ◽  
Feng Liu ◽  
Shugao Ye ◽  
...  

Abstract Background The effect of donor lung colonized bacteria on the prognosis of lung transplantation is not clear. We used the technique of next-generation sequencing (NGS) to detect the colonized bacteria from the lower respiratory tract and analyzed whether the colonized bacteria of donor lung could affect the outcomes of lung transplantation. Methods Seventeen patients who underwent lung transplantation from March 2018 to June 2018 at Wuxi People’s Hospital affiliated to Nanjing Medical University were included in this study. Twelve cases of donor lung were obtained, and 17 lung transplants were performed, including 12 single lung transplantation and 5 bilateral lung transplantation. The colonized bacteria in the lower lobe tissue of donor lung were detected by NGS, and the bacteria culture method was used to detect the bacteria in the airway secretion before and after the operation. The information of length of extracorporeal membrane oxygenation (ECMO) support, mechanical ventilation time, length of intensive care unit (ICU) stay, duration of fever and length of hospital stay were collected for prognostic analysis. Results Compared with bacterial culture methods, the positive rate by using NGS in the lungs were higher (52.9% vs 41.2%). Among the patients who were transplanted with donor lungs with detected bacteria by NGS before surgery, only one patient (1/9) developed the same bacteria after lung transplantation. Based on results of NGS and bacterial culture, there was no association between the colonized bacteria in donor lungs and the patients’ outcomes of immediate posttransplant period. Conclusion NGS showed more sensitive than bacterial culture for detection of bacteria. The colonized bacteria in different parts of the lung are inconsistent. There is no association between the colonized bacteria in donor lungs and short-term outcome of lung transplantation patients.


2020 ◽  
Author(s):  
Dong Liu ◽  
Ji Zhang ◽  
Bo Wu ◽  
Feng Liu ◽  
Shugao Ye ◽  
...  

Abstract Background: The effect of donor lung pathogenic bacteria on the prognosis of lung transplantation is not clear. We used the technique of next-generation sequencing (NGS) to detect the pathogenic bacteria from the lower respiratory tract and analyzed whether the colonized bacteria of donor lung affect the outcomes of lung transplantation.Methods: All patients who underwent lung transplantation from March 2018 to June 2018 at the Wuxi People's Hospital affiliated to Nanjing Medical University were included in this study. Twelve cases of donor lung were obtained, and 17 lung transplants were performed, including 12 single lung transplantation and 5 bilateral lung transplantation. The colonized bacteria in the lower lobe tissue of donor lung were detected by NGS, and the bacteria culture method was used to detect the bacteria in the airway secretion before and after the operation. The information of extracorporeal membrane oxygenation (ECMO) support time, mechanical ventilation time, intensive care unit (ICU) stay time,duration of fever and hospital length of staywere collected for prognostic analysis.Results: Compared with bacterial culture methods, the positive rate of bacteriaby using NGS in the lungs were higher (52.9% vs 41.2%). Among the patients who had detected bacteria by NGS in donor lungs before surgery, only one patient (1/9) developed the same bacteria after lung transplantation.Either NGS or bacterial culture methods, there is no association between the colonized colonization bacteria in donor lungs and the patient outcomes of immediate posttransplant period.Conclusion: The detection of bacteria by using NGS is more sensitive than normal bacterial culture. The colonized bacteria in different parts of the lung are inconsistent. There is no association between the colonized bacteria in donor lungs and short-term outcome of lung transplantation patients.


2020 ◽  
Author(s):  
Dong Liu ◽  
Ji Zhang ◽  
Bo Wu ◽  
Feng Liu ◽  
Shugao Ye ◽  
...  

Abstract Background: The effect of donor lung colonized bacteria on the prognosis of lung transplantation is not clear. We used the technique of next-generation sequencing (NGS) to detect the colonized bacteria from the lower respiratory tract and analyzed whether the colonized bacteria of donor lung could affect the outcomes of lung transplantation.Methods: 17 patients who underwent lung transplantation from March 2018 to June 2018 at Wuxi People's Hospital affiliated to Nanjing Medical University were included in this study. Twelve cases of donor lung were obtained, and 17 lung transplants were performed, including 12 single lung transplantation and 5 bilateral lung transplantation. The colonized bacteria in the lower lobe tissue of donor lung were detected by NGS, and the bacteria culture method was used to detect the bacteria in the airway secretion before and after the operation. The information of length of extracorporeal membrane oxygenation (ECMO) support, mechanical ventilation time, length of intensive care unit (ICU) stay, duration of fever and length of hospital stay were collected for prognostic analysis.Results: Compared with bacterial culture methods, the positive rate by using NGS in the lungs were higher (52.9% vs 41.2%). Among the patients who had detected bacteria by NGS in donor lungs before surgery, only one patient (1/9) developed the same bacteria after lung transplantation. Based on results of NGS and bacterial culture, there was no association between the colonized bacteria in donor lungs and the patients’ outcomes of immediate posttransplant period. Conclusion: NGS showed more sensitive than bacterial culture for detection of bacteria. The colonized bacteria in different parts of the lung are inconsistent. There is no association between the colonized bacteria in donor lungs and short-term outcome of lung transplantation patients.


Author(s):  
Moni Roy ◽  
Nikhut Siddique ◽  
Bindu Bathina ◽  
Sharjeel Ahmad

Toxoplasma gondii is a known cause of encephalitis in human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients. Toxoplasma pneumonitis is a manifestation of extracerebral toxoplasmosis and can be clinically indistinguishable from other opportunistic infections including Pneumocystis jirovecii pneumonia (PJP) and miliary tuberculosis. In this case report, Toxoplasma pneumonitis and disseminated toxoplasmosis was diagnosed using next-generation sequencing (NGS) and polymerase chain reaction (PCR) assessment. NGS can detect microbial cell-free DNA (cfDNA) circulating in the plasma of over 1,000 pathogens. This case is a rare presentation of Toxoplasma pneumonitis in the absence of neurological symptoms and we discuss the use of NGS of microbial cfDNA and PCR tests that may be utilized for the timely diagnosis of such challenging cases.


2019 ◽  
Vol 13 (1) ◽  
pp. 7-11 ◽  
Author(s):  
Yang Zhou ◽  
Vagish Hemmige ◽  
Sudeb C. Dalai ◽  
David K. Hong ◽  
Kenneth Muldrew ◽  
...  

Background:AIDS-associated Opportunistic Infections (OIs) have significant morbidity and mortality and can be diagnostically challenging, requiring invasive procedures as well as a combination of culture and targeted molecular approaches.Objective:We aimed to demonstrate the clinical utility of Next-generation Sequencing (NGS) in pathogen identification; NGS is a maturing technology enabling the detection of miniscule amounts of cell-free microbial DNA from the bloodstream.Methods:We utilized a novel Next-generation Sequencing (NGS) test on plasma samples to diagnose a series of HIV-associated OIs that were diagnostically confirmed through conventional microbial testing.Results:In all cases, NGS test results were available sooner than conventional testing. This is the first case series demonstrating the utility of whole-genome NGS testing to identify OIs from plasma in HIV/AIDS patients.Conclusion:NGS approaches present a clinically-actionable, comprehensive means of diagnosing OIs and other systemic infections while avoiding the labor, expense, and delays of multiple tests and invasive procedures.


2020 ◽  
Author(s):  
Min Ding ◽  
Chunfeng Yang ◽  
Yu-mei Li

Abstract BackgroundLegionella pneumophila is responsible for hospital or community-acquired pneumonia in adults. Immunocompromised patients with Legionella pneumophila infection are associated with rapidly severe clinical course and high mortality rates. Legionella pneumophila infection is rare in children, especially combined with extrapulmonary manifestations. In this report, we describe 2 children of severe hospital-acquired pneumonia and septic shock resulting from Legionella pneumophila. Standardized metagenomics next-generation sequencing allowed early diagnosis. Appropriate antibiotic therapy and timely extracorporeal life support were effective in achieving complete recovery. This is the first report of children with septic shock related to Legionella pneumophila infections diagnosed by metagenomics next-generation sequencing and recovered successfully.Case presentationThere were 2 cases about septic shock resulting from Legionella pneumophila. One was a six-month girl with congenital biliary atresia who underwent liver transplantation. She was suspected for rejecting the liver and admitted to hospital. The other one was a five-year-old boy with Burkitt lymphoma who was in the end of early chemotherapy. They both presented with fever, cough or shortness of breath during hospitalization. And they were transferred to PICU because of worsening dyspnea and decreased blood pressure. Patients were diagnosed by severe sepsis with septic shock likely resulting from hospital-acquired pneumonia. Metagenomics next-generation sequencing indicated L. pneumophila in blood and sputum. Aggressive intravenous fluids resuscitation and vasopressors were initiated on arrival to PICU, and they were placed on mechanical ventilation and continuous renal replacement therapy. Intravenous antibiotic therapy followed by azithromycin. Finally, the patients recovered without any long-term sequelae.ConclusionsThough sepsis or sepsis shock caused by Legionella pneumophila is rare in children, it can occur at high-risk population. Metagenomics next-generation sequencing is useful for conforming hard-to-culture pathogens and severely ill patients. The report remind pediatric physicians that we should be aware that Legionella pneumophila can cause severe sepsis or sepsis shock, especially in immunocompromised children. It is significant to select appropriate samples and pathogen detection methods in the early stage of disease.


2020 ◽  
pp. 106689692093777
Author(s):  
Janet Pineda-Díaz ◽  
Irit Solar ◽  
Dov Hershkovitz ◽  
Ido Drukman ◽  
Osnat Sher

Inflammatory myofibroblastic tumor (IMT) is a lesion of intermediate biological potential with local recurrences and rare metastases found in multiple anatomical locations. We present a case of a pure intraarticular IMT of the knee, a location that has not been previously documented, with genetic confirmation of ALK-CARS fusion detected with next-generation sequencing. A 20-year-old healthy male was admitted to the orthopedic oncology department due to several months of pain and restriction in movement of his left knee. On magnetic resonance imaging, multiple intraarticular nodular lesions were seen. The patient underwent 2 synovectomies within the course of 1 year. The initial biopsy was interpreted as nodular fasciitis. The second biopsy revealed exuberant tissue displaying compact fascicles of spindle cells intermixed with myxoid areas in a background of inflammatory cells, highly suggestive for IMT. Due to the unusual intraarticular location, equivocal ALK immunostaining and the differential diagnosis with nodular fasciitis, we performed targeted next-generation sequencing using Archer FusionPlex Sarcoma panel, which can identify multiple fusions in a single assay. An ALK-CARS fusion was found, supporting the diagnosis of IMT. This report emphasizes the added value of broad molecular analysis in cases with unusual clinical presentation, equivocal immunohistochemistry, and a wide differential diagnosis.


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