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

ABSTRACT: 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.

SUBMITTER: Michel C

PROVIDER: S-EPMC8290067 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundsThe incidence of angiostrongyliasis is increasing in recent decades due to the expanding endemic areas all over the world. Clinicians face tremendous challenge of diagnosing angiostrongyliasis because of the lack of awareness of the disease and less effective definitive laboratory tests.Case presentationA 27-year-old man initially manifested skin itching, emesis, myalgia and quadriparesis. With progressive weakness of four limbs and elevated protein in the cerebrospinal fluid (CSF), he was diagnosed as Guillain-Barré syndrome and treated with intravenous methylprednisolone and immunoglobulin. However, the patient deteriorated with hyperpyrexia, headache and then persistent coma. The routine tests for Angiostrongylus cantonensis (A. cantonensis) with both the CSF and the serum were all negative. In contrast, the metagenomic next-generation sequencing (mNGS) was applied with the serum sample and the CSF sample in the middle phase. The central nervous system (CNS) angiostrongyliasis was diagnosed by mNGS with the mid-phase CSF, but not the mid-phase serum. At the same time, the CSF analysis revealed eosinophils ratio up to 67%. The discovery of A. cantonensis was confirmed by PCR with CSF later. Unfortunately, the patient died of severe angiostrongyliasis. During his hospitalization, mNGS was carried out repeatedly after definitive diagnosis and targeted treatment. The DNA strictly map reads number of A. cantonensis detected by mNGS was positively correlated with the CSF opening pressure and clinical manifestations.ConclusionsThe case of A. cantonensis infection highlights the benefit of mNGS as a target-free identification in disclosing the rare CNS angiostrongyliasis in the unusual season, while solid evidence from routine clinical testing was absent. The appropriate sample of mNGS should be chosen according to the life cycle of A. cantonensis. Besides, given the fact that the DNA reads number of A. cantonensis fluctuated with CSF opening pressure and clinical manifestations, whether mNGS could be applied as a marker of effectiveness of treatment is worth further exploration.

Project description:Cat-scratch disease (CSD) is an anthropozoonotic infection caused by Bartonella henselae, and it is one of the most common causes of lymph node infections in children and adolescents. B. henselae, belonging to the genus Bartonella, is a common human pathogen of human beings. CSD commonly develops as a result of cat scratches and bites or when injured skin comes into contact with cat saliva. The manifestation of CSD clinically differs for each patient based on their immune system. Individuals who have healthy immune systems generally manifest minimal clinical symptoms and do not necessitate any form of treatment. However, patients who have hypo-immunity require prompt medical attention due to the potential manifestation of severe symptoms that affect multiple systems of the body. Long latency and atypical clinical manifestations are characteristics of CSD. Bartonella isolation and identification are challenging procedures that require specialized equipment. There is no gold standard method for CSD diagnosis, and misdiagnosis and missed diagnosis rates are typically high. We present the case of a middle-aged male patient who developed fever, chills, anal distension, dizziness, and muscle pain for 10 days. The patient had a documented history of cat bites 1 month prior to the onset of symptoms. Following admission, he underwent an examination to determine superficial lymphadenopathy and hypoimmunity. Additionally, he had a fever during the disease. As the patient refused a needle biopsy of lymph nodes, metagenomic next-generation sequencing (mNGS) was employed and B. henselae was detected in the peripheral blood. The patient was diagnosed with CSD and treated with a combination of azithromycin and doxycycline. The fever symptoms were alleviated, and the patient was ultimately discharged. As a result of this case, we suggest that mNGS be used as a crucial supplementary diagnostic tool for individuals with compromised immune systems who may have CSD, especially when conventional diagnostic methods are inconclusive.

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

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