Pneumocystis jiroveci pneumonia, Nocardia brasiliensis, and Mycobacterium tuberculosis co-infection in a myasthenia gravis patient

Abstract

Rationale: Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junctions that leads to fluctuating weakness and disabling fatigability. Due to difficulty in breathing caused by weakness of the respiratory muscles, patients with MG are more susceptible to pneumonia and other respiratory infections. As many patients with MG are given immunosuppressive therapy, this makes them more prone to infections. However, coinfection with 3 pathogens is very rare. Patient concerns: Here, we report the case of a 41-year-old gentleman with MG who was receiving long-term steroid therapy. He presented with a cough with pale brown expectoration that occurred without obvious inducement, severe pain in the scapula, as well as swelling and weakness of both legs. Despite undergoing treatment, but his symptoms did not improve, prompting two additional hospital admissions over a period of several months. Diagnosis: Bronchoscopy and bronchoalveolar lavage (BAL) were performed, revealing the presence of Pneumocystis jirovecii , Nocardia brasiliensis, and Mycobacterium tuberculosis (MTB). N brasiliensis was identified by positive modified acid-fast Kinyoun staining as well as a positive colony culture identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry from the BAL sample. MTB was confirmed using GeneXpert, and due to the limitations of the culture conditions, methenamine silver stain was used to confirm Pneumocystis jirovecii. Next-generation sequencing (NGS) assay of the BAL samples also confirmed these pathogens. Interventions: The patient was transferred to a designated tuberculosis hospital and received anti-infective and anti-TB treatment. Outcomes: During treatment at the designated hospital, the patient developed gastrointestinal bleeding and impaired liver function. One month later, he developed multiple organ failure, consolidation of the left lower lung, and pan-drug resistant bacteremia. He refused further treatment and was discharged Conclusion: In conclusion, physicians should be aware of the predisposition of MG patients to co-infections, especially patients with metabolic disorders, to avoid inadequate treatment and poor patient outcomes. Due to the limitations of culture conditions, NGS should be considered as a new technique for identifying pathogens.

Rapid Genomic Diagnosis of Fungal Infections in the Age of Next-Generation Sequencing

“…Excluding P. jirovecii, which is generally unculturable, out of the remaining 274 fungi detected by NGS, only 105 (~38%) were recovered by fungal culture from the same or different specimens from the respective patients [26,[29][30][31][32][33][34][35][36][37][38][39]43,45,46,49,52,54,57,59,62,64,66,67,71,73,76,77]. The majority of P. jirovecii infections diagnosed by NGS were reported in case series [34,36,39,41,48,53,55,58,62,64,65,67,72,75]. All the patients unanimously suffered from pneumonia.…”

“…Lastly, publications were searched using specific fungal names and after manual examination five extra articles were added. Therefore, in total 52 articles were included in this review [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 ].…”

“…It was a case of allergic bronchopulmonary mycosis where A. fumigatus and Schizophyllum commune sequences were detected in the homogenised sputum and mucoid plugs of the patient [ 26 ]. Since then, up to the time of writing, a total of 319 cases of fungal infections diagnosed by NGS were described in the literature, with some in case reports and others in case series or cohorts [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 ]. In 40 out of the 319 cases (12.5%), more than 1 fungus was detected by NGS [ 26 , ...…”

“…The majority of P. jirovecii infections diagnosed by NGS were reported in case series [ 34 , 36 , 39 , 41 , 48 , 53 , 55 , 58 , 62 , 64 , 65 , 67 , 72 , 75 ]. All the patients unanimously suffered from pneumonia.…”

“…In contrast, for the other immunocompromised patients, the fungal load is usually low and bronchoscopic examination has to be performed to collect samples that give higher yield. For the cases of P. jirovecii pneumonia diagnosed by NGS, less than 20% were P. jirovecii positive by microscopic examination of the patients’ bronchoalveolar lavage or sputum samples after silver methenamine or immunofluorescence staining [ 34 , 39 , 53 , 58 , 62 , 64 , 65 , 67 ].…”