Observational study of the clinical utility of sulfamethoxazole serum level monitoring in the treatment of brain abscesses due to Nocardia species.

ABSTRACT: Although there is a lack of data in trimethoprim-sulfamethoxazole (TMP-SMX) serum monitoring utility for invasive nocardial infections, therapeutic drug monitoring is widely used to optimize dosing and avoid adverse reactions that may cause treatment interruption.We retrospectively reviewed all adults who received TMP-SMX to treat nocardial brain abscess and had SMX serum level testing from 2010 to 2020.Twenty-two patients received treatment with TMP-SMX for Nocardia species brain abscess and 16 (72.7%) had a reported SMX level, with a median patient age of 65.5 years (interquartile range, IQR 59.5-72.5). Compared to those who did not have a documented SMX serum level, patients with SMX levels had a shorter median course of TMP-SMX treatment (322 days [IQR 188-365] vs. 365 [IQR 224-365]; P = .31) and higher therapeutic induction dose (10 [62.5%] vs. 3 [50%]; P = .92). Similarly, they were more frequently on hemodialysis (3 [13.6%] vs. 1 [4.5%]; P = > .99). The median peak level was 158.5 (IQR 120-218) µg/mL, collected at 2 hours (75%) post-administration in the induction phase (81.3%). Patients with documented SMX levels had fewer reported drug toxicity (5 [31.3%] vs. 4 [66.7%]; P = .1) than those without SMX levels. Among the five patients who reported TMP-SMX-related toxicity, 4 (80%) had an SMX peak level >150 µg/mL. There was no difference in the cure, relapse, and death rates among the two groups.While SMX level was not associated with Nocardia species brain abscess cure rates and mortality, most patients with SMX peak >150 µg/mL experienced drug toxicity.

Molecular Identification of Nocardia seriolae and Comparative Analysis of Spleen Transcriptomes of Hybrid Snakehead (Channa maculata Female × Channa argus Male) With Nocardiosis Disease.

Hybrid snakehead (Channa maculata female × Channa argus male) is a new freshwater aquaculture fish species in southern China. During intensive aquaculture, hybrid snakeheads are often infected by Nocardia seriolae. In this study, hybrid snakehead infected suspiciously by N. seriolae in an artificial breeding pond were examined. Diseased hybrid snakeheads swam slowly without food intake, and the clinical symptoms included skin wound, anal swelling and ascites, and white granulomatous in liver, spleen, and kidney of fish. Through bacterial isolation, 16S rDNA sequencing, fluorescence in situ hybridization (FISH) and artificial infection experiment, the pathogen was identified as N. seriolae. Furthermore, the spleen samples from diseased and healthy male hybrid snakeheads in the same pond were used for RNA-Seq analysis. A total of 3,512 unique transcripts (unigenes) were identified as differentially expressed genes (DEGs), and 1,886 of them were up-regulated in diseased fish. The expression patterns of 20 DEGs were verified by quantitative polymerase chain reaction (qPCR). Several immune-related pathways and many immune-related genes were identified. qPCR results showed that the expression patterns of immune-related genes in the liver and kidney of diseased fish were comparable to that in the spleen. This study provides deep-sequencing data of hybrid snakehead spleen and will help understand the immune response of hybrid snakehead to N. seriolae. It is also helpful for the biomarker screening of fish-borne Nocardia spp. and the breeding of nocardiosis-resistant fish species.

Nocardia coffeae sp. nov., an endophytic actinobacterium isolated from the root of Coffea arabica (L.).

The polyphasic taxonomic study of a novel endophytic actinobacterium strain (CA2R105T) was carried out. The strain formed fragmented substrate mycelium and showed chemotaxonomic properties typical of members of the genus Nocardia, i.e. the presence of mycolic acid and MK-8 (H4ω-cycl) in its cells. Strain CA2R105T exhibited the highest 16S rRNA gene sequence similarity to Nocardia jiangxiensis NBRC 101359T (99.2%). The genome-based taxonomic analysis revealed low average nucleotide identity-blast and digital DNA-DNA hybridization values (<93.7, and <65.2%, respectively) to its closest relative. Moreover, many different phenotypic characteristics were observed between strain CA2R105T and all related Nocardia-type strains. This taxonomic evidence suggested that strain CA2R105T should be judged as representing a novel species of the genus Nocardia and the name, Nocardia coffeae sp. nov. is proposed. The type strain is CA2R105T (=TBRC 11247T=NBRC 114292T).

Nocardiosis in renal transplant patients.

Renal transplant patients are immunosuppressed and are at increased risk of opportunistic infections, including Nocardia infection. In renal transplant patients, information on the incidence and risk factors associated with nocardiosis is limited. To address the incidence and risk factors associated with nocardiosis in a large renal transplant population, we used the US Renal Data System (USRDS). Sequelae of allograft failure or rejection after infection were also examined. Demographics, clinical risk factors, Nocardia diagnosis, and allograft failure following Nocardia infection were queried in USRDS renal transplant patients using International Classification of Diseases, Ninth Revision (ICD-9) codes in billing claims and Centers for Medicare and Medicaid Services Form 2728. Generalized linear models were used to determine the risk factors associated with nocardiosis, and Cox proportional hazards models were used to examine the association of risk factors with graft failure among patients with Nocardia infection. Of 203,233 renal transplant recipients identified from 2001 to 2011, 657 (0.32%) were diagnosed with Nocardia infection. Pneumonia was the most frequent presentation (15.2%), followed by brain abscess (8.4%). Numerous factors associated with increased Nocardia infection included age >65 years (OR=2.10, 95% CI 1.71 to 2.59), history of transplant failure (OR=1.28, CI 1.02 to 1.60) or history of rejection (OR=4.83, CI 4.08 to 5.72), receipt of a deceased donor transplant (OR=1.23, CI 1.03 to 1.46), and treatment with basiliximab (OR=1.25, CI 1.00 to 1.55), cyclosporine (OR=1.30, CI 1.03 to 1.65), tacrolimus (OR=2.45, CI 2.00 to 3.00), or thymoglobulin (OR=1.89, CI 1.59 to 2.25). In patients with nocardiosis administration of antithymocyte globulin (HR=2.76), chronic obstructive pulmonary disease (HR=2.47), and presentation of Nocardia infection with brain abscess (HR=1.85) were associated with an increased risk of graft failure. This study provides new information to enhance early recognition and targeted treatment of nocardiosis in renal transplant patients.

Evaluation of antimicrobial susceptibility testing of Nocardia spp. isolates by broth microdilution with resazurin and spectrophotometry.

BACKGROUND: Nocardia species are ubiquitous in natural environments and can cause nocardiosis. In the present study, the use of Resazurin salt and Spectrophotometry were proposed as alternative methods to reduce subjectivity in the interpretation of susceptibility results to antimicrobials by the broth microdilution method for Nocardia spp. RESULTS: The susceptibility of Nocardia spp. isolates to Amikacin, Ciprofloxacin, Minocycline and Trimethoprim-Sulfamethoxazole was evaluated by Minimum Inhibitory Concentration (MIC) determinations by the broth microdilution method. To verify cellular growth, the colour-changing dye Resazurin was applied, the Optical Densities were measured on a spectrophotometer, and both were compared to Clinical and Laboratory Standards Institute (CLSI) Gold Standard method (visual MIC determination). Percentages of essential and categorical agreements and interpretative categorical errors were calculated within each method (intra-reading) and between them (inter-reading). The Gold Standard visual reading demonstrated 100% of essential and categorical intra-reading agreements for Amikacin, and there was no error when compared with the alternative methods. For Ciprofloxacin, the comparison between the Gold Standard and the Spectrophotometric reading showed 91.5% of essential agreement. In the categorical intra-reading analysis for Minocycline, there were 88.1 and 91.7% in the Gold Standard and in the Spectrophotometric readings, respectively, and 86.4% of concordance between them. High rates of categorical agreement were also observed on the Trimethoprim-Sulfamethoxazole analyses, with 93.7% for the Gold Standard, 84.9% for the Resazurin readings, and 80.5% between them. CONCLUSIONS: The alternative methods with Resazurin and Spectrophotometric readings showed high agreement rates with the Gold Standard.

MLSA phylogeny and antimicrobial susceptibility of clinical Nocardia isolates: a multicenter retrospective study in China.

BACKGROUND: With the increase of detection rate and long treatment period, nocardiosis has become a noticeable problem in China. However, there are limited large-scale studies on the epidemiology and antimicrobial susceptibility profiles of clinical Nocardia spp. in China. The present study aimed to explore the species distribution and drug susceptibility pattern of 82 clinical Nocardia isolates from three tertiary hospitals in China by multilocus sequence analysis (MLSA) and broth microdilution (BMD) method. RESULTS: Pulmonary nocardiosis (90.2%) was the most common clinical presentation of infection. N. cyriacigeorgica (n = 33; 40.2%) and N. farcinica (n = 20; 24.4%) were the most frequently encountered Nocardia species, followed by N. otitidiscaviarum (n = 7; 8.5%), N. abscessus (n = 5; 6.1%), N. asiatica (n = 4; 4.9%), and N. wallacei (n = 4; 4.9%). Trimethoprim/sulfamethoxazole (SXT) remained high activity against all Nocardia isolates (susceptibility rate: 98.8%). Linezolid and amikacin were also highly active; 100 and 95.1% of all isolates demonstrated susceptibility, respectively. Except for N. otitidiscaviarum, all the Nocardia isolates exhibited high susceptibility rates to imipenem. The resistance rates of all isolates to clarithromycin and ciprofloxacin were 92.7 and 73.2%, respectively, but the resistance rate of N. farcinica to ciprofloxacin was only 25%. CONCLUSIONS: The clinically isolated Nocardia spp. had diverse antimicrobial susceptibility patterns, which were similar to the reports by other groups elsewhere, but some differences were also observed, mainly including imipenem and ciprofloxacin. According to this study, SXT still can be the first choice for empirical therapy due to the low resistance rate. Linezolid can be chosen when a patient is allergic to SXT, and amikacin and imipenem can be the choice in a combination regimen.

Nocardia acididurans sp. nov., an acid-tolerant actinobacterium isolated from bio-fertilizer of Musa species.

A novel acid-tolerant actinobacterium (strain LPG 2T), which formed fragmented substrate mycelia, was isolated from bio-fertiliser of Musa spp. collected from Lampang Province, Thailand. Its morphological and chemotaxonomic properties, e.g., the presence of mycolic acid and MK-8 (H4ω-cycl) in the cells, showed that strain LPG 2T was a member of the genus Nocardia. 16S rRNA gene sequence analysis revealed that this strain was closely related to Nocardia otitidiscaviarum NBRC 14405T (98.7 %). The low average nucleotide identity-blast and digital DNA-DNA hybridization values (<78.6 and <24.0 %, respectively), and several phenotypic differences between strain LPG 2T and its related Nocardia type strains, indicated that the strain merits classification as representing a novel species of the genus Nocardia, for which we propose the name Nocardia acididurans sp. nov. The type strain is LPG 2T (=TBRC 11242T=NBRC 114293T).

Disseminated nocardiosis caused by Nocardia farcinica in a patient with colon cancer: A case report and literature review.

RATIONALE: Nocardiosis is an uncommon and potentially life-threatening infection that usually affects immunocompromised hosts. No clinical guidelines have been established for managing this rare disease, and the optimal treatment modality remains unclear. Nocardia farcinica, a relatively infrequent pathogen of nocardiosis, causes a clinically aggressive infection. In addition to our patient data, our search of the literature for patients who presented with empyema caused by N. farcinica will provide fundamental information for optimal treatment modalities. PATIENT CONCERNS: A 64-year-old man was diagnosed with empyema, 4 days following surgery for sigmoid colon cancer. Brain lesions were evaluated only after N. farcinica was isolated and identified as the causative pathogen through repeated culture tests. DIAGNOSES: N. farcinica was isolated from the pleural effusion and confirmed as the pathogen through 16S rRNA sequencing. INTERVENTIONS: The patient was successfully treated with tube thoracotomy, neurosurgical evacuation, and a combination of trimethoprim/sulfamethoxazole plus imipenem. Long-term antibiotic therapy was required to prevent recurrence. OUTCOMES: Pyothorax showed a good clinical response to antimicrobial therapy and drainage of pleural effusion, whereas brain abscess did not respond to medical therapy and required surgery. The patient eventually recovered and continued chemotherapy as treatment for sigmoid colon cancer. LESSONS: Although extremely rare, this report demonstrates the importance of considering Nocardia infection as the differential diagnosis in immunocompromised patients who present with empyema. In particular, because of the N. farcinica infection's tendency to spread and the resistance of the organism to antibiotics, aggressive evaluation of metastatic lesions and standardized support from microbiological laboratories are important. Surgery may be required in some patients with brain abscesses to improve the chance of survival.

Nocardia huaxiensis sp. nov., an actinomycete isolated from human skin.

A novel actinomycete, designated as strain WCH-YHL-001T, was isolated from skin biopsy specimens of a patient at West China Hospital, Chengdu, Sichuan Province, PR China. The cells were Gram-positive, aerobic, heterotrophic and non-motile. They formed an extensive substrate with short aerial mycelia, whose branches fragmented into rod-shaped elements. Growth occurred at 10-40 °C, pH 5.0-12.0 and with NaCl concentrations of 0-4.0 % (w/v). The major cellular fatty acids of strain WCH-YHL-001T were C16 : 0, C18 : 1 ω9c, C18 : 0 10-methyl and summed feature 3. The predominant respiratory quinone was MK-8 (H4ω-cycl). The major polar lipids were phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylinositol mannoside, unknown phospholipids and unidentified glycolipids. The diagnostic diamino acid of peptidoglycan was meso-diaminopimelic acid. The whole-cell sugar pattern consisted of arabinose and glucose. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain WCH-YHL-001T belonged to the genus Nocardia. The average nucleotide identity (ANI) and in silico DNA-DNA hybridization (isDDH) values between strain WCH-YHL-001T and type strains of Nocardia species were lower than the cut-offs (≥95-96 % for ANI and ≥70 % for isDDH) required to define a bacterial species. The genomic DNA G+C content was 67.8 mol%. Phylogenetic, physiological and chemotaxonomic data suggested that strain WCH-YHL-001T represented a novel species of the genus Nocardia, for which the name Nocardia huaxiensis sp. nov. is proposed, with the type strain WCH-YHL-001T (=GDMCC 4.181T=JCM 34475 T=NBRC 114973T).

A case report of brain abscess caused by Nocardia farcinica.

BACKGROUND: Brain abscess due to the Nocardia genus is rarely reported and it is usually found in immunocompromised patients. Treatment of Nocardia brain abscess is troublesome and requires consideration of the severity of the underlying systemic disease. The difficulties in identifying the bacterium and the frequent delay in initiating adequate therapy often influence the prognosis of patients. CASE PRESENTATION: Here, we report a rare case of brain abscess caused by Nocardia farcinica. The patient's medical history was complicated: he was hospitalized several times, but no pathogens were found. At last, bacteria were found in the culture of brain abscess puncture fluid; the colony was identified as Nocardia farcinica by mass spectrometry. Targeted antibiotic treatment was implemented, brain abscess tended to alleviate, but the patient eventually developed fungal pneumonia and died of acute respiratory distress syndrome (ARDS). CONCLUSION: Brain abscess caused by Nocardia farcinica can appear in non-immunocompromised individuals. Early diagnosis, reasonable surgical intervention, and targeted antibiotic treatment are critical for Nocardia brain abscess treatment. In the treatment of Nocardia brain abscess, attention should paid be to the changes in patients' immunity and infection with other pathogens, especially fungi, avoided.

Identification and antimicrobial susceptibility profiles of Nocardia species clinically isolated in Japan.

The aims of the present study were to profile the antimicrobial susceptibility patterns of a diverse range of Nocardia species isolated in Japan, and to determine the ability of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for species/complex identification. Identification of 153 clinical isolates was performed by full-length 16S rRNA gene sequencing as a reference method to evaluate the usefulness of MALDI-TOF MS identification. Antimicrobial susceptibility testing (AST) for 14 antibiotics was performed using the broth microdilution method against 146 of the isolates. Among the total 153 clinical isolates, Nocardia farcinica complex (25%) was the most common species, followed by Nocardia cyriacigeorgica (18%), Nocardia brasiliensis (9%), Nocardia nova (8%), and Nocardia otitidiscaviarum (7%). Among 150 isolates identified to the species/complex level by 16S rRNA gene sequencing, MALDI-TOF MS with the use of a supplemental Nocardia library (JMLD library ver.ML01) correctly identified 97.3% (n = 146) to the species/complex level and 1.3% (n = 2) to the genus level. Among the 146 Nocardia isolates that underwent AST, the susceptibilities were 100% to linezolid, 96% to amikacin, 94% to trimethoprim-sulfamethoxazole, and 76% to imipenem. None of the trimethoprim-sulfamethoxazole-resistant isolates carried either plasmid-mediated sulfonamide-resistant genes (sul1, sul2) or trimethoprim-resistant genes (dfrA).

A rare case of pulmonary nocardiosis comorbid with Sjogren's syndrome.

BACKGROUND: Nocardia is an opportunistic pathogen, which occurs in patients with autoimmune diseases and immune dysfunction, and can cause bacteremia and other life-threatening complications. The clinical manifestations of Nocardia pneumonia are similar to tuberculous and other clinical common bacterial pneumonia, but its antibacterial treatments are different and detection methods are unique, which may lead patients to suffer for many years due to clinical misdiagnosis and missed diagnosis. METHODS: Imaging and laboratory examinations were performed for preliminary diagnosis, and next-generation sequencing was used to identify the exact species type of Nocardia in the bronchoalveolar lavage fluid (BALF) of the patient. RESULTS: Imaging and laboratory parameters preliminarily implied that the patient was infected with Nocardia with Sjogren's syndrome (SS), and NGS showed that the strain was N. terpenica. CONCLUSIONS: Accurate etiological diagnosis and corresponding antibiotics are key to improve the prognosis of pulmonary nocardiosis in this case. Nocardia pneumonia is rare in clinical practice; it is of great medical significance to improve the understanding of pulmonary nocardiosis.

Pulmonary nocardiosis caused by Nocardia abscessus mimicking pulmonary thromboembolism in a patient with atypical anti-glomerular basement membrane glomerulonephritis.

Nocardia species are opportunistic bacteria that are frequently contagious by inhalation. Recently, Nocardia abscessus has been described as a different species. We report a 54-year-old male who presented with acute pleuritic chest pain, mimicking pulmonary thromboembolism on the 5th day of discharge from the hospital. The patient was receiving immunosuppressive therapy for newly diagnosed atypical anti-glomerular basement membrane disease. Thorax computed tomography revealed a 17x19 mm soft tissue lesion in the lateral segment of the middle lobe of the right lung. After further examinations, a biopsy decision was made and Nocardia abscessus was isolated in the aerobic culture of the aspiration material.

First evidence of fish nocardiosis in Mexico caused by Nocardia seriolae in farmed red drum (Sciaenops ocellatus, Linnaeus).

Between August and December 2013, the offshore cages of a commercial marine farm culturing red drum Sciaenops ocellatus in Campeche Bay Mexico were affected by an outbreak of an ulcerative granulomatous disease with up to 70% cumulative mortality. Thirty-one adults displaying open ulcers on the skin were submitted for diagnosis. At necropsy, multiple white-yellowish nodules (0.1-0.5 cm in diameter) were present in all internal organs, where the kidney and the spleen were the most severely affected. Histopathology evinced typical systemic granulomatous formations. Gram and Ziehl-Neelsen stains on tissue imprints, bacterial swabs and tissue sections revealed Gram-positive, acid-fast, branching beaded long rod filamentous bacteria. Tissue samples resulted positive for nocardiosis with a Nocardia genus-specific nested PCR. Definite identification at the species level and taxonomic positioning of the fastidious pathogen were achieved through a specific Nocardia seriolae PCR and by sequencing the gyrB gene of pure isolates. After administration of antibiotics during fry production, a posterior follow-up monitoring (from 2014 to 2017) detected mild but recurrent outbreaks of the bacteria with no seasonality pattern. To the extent of our knowledge, this is the first report of piscine nocardiosis in Mexico and the first time this disease is detected in red drum.

Nocardia kroppenstedtii: a rare pathogen isolated from the spinal vertebral abscess of a patient on long-term immunosuppressive therapy.

OBJECTIVE: Nocardia kroppenstedtii was isolated from the spinal vertebral abscess of a 78-year-old patient presenting with mid-thoracic pain and bilateral lower limb weakness and numbness. The patient was on long-term immunosuppressive therapy with steroids for underlying autoimmune hemolytic anemia. Investigations showed a T5 pathological fracture and vertebra plana with the erosion of the superior and inferior endplates. There was evidence of paraspinal collection from the T4-T6 vertebrae with an extension into the spinal canal. Analysis of Nocardia 16S rRNA (99.9%, 1395/1396 nt) and secA1 gene (99.5%, 429/431 nt) fragments showed the highest sequence similarity with Nocardia kroppenstedtii type strain (DQ157924), and next with Nocardia farcinica (Z36936). The patient was treated with intravenous carbapenem and oral trimethoprim-sulfamethoxazole for four weeks, followed by another six months of oral trimethoprim-sulfamethoxazole. Despite the improvement of neurological deficits, the patient required assistive devices to ambulate at discharge. This study reports the first isolation of N. kroppenstedtii from the spinal vertebral abscess of a patient from Asia. Infections caused by N. kroppenstedtii may be underdiagnosed as the bacterium can be misidentified as N. farcinica in the absence of molecular tests in the clinical laboratory.

How do I manage nocardiosis?

BACKGROUND: Nocardiosis is a rare infection that is often difficult to treat and may be life-threatening. There is no consensus on its management. OBJECTIVES: Our aim was to provide the current evidence for the diagnosis and management of individuals with nocardiosis, and to propose a management approach for this uncommon infection. SOURCES: We systematically searched the medical literature on nocardiosis for studies published between 2010 and 2020 and describing ten or more individuals. CONTENT: Nocardiosis, a primarily opportunistic infection which may occur in immunocompetent persons, most commonly involves the lungs and frequently disseminates to other sites including the central nervous system. The reference standard for Nocardia species identification is molecular biology, and the preferred method for antibiotic susceptibility testing (AST) is broth microdilution. Monotherapy seems appropriate for patients with primary skin nocardiosis or non-severe pulmonary disease; we reserve a multidrug regimen for more severe infections. Species identification and AST results are often missing at initiation of antibiotics. Trimethoprim-sulfamethoxazole is the preferred agent for initial therapy, because Nocardia is very often susceptible to this agent, and because it has been the keystone of nocardiosis treatment for years. Linezolid, to which Nocardia is almost always susceptible, may be an alternative. When combination therapy is required, the repertoire of companion drugs includes third-generation cephalosporins, amikacin and imipenem. Therapeutic modifications should take into account clinical response to initial therapy and AST results. Treatment duration of 6 months is appropriate for most situations, but longer durations are preferred for disseminated nocardiosis and shorter durations are reasonable in low-risk situations. Secondary prophylaxis may be considered in selected individuals with permanent immunosuppression. IMPLICATIONS: We hereby provide the clinician with an easy-to-use algorithm for the management of individuals with nocardiosis. We also illuminate gaps in evidence and suggest future research directions.

Pneumocystis jiroveci pneumonia, Nocardia brasiliensis, and Mycobacterium tuberculosis co-infection in a myasthenia gravis patient: A case report.

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.