Kansasii Infection Research Articles

Mycobacterium kansasii Infection in a Farmed White-Tailed Deer (Odocoileus virginianus) in Florida, USA.

A 7-year-old farmed white-tailed deer doe was transported to a Levy County, Florida property and began to decline in health, exhibiting weight loss and pelvic limb weakness. The doe prematurely delivered live twin fawns, both of which later died. The doe was treated with corticosteroids, antibiotics, gastric cytoprotectants, and B vitamins but showed no improvement. The doe was euthanized, and a post mortem examination was performed under the University of Florida's Cervidae Health Research Initiative. We collected lung tissue after the animal was euthanized and performed histological evaluation, using H&E and Ziehl-Neelsen (ZN) staining, and molecular evaluation, using conventional PCR, followed by Sanger sequencing. The microscopic observations of the H&E-stained lung showed multifocal granuloma, while the ZN-stained tissue revealed low numbers of beaded, magenta-staining rod bacteria inside the granuloma formation. Molecular analysis identified the presence of Mycobacterium kansasii. This isolation of a non-tuberculous Mycobacterium in a white-tailed deer emphasizes the importance of specific pathogen identification in cases of tuberculosis-like disease in farmed and free-ranging cervids. We report the first case of M. kansasii infection in a farmed white-tailed deer (Odocoileus virginianus) in Florida. Although M. kansasii cases are sporadic in white-tailed deer, it is important to maintain farm biosecurity and prevent farmed cervids from contacting wildlife to prevent disease transmission.

Haemophagocytic lymphohistiocytosis caused by GATA2 deficiency: a report on three patients

BackgroundHaemophagocytic lymphohistiocytosis (HLH) is a syndrome that occurs in patients with severe systemic hyperinflammation. GATA binding protein 2 (GATA2) is a transcription factor and key component in haematopoiesis and stem cell biology.Case presentationThree patients with HLH, one with Mycobacterium avium infection, one with Epstein–Barr virus (EBV) infection, and one with Mycobacterium kansasii infection, were all subsequently found to have a defect in the GATA2 gene through genetic testing.ConclusionsGATA2 deficiency syndrome should be considered in patients with myelodysplastic syndrome, nontuberculous mycobacterium infection and HLH. In addition, the GATA2 gene variant may be a genetic defect that could be the cause of the primary HLH. However, further studies are needed to confirm the role of GATA2 pathogenic variants in the pathogenesis of HLH.

Multiple refractory intracellular pathogen infections in a human immunodeficiency virus-negative patient with anti-interferon-γ autoantibodies: a case report

BackgroundThe clinical presentation of adult-onset immunodeficiency with anti-interferon (IFN)-γ autoantibodies with intracellular pathogens can be highly variable, which can lead to misdiagnosis during the early stage of disease.Case presentationWe report a complex case of a 54-year-old Chinese male who was human immunodeficiency virus-negative. He had a presence of anti-IFN-γ autoantibodies and suffered from various intracellular pathogenic infections. The patient was admitted to our hospital for the first time in July 2016 with severe pneumonia, and he experienced multiple pneumonia infections between 2017 and 2019. In March 2019, the patient was hospitalized due to pulmonary lesions and multiple-bone destruction. During hospitalization, the patient was confirmed to have disseminated Talaromyces marneffei infection and was successfully treated with antifungal therapy for 1 year. In June 2021, Mycobacterium kansasii infection was detected by positive culture and progressive bone destruction. A high concentration of anti-IFN-γ antibodies was observed in the patient’s serum. In addition, Listeria monocytogenes was isolated by blood culture, and the presence of L. monocytogenes in cerebrospinal fluid was confirmed by next-generation sequencing. Following anti-non-tuberculous mycobacteria (NTM) therapy and anti-bacterial therapy, the patient’s symptoms, pulmonary lesions, and bone destruction gradually improved.ConclusionsAlthough the clinical presentation of adult-onset immunodeficiency with anti-IFN-γ autoantibodies can be highly variable, the diagnosis should be considered if patients suffer from unexplained repeated bacterial or opportunistic infections.Conventional and advanced molecular testing should be used, as needed, for microbiological diagnoses among this special immunodeficient population.

Multiple Bone Destruction Secondary to Mycobacterium kansasii Pulmonary Disease: A Case Report.

Mycobacterium kansasii infections predominantly manifest in immunocompromised people and are primarily responsible for lung disease and systemic disseminated infection. Osteopathy is a rare consequence of M. kansasii infection. Here, we present imaging data from a 44-year-old immunocompetent Chinese woman diagnosed with multiple bone destruction, particularly of the spine, secondary to M. kansasii pulmonary disease, which is easily misdiagnosed. The patient underwent an emergency operation after experiencing unexpected incomplete paraplegia during hospitalization, indicating an aggravation of bone destruction. Preoperative sputum testing and next-generation sequencing of DNA and RNA of intraoperative samples confirmed the diagnosis of M. kansasii infection. Treatment with anti-tuberculosis therapy and the subsequent patient response supported our diagnosis. Given the rarity of osteopathy secondary to M. kansasii infection in immunocompetent individuals, our case offers some insight into this diagnosis.

The Induction of Antigen 85B-Specific CD8+ T Cells by Recombinant BCG Protects against Mycobacterial Infection in Mice.

Mycobacterium tuberculosis (Mtb) infection remains a major health problem worldwide. Although the Bacillus Calmette-Guérin (BCG) vaccine is the most widely used vaccination for preventing tuberculosis (TB), its efficacy is limited. We previously developed a new recombinant BCG (rBCG)-based vaccine encoding the Ag85B protein of M. kansasii (Mkan85B), termed rBCG-Mkan85B, and its administration is followed by boosting with plasmid DNA expressing the Ag85B gene (DNA-Mkan85B). Previously, we identified MHC-I (H2-Kd)-restricted epitopes that highly cross-react with those of Mtb in BALB/c (H2d) and CB6F1 (H2b/d) mice. We also reported that the rBCG-Mkan85B/DNA-Mkan85B prime-boost vaccination protocol protected CB6F1 mice against M. kansasii infection. In this study, to investigate the protective effect of our novel rBCG against Mtb infection, CB6F1 mice were either left unimmunized or immunized with the BCG, rBCG-Mkan85B, or rBCG-Mkan85B/DNA-Mkan85B vaccine for 10 weeks prior to inhalation exposure to the virulent Mtb Erdman strain for another 6 weeks. Compared with the BCG and rBCG-Mkan85B vaccinations, the rBCG-Mkan85B/DNA-Mkan85B prime-boost vaccination protocol significantly reduced the numbers of pulmonary colony-forming units (CFUs). Moreover, the rBCG-Mkan85B/DNA-Mkan85B prime-boost vaccination induced antigen-specific polyfunctional CD4+ and CD8+ T cells. These results suggest that CD8+ T-cell immunity to immunodominant epitopes of Mtb is enhanced by rBCG vector-based immunization. Thus, rBCG vector-based vaccinations may overcome the limited ability of the current BCG vaccine to elicit TB immunity.

Performance of Interferon-γ Release Assays in Patients with Mycobacterium kansasii Infection.

To evaluate the performance of interferon-γ release assays (IGRAs) in patients with Mycobacterium kansasii infection. Consecutive patients between May 2012 and June 2021 who had positive for mycobacterial cultures and who underwent IGRAs (T-SPOT.TB or QuantiFERON-TB Gold [QFT-G]) were included in the analysis. The IGRA positivity rates among patients with M. kansasii isolates were then calculated. If M. kansasii was identified in at least two sputum samples or in sterile samples, M. kansasii disease was then diagnosed. Otherwise, colonisation was considered. During the study period, 54 patients with M. kansasii infection underwent T-SPOT.TB (n=48) or QFT-G (n=6) assays. The mean age was 44.1±13.4 years, 85.2% (46/54) were male. Eight patients were diagnosed with M. kansasii disease and another 46 patients were considered to have colonisation. Twenty-four patients (T-SPOT.TB, n=23; QFT-G, n=1) were positive for IGRAs, for an overall rate of 44.4% (24/54; T-SPOT.TB, 47.9% [23/48]; QFT-G, 16.7% [1/6]) for IGRAs, 25.0% (2/8) for M. kansasii disease, and 47.8% (22/46) for colonisation. Positive IGRA rates were relatively low in patients with M. kansasii infection. More efforts are required to improve the performance of IGRAs in diagnosing M. kansasii infection.

A case report of multiple Mycobacterium Kansasii bone infection with pathological fracture of T11 vertebral body and thoracic spinal cord injury

Rationale: Cases of vertebral infection with bone destruction and spinal cord injury caused by Mycobacterium kansasii infection are rarely reported, and the infection is usually associated with severe immunosuppression. Patient concerns: A 62-year-old male patient was hospitalized for 10 days due to recurrent low back pain with diminished skin sensation below the umbilical level. Diagnosis: The patient had no underlying disease. MRI showed multiple bone destruction lesions throughout the body, pathological fractures of the T11 vertebral body, and compression and degeneration of the thoracic spinal cord. Complete back abscess puncture examination, CT-guided vertebral puncture examination, metagenomic next-generation sequencing and bone marrow puncture and other examinations to confirm the diagnosis of Mycobacterium kansasii infection. Intervention: According to the drug susceptibility test of pathogenic bacteria, combined antiinfective treatment was given. After 3 weeks of drug treatment, the patient underwent thoracic posterior debridement, spinal canal decompression, and pedicle screw internal fixation. Outcome: The skin sensation of the patient’s lower limbs was improved 1 month after the operation compared with that before the operation. After adhering to oral drug treatment, the inflammatory index decreased steadily. Four months after the operation, the skin sensation of the patient’s lower extremities returned to normal. Lessons: Regular, adequate, and full course of drug treatment is the key to the treatment of Mycobacterium kansasii infection. Next-generation metagenomic sequencing can improve the efficiency and accuracy of the detection of Mycobacterium kansasii. For patients with abscesses and spinal nerve compression, surgical decompression and abscess removal are effective treatment options.

Mutations du gène GATA2 : à propos de 3 cas

IntroductionHeterozygous germline mutations of GATA2 gene (guanine-adenine-thymine-adenine binding protein 2) are hereditary mutations that can be pathogenic, sometimes occurring sporadically, responsible for a florid clinical-biological picture, sometimes serious and quickly leading to the death. Case reportsWe reported two women and one man with germline mutations in the GATA2 gene. The first patient, aged 19, initially presented with monocytopenia and chronic lymphedema of the four limbs, suggestive of Emberger syndrome. The second patient, 28-years-old, presented with a disseminated atypical mycobacterium (Mycobacterium kansasii) infection, raising suspicion of an immune deficiency such as MonoMAC syndrome (deficiency syndrome of dendritic cells, monocytes, B lymphocytes and NK cells). The last patient, 30-years-old, presented with pancytopenia, leading to the diagnosis of a family form of myelodysplastic syndromes and acute myeloid leukemia characterized by a mutation of the GATA2 gene. ConclusionsEach case illustrates a typical clinical presentation of GATA2 deficiency, although the evolution of these syndromes ultimately reveals a complex, heterogeneous and intricate picture of hematological, dermatological, infectious, pulmonary, ENT or oncological symptoms. Mutations in the GATA2 gene remain a diagnostic and therapeutic challenge for the internist, and require multidisciplinary management given the florid picture that can be of interest to all specialties. The clinical spectrum of these GATA2 mutations as well as the latest management recommendations from the recent litterature and the “GATA2 club” are described in this article.

Evaluation of the MeltPro Myco Assay for the Identification of Non-Tuberculous Mycobacteria.

PurposeThe purpose of this study was to evaluate a new commercial kit for Mycobacterium species identification and compare its results with that of the commonly used GenoType Mycobacterium CM assay. In addition, we were committed to identifying the main frequent species of nontuberculous mycobacteria (NTM) in Fujian.MethodsA total of 261 clinical strains, collected at the Center for Disease Control and Prevention of Fujian Province, China, were preliminarily identified as NTM based on p-nitrobenzoic acid (PNB) growth test. The genomic DNA of all 261 strains was extracted and subjected to species identification using MeltPro Myco assay and GenoType Mycobacterium CM assay. The results of the latter were used as a control to calculate the positive agreement, negative agreement, agreement and the total agreement of the former. For samples with inconsistent detection results, sequencing was performed for verification.ResultsCompared to GenoType Mycobacterium CM assay, the total agreement of MeltPro Myco assay was 96.55% (252/261 strains). Both the positive and negative agreement of MeltPro Myco assay in identifying M. intracellulare, M. abscessus, M. kansasii, M. fortuitum, M. avium, M. gordonae, M. scrofulaceum, and mixed infections were higher than 99.00%, but the positive agreement of M. chelonae was relatively low at only 33.33%. In Fujian, the predominant strain of NTM was M. intracellulare (64.36%, 130/202 strains), followed by M. abscessus (19.31%, 39/202 strains), M. kansasii (4.46%, 9/202 strains), and M. fortuitum (3.96%, 8/202 strains).ConclusionThe reliability of MeltPro Myco assay for identifying mycobacterium species was strongly demonstrated in this study, which greatly supports its usage for the clinical identification of mycobacteria. The present study also showed that the distribution of mycobacteria in Fujian, China, was significantly different from that in other regions and provided important data for future epidemiological study of NTM.

Rifampin Pharmacokinetics/Pharmacodynamics in the Hollow-Fiber Model of Mycobacterium kansasii Infection.

ABSTRACTThere is limited high-quality evidence to guide the optimal treatment of Mycobacterium kansasii pulmonary disease. We retrospectively collected clinical data from 33 patients with M. kansasii pulmonary disease to determine the time-to-sputum culture conversion (SCC) upon treatment with a standard combination regimen consist of isoniazid-rifampin-ethambutol. Next, MIC experiments with 20 clinical isolates were performed, followed by a dose-response study with the standard laboratory strain using the hollow-fiber system model of M. kansasii infection (HFS-Mkn). The inhibitory sigmoid maximum effect (Emax) model was used to describe the relationship between the bacterial burden and rifampin concentrations. Finally, in silico clinical trial simulations were performed to determine the clinical dose to achieve the optimal rifampin exposure in patients. The SCC rate in patients treated with combination regimen containing rifampin at 10 mg/kg of body weight/day was 73%, the mean time to SSC was 108 days, and the mean duration of therapy was 382 days. The MIC of the M. kansasii laboratory strain was 0.125 mg/L, whereas the MICs of the clinical isolates ranged between 0.5 and 4 mg/L. In the HFS-Mkn model, a maximum kill (Emax) of 7.82 log10 CFU/mL was recorded on study day 21. The effective concentration mediating 80% of the Emax (EC80) was calculated as the ratio of the maximum concentration of drug in serum for the free, unbound fraction (fCmax) to MIC of 34.22. The target attainment probability of the standard 10-mg/kg/day dose fell below 90% even at the MIC of 0.0625 mg/L. Despite the initial kill, there was M. kansasii regrowth with the standard rifampin dose in the HFS-Mkn model. Doses higher than 10 mg/kg/day, in combination with other drugs, need to be evaluated for better treatment outcome.

Unusual Presentation of Disseminated Mycobacterium kansasii Infection in Renal Transplant Recipients and Rapid Diagnosis Using Plasma Microbial Cell-free DNA Next-generation Sequencing.

Unusual Presentation of Disseminated Mycobacterium kansasii Infection in Renal Transplant Recipients and Rapid Diagnosis Using Plasma Microbial Cell-free DNA Next-generation Sequencing.

Multifocal Mycobacterium kansasii osteomyelitis in a patient on ruxolitinib

• The presence of non-caseating granulomas on biopsy does not preclude mycobacterial infection, and should trigger careful investigation. • JAK inhibitors such as ruxolitinib increase the risk of mycobacterial infections, making specific investigations critical to diagnostic certainty. • M. Kansasii infection in bones and joints is rare, and is mainly found in immunosuppressed patients. • Biopsy and culture including specifically for mycobacteria should be initiated if there is any clinical suspicion. Mycobacterium kansasii spinal infection is rare. This is the first reported case in a patient taking ruxolitinib. A 69-year-old woman attended the emergency department with severe debilitating lumbar back pain and right sided flank pain. She had experienced persistent right lower chest wall pain following 4 weeks of coryzal symptoms but denied fever or weight loss. She was being treated with ruxolitinib for myelofibrosis. C reactive protein was 9 mg/L. CT and MRI showed bilateral hilar and mediastinal lymphadenopathy, and lytic lesions in the T10 vertebral body and left iliac bone. Noncaseating granuloma were found on endobronchial ultrasound guided lymph node biopsy and on biopsy of the iliac crest, with sarcoid considered a possible diagnosis. On two occasions the patient had pain so severe that she required hospitalisation. Pulsed intravenous corticosteroids was given with symptomatic improvement. Iliac bone biopsy grew Mycobacterium Kansasii at 6-week culture. The patient completed 12 months of treatment (12 months rifampicin and isoniazid, 6 months ethambutol), with resulotion of pain. We present a challenging case of mycobacterial osteomyelitis where there was initial diagnostic uncertainty. Sarcoidosis can involve multiple bony lesions but would not typically cause a spondylodiscitis. A recent pharmacovigilance report highlights that JAK inhibitors such as ruxolitinib increase the risk of mycobacterial infections, making specific investigations critical to diagnostic certainty.

645. Rapid Diagnosis of Disseminated Mycobacterium kansasii infection in Renal Transplant Recipients Using Plasma Microbial Cell Free DNA Next Generation Sequencing

BackgroundDisseminated Mycobacterium kansasii infection is rare in kidney transplant recipients. The diagnosis may not be suspected readily due to non-specific clinical presentation. The diagnosis and treatment can be further delayed due to poor sensitivity of culture (especially of extra-pulmonary sites) and slow growth in culture media. Accurate and rapid diagnosis of disseminated M. kansasii infections in transplant recipients is important for antimicrobial management.MethodsTwo cases of disseminated M. kansasii infections with unusual presentation in which rapid diagnosis was made using the Karius test (KT) are presented. The KT is a CLIA certified/CAP-accredited next-generation sequencing (NGS) plasma test that detects microbial cell-free DNA (mcfDNA). After mcfDNA is extracted and NGS performed, human reads are removed, and remaining sequences are aligned to a curated database of >1400 organisms. Organisms present above a statistical threshold are reported.ResultsCase 1: A 31-year female kidney transplant recipient presented with a thyroglossal duct cyst, as well as swelling of her right metacarpophalangeal joint and left 3rd finger. AFB culture of the thyroglossal cyst aspiration done on post admission day (PAD) 2 took 27 days to be identified as M. kansasii (on PAD 29) whereas plasma sent for KT on PAD 5 reported a positive test for M. kansasii at 284 molecules/microliter (MPM) in 4 days (on PAD 9). Case 2: A 59-year male kidney transplant recipient presented with generalized weakness, arthralgia, pericardial effusion, cytopenia, weight loss and intermittent fevers. Plasma sent for KT on PAD 12 was reported positive for M. kansasii at 1314 MPM in 3 days (on PAD 15). PET CT done simultaneously was consistent with an infection of an old AV graft in the left upper extremity. The AFB culture of the resected graft was confirmed as M. kansasii in 22 days on PAD 36. After the KT was available (before confirmation of M. kansasii on culture), the first patient underwent modification of empiric treatment and the second patient was started on specific treatment for M. kansasii.Table of M. kansasii cases Rapid diagnosis of disseminated M. kansasii infectionConclusionOpen-ended NGS plasma testing for mcfDNA identified disseminated M kansasii infection much earlier than standard microbiology and thus helped in initiation and modification of pathogen directed treatment.Disclosures All Authors: No reported disclosures

Recombinant BCG-Prime and DNA-Boost Immunization Confers Mice with Enhanced Protection against Mycobacterium kansasii.

The incidence of infections with nontuberculous mycobacteria (NTM) has been increasing worldwide. The emergence of multidrug-resistant NTM is a serious clinical concern, and a vaccine for NTM has not yet been developed. We previously developed a new recombinant Bacillus Calmette–Guérin (rBCG) vaccine encoding the antigen 85B (Ag85B) protein of Mycobacterium kansasii—termed rBCG-Mkan85B—which was used together with a booster immunization with plasmid DNA expressing the same M. kansasii Ag85B gene (DNA-Mkan85B). We reported that rBCG-Mkan85B/DNA-Mkan85B prime–boost immunization elicited various NTM strain-specific CD4+ and CD8+ T cells and induced Mycobacterium tuberculosis-specific immunity. In this study, to investigate the protective effect against M. kansasii infection, we challenged mice vaccinated with a rBCG-Mkan85B or rBCG-Mkan85B/DNA-Mkan85B prime–boost strategy with virulent M. kansasii. Although BCG and rBCG-Mkan85B immunization each suppressed the growth of M. kansasii in the mouse lungs, the rBCG-Mkan85B/DNA-Mkan85B prime–boost vaccination reduced the bacterial burden more significantly. Moreover, the rBCG-Mkan85B/DNA-Mkan85B prime–boost vaccination induced antigen-specific CD4+ and CD8+ T cells. Our data suggest that rBCG-Mkan85B/DNA-Mkan85B prime–boost vaccination effectively enhances antigen-specific T cells. Our novel rBCG could be a potential alternative to clinical BCG for preventing various NTM infections.

Determination of Clinical Characteristics of Mycobacterium kansasii-Derived Species by Reanalysis of Isolates Formerly Reported as M. kansasii.

BackgroundSeven genotypic subtypes of Mycobacterium kansasii were recently demonstrated to represent distinct species based on phylogenomic analysis. Mycobacterium kansasii sensu stricto (formerly known as subtype 1) is most frequently associated with human diseases; only a few studies have compared the diverse clinical characteristics of M. kansasii subtypes, including their drug susceptibilities. We determined the actual incidence of infections caused by each subtype of M. kansasii and identified their clinical characteristics.MethodsWe subtyped isolates identified as M. kansasii over the last 10 years at a tertiary care hospital. Percent identity score of stored sequencing data was calculated using curated reference sequences of all M. kansasii subtypes. Clinical characteristics were compared between those classified as subtype 1 and other subtypes. Student’s t-test, Wilcoxon rank-sum test, and Fisher’s exact test were used for comparisons.ResultsOverall, 21.7% of the isolates were identified as species distinct from M. kansasii. The proportion of patients with subtype 1 M. kansasii infection who received treatment was significantly higher than that of patients with other subtype infections (55.3% vs. 7.7%, P=0.003). Only patients with subtype 1 infection received surgical treatment. Non-subtype 1 M. kansasii isolates showed a higher frequency of resistance to ciprofloxacin and trimethoprim/sulfamethoxazole.ConclusionsNon-subtype 1 M. kansasii isolates should be separately identified in routine clinical laboratory tests for appropriate treatment selection.

A Murine Model of Mycobacterium kansasii Infection Reproducing Necrotic Lung Pathology Reveals Considerable Heterogeneity in Virulence of Clinical Isolates.

Among non-tuberculous mycobacteria, Mycobacterium kansasii is one of the most pathogenic, able to cause pulmonary disease indistinguishable from tuberculosis in immunocompetent susceptible adults. The lack of animal models that reproduce human-like lung disease, associated with the necrotic lung pathology, impairs studies of M. kansasii virulence and pathogenicity. In this study, we examined the ability of the C57BL/6 mice, intratracheally infected with highly virulent M. kansasii strains, to produce a chronic infection and necrotic lung pathology. As a first approach, we evaluated ten M. kansasii strains isolated from Brazilian patients with pulmonary disease and the reference strain M. kansasii ATCC 12478 for virulence-associated features in macrophages infected in vitro; five of these strains differing in virulence were selected for in vivo analysis. Highly virulent isolates induced progressive lung disease in mice, forming large encapsulated caseous granulomas in later stages (120–150 days post-infection), while the low-virulent strain was cleared from the lungs by day 40. Two strains demonstrated increased virulence, causing premature death in the infected animals. These data demonstrate that C57BL/6 mice are an excellent candidate to investigate the virulence of M. kansasii isolates. We observed considerable heterogeneity in the virulence profile of these strains, in which the presence of highly virulent strains allowed us to establish a clinically relevant animal model. Comparing public genomic data between Brazilian isolates and isolates from other geographic regions worldwide demonstrated that at least some of the highly pathogenic strains isolated in Brazil display remarkable genomic similarities with the ATCC strain 12478 isolated in the United States 70 years ago (less than 100 SNPs of difference), as well as with some recent European clinical isolates. These data suggest that few pathogenic clones have been widely spread within M. kansasii population around the world.

Mycobacterium kansasii infection in a psoriasis patient treated with adalimumab and switch to apremilast: First report and literature review.

Patient under anti-TNF-alpha treatment have an increased risk of mycobacterial infections, particularly tuberculosis. Only four case reports of Mycobacterium kansasii infection under anti-TNF-α treatment (two with etanercept, two with infliximab) have been reported, but none under adalimumab. A 72-year-old man treated with adalimumab for psoriasis vulgaris and arthropathic psoriasis, complained on nocturnal cough, occasional hemoptysis and the new onset of ill-defined, reddish, asymptomatic persistent plaques-nodules covered by serum crusts on his back, on the dorsum of the right hand and right middle finger. Routine laboratory investigations, HIV and TB screening (QuantiFERON-TB-Gold test) were all within normal limits. A skin biopsy was inconclusive and special staining resulted negative for microorganisms. Only PCR identified M. kansasii. The patient stopped adalimumab and started anti-TB treatment with gradual improvement of the skin lesions. At 26 months follow-up visit no signs or symptoms of relapse of M. kansasii disease occurred.

Pharmacokinetic interactions of psychotropic medications in patients with schizophrenia suffering from atypical mycobacterial infections

IntroductionMycobacterium kansasii is a nontuberculous mycobacterium that causes infection associated with past or current tuberculosis disease. Clinical syndromes and radiological findings are mostly indistinguishable from that of Mycobacterium tuberculosis, thus requiring microbiological confirmation.ObjectivesWe report a case of a 44-year-old man diagnosed with schizophrenia and Mycobacterium kansasii infection.MethodsCase report and non-systematic narrative review from PubMed.ResultsCase report: Patient with schizophrenia who was admitted at the inpatient unit presenting psychotic exacerbation with high levels of excitement. Risperidone 6 mg/day and valproate 500 mg/day were initiated. He was also diagnosed with a M. kansasii lung infection, with radiological findings of past tuberculosis disease. Before the microbiological confirmation, it was necessary to start rifampicin, requiring an increase in doses of both psychotropic drugs. Review: (1)Comorbidity of mycobacterial infections and schizophrenia. Several studies have shown that people with severe mental illness have higher rates of tuberculosis compared with the general population. Although the relationship between tuberculosis and M. Kansasii infection is known, few literature is available with regard to the association of M. Kansasii and schizophrenia. (2)Interactions between antipsychotics and mood stabilizers with rifampicin. Rifampicin is mainly metabolized by CYP3A4 and transported by P-glycoprotein. Add-on with rifampicin have been reported to reduce clozapine and olanzapine plasma levels (despite both are metabolized by CYP1A2), reduce haloperidol and risperidone levels (possible role of P-glycoprotein in this interaction), as well as for valproate.ConclusionsTreatment of comorbid infections in people with schizophrenia remains a challenge. Antibiotics used to treat mycobacterial infections can modify the pharmacokinetic of psychotropic drugs.DisclosureNo significant relationships.

Performance of Interferon-Gamma Release Assays in the Diagnosis of Nontuberculous Mycobacterial Diseases-A Retrospective Survey From 2011 to 2019.

There is an urgent need for precise diagnosis to distinguish nontuberculous mycobacterial (NTM) diseases from pulmonary tuberculosis (PTB) and other respiratory diseases. The aim of this study is to evaluate the diagnostic performance of Interferon-gamma (IFN-γ) release assays (IGRAs), including antigen-specific peripheral blood-based quantitative T cell assay (T-SPOT.TB) and QuantiFERON-TB-Gold-Test (QFT-G), in differentiating NTM infections (N = 1,407) from culture-confirmed PTB (N = 1,828) and other respiratory diseases (N = 2,652). At specie level, 2.56%, 10.73%, and 16.49% of NTM-infected patients were infected by Mycobacterium kansasii, M. abscessus, and with M. avmm-intracellulare complex (MAC), respectively. Valid analyses of T-SPOT.TB (ESAT-6, CFP-10) and QFT-G were available for 37.03% and 85.79% in NTM-infected patients, including zero and 100% (36/36) of M. kansasii infection, 21.85% (33/151) and 92.05% (139/151) of M. abscessus infection, and 17.67% (41/232) and 91.24% (211/232) of MAC infection. Based on means comparisons and further ROC analysis, T-SPOT.TB and QFT-G performed moderate accuracy when discriminating NTM from PTB at modified cut-off values (ESAT-6 < 4 SFCs, CFP-10 < 3 SFCs, and QFT-G < 0.667 IU/ml), with corresponding AUC values of 0.7560, 0.7699, and 0.856. At species level of NTM, QFT-G effectively distinguished between MAC (AUC=0.8778), M. kansasii (AUC=0.8834) or M. abscessus (AUC=0.8783) than T-SPOT.TB. No significant differences in discriminatory power of these three IGRA tools were observed when differentiating NTM and Controls. Our results demonstrated that T-SPOT.TB and QFT-G were both efficient methods for differentiating NTM disease from PTB, and QFT-G possessed sufficient discriminatory power to distinguish infections by different NTM species.

Systemic Mycobacterium kansasii Infection in Two Related Cats.

Mycobacterial infections are a major concern in veterinary medicine because of the difficulty achieving an etiological diagnosis, the challenges and concerns of treatment, and the potential zoonotic risk. Mycobacterium kansasii, a slow-growing non-tuberculous mycobacteria, causes disease in both humans and animals. While infections have been well described in humans, where it may be misdiagnosed as tuberculosis, there are fewer reports in animals. Only four cases have been reported in the domestic cat. This case report describes systemic M. kansasii infection in two sibling indoor-only cats that presented two and half years apart with cutaneous disease that was found to be associated with osteolytic and pulmonary pathology. Infection with M. kansasii was confirmed in both cats by polymerase chain reaction on fine-needle aspirate of a lumbosacral soft tissue mass in one cat and on a tissue punch biopsy of a skin lesion in the other; interferon-gamma release assay inferred M. avium-complex and M. tuberculosis-complex infection in the two cats, respectively. Both patients made a full recovery following antimicrobial therapy with rifampicin, azithromycin, and pradofloxacin (plus N-acetyl cysteine in cat 2). This report highlights successful treatment of systemic M. kansasii mycobacteriosis in the cat and the challenge of accurately diagnosing this infection.