Disseminated nontuberculous mycobacterial infection with cryptic immunodeficiency mimicking malignancy: a case report.

BACKGROUND: Nontuberculous mycobacteria (NTM) usually invades vulnerable hosts. Disseminated NTM (dNTM) infection can affect nearly all organs and be easily misdiagnosed as metastatic carcinoma or other systemic diseases, especially in seemingly immunocompetent hosts. Identification of underlying immunodeficiency is critical for the diagnosis and treatment of dNTM. Adult-onset immunodeficiency (AOID) with anti-IFN-γ autoantibodies has recently been recognized as a crucial but frequently neglected risk factor for dNTM infection. Frequent relapses of infection are common in AOID patients despite appropriate anti-infective treatment and B-cell-depleting therapy has shown some promising results. Herein, we report a case of dNTM infection mimicking malignancy in an AOID patient who was successfully treated with rituximab. CASE PRESENTATION: A middle-aged male presented with fever, productive cough, multifocal skin abscesses and multiple osteolytic lesions with pathological fractures. Chest CT revealed consolidation of the lingula while bronchoscopy showed a mass completely blocking the airway opening of the inferior lingual segment. Metagenomic next-generation sequencing and mycobacterial culture of skin pus and bronchoalveolar lavage fluid reported Mycobacterium Colombiense, confirming the diagnosis of dNTM infection. However, anti-NTM antibiotics alone failed to prevent disease relapse and progression. Further evaluation indicated undetectable serum IFN-γ concentration and high-titer autoantibodies against IFN-γ, suggesting that AOID was the underlying reason for dNTM. Rituximab was added to treatment and successfully controlled the infection without relapse at one-year follow-up. CONCLUSION: We reported a rare case of disseminated Mycobacterium Colombiense infection manifested with pulmonary mass, pathological fracture and dermapostasis in a host with AOID. Our case demonstrated that AOID should be screened when patients get the episode of disseminated NTM infection particularly when other risk factors are excluded. Besides prolonged anti-NTM therapy, AOID-associated NTM infection should be treated with B-cell-depleting therapy to prevent recurrence.

A case report of fatal disseminated Mycobacterium colombiense infection in a renal transplant recipient.

We report the first case of disseminated Mycobacterium colombiense infection in a solid organ transplant recipient. Co-infection with Cryptococcus neoformans led to fatal multisystem organ failure. We review the pathogen and host factors contributing to these opportunistic infections.

Disseminated Mycobacterium colombiense infection mimicking malignancy: A case report.

Mycobacterium colombiense, an infrequently reported non-tuberculous mycobacterium, is characterized by its slow-growing nature and capacity to simulate malignancies in clinical presentation. This report details a case of disseminated M. colombiense infection initially misidentified as cancer due to atypical symptoms, negative etiological tests, and imaging suggestive of a neoplastic disease. However, comprehensive diagnostic investigations, including a bone marrow biopsy and flow cytometry analysis, excluded malignancy as the diagnosis. The patient subsequently developed palpable masses, from which a definitive diagnosis was made using metagenomic Next-Generation Sequencing (mNGS) and culture of aspirate. A regimen of clarithromycin, ethambutol, rifampin, and amikacin was administered, leading to substantial improvement and resumption of activities at the eight-month follow-up. This case highlights the diagnostic challenges posed by the nonspecific clinical presentation of disseminated M. colombiense infection and the importance of rigorous investigation to avoid grave misdiagnosis and treatment delays.

Coinfection of Cytomegalovirus, Pneumocystis jirovecii pneumonia, COVID-19, and Mycobacterium colombiense in an AIDS patient: A case report.

We present an AIDS patient coinfected with Cytomegalovirus, Pneumocystis jirovecii pneumonia, nontuberculous mycobacteria, and COVID-19, who finally recovered from the coinfection. The 36-year-old man had two hospitalizations. In the first hospitalization, the patient was diagnosed with Cytomegalovirus, Pneumocystis jirovecii pneumonia, HIV, and COVID-19 quickly and accurately, and the corresponding treatment worked well. The second hospitalization can be divided into four stages: (1) Persistent fever period; (2) Persistent fever and Pulmonary Progression; (3) ICU period; and (4) Pneumothorax period. During the second hospitalization, the diagnosis of Mycobacterium colombiense was hard because the NGS, acid-fast bacilli, and culture of vomit, sputum, and bronchoalveolar lavage fluid were all negative. Still, we detected acid-fast bacilli in the blood mycobacterium culture. In conclusion, we report a severe pneumonia AIDS patient coinfected with Cytomegalovirus, Pneumocystis jirovecii pneumonia, COVID-19, and Mycobacterium colombiense who finally recovered from the disease. Nontuberculous mycobacteria infection is common in HIV patients, but bronchoalveolar lavage fluid NGS cannot identify nontuberculous mycobacteria in our report. Traditional blood culture was useful in detecting acid-fast bacilli in our study and then detecting the pathogens with NGS. Combining traditional microbial culture and emerging rapid NGS methods is more conducive to clinical diagnosis and treatment.

Clinical features of rare disseminated Mycobacterium colombiense infection in nine patients who are HIV-negative in Guangxi, China.

OBJECTIVES: Localized or disseminated infection caused by different nontuberculous mycobacteria (NTM) species has been increasingly reported in recent years, but reports of Mycobacterium colombiense infection are extremely rare. Herein, we analyzed the clinical features of patients with disseminated M. colombiense infection. METHODS: Patients diagnosed with disseminated M. colombiense infection between February 4, 2016 and August 25, 2021 at the First Affiliated Hospital of Guangxi Medical University were retrospectively analyzed. RESULTS: NTM infection was diagnosed in 248 HIV-negative patients. Of these, nine patients with disseminated M. colombiense infection were enrolled. Five of these patients were positive for anti-interferon-γ autoantibodies. The lung, lymph nodes, bones, and joints were the most commonly involved organs. Anemia, fever, lymphadenopathy, cough and expectoration, and ostealgia were the most common symptoms. The levels of white blood cells and neutrophils were increased in eight patients. M. colombiense was detected by both metagenomic next-generation sequencing (mNGS) and culture in four patients and only by mNGS in the remaining five patients. All patients received combination anti-NTM therapy; five underwent surgery. The condition of eight patients improved, and one died during the treatment. CONCLUSION: Patients infected with M. colombiense can present as disseminated infections, easily involving multiple organs, such as the lung, lymph nodes, bone, and joints, with fever, lymphadenopathy, and increased white blood cell and neutrophil counts. mNGS plays a crucial role in the early diagnosis of M. colombiense infection. Once diagnosed, timely and effective anti-NTM therapy, combined with local surgery if necessary, can improve the prognosis of patients with this condition.

Mycobacterium colombiense Pneumonia in HIV-Infected Patients: Three Case Reports and a Literature Review.

Background: Mycobacterium colombiense pneumonia in HIV-infected patients is relatively unusual but is associated with a high mortality rate, as well as high rates of misdiagnosis and delayed diagnosis. Clinical metagenome next-generation sequencing (mNGS) may have potential for its accurate and timely diagnosis. Case Presentation: We retrospectively reviewed the medical records of three HIV-infected patients who presented with M. colombiense pneumonia in Zhejiang Province between January 2019 and December 2020. No specific clinical presentations or radiological manifestations were found in any of the patients. The detection of M. colombiense is 28-55 days earlier using mNGS on bronchoalveolar lavage fluid (BALF) compared to traditional culture methods. A combined treatment of rifabutin, clarithromycin, or azithromycin, and ethambutol did not provide timely relief of symptoms in these three patients. In the early stage of treatment, moxifloxacin and linezolid were used for several weeks. The average course of treatment for all three patients was close to 17 months. Conclusion: We recommend early BALF mNGS for fast and accurate diagnosis of M. colombiense pneumonia in HIV-infected patients with low CD4 counts and long duration of symptoms. Further, moxifloxacin and linezolid may be beneficial in the early stage of treatment.

Diagnostic and Therapeutic Challenges in Disseminated Mycobacterium colombiense Infection Caused by Interferon-γ Neutralizing Autoantibodies.

Adult-onset immunodeficiency due to interferon-γ-neutralizing autoantibodies (nIFNγ-autoAbs) can remain underdiagnosed. We present a case of severe Mycobacterium colombiense infection with nIFNγ-autoAbs. To ensure early diagnosis, clinicians should have a high index of suspicion in patients of Asian descent with opportunistic infections and perform QuantiFERON-TB assay for disease screening.

Identification and drug susceptibility testing of the subspecies of Mycobacterium avium complex clinical isolates in mainland China.

OBJECTIVES: The Mycobacterium avium complex (MAC), comprising a series of subspecies, has a worldwide distribution, with differences in drug susceptibility among subspecies. This study aimed to assess the composition of MAC and susceptibility differences among subspecies in mainland China. METHODS: A total of 287 MAC clinical strains were included in the study. Multitarget sequences were applied to accurately identify subspecies, and a microdilution method was used to evaluate minimum inhibitory concentrations (MICs) among subspecies using Sensititre SLOMYCO plates. RESULTS: Mycobacterium intracellular (N = 169), Mycobacterium avium (N = 52), Mycobacterium chimaera (N = 22), Mycobacterium marseillense (N = 25), Mycobacterium colombiense (N = 14), Mycobacterium yongonense (N = 4), Mycobacterium vulneris (N = 3) and Mycobacterium timonense (N = 2) were isolated from MAC. Clarithromycin, amikacin and rifabutin showed lower MIC50 and MIC90 values than other drugs, and the resistance rates of clarithromycin, amikacin, linezolid and moxifloxacin were 6.3%, 10.5%, 51.9% and 46.3%, respectively. The resistance rates of clarithromycin and moxifloxacin in the initial treatment group were significantly lower than those in the retreatment group (4.09% vs. 12.94%; 30.41% vs. 75.29%; P < 0.05). Drug susceptibility differences were observed in clarithromycin and moxifloxacin among the five major subspecies (P < 0.05); however, those statistically significant differences disappeared when MACs were divided into two groups according to previous anti-tuberculosis (anti-TB) treatment history. CONCLUSION: This study revealed that MAC, primarily comprising M. intracellulare, was susceptible to clarithromycin, amikacin and rifabutin. Drug susceptibility among subspecies did not exhibit intrinsic differences in our study. Previous anti-TB treatment patients are more resistant to drugs; thus, attention should be given to those patients in the clinic.

Mycobacterium colombiense and Mycobacterium avium Complex Causing Severe Pneumonia in a Patient with HIV Identified by a Novel Molecular-Based Method.

Non-tuberculous mycobacteria are conditional pathogens that can cause many diseases, among which pulmonary infections are the most common (65-90%). Mycobacterium avium and Mycobacterium abscessus are non-tuberculous mycobacteria most often associated with lung diseases. Mass spectrometry diagnostic techniques were not effective in Mycobacterium avium complex infection. We report a case of Mycobacterium colombiense and Mycobacterium avium complex causing severe pneumonia in an adult with HIV. Our group developed a novel molecular-based method to identify Mycobacterium species. Novel techniques such as molecular cloning which we have described here can make up for the inability of matrix-assisted laser desorption ionization-time of flight mass spectrometry to distinguish the multiple microorganisms present, and may add to the diagnostic toolkit and increase the accuracy and rapidity of diagnosis in the future.

Evidence of an environmental reservoir for emergent Mycobacterium colombiense.

Mycobacterium colombiense, which belongs to the M. avium complex, is reported to have been isolated from cases of disseminated infection in both immunocompromised and immunocompetent patients. During the isolation of protists from water samples in French Guyana, we co-isolated a flagellated green alga (Polytoma sp.) and a mycobacterium identified as M. colombiense.

A case report of disseminated Mycobacterium colombiense infection in an HIV patient.

Mycobacterium colombiense is a newly recognized member of the Mycobacterium avium complex, and only a few cases of infections caused by this pathogen have been reported. We present an imported case of disseminated disease caused by M. colombiense in an HIV patient in early February 2017.

Differential drug susceptibility patterns of Mycobacterium chimaera and other members of the Mycobacterium avium-intracellulare complex.

OBJECTIVES: To determine MIC distributions for Mycobacterium chimaera, Mycobacterium intracellulare, Mycobacterium colombiense and Mycobacterium avium, and to derive tentative epidemiological cut-off (ECOFF) values. METHODS: A total of 683 bacterial isolates (M. chimaera, n = 203; M. intracellulare, n = 77; M. colombiense, n = 68; M. avium, n = 335) from 627 patients were tested by broth microdilution according to CLSI protocol M24-A2 on Sensititre RAPMYCOI plates. MICs were interpreted based on CLSI breakpoints for clarithromycin, and tentative breakpoints for amikacin, moxifloxacin and linezolid. Tentative ECOFFs were determined by visual approximation and the ECOFFinder algorithm. RESULTS: Modal MIC, MIC50 and MIC90 values were within ± one dilution step from the respective aggregated data set for 47/48 (97.9%), 48/48 (100%) and 48/48 (100%) species-drug combinations. Clarithromycin wild-type populations were mostly classified as susceptible (MIC90 4-8 mg/L; S ≤8 mg/L). Rifabutin MICs were lower than those of rifampicin. Tentative moxifloxacin, linezolid and amikacin breakpoints split wild-type populations. No ECOFFs could be set for rifampicin, ethambutol, ciprofloxacin, isoniazid, trimethoprim/sulfamethoxazole and doxycycline because of truncation of MIC distributions. Agreement between the visually determined and the modelled 97.5% ECOFFs was 90.9%. All 99.0% ECOFFs were one titre step higher than by visual approximation. CONCLUSIONS: Drug susceptibility patterns of M. chimaera are comparable to those of closely related species. Except for clarithromycin, breakpoints for Mycobacterium avium-intracellulare complex should be re-evaluated. Statistical determination of the 99.0% ECOFF may be superior to visual approximation.

Investigation of non-tuberculous mycobacteria in a primary hospital from southeastern China.

INTRODUCTION: Non-tuberculous mycobacterium (NTM) can colonize the human body, leading to opportunistic infection. This study was conducted to analyze the NTM species composition in a primary hospital and investigate the potential features of the patients with different NTM species. METHODOLOGY: Mycobacterial strains were collected from the patients admitted at the hospital from January 2016 to May 2019. MPB64 assay was used to screen NTM strains and confirmed by Rv0577 amplification. The species were identified by hsp65 sequencing. The clinical records of patients with NTM were retrospectively reviewed. RESULTS: Among the 122 identified NTM isolates, the most common strains were Mycobacterium avium complex (MAC, n = 102, 83.6%), Mycobacterium abscessus (n = 9, 7.4%) and Mycobacterium lentiflavum (n = 5, 4.1%). The predominant species among MAC were Mycobacterium chimaera (n = 57, 46.7%), followed by Mycobacterium intracellulare (n = 25, 20.5%) and Mycobacterium colombiense (n = 17, 13.9%). A significantly lower percentage of positive acid-fast assay was observed in Mycobacterium colombiense positive patients than in those with Mycobacterium intracellulare and Mycobacterium chimaera. Mycobacterium intracellulare was more frequently isolated in patients from the infectious department than in other MAC members. CONCLUSIONS: A predominant prevalence of Mycobacterium chimaera in Dongyang of Zhejiang Province was different from other regions in China, indicating that its prevalence has been likely underestimated. The heterogeneity in clinical features, caused by different MAC members, required an accurate species identification of the NTM isolated in the primary hospitals.

Clinical features of patients with bacteraemia caused by Mycobacterium avium complex species and antimicrobial susceptibility of the isolates at a medical centre in Taiwan, 2008-2014.

Advanced molecular typing methods have greatly expanded the taxonomy of Mycobacterium avium complex (MAC) species; however, little is known about the epidemiology and clinical features of bacteraemia caused by different MAC species. In this study, the clinical characteristics of patients treated for MAC bacteraemia in a tertiary-care centre in northern Taiwan during 2008-2014 were investigated. Isolates were identified to species level by rpoB gene and 16S-23S rRNA internal transcribed spacer region sequencing. Among 30 patients with bacteraemia due to MAC, the majority (n = 26) had concomitant human immunodeficiency virus (HIV) infection. Of the 30 blood isolates obtained from patients, 24 were M. avium subsp. hominissuis, 4 were Mycobacterium colombiense and 2 were Mycobacterium intracellulare. All four M. colombiense isolates were from HIV-infected patients. Bacteraemia due to M. colombiense was associated with higher 30-day mortality than bacteraemia due to M. avium subsp. hominissuis [2/4 (50%) vs. 1/24 (4%); P = 0.045, Fisher's exact test]. All four M. colombiense isolates were susceptible to clarithromycin, moxifloxacin and linezolid. Among the five patients who received ethambutol treatment and four patients who received fluoroquinolone treatment for various durations between positive MAC cultures, two and three patients, respectively, had isolates with significantly increased (≥4-fold) ethambutol and fluoroquinolone minimum inhibitory concentrations. M. colombiense was the second leading causative pathogen of MAC bacteraemia, comprising 15% of all MAC isolates obtained from HIV-positive patients. Monitoring the susceptibility of MAC isolates to ethambutol and fluoroquinolones is warranted in patients with persistent MAC bacteraemia.

A fatal case of pulmonary infection by Mycobacterium colombiense in Para State, Amazon Region, Brazil.

Mycobacterium avium complex (MAC) is a heterogeneous group of species found in several environmental sources and that exhibit variable degrees of pathogenicity. Among the MAC members, Mycobacterium colombiense has been related to pulmonary disease and disseminated infection in HIV-infected patients in Colombia. Lymphadenopathy cases have also been reported. We have described a fatal case of M. colombiense pulmonary disease in a Brazilian patient without evidence of HIV infection or other known causes of immunosuppression.

Deciphering the virulence factors of the opportunistic pathogen Mycobacterium colombiense.

Mycobacterium avium complex (MAC) contains clinically important nontuberculous mycobacteria worldwide and is the second largest medical complex in the Mycobacterium genus after the Mycobacterium tuberculosis complex. MAC comprises several species that are closely phylogenetically related but diverse regarding their host preference, course of disease, virulence and immune response. In this study we provided immunologic and virulence-related insights into the M. colombiense genome as a model of an opportunistic pathogen in the MAC. By using bioinformatic tools we found that M. colombiense has deletions in the genes involved in p-HBA/PDIM/PGL, PLC, SL-1 and HspX production, and loss of the ESX-1 locus. This information not only sheds light on our understanding the virulence mechanisms used by opportunistic MAC pathogens but also has great potential for the designing of species-specific diagnostic tools.

Pushing the equilibrium of regio-complementary carboxylation of phenols and hydroxystyrene derivatives.

The enzymatic carboxylation of electron-rich aromatics, which represents a promising 'green' equivalent to the chemical Kolbe-Schmitt reaction, is thermodynamically disfavored and is therefore impeded by incomplete conversions. Optimization of the reaction conditions, such as pH, temperature, substrate concentration and the use of organic co-solvents and/or ionic liquids allowed to push the conversion in favor of carboxylation by a factor of up to 50%. Careful selection of the type of bicarbonate salt used as CO2 source was crucial to ensure optimal activities. Among two types of carboxylases tested with their natural substrates, benzoic acid decarboxylase from Rhizobium sp. proved to be significantly more stable than phenolic acid decarboxylase from Mycobacterium colombiense; it tolerated reaction temperatures of up to 50 °C and substrate concentrations of up to 100mM and allowed efficient biocatalyst recycling.