Nontuberculous Mycobacterial Infection Research Articles

Histologic Features of Mycobacterial Spindle Cell Pseudotumors: A Multi-institutional Clinicopathologic Analysis of 14 Cases.

Mycobacterial spindle cell pseudotumors (MSPs) are a rare and diagnostically challenging manifestation of non-tuberculous mycobacterial (NTM) infections. Proper recognition of these pseudotumors is important because they are treatable and benign. In this study, we evaluated the morphologic patterns of MSPs to improve their pathologic identification. Clinical and morphologic features of 14 MSPs were analyzed. Histologic factors evaluated included the architectural growth pattern of spindled or epithelioid macrophages, granulomas and their location within the lesion, neutrophilic microabscesses, multinucleated giant cells, necrosis, and effacement of background tissue. The composition of inflammatory infiltrates, organism density by acid-fast staining, and stromal changes were also assessed. In addition, 8 of 14 cases underwent molecular microbiology identification by a clinical amplicon-sequencing assay for non-tuberculous mycobacteria. MSP sites included 2 bowel, 10 lymph nodes, 1 liver, and 1 extremity. Cases with available clinical history (n=10) all occurred in immunocompromised patients. All demonstrated effacement of normal structures with spindled cells arranged in a storiform or fascicular architectural pattern. In addition, all cases showed lymphocytic inflammation, with prominent concurrent neutrophilic inflammation in 50% (7/14) of cases. Other morphologic findings included foamy histiocytes (64%, 9/14), peripherally situated granulomas (21%, 3/14), and neutrophilic microabscesses (21%, 3/14). All tested cases were positive for NTM by PCR methods. Mycobacterium avium was the most commonly isolated pathogen (6/8). Mycobacterial spindle cell pseudotumors show predominantly spindled morphology that may be mistaken as a neoplasm. Surgical pathologists who evaluate lymph nodes, soft tissue, and gastrointestinal tissues should be aware of this spindled tumefactive phenomenon in the setting of immunocompromised patients. Recognition of key morphologic features of neutrophilic inflammation, peripheral granulomas, or foamy histiocytes within a spindled lesion can help guide the pathologist to a correct diagnosis of an inflammatory process secondary to infection rather than a spindle cell neoplasm. Accurate diagnosis to facilitate appropriate antimicrobial and/or surgical therapy requires a comprehensive evaluation combining clinical, histopathologic, and microbiological findings.

Severe Impairment of T-cell Immunity and Pulmonary GvHD Are Major Risk Factors for Nontuberculous Mycobacterial Infection After Pediatric Allogeneic Hematopoietic Stem Cell Transplantation.

Hematopoietic stem cell transplant recipients are prone to infectious complications. Infections caused by nontuberculous mycobacteria have increased in adults but literature in children is scarce. We report 6 episodes of disseminated or pulmonary nontuberculous mycobacteria infection among 5 pediatric hematopoietic stem cell transplant recipients. All but one were caused by Mycobacterium avium complex. Four patients died, 2 related to nontuberculous mycobacteria infection.

125 Recurrent Non-tuberculous Mycobacterial infection in unusual area in a combined immunodeficiency – single case report

125 Recurrent Non-tuberculous Mycobacterial infection in unusual area in a combined immunodeficiency – single case report

Trends in Non-Tuberculous Mycobacterial Lung Disease and Treatment Outcomes in a Low-Tuberculosis Prevalence Setting: A Retrospective Analysis.

Information on the management of non-tuberculous mycobacterial (NTM) lung infection and disease is scarce. The aim of this study was to investigate the trends in NTM lung infections, and the factors associated with the initiation of treatment and treatment outcomes. A retrospective analysis was carried out on patient medical records from Haukeland University Hospital, Bergen, Norway, from 2000 to 2021. Among 154 patients with NTM lung infection, the majority (70%) were older than 65 years, and 49% had an underlying pulmonary comorbidity. The most frequently observed mycobacterial species was M. avium complex (MAC), followed by M. malmoense and M. abscessus. In total, 72 (47%) patients received antibiotic treatment. Patients with high symptom scores, aged below 65, and with MAC infection had more than three times the odds of receiving antibiotic treatment. A favourable response and culture conversion was observed in 53 of 72 (74%) patients. However, 17 (32%) of them had a relapse. Out of 82 patients who did not receive treatment, 45 (55%) had spontaneous culture conversion, and 8 (18%) of them had a relapse. No factor was identified to be significantly associated with a favourable treatment response. A favourable response to treatment was seen in 74% of patients with a high relapse rate.

Efficacy of SPR720 in murine models of non-tuberculous mycobacterial pulmonary infection.

Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is increasing worldwide, with Mycobacterium avium complex (MAC) and Mycobacterium abscessus as the predominant pathogens. Current treatments are poorly tolerated and modestly effective, highlighting the need for new treatments. SPR719, the active moiety of the benzimidazole prodrug SPR720, inhibits the ATPase subunits of DNA gyrase B, a target not exploited by current antibiotics, and therefore, no cross-resistance is expected with standard-of-care (SOC) agents. To evaluate the in vitro activity of SPR719 against MAC and M. abscessus clinical isolates, including those resistant to SOC agents, and in vivo efficacy of SPR720 in murine non-tuberculous mycobacteria (NTM) pulmonary infection models. NTM isolates were tested for susceptibility to SPR719. Chronic C3HeB/FeJ and severe combined immunodeficient murine models of pulmonary infection were used to assess efficacy of SPR720 against MAC and M. abscessus, respectively. SPR719 was active against MAC (MIC90, 2 mg/L) and M. abscessus (MIC90, 4 mg/L) clinical isolates. Efficacy of SPR720 was demonstrated against MAC pulmonary infection, both as a monotherapy and in combination with SOC agents. SPR720 monotherapy exhibited dose-dependent reduction in bacterial burden, with the largest reduction observed when combined with clarithromycin and ethambutol. Efficacy of SPR720 was also demonstrated against M. abscessus pulmonary infection where monotherapy exhibited a dose-dependent reduction in bacterial burden with further reductions detected when combined with SOC agents. In vitro activity of SPR720 against common NTM pathogens and efficacy in murine infections warrant the continued clinical evaluation of SPR720 as a new oral option for the treatment of NTM-PD.

Pulmonary Artery Aneurysm in a Patient with Nontuberculous Mycobacteria Infection.

Nontuberculous mycobacterial (NTM) infection sometimes leads to the development of pulmonary artery aneurysm (PAA), a rare but life-threatening complication. We herein report a 64-year-old woman with a history of NTM infection who presented with severe hemoptysis. Computed tomography revealed a ruptured PAA, which was treated successfully with pulmonary artery embolization. Subsequent right total pneumonectomy was performed to control infection. This case emphasizes the need to consider PAA in patients with NTM infection who present with hemoptysis. Early detection and appropriate management are critical for preventing this fatal complication.

An early and trustable indicator suggestive of non-tuberculosis mycobacteria isolation in a high tuberculosis burden setting

Distinguishing between nontuberculous mycobacterial (NTM) lung infections and pulmonary tuberculosis becomes challenging due to their similar clinical manifestations and radiological images. Consequently, instances of delayed diagnosis or misdiagnosis are highly frequent. A feasible and reliable indicator of the existence of NTM in the early stages of the disease would help to solve this dilemma. In this study, we evaluated the potential of smear-positive and Xpert assay (Cepheid, USA) negative outcomes as an early indicator of possible NTM infection in a high TB-burden setting retrospectively and prospectively. During the study period, 12·77% (138/1081) of the smear-positive cases yielded negative outcomes with the simultaneous Xpert assay. From the 110 patients who yielded smear-positive/Xpert-negative outcomes and cultivated strain as well, 105 (95·45%) were proved to have NTM isolated. By incorporating an additional criterion of a negative result from the Interferon-gamma release assay, the accuracy of the screening method reached 100%. Regarding the NTM presence prediction value, smear-positive/Xpert-negative has a sensitivity of 24·86% (45/181) in all NTM isolated cases but 93·75-96·55% accuracy in retrospective study or 93·75% accuracy in prospective study in smear-positive NTM isolated cases. In addition, the specificity was ∼99·47% (943/948) in smear-positive tuberculosis cases. The clue of the presence of NTM could be obtained on the first day of the hospital visit due to the point of care (POC) feature of smear testing and Xpert assay. About one-fourth of the NTM-isolated patients would benefit from this rapid, convenient, and reliable screening strategy in the given circumstance. Smear-positive/Xpert-negative outcome is an early, trustable indicator that is indicative of NTM isolation.

Tuberculosis and Nontuberculous Mycobacterial Infections in Patients with Spondyloarthritis: A Population-Based Study.

Background and Objectives: Tuberculosis is caused by Mycobacterium tuberculosis (MTB), while nontuberculous mycobacteria (NTM) encompass a group of mycobacterial species that are distinct from the MTB complex and leprae. Spondyloarthritis (SpA) is a group of chronic inflammatory diseases with shared clinical characteristics and is treated with biological agents; however, their use may elevate the risk of MTB and NTM infections. This study aimed to compare the incidence and risk of MTB and NTM infections in patients with SpA, including ankylosing spondylitis (AS) and psoriatic arthritis (PsA), using a population-based approach. Materials and Methods: This study included 2333 patients with SpA and 9332 age- and sex-matched controls from the Korea National Health Insurance Service-National Sample Cohort database from 2002 to 2019. The patients were identified using the International Classification of Diseases-10 codes for AS, PsA, MTB, and NTM. Results: The results showed that a negligible percentage of patients with SpA developed NTM (0.002%) and MTB (0.016%), with no significant difference in the incidence rate ratio (IRR) compared to controls. Among patients with SpA treated with biologics, the IRRs for NTM and MTB were 5.66 and 3.069, respectively; however, these were not statistically significant. No cases of NTM or MTB infection were reported in female patients with SpA treated with biologics. In both the SpA patient group and the control group, the incidence of MTB was higher in individuals over 60 years old compared to those under 60 years old. Cox proportional hazard analysis revealed a significant adjusted hazard ratio of 1.479 for MTB in patients with SpA after adjusting for age, sex, smoking history, insurance level, and comorbidities. However, this significance was not maintained when biological therapy was further adjusted. Conclusions: Our study indicated that the risks of NTM and MTB infection are not elevated in patients with SpA. Although biological use may potentially increase the risk of MTB infection, it does not lead to a significant increase in incidence rates. Proactive screening for latent tuberculosis and adequate prophylaxis using biologics can effectively manage the risk of NTM and MTB infections.

Two Decades of Insights into Nontuberculous Mycobacterial Hand Infections.

The objective of our study is to describe the clinical presentation, management, and outcome of a large cohort with nontuberculous mycobacteria (NTM) hand infection. We reviewed the medical records of all adults (≥18 years) managed at the Mayo Clinic (Rochester, MN) for NTM hand infection between 1998 and 2018. Our cohort included 81 patients. The median age was 61.3 (interquartile range 51.7, 69.6) years; 39.5% were immunocompromised, and 67.9% reported a triggering exposure preceding infection. Infection was deep in 64.2% and disseminated in 3.7%. Up to 16.0% received intralesional steroids because of misdiagnosis with an inflammatory process. Immunocompromised patients had deeper infection, and fewer reports of a triggering exposure. Mycobacterium marinum, Mycobacterium avium complex, and Mycobacterium chelonae/abscessus complex were the most common species. The median antibiotic duration was 6.1 (interquartile range 4.6, 9.9) months. Deep infection and infection with species other than M marinum were associated with using a greater number of antibiotics for combination therapy and an extended duration of treatment. Immunosuppression was also associated with longer courses of antibiotic therapy. Surgery was performed in 86.5% and 32.4% required multiple procedures. Ten patients, mostly with superficial infections, were treated with antibiotics alone. The 5-year cumulative rate of treatment failure was 30.3% (95% confidence interval, 20.9-44.0). Immunosuppression and intralesional steroid use were risk factors for failure. Treatment of NTM hand infection usually requires surgery and antibiotics, but antibiotics alone may occasionally be attempted in select cases. Immunosuppression and intralesional steroids are risk factors for treatment failure.

Netuberkulózní mykobakteriální infekce v dětském věku

Introduction: Nontuberculous mycobacterial (NTM) infection of lymph nodes in young children is a rare disease. The increasing incidence has been observed after termination of vacciation in Czech Republic in November 2010. Aim of the study: To provide an overview of the clinical picture, dia gnostic options and therapeutic approach in children with neck lymph nodes aff ected by non-tuberculous mycobacteria. Methods: Retrospective cohort study of patients with confi rmed NTM infection treated at the Clinic of Otorhinolaryngology and Head and Neck Surgery of Faculty Hospital Hradec Kralove from 2010 to 2021. The inclusion criterion was proof of the causative agent of the disease (nontuberculous mycobacteria) by culture or molecular bio logical technique (PCR). Results: A total of 19 children with an average age of 26 months (range 12–42, SD 7.27) were enrolled. The most frequent pathogen was Mycobacterium avium (N = 16). Culture examination was positive in 84% (N = 16) of cases, PCR was positive in 47% of patients (N = 9). All children from the group underwent both surgical and antibio tic treatment. The most frequently used antibio tics were a combination of a macrolide antibio tic (clarithromycin) with an antituberculotic drug (rifampicin). In 6 children, an incision was made along with drainage of the lesion and for the duration of the infl ammation a complete extirpation of the pathological tissue under general anaesthesia followed. A total of 15 children underwent probatory extirpation of the pathological neck lymph node. We performed block dissections of the infected tissue in 7 children for residual infl ammation. Conclusion: The most eff ective treatment of the infection seems to be the exstirpation of all aff ected lymph nodes with surrounding tissue and combination of antibio tic (macrolide) with antituberculotic agent (rifampicin). Key words mycobacterial infection – nontuberculous mycobacteria – cervical lymphadenitis – children

Mycobacterium xenopi vertebral osteomyelitis in a patient with systemic lupus erythematosus: illustrative case.

Mycobacterium xenopi is a common nontuberculous Mycobacterium (NTM) that is slow growing and an infrequent cause of infection. When infections do occur, it is by exposure to contaminated soil or water or to infectious aerosols. Nontuberculous mycobacterial infections in the spine are exceedingly rare. Risk factors can include immunosuppression, particularly human immunodeficiency virus; however, other systemic diseases such as systemic lupus erythematosus (SLE) have been reported. The authors report a case of cord compression due to M. xenopi vertebral osteomyelitis with an epidural abscess in a patient with SLE on hydroxychloroquine and recent steroid use. The authors explore the presentation of a patient who developed acute neurological deficits concerning for spinal pathology secondary to NTM. Although considered a rare occurrence, patients with autoimmune pathologies are susceptible to infection by unusual organisms. Standard treatment of autoimmune diseases can predispose patients to infection and warrant surgical correction to prevent long-term neurological deficits. There is still much work and research to be done in the exploration and understanding of nontuberculous mycobacterial infection, pathophysiology, and treatment in the immunocompetent population and in patients with autoimmune disorders.

Pharmacotherapeutic Considerations in the Treatment of Nontuberculous Mycobacterial Infections: A Primer for Clinicians.

Nontuberculous mycobacteria (NTM) can cause a variety of infections, including serious pulmonary disease. Treatment encompasses polypharmacy, with a targeted regimen of 2-5 active medications, depending on site of infection, species, and clinical characteristics. Medications may include oral, intravenous, and inhalational routes. Medication acquisition can be challenging for numerous reasons, including investigational status, limited distribution models, and insurance prior authorization. Additionally, monitoring and managing adverse reactions and drug interactions is a unique skill set. While NTM is primarily medically managed, clinicians may not be familiar with the intricacies of medication selection, procurement, and monitoring. This review offers insights into the pharmacotherapeutic considerations of this highly complex disease state, including regimen design, medication acquisition, safety monitoring, relevant drug-drug interactions, and adverse drug reactions.

Risk of Potential Invasive Non-Tuberculous Mycobacterial Infection in Major Cardiothoracic Surgeries.

Nontuberculous Mycobacteria (NTM) commonly colonise municipal water supplies and cause healthcare-associated outbreaks. Although the infections are rare, they are associated with high mortality. Aerosolization of NTM from colonised Heater cooler devices causes invasive infections in cardiac surgery patients. These units are widely used in open-chest heart surgery as an essential part of extracorporeal circulation but have been suggested as being a risk for infection. Water disinfection as well as effective engineering-related mitigation strategies should be designed to decrease the burden of NTM in the hospital water supply. Key Words: Nontuberculous Mycobacteria, Heater cooler devices, Endocarditis, Water, Cardiothoracic surgeries.

Nontuberculous Mycobacterial Infections in Pediatric Solid Organ Transplant and Hematopoietic Cell Transplant Recipients.

The diagnosis of nontuberculous mycobacterial infections is challenging in pediatric solid organ transplant and hematopoietic cell transplant recipients due to the absence of specific clinical manifestations, limitations of sampling, prolonged times for culture and identification, and difficulty discerning colonization from clinical disease. Treatment is dependent on the nontuberculous mycobacterial species, disease type, and pattern of drug resistance. Treatment of nontuberculous mycobacterial infections involves prolonged durations of therapy using multiple medications, which are limited by toxicities and drug-drug interactions.

Susceptibility to mycobacterial infection in VEXAS syndrome.

VEXAS is a recently described acquired auto-inflammatory and hematologic syndrome caused by somatic mutations in UBA1. To date, VEXAS is not a recognized cause of acquired immunodeficiency. Two of our 10 VEXAS patients developed a disseminated Mycobacterium avium infection. To shed light on this observation, we retrospectively studied all patients with disseminated non-tuberculous mycobacterial infections (NTMi) seen at our institution over 13 years. Inclusion criteria were a positive blood/bone marrow culture, or 2 positive cultures from distinct sites, or one positive culture with 2 involved sites. patient 1 presented with fever, rash, orbital cellulitis and lung infiltrates. Patient 2 presented with fever and purpura. In both cases, Mycobacterium avium was identified on bone marrow culture. Twenty cases of disseminated NTMi were reviewed. Among 11 HIV-negative patients, three had chronic immune-mediated disease; three had untreated myeloid neoplasm; two had VEXAS; one had undergone kidney transplantation; one had GATA-2 deficiency; and one had no identified aetiology. None had lymphoid neoplasia or had undergone bone marrow transplantation. HIV-negative cases had higher CD4 counts than HIV-positive patients (median CD4: 515/mm3 vs 38/mm3, p< 0.001). Monocytopenia was present in seven cases. At 2 years, six patients had died, including both VEXAS patients. VEXAS patients have an intrinsic susceptibility to disseminated NTMi, which may result from monocytic dysfunction. NTMi can mimic VEXAS flare. Clinicians should maintain a high suspicion for opportunistic infections before escalating immunosuppressive therapy. Further studies are needed to confirm and better decipher the herein reported observations.

Subcutaneous infection caused by Mycobacterium abscessus following botulinum toxin injections: A case report and literature review.

The rapid development of cosmetic injections has led to an increased incidence of nontuberculous mycobacterial (NTM) infection. Here, we presented a case of cutaneous Mycobacterium abscessus infection subsequent to botulinum toxin injection for treating masseter hypertrophy, and reviewed the literature on skin and soft tissue infections caused by NTM after cosmetic injections. The patient underwent surgical excision and regular antibiotic therapy and has had nearly 2 months of follow-up without any signs of infection. The diagnosis and treatment of NTM infection have always been challenging, and further research is needed to standardize and guide the treatment.

Development of 2nd generation aminomethyl spectinomycins that overcome native efflux in Mycobacterium abscessus.

Mycobacterium abscessus (Mab), a nontuberculous mycobacterial (NTM) species, is an emerging pathogen with high intrinsic drug resistance. Current standard-of-care therapy results in poor outcomes, demonstrating the urgent need to develop effective antimycobacterial regimens. Through synthetic modification of spectinomycin (SPC), we have identified a distinct structural subclass of N-ethylene linked aminomethyl SPCs (eAmSPCs) that are up to 64-fold more potent against Mab over the parent SPC. Mechanism of action and crystallography studies demonstrate that the eAmSPCs display a mode of ribosomal inhibition consistent with SPC. However, they exert their increased antimicrobial activity through enhanced accumulation, largely by circumventing efflux mechanisms. The N-ethylene linkage within this series plays a critical role in avoiding TetV-mediated efflux, as lead eAmSPC 2593 displays a mere fourfold susceptibility improvement against Mab ΔtetV, in contrast to the 64-fold increase for SPC. Even a minor shortening of the linkage by a single carbon, akin to 1st generation AmSPC 1950, results in a substantial increase in MICs and a 16-fold rise in susceptibility against Mab ΔtetV. These shifts suggest that longer linkages might modify the kinetics of drug expulsion by TetV, ultimately shifting the equilibrium towards heightened intracellular concentrations and enhanced antimicrobial efficacy. Furthermore, lead eAmSPCs were also shown to synergize with various classes of anti-Mab antibiotics and retain activity against clinical isolates and other mycobacterial strains. Encouraging pharmacokinetic profiles coupled with robust efficacy in Mab murine infection models suggest that eAmSPCs hold the potential to be developed into treatments for Mab and other NTM infections.

Automated Machine Learning with Radiomics for Predicting Chronicity of Pulmonary Nodules in Patients with Nontuberculous Mycobacterial Lung Infection

Automated Machine Learning with Radiomics for Predicting Chronicity of Pulmonary Nodules in Patients with Nontuberculous Mycobacterial Lung Infection

Nontuberculous Mycobacterial Infections and Management for the Inpatient Dermatologist

Nontuberculous Mycobacterial Infections and Management for the Inpatient Dermatologist

Management Challenges of Extrapulmonary Nontuberculous Mycobacterial Infection: A Single-Center Case Series and Literature Review.

Extrapulmonary nontuberculous mycobacterial (NTM) disease remains largely enigmatic, yet these mycobacteria are increasingly acknowledged as important opportunistic pathogens in humans. Traditionally, NTM infections have been identified across various anatomical locations, with the respiratory system being the most affected and best understood. Historically, extrapulmonary NTM infection was predominantly associated with HIV/AIDS, with Mycobacterium avium lymphadenopathy being the most commonly reported. Today, however, because of the expanding utilization of immunosuppressive therapies and the demographic shift towards an aging population, an increasing number of NTM infections are expected and seen. Hence, a heightened index of suspicion is essential, necessitating a multifaceted approach to identification and drug sensitivity testing to improve treatment outcomes. In extrapulmonary NTM management, expert consultation is strongly recommended to determine the most efficacious treatment regimen, as individualized, patient-tailored therapies are often required. Furthermore, the economic burden of NTM disease is considerable, accompanied by high rates of hospitalization. To optimize the management of these intricate infections, there is an urgent need for comprehensive data on incidence, prevalence, and outcomes. This case-based series delves into the intricate nature of extrapulmonary NTM infections, focusing on both rapid and slow-growing NTM species, and explores therapeutic options, resistance mechanisms, and host-related immunological factors.