Fracture-associated infection with Mycobacterium smegmatis in a 16-year old patient.

We present a patient who suffered an agricultural rollover trauma and developed a fracture-associated tissue infection caused by Mycobacterium smegmatis. Since cases are rare, treatment of infections with M. smegmatis requires an interprofessional approach and the combination of surgery and adjunctive antimicrobial treatment.

Factors Associated With Extrapulmonary Tuberculosis in Southeastern Mexico: A Case-Control Study.

INTRODUCTION: Extrapulmonary tuberculosis (EPTB) is a disease that can affect any organ or tissue. Due to its potential to cause more dangerous sequelae and the barriers to its timely diagnosis, greater clinical awareness of this disease is crucial. This study aimed to identify the factors associated with EPTB in the population of Oaxaca, Mexico. METHODS: This is an unpaired case-control study. The cases were patients with EPTB+ while the controls were patients with pulmonary tuberculosis (PTB+) registered in the Tuberculosis Epidemiological Surveillance System. Sociodemographic, clinical, and microbiological variables were recovered. Bivariate analyses were performed and logistic regression analyses were performed to calculate the odds ratio (OR). RESULTS: A total of 75 EPTB+ cases and 300 PTB+ controls were included. Of the total sample, 57.1% were men and 60.3% indigenous. The most frequent clinical presentations of EPTB+ were nodal (21.3%), miliary (21.3%), and breast (20.0%). According to logistic regression analysis, age <40 years (OR: 2.25 (95% CI: 1.13-4.49), female sex (OR: 1.92 (95% CI: 1.03-3.56)], urban residence (OR: 2.25 (95% CI: 1.11-4.55)), comorbidity with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) (OR: 3.46 (95% CI: 1.31-9.10)), dyspnea (OR: 2.67 (1.22-5.82)), and adenopathy (OR: 3.38 (95% CI: 1.42-8.06)) were positively associated with EPTB+. CONCLUSION: These results can serve as a basis for screening EPTB+, thus improving the preventive and diagnostic capacity of local health services, taking as a starting point women under 40 years of age and patients with HIV/AIDS in urban areas, as well as the presence of adenopathy and dyspnea as clinical characteristics of the disease.

Drug Persistence and Incidence of Active Tuberculosis of Tumor Necrosis Factor Alpha Inhibitors Versus Tocilizumab as the First-Line Biological Treatment in Patients with Rheumatoid Arthritis: A Nationwide Population-Based Retrospective Cohort Analysis.

INTRODUCTION: Drug persistence may be a surrogate marker that reflects both long-term efficacy and safety in clinical settings, and tuberculosis (TB) is considered as one of the most important opportunistic infections after the biological treatment in rheumatoid arthritis (RA). We aimed to compare drug persistence and incidence of TB between tumor necrosis factor alpha (TNFα) inhibitors and tocilizumab in patients with RA using data from the Korean Health Insurance Review and Assessment Service database. METHODS: In this analysis, 5449 patients with RA who started TNFα inhibitors, such as adalimumab, etanercept, infliximab, and golimumab or tocilizumab, as the first-line biological therapy between January 2014 and December 2017 were analyzed and followed up until December 2019. Drug persistence was defined as the duration from initiation to first discontinuation, and TB was defined as the prescription of > 2 anti-TB medications after the initiation of biologics. RESULTS: TNFα inhibitors and tocilizumab were prescribed in 4202 (adalimumab, 1413; etanercept, 1100; infliximab, 769; golimumab 920) and 1247 patients with RA, respectively. During the analysis period, 2090 (49.7%) and 477 (38.3%) patients with RA discontinued TNFα inhibitors and tocilizumab, respectively, and 42 patients with RA developed TB (TNFα inhibitors, 33; tocilizumab, 9). After adjustment for confounding factors, TNFα inhibitors were significantly associated with a higher risk of discontinuation compared with tocilizumab (hazard ratio (HR) 1.63, p < 0.001). In subgroup analysis, all types of TNFα inhibitors, except for infliximab, demonstrated a significantly lower persistence rate compared with tocilizumab. There was no significant difference in TB incidence between tocilizumab and TNFα inhibitors. In subgroup analysis, infliximab has a significantly higher risk of TB compared with tocilizumab (HR 2.84, p = 0.02). CONCLUSION: In this analysis, tocilizumab had longer persistence than TNFα inhibitors with a similar incidence of TB. Our analysis has limitations: (1) The HIRA database lacks clinical details like disease activity and joint damage extent, potentially influencing the analysis results. (2) Reasons for discontinuing biological agents were not available. (3) TB diagnoses may be inaccurate because of missing microbiological results. (4) We did not analyze the impact of treating latent TB infection on TB development post-biological treatment, despite mandatory screening in Korea.

Leprosy reactions: Unraveling immunological mechanisms underlying tissue damage in leprosy patients.

Leprosy is a chronic granulomatous infectious and disabling disease caused by two mycobacteria, Mycobacterium leprae and Mycobacterium lepromatosis. Acute inflammatory responses, known as leprosy reactions, are significant contributors to disabilities. Three types of leprosy reactions have been identified based on excessive cytokine release (e.g. type 1) or the accumulation of immune complexes in tissues inducing multiorgan damage (e.g. types 2 and 3). The type of leprosy reaction has implications on treatment and management strategies, yet are not well understood by health workers caring for leprosy patients. We attempt to describe the immunologic mechanisms behind the different leprosy reactions and the rationale for tailoring clinical treatment and management to the particular type of leprosy reaction based on the underlying immunologic situation.

Characterization of Mycobacterium orygis, Mycobacterium bovis, and Mycobacterium caprae Infections in Humans in Western Canada.

Epidemiologic research on zoonotic tuberculosis historically used Mycobacterium bovis as a surrogate measure, however, increased reports of human tuberculosis caused by other animal-associated Mycobacterium tuberculosis complex members like Mycobacterium orygis necessitates their inclusion. We performed a retrospective cohort study including persons infected with any animal-lineage M. tuberculosis complex species in Alberta, Canada, from January 1995 to July 2021, identifying 42 patients (20 M. bovis, 21 M. orygis, one M. caprae). Demographic, epidemiologic and clinical characteristics were compared against persons with culture-confirmed M. tuberculosis infection. The proportion of culture-positive infections caused by M. orygis increased continuously from 2016-2020. Significantly more females at a higher median age were impacted by M. orygis, with all patients originating from South Asia. M. bovis caused significantly more extra-pulmonary disease, and disproportionately impacted young females, particularly those pregnant or post-partum. All infections were acquired abroad. These findings can aid in developing targeted public health interventions.

Sarcopenia assessed using a questionnaire can predict in-hospital mortality in older patients with pulmonary tuberculosis.

BACKGROUND & AIMS: Pulmonary tuberculosis is a severe disease with a high mortality rate. However, whether sarcopenia is a risk factor for in-hospital mortality remains unclear. The SARC-F (five items: strength, assistance in walking, rising from a chair, climbing stairs, and falls) is a questionnaire developed to screen for sarcopenia. This study aimed to determine whether the high risk of sarcopenia, assessed using the SARC-F questionnaire, affects in-hospital mortality in older patients with pulmonary tuberculosis. METHODS: This was a retrospective, observational study. We included patients with active pulmonary tuberculosis aged ≥65 years who required inpatient treatment between 30 April 2021 and 30 November 2022. We assessed sarcopenia using SARC-F, and SARC-F ≥ 4 points at admission was defined as a high risk of sarcopenia. The primary outcome was all-cause mortality during hospitalisation. We extracted information on age, sex, body mass index, comorbidities, blood and biochemical tests, modified Glasgow Prognostic Score, calf circumference, geriatric nutritional risk index, physiotherapy, and length of hospital stay from medical records. RESULTS: We included 147 patients (mean age: 83.0 ± 7.8 years; males: 61.9%). Ninety-three (63.3%) patients had a high risk of developing sarcopenia. Patients with a high risk of sarcopenia were significantly older (mean: 85.0 ± 7.1 years), had a lower body mass index (median: 18.1 kg/m2, range: 16.1-20.5 kg/m2), had a higher modified Glasgow Prognostic Score (median: 2, range: 2-2), and had a lower calf circumference (mean: 26.8 ± 3.6 cm), had a lower geriatric nutritional risk index (mean: 72.2 ± 12.9) than those without high-risk sarcopenia. More patients with a high risk of sarcopenia underwent physiotherapy (93.5%) than those without high-risk sarcopenia (P < 0.01, all). Kaplan-Meier survival curves showed that patients with a high risk of sarcopenia had significantly lower overall survival than those without high-risk sarcopenia (log-rank test, P = 0.001). Logistic regression analysis for in-hospital mortality showed that a high risk of sarcopenia significantly affected in-hospital mortality (odds ratio [OR]: 6.425, 95% confidence interval [CI]: 1.399-47.299). In addition, logistic regression analysis for each item of SARC-F showed that assistance in walking (OR: 3.931, 95% CI: 1.816-9.617) and rising from a chair (OR: 2.458, 95% CI: 1.235-5.330) significantly affected in-hospital mortality. CONCLUSION: A high risk of sarcopenia, as assessed using SARC-F at admission, was a risk factor for in-hospital mortality in older patients with pulmonary tuberculosis. Among the SARC-F items, assistance in walking and rising from a chair were the risk factors for in-hospital mortality.

Scrofuloderma of the chest with mediastinal TB.

Cutaneous tuberculosis is a rare manifestation of extrapulmonary tuberculosis caused by Mycobacterium tuberculosis in most cases and rarely by Mycobacterium bovis. Diagnosis may be challenging due to a wide range of clinical findings and similarities to other chronic dermatoses, leading to delayed treatment. We present a case of scrofuloderma in a 4-year-old girl that arose from a contiguous spread from the anterior mediastinum with associated pulmonary involvement.

Nasal Septal Perforation and Widespread Skin Lesions Caused by Mycobacterium chelonae Infection Mimicking Granulomatosis with Polyangiitis.

Mycobacterium chelonae, a rapidly growing mycobacterium found in the natural environment, is known to cause localized lesions in the skin, soft tissue, and bone through traumatic inoculation, but widespread lesions are uncommon. We herein report an immunocompromised 79-year-old man suspected of having polyangiitis granulomatosis due to weight loss, epistaxis, and nasal crusts with impending septal perforation who was subsequently diagnosed with mucocutaneous and bone disease caused by widespread M. chelonae infection. Given these findings, clinicians should be aware of the tendency to develop unusual widespread lesions in immunocompromised patients, which can present a clinical picture similar to systemic vasculitides, such as granulomatosis with polyangiitis.

Whole-genome sequencing predicting phenotypic antitubercular drug resistance: meta-analysis.

BACKGROUND: For simultaneous prediction of phenotypic drug susceptibility test (pDST) for multiple anti-tuberculosis drugs, the whole genome sequencing (WGS) data can be analyzed using either catalogue-based approach, wherein one causative mutation suggests resistance, (e.g., WHO catalog) or non-catalogue-based approach using complicated algorithm (e.g., TB-profiler, machine learning). The aim was to estimate the predictive ability of WGS-based tests with pDST as the reference, and to compare the two approaches. METHODS: Following the systematic literature search, the diagnostic test accuracies for 14 drugs were pooled using a random-effect bivariate model. RESULTS: Out of 779 articles, 44 articles with 16,821 specimens for meta-analysis and 13 articles not for meta-analysis were adopted. The areas under summary receiver operating characteristic curve suggested "excellent" (0.97-1.00) for 2 drugs (isoniazid 0.975, rifampicin 0.975), "very good" (0.93-0.97) for 8 drugs (pyrazinamide 0.946, streptomycin 0.952, amikacin 0.968, kanamycin 0.963, capreomycin 0.965, para-aminosalicylic acid 0.959, levofloxacin 0.960, ofloxacin 0.958), and "good" (0.75-0.93) for 4 drugs (ethambutol 0.926, moxifloxacin 0.896, ethionamide 0.878, prothionamide 0.908). The non-catalogue-based and catalogue-based approaches had similar ability for all drugs. CONCLUSION: WGS accurately identifies isoniazid and rifampicin resistance. For most drugs, positive WGS results reliably predict pDST positive. The two approaches had similar ability.

Epidemiology of Mycobacterium abscessus.

BACKGROUND: Nontuberculous mycobacteria (NTM) are highly abundant in soil, dust, and water sources, making human-pathogen contact frequent and recurrent. NTM represents over 200 species/subspecies; some are considered strict or opportunistic pathogens. Mycobacterium abscessus, often regarded as one of the most antibiotic-resistant mycobacteria, is the second most frequent NTM pulmonary disease pathogen. OBJECTIVES: To describe the epidemiology of M. abscessus through a literature review focusing on clinical aspects. SOURCES: We conducted searches on PubMed and Web of Knowledge for articles published from 2010 to the present using the keywords 'Mycobacterium abscessus', 'Nontuberculous mycobacteria', and 'epidemiology'. Our search prioritized original reports on the occurrence of NTM and M. abscessus infection/disease. CONTENT: Advanced molecular and genetic diagnostic techniques have refined the M. abscessus complex (MABC) microbiological classification over the last few decades. MABC can adhere to surfaces and form a biofilm. This characteristic and its resistance to common disinfectants allow these microorganisms to persist in the water distribution systems, becoming a constant reservoir. The frequency and manifestation of NTM species vary geographically because of environmental conditions and population susceptibility differences. MABC lung disease, the most frequent site of NTM infection in humans, is often seen in patients with underlying lung diseases such as bronchiectasis, whereas MABC disseminated disease is related to immunosuppression. Skin and soft tissue infections are associated with surgical or injection procedures. Epidemiological evidence suggests an overall increase in MABC infection and disease in the last decade. IMPLICATIONS: Establishing the burden of this disease is challenging because of varying measures of incidence and prevalence, referral bias, and differences in medical practices and reporting. Furthermore, environmental and structural determinants, infection routes, and MABC pulmonary disease mechanisms require additional investigation. This review contributes to a better understanding of the epidemiology of MABC, which could inform clinical practice and future research.

Nontuberculous Mycobacterial Pulmonary Disease in the Immunocompromised Host.

The immunocompromised host is at an increased risk for pulmonary and extrapulmonary NTM infections. Where data are available in these specific populations, increased mortality is observed with NTM disease. Prior to starting therapy for NTM disease, providers should ensure diagnostic criteria are met as treatment is long and often associated with significant side effects and toxicities. Treatment should involve 2 to 4 agents and be guided by cultures and antimicrobial susceptibilities. Drug interactions are important to consider, especially in those with HIV or transplant recipients. Whenever possible, immunosuppression should be reduced or changed.

Treatment of non-tuberculosis mycobacteria skin infections.

Non-tuberculosis mycobacteria (NTM) skin infections have become increasingly prevalent in recent years, presenting a unique challenge in clinical management. This review explored the complexities of NTM infections localized to the superficial tissues and provided valuable insights into the optimal therapeutic strategies. The antibiotic selection should base on NTM species and their susceptibility profiles. It is recommended to adopt a comprehensive approach that considers the unique characteristics of superficial tissues to improve treatment effectiveness and reduce the incidence of adverse reactions, infection recurrence, and treatment failure. Infection control measures, patient education, and close monitoring should complement the treatment strategies to achieve favorable outcomes in managing NTM skin infections. Further efforts are warranted to elucidate factors and mechanisms contributing to treatment resistance and relapse. Future research should focus on exploring novel treatment options, innovative drug development/delivery platforms, and precise methodologies for determining therapeutic duration. Longitudinal studies are also needed to assess the long-term safety profiles of the integrated approaches.

Mycobacterium abscessus Meningitis Associated with Stem Cell Treatment During Medical Tourism.

Mycobacterium abscessus infections have been reported as adverse events related to medical tourism. We report M. abscessus meningitis in a patient who traveled from Colorado, USA, to Mexico to receive intrathecal stem cell injections as treatment for multiple sclerosis. We also review the management of this challenging central nervous system infection.

Characteristics and Outcomes of Anti-interferon Gamma Antibody-Associated Adult Onset Immunodeficiency.

PURPOSE: Anti-interferon gamma antibody (AIGA) is a rare cause of adult onset immunodeficiency, leading to severe disseminated opportunistic infections with varying outcomes. We aimed to summarize the disease characteristics and to explore factors associated with disease outcome. METHODS: A systematic literature review of AIGA associated disease was conducted. Serum-positive cases with detailed clinical presentations, treatment protocols, and outcomes were included. The patients were categorized into controlled and uncontrolled groups based on their documented clinical outcome. Factors associated with disease outcome were analyzed with logistic regression models. RESULTS: A total of 195 AIGA patients were retrospectively analyzed, with 119(61.0%) having controlled disease and 76 (39.0%) having uncontrolled disease. The median time to diagnosis and disease course were 12 months and 28 months, respectively. A total of 358 pathogens have been reported with nontubercular mycobacterium (NTM) and Talaromyces marneffei as the most common pathogens. The recurrence rate was as high as 56.0%. The effective rates of antibiotics alone, antibiotics with rituximab, and antibiotics with cyclophosphamide were 40.5%, 73.5%, and 75%, respectively. In the multivariate logistic analysis, skin involvement, NTM infection, and recurrent infections remained significantly associated with disease control, with ORs of 3.25 (95% CI 1.187 ~ 8.909, P value = 0.022), 4.74 (95% CI 1.300 ~ 17.30, P value = 0.018), and 0.22 (95% CI 0.086 ~ 0.551, P value = 0.001), respectively. The patients with disease control had significant AIGA titer reduction. CONCLUSIONS: AIGA could cause severe opportunistic infections with unsatisfactory control, particularly in patients with recurrent infections. Efforts should be made to closely monitor the disease and regulate the immune system.

Type 2 Diabetes Mellitus- and Complication-Related Risk of Nontuberculous Mycobacterial Disease in a South Korean Cohort.

We aimed to investigate whether type 2 diabetes mellitus (T2DM) and diabetes-related complications constitute significant risk factors for nontuberculous mycobacterial (NTM) disease. Data from the National Health Insurance Service-National Sample Cohort (which represents 2.2% of the total South Korean population) recorded between 2007 and 2019 were extracted to establish the NTM-naive T2DM cohort (n = 191,218) and the 1:1 age- and sex-matched NTM-naive matched cohort (n = 191,218). Intergroup comparisons were performed to determine differences in the NTM disease risk of the two cohorts during the follow-up period. During median follow-up of 9.46 and 9.25 years, the incidence of NTM disease was 43.58/100,000 and 32.98/100,000 person-years in the NTM-naive T2DM and NTM-naive matched cohorts, respectively. Multivariable analysis showed that T2DM alone did not confer a significant risk for incident NTM disease, although T2DM with ≥2 diabetes-related complications significantly increased NTM disease risk (adjusted hazard ratio [95% confidence interval], 1.12 [0.99 to 1.27] and 1.33 [1.03 to 1.17], respectively). In conclusion, the presence of T2DM with ≥2 diabetes-related complications significantly increases the risk for NTM disease. IMPORTANCE We assessed whether patients with T2DM are at higher risk for incident NTM disease through analysis of NTM-naive matched cohorts from the data of a national population-based cohort which represents 2.2% of the total South Korean population. Although T2DM alone is not a statistically significant risk factor for NTM disease, T2DM significantly increases the risk of NTM disease in those with ≥2 diabetes-related complications. This finding suggested that patients with T2DM with a larger number of complications should be considered a high-risk group for NTM disease.

Vertebral Osteomyelitis Caused by Mycobacterium arupense Mimicking Tuberculous Spondylitis: First Reported Case and Literature Review.

Mycobacterium arupense is a slow-growing, nontuberculous mycobacterium widely found in the environment and is known to cause tenosynovitis and osteomyelitis, mainly in the hands and wrists. We present the first case of vertebral osteomyelitis caused by M arupense in a 78-year-old man with renal cell carcinoma. The patient had a history of tuberculous pleuritis in childhood. Although the nucleic acid amplification test of the vertebral tissue for Mycobacterium tuberculosis was negative, we initiated tuberculosis treatment based on the history and pathological findings of auramine-rhodamine-positive organisms and epithelioid cell granulomas. Subsequently, the isolated mycobacterium was identified as M arupense by genome sequencing. Accordingly, the treatment regimen was changed to a combination of clarithromycin, ethambutol, and rifabutin. Owing to a subsequent adverse event, rifabutin was switched to faropenem, and the patient was treated for a total of 1 year. In previous literature, we found 15 reported cases of bone and soft tissue infections caused by M arupense, but none of them had vertebral lesions. Physicians should be aware that M arupense can cause vertebral osteomyelitis mimicking tuberculous spondylitis. In addition, molecular testing of isolated mycobacteria is essential for diagnosis, even if tuberculous spondylitis is suspected.

Phage Therapy for Nontuberculous Mycobacteria: Challenges and Opportunities.

Non-tuberculous mycobacterium (NTM) infections are often clinically challenging, with lengthy antibiotic regimens that fail to resolve the infections with few good outcomes remaining. Mycobacteriophages-viruses that infect Mycobacterium hosts-show promise as therapeutic agents for NTM infections and have been used in 20 compassionate use cases. Favorable outcomes were observed in many but not all cases, although the phages show exceptional safety profiles and no evidence of phage resistance was observed, even when only a single phage was administered. Phage-specific antibodies are commonly present following intravenous administration and are often neutralizing for the phage in vitro. However, phage neutralization does not consistently correlate with poor treatment outcomes and may not be a therapeutic limitation in all patients, even when immunocompetent. Currently, the therapeutic potential of phages is substantially limited by the great variation in phage susceptibility and a relatively small repertoire of therapeutically useful phages. As many as 45% of clinical isolates can have a smooth colony morphotype, and phages that both efficiently infect and kill these strains have yet to be described. In contrast, ~ 75% of rough strains are susceptible to and killed by one or more phages and therapeutic options can be considered on a compassionate use basis. Although therapies must currently be personalized, elucidating the determinants of phage host specificity, expanding the useful phage repertoire, and identifying the key determinants of clinical outcomes will reveal their full therapeutic potential.

Catheter-Related Bloodstream Infection Caused by Mycolicibacterium iranicum, California, USA.

We describe a case of catheter-related bacteremia caused by Mycolicibacterium iranicum in the United States. The case highlights the value of using next-generation sequencing to identify infrequent and emerging pathogens and the challenges associated with choosing appropriate treatments because of limited knowledge of drug resistance mechanisms in those emerging pathogens.

Disseminated tuberculosis in a lung transplant recipient presenting as tenosynovitis, subcutaneous nodules, and liver abscesses.

Tuberculosis is of particular concern in lung transplant recipients. We present the case of a patient who received a double lung transplant from a deceased donor from Mexico and developed disseminated tuberculosis 60 days post-transplant manifested as tenosynovitis, liver abscesses, and subcutaneous nodules with no definitive lung allograft involvement. The recipient did not have evidence of tuberculosis on explanted lungs, had a negative interferon gamma release assay pre-transplant, and did not have risk factors for this infection. Mycobacterium tuberculosis should remain in the differential diagnosis of early post-transplant infections with atypical presentations, evidence of dissemination, or lack of improvement with appropriate antimicrobial coverage, even in the absence of typical lung findings.

Incidence of Nontuberculous Mycobacterial Pulmonary Infection, by Ethnic Group, Hawaii, USA, 2005-2019.

To further clarify differences in the risk for nontuberculous mycobacterial pulmonary infection (NTM-PI) among ethnic populations in Hawaii, USA, we conducted a retrospective cohort study among beneficiaries of Kaiser Permanente Hawaii (KPH). We abstracted demographic, socioeconomic, clinical, and microbiological data from KPH electronic health records for 2005-2019. An NTM-PI case-patient was defined as a person from whom >1 NTM pulmonary isolate was obtained. We performed Cox proportional hazards regression to estimate incidence of NTM-PI while controlling for confounders. Across ethnic groups, risk for NTM-PI was higher among persons who were underweight (body mass index [BMI] <18.5 kg/m2). Among beneficiaries who self-identified as any Asian ethnicity, risk for incident NTM-PI was increased by 30%. Low BMI may increase susceptibility to NTM-PI, and risk may be higher for persons who self-identify as Asian, independent of BMI.