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Annals of the American Thoracic Society Aug 2023Population-based data on the epidemiology of nontuberculosis mycobacterial (NTM) infections are limited, particularly with respect to variation in NTM infection among...
Population-based data on the epidemiology of nontuberculosis mycobacterial (NTM) infections are limited, particularly with respect to variation in NTM infection among racial groups and socioeconomic strata. Wisconsin is one of a handful of states where mycobacterial disease is notifiable, allowing large, population-based analyses of the epidemiology of NTM infection in this state. To estimate the incidence of NTM infection in Wisconsin adults, describe the geographic distribution of NTM infection across the state, identify the frequency and type of infection caused by different NTM species, and investigate associations between NTM infection and demographics and socioeconomic status. We conducted a retrospective cohort study using laboratory reports of all NTM isolates from Wisconsin residents submitted to the Wisconsin Electronic Disease Surveillance System from 2011 to 2018. For the analyses of NTM frequency, multiple reports from the same individual were enumerated as separate isolates when nonidentical, collected from different sites or collected more than one year apart. A total of 8,135 NTM isolates from 6,811 adults were analyzed. complex accounted for 76.4% of respiratory isolates. The group was the most common species isolated from skin and soft tissue. The annual incidence of NTM infection was stable over the study period (from 22.1 per 100,000 to 22.4 per 100,000). The cumulative incidence of NTM infection among Black (224 per 100,000) and Asian (244 per 100,000) individuals was significantly higher compared with that among their White counterparts (97 per 100,000). Total NTM infections were significantly more frequent ( < 0.001) in individuals from disadvantaged neighborhoods, and racial disparities in the incidence of NTM infection generally remained consistent when stratified by measures of neighborhood disadvantage. More than 90% of NTM infections were from respiratory sites, with the vast majority caused by complex. Rapidly growing mycobacteria predominated as skin and soft tissue pathogens and were important minor respiratory pathogens. We found a stable annual incidence of NTM infection in Wisconsin between 2011 and 2018. NTM infection occurred more frequently in non-White racial groups and in individuals experiencing social disadvantage, suggesting that NTM disease may be more frequent in these groups as well.
Topics: Adult; Humans; Nontuberculous Mycobacteria; Wisconsin; Retrospective Studies; Mycobacterium Infections, Nontuberculous; Mycobacterium avium Complex
PubMed: 36812384
DOI: 10.1513/AnnalsATS.202205-425OC -
Frontiers in Immunology 2023Tuberculosis (TB), caused by (Mtb) and Coronavirus disease-2019 (COVID-19), whose etiologic agent is severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), are... (Review)
Review
Tuberculosis (TB), caused by (Mtb) and Coronavirus disease-2019 (COVID-19), whose etiologic agent is severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), are currently the two deadliest infectious diseases in humans, which together have caused about more than 11 million deaths worldwide in the past 3 years. TB and COVID-19 share several aspects including the droplet- and aerosol-borne transmissibility, the lungs as primary target, some symptoms, and diagnostic tools. However, these two infectious diseases differ in other aspects as their incubation period, immune cells involved, persistence and the immunopathological response. In this review, we highlight the similarities and differences between TB and COVID-19 focusing on the innate and adaptive immune response induced after the exposure to Mtb and SARS-CoV-2 and the pathological pathways linking the two infections. Moreover, we provide a brief overview of the immune response in case of TB-COVID-19 co-infection highlighting the similarities and differences of each individual infection. A comprehensive understanding of the immune response involved in TB and COVID-19 is of utmost importance for the design of effective therapeutic strategies and vaccines for both diseases.
Topics: Humans; Mycobacterium tuberculosis; SARS-CoV-2; COVID-19; Latent Tuberculosis; Immunity; Communicable Diseases
PubMed: 37662901
DOI: 10.3389/fimmu.2023.1244556 -
Microbiology Spectrum Aug 2023We evaluated the clinical characteristics and treatment outcomes of 35 patients diagnosed with Mycobacterium fortuitum-pulmonary disease (M. fortuitum-PD). Prior to...
We evaluated the clinical characteristics and treatment outcomes of 35 patients diagnosed with Mycobacterium fortuitum-pulmonary disease (M. fortuitum-PD). Prior to treatment, all isolates were sensitive to amikacin and 73% and 90% were sensitive to imipenem and moxifloxacin, respectively. Approximately two-thirds of the patients (24 of 35) remained stable without antibiotic treatment. Of 11 patients requiring antibiotic treatment, the majority (81%, 9 of 11) achieved a microbiological cure with susceptible antibiotics. Mycobacterium fortuitum (M. fortuitum) is a rapidly growing mycobacterium that causes M. fortuitum-pulmonary disease (PD). It is common among individuals with preexisting lung conditions. Limited data exist regarding treatment and prognosis. Our study examined patients with M. fortuitum-PD. Two-thirds of them remained stable without antibiotics. Among those requiring treatment, 81% achieved a microbiological cure with suitable antibiotics. In many cases, M. fortuitum-PD follows a stable course without antibiotics, and when necessary, a favorable treatment response can be achieved with the appropriate antibiotics.
Topics: Humans; Mycobacterium fortuitum; Mycobacterium Infections, Nontuberculous; Anti-Bacterial Agents; Treatment Outcome; Microbial Sensitivity Tests; Lung Diseases
PubMed: 37428038
DOI: 10.1128/spectrum.02051-23 -
Antimicrobial Agents and Chemotherapy Oct 2023Infections due to nontuberculous mycobacteria (NTM) continue to increase in prevalence, leading to problematic clinical outcomes. Omadacycline (OMC) is an...
Long-term evaluation of clinical success and safety of omadacycline in nontuberculous mycobacteria infections: a retrospective, multicenter cohort of real-world health outcomes.
Infections due to nontuberculous mycobacteria (NTM) continue to increase in prevalence, leading to problematic clinical outcomes. Omadacycline (OMC) is an aminomethylcycline antibiotic with FDA orphan drug and fast-track designations for pulmonary NTM infections, including (MAB). This multicenter retrospective study across 16 U.S. medical institutions from January 2020 to March 2023 examined the long-term clinical success, safety, and tolerability of OMC for NTM infections. The cohort included patients aged ≥18 yr, who were clinically evaluable, and` had been treated with OMC for ≥3 mo without a previous diagnosis of cystic fibrosis. The primary outcome was 3 mo clinical success, with secondary outcomes including clinical improvement and mortality at 6- and 12 mo, persistence or reemergence of infection, adverse effects, and reasons for OMC utilization. Seventy-five patients were included in this analysis. Most patients were female (48/75, 64.0%) or Caucasian (58/75, 77.3%), with a median (IQR) age of 59 yr (49-67). Most had NTM pulmonary disease (33/75, 44.0%), skin and soft tissue disease (19/75, 25.3%), or osteomyelitis (10/75, 13.3%), and (60/75, 80%) was the most commonly isolated NTM pathogen. The median (IQR) treatment duration was 6 mo (4 - 14), and the most commonly co-administered antibiotic was azithromycin (33/70, 47.1%). Three-month clinical success was observed in 80.0% (60/75) of patients, and AEs attributable to OMC occurred in 32.0% (24/75) of patients, leading to drug discontinuation in 9.3% (7/75).
Topics: Humans; Female; Male; Retrospective Studies; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Cystic Fibrosis; Mycobacterium abscessus; Anti-Bacterial Agents; Outcome Assessment, Health Care
PubMed: 37768312
DOI: 10.1128/aac.00824-23 -
International Journal of Infectious... Oct 2023Mycobacterium iranicum is characterized by rapid growth and orange-pigmented scotochromogenic colonies. However, it is uncommon for M. iranicum to invade the central...
Mycobacterium iranicum is characterized by rapid growth and orange-pigmented scotochromogenic colonies. However, it is uncommon for M. iranicum to invade the central nervous system. A man nearly 60 years old was referred to our hospital because of a seizure and unconsciousness. After admission, the patient had fever and dizziness without obvious abnormalities in the cerebrospinal fluid, except for an increase in neutrophils. Metagenomic next-generation sequencing and DNA testing were positive for M. iranicum. The patient was treated with imipenem, minocycline, moxifloxacin, and linezolid, and he gradually recovered during follow-up.
Topics: Male; Humans; Middle Aged; Mycobacteriaceae; Mycobacterium Infections; Meningitis, Bacterial; Epilepsy
PubMed: 37327856
DOI: 10.1016/j.ijid.2023.06.002 -
Journal of Clinical Immunology Oct 2023Anti-interferon gamma antibody (AIGA) is a rare cause of adult onset immunodeficiency, leading to severe disseminated opportunistic infections with varying outcomes. We...
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.
Topics: Humans; Adult; Mycobacterium Infections, Nontuberculous; Retrospective Studies; Reinfection; Autoantibodies; Interferon-gamma; Immunologic Deficiency Syndromes; Opportunistic Infections; Anti-Bacterial Agents
PubMed: 37365453
DOI: 10.1007/s10875-023-01537-0 -
Clinics in Chest Medicine Dec 2023Patients with nontuberculous mycobacterial (NTM) lung infection require life-long attention to their bronchiectasis, whether or not their NTM infection has been cured.... (Review)
Review
Patients with nontuberculous mycobacterial (NTM) lung infection require life-long attention to their bronchiectasis, whether or not their NTM infection has been cured. The identification of the cause of bronchiectasis and/or coexisting diseases is important because it may affect therapeutic strategies. Airway clearance is the mainstay of bronchiectasis management. It can include multiple breathing techniques, devices, and mucoactive agents. The exact airway clearance regimen should be customized to each individual patient. Chronic pathogenic airway bacteria, such as Pseudomonas aeruginosa, may warrant consideration of eradication therapy and/or chronic use of maintenance inhaled antibiotics.
Topics: Humans; Bronchiectasis; Lung; Mycobacterium Infections, Nontuberculous; Lung Diseases; Nontuberculous Mycobacteria; Anti-Bacterial Agents
PubMed: 37890912
DOI: 10.1016/j.ccm.2023.07.005 -
Infection and Immunity Jul 2023Immune networks that control antimicrobial and inflammatory mechanisms have overlapping regulation and functions to ensure effective host responses. Genetic interaction...
Immune networks that control antimicrobial and inflammatory mechanisms have overlapping regulation and functions to ensure effective host responses. Genetic interaction studies of immune pathways that compare host responses in single and combined knockout backgrounds are a useful tool to identify new mechanisms of immune control during infection. For disease caused by pulmonary Mycobacterium tuberculosis (Mtb) infections, which currently lacks an effective vaccine, understanding the genetic interactions between protective immune pathways may identify new therapeutic targets or disease-associated genes. Previous studies have suggested a direct link between the activation of NLRP3-Caspase1 inflammasome and the NADPH-dependent phagocyte oxidase complex during Mtb infection. Loss of the phagocyte oxidase complex alone resulted in increased activation of Caspase1 and IL-1β production during Mtb infection, resulting in failed disease tolerance during the chronic stages of disease. To better understand this interaction, we generated mice lacking both , a key subunit of the phagocyte oxidase, and . We found that Mtb infection of macrophages resulted in the expected loss of IL-1β secretion but an unexpected change in other inflammatory cytokines and bacterial control. Mtb infected mice rapidly progressed to severe TB, succumbing within 4 weeks to disease characterized by high bacterial burden, increased inflammatory cytokines, and the recruitment of granulocytes that associated with Mtb in the lungs. These results uncover a key genetic interaction between the phagocyte oxidase complex and Caspase1/11 that controls protection against TB and highlight the need for a better understanding of the regulation of fundamental immune networks during Mtb infection.
Topics: Animals; Mice; Oxidoreductases; Tuberculosis; Mycobacterium tuberculosis; Tuberculosis, Pulmonary; Phagocytes; Cytokines
PubMed: 37314361
DOI: 10.1128/iai.00060-23 -
Clinics in Chest Medicine Dec 2023Mycobacterium abscessus pulmonary disease is highly antibiotic-resistant, and the current armamentarium of antibiotics yields poor treatment outcomes with significant... (Review)
Review
Mycobacterium abscessus pulmonary disease is highly antibiotic-resistant, and the current armamentarium of antibiotics yields poor treatment outcomes with significant drug toxicity. Macrolide susceptibility is a key prognostic factor. Optimal drug combinations, duration of therapy, and management of refractory disease are unknown. Surgical resection, performed at centers with experience in surgical management of nontuberculous mycobacterial pulmonary disease, may produce favorable outcomes in select patients. Multiple emerging therapeutic candidates hold promise for more efficacious and tolerable treatment options.
Topics: Humans; Mycobacterium abscessus; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Lung Diseases; Anti-Bacterial Agents
PubMed: 37890916
DOI: 10.1016/j.ccm.2023.06.010 -
The Journal of Infectious Diseases Dec 2023Pregnancy and human immunodeficiency virus (HIV) may influence tuberculosis infection detection using interferon (IFN)-γ release assay (QFT-Plus; Qiagen) and tuberculin...
BACKGROUND
Pregnancy and human immunodeficiency virus (HIV) may influence tuberculosis infection detection using interferon (IFN)-γ release assay (QFT-Plus; Qiagen) and tuberculin skin test (TST).
METHODS
Participants in Western Kenya underwent QFT-Plus and TST in pregnancy, 6 weeks postpartum (6wkPP) and 12 months postpartum (12moPP).
RESULTS
400 participants (200 with HIV [WHIV], 200 HIV-negative) enrolled during pregnancy (median 28 weeks' gestation [interquartile range, 24-30]). QFT-Plus positivity prevalence was higher than TST in pregnancy (32.5% vs 11.6%) and through 12moPP (6wkPP, 30.9% for QFT-Plus vs 18.0% for TST; 12moPP, 29.5% vs 17.1%; all P < .001), driven primarily by QFT-Plus-positive/TST-negative discordance among HIV-negative women. Tuberculosis infection test conversion incidence was 28.4/100 person-years (PY) and higher in WHIV than HIV-negative women (35.5 vs 20.9/100 PY; hazard ratio, 1.73 [95% confidence interval, 1.04-2.88]), mostly owing to early postpartum TST conversion among WHIV. Among QFT-Plus-positive participants in pregnancy, Mycobacterium tuberculosis (Mtb)-specific IFN-γ responses were dynamic through 12moPP and lower among WHIV than HIV-negative women with tuberculosis infection at all time points.
CONCLUSIONS
QFT-Plus had higher diagnostic yield than TST in peripartum women. Peripartum QFT-Plus positivity was stable and less influenced by HIV than TST. Mtb-specific IFN-γ responses were dynamic and lower among WHIV. Tuberculosis infection test conversion incidence was high between pregnancy and early postpartum, potentially owing to postpartum immune recovery.
Topics: Pregnancy; Humans; Female; Peripartum Period; HIV; Tuberculosis; Tuberculin Test; Latent Tuberculosis; Mycobacterium tuberculosis; HIV Infections; Interferon-gamma Release Tests
PubMed: 37768184
DOI: 10.1093/infdis/jiad416