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Journal of Crohn's & Colitis Aug 2021
Topics: Animals; Crohn Disease; Humans; Mycobacterium avium subsp. paratuberculosis; Polymerase Chain Reaction
PubMed: 33735385
DOI: 10.1093/ecco-jcc/jjab027 -
Ochsner Journal 2021Nontuberculous mycobacteria are an uncommon pathogen for musculoskeletal infection and are difficult to treat because of delays in diagnosis, prolonged treatment...
Nontuberculous mycobacteria are an uncommon pathogen for musculoskeletal infection and are difficult to treat because of delays in diagnosis, prolonged treatment requiring both antimycobacterial therapy and surgical debridement, and high rates of resistance to antimycobacterial therapy. We report the case of an 88-year-old male with recurrent complex tenosynovitis despite receiving multiple courses of pharmacologic therapy and surgical debridement. Nontuberculous mycobacterial musculoskeletal infections can be difficult to diagnose and equally difficult to treat. A combination of antimycobacterial therapy and surgical debridement is often required; however, the rate of treatment failure remains high, particularly with rapidly growing mycobacteria such as .
PubMed: 33828430
DOI: 10.31486/toj.19.0010 -
International Journal of Molecular... Mar 2022Civilization factors are responsible for the increasing of human exposure to mycobacteria from environment, water, and food during the last few decades. Urbanization,... (Review)
Review
Civilization factors are responsible for the increasing of human exposure to mycobacteria from environment, water, and food during the last few decades. Urbanization, lifestyle changes and new technologies in the animal and plant industry are involved in frequent contact of people with mycobacteria. Type 1 diabetes is a multifactorial polygenic disease; its origin is conditioned by the mutual interaction of genetic and other factors. The environmental factors and certain pathogenetic pathways are shared by some immune mediated chronic inflammatory and autoimmune diseases, which are associated with triggers originating mainly from subspecies , an intestinal pathogen which persists in the environment. Type 1 diabetes and some other chronic inflammatory diseases thus pose the global health problem which could be mitigated by measures aimed to decrease the human exposure to this neglected zoonotic mycobacterium.
Topics: Animals; Diabetes Mellitus, Type 1; Humans; Intestines; Mycobacterium; Mycobacterium avium subsp. paratuberculosis; Paratuberculosis
PubMed: 35409018
DOI: 10.3390/ijms23073657 -
Journal of Global Antimicrobial... Sep 2021The incidence of infections due to Mycobacterium avium complex (MAC) and Mycobacterium abscessus (MABS) is increasing worldwide. Current antimycobacterial agents are not... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The incidence of infections due to Mycobacterium avium complex (MAC) and Mycobacterium abscessus (MABS) is increasing worldwide. Current antimycobacterial agents are not sufficiently effective against nontuberculous mycobacteria (NTM) and there is a need for new drugs. This study aimed to estimate the overall in vitro activity of clofazimine (CFZ) against MAC and MABS clinical isolates.
METHODS
We systematically searched four databases up to 1 March 2020 to identify relevant studies. Studies were included if they used the Clinical and Laboratory Standards Institute (CLSI) criteria for drug susceptibility testing (DST). We assessed the pooled in vitro CFZ resistance rate in MAC and MABS clinical isolates using a random- effects model. Sources of heterogeneity were evaluated using Cochran's Q and the I statistic. Potential for publication bias was explored using Begg's and Egger's tests. All analyses were conducted using Stata 14.0.
RESULTS
A total of 20 publications (11 reports for MAC and 15 for MABS) were included. The pooled rates of in vitro resistance to CFZ in clinical isolates of MAC and MABS were 9.0% [95% confidence interval (CI) 3.0-17.0%] and 16.0% (95% CI 4.0-34.0%), respectively. There was no evidence of publication bias.
CONCLUSION
This study reports the frequency of CFZ resistance in clinical isolates of MAC and MABS. According to the results, establishing accurate DST methods for detecting CFZ resistance, performing DST for all NTM isolates to provide effective treatment, and continuous monitoring of drug resistance are suggested for the prevention and control of CFZ-resistant NTM.
Topics: Clofazimine; Humans; Microbial Sensitivity Tests; Mycobacterium abscessus; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Mycobacterium tuberculosis
PubMed: 34153525
DOI: 10.1016/j.jgar.2021.06.002 -
Journal of the Formosan Medical... Jun 2020Mycobacterium avium complex (MAC) is the major pathologic nontuberculous mycobacteria causing lung disease (LD) in humans worldwide. Although the burden of MAC-LD has... (Review)
Review
Mycobacterium avium complex (MAC) is the major pathologic nontuberculous mycobacteria causing lung disease (LD) in humans worldwide. Although the burden of MAC-LD has increased over the past two decades, treatment remains difficult because of intolerance of long-term antibiotics, lack of adherence to guidelines, and disease recurrence. The current guidelines recommend antibiotic initiation for patients with MAC-LD and severe disease and in those with disease progression. Thus, physicians should consider antibiotic treatment for patients with MAC-LD and cavitary pulmonary lesions or symptomatic non-cavitary nodular bronchiectasis pattern at initial visits and also for those with clinical deterioration during follow-up. The standard three-drug regimen should be macrolide, rifamycin, and ethambutol. Physicians should monitor side effects in patients and maintain the regimen for 12 months, beginning from when sputum conversion has been obtained. With adherence to guideline-based therapy, treatment is successful in two thirds of treatment-naïve patients without macrolide resistance. Without adherence, macrolide resistance can occur, which leads to poor outcomes in patients with MAC-LD. Although the discovery of new treatment options is warranted, adherence to guidelines remains most crucial in treating patients with MAC-LD. It is worth mentioning that the majority of current recommendations are based on observational studies or small-scale clinical trials.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Humans; Lung Diseases; Macrolides; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Retrospective Studies
PubMed: 32446754
DOI: 10.1016/j.jfma.2020.05.006 -
Internal Medicine (Tokyo, Japan) Jan 2022Nontuberculous mycobacterial (NTM) infections are an emerging problem. Common organisms include Mycobacterium avium, M. intracellulare, and M. kansasii, along with the...
Nontuberculous mycobacterial (NTM) infections are an emerging problem. Common organisms include Mycobacterium avium, M. intracellulare, and M. kansasii, along with the M. avium intracellulare complex (MAC), which includes both M. avium and M. intracellulare. Typically, NTM infections affect the lungs and subsequently demonstrate a chronic course. Therefore, persistent respiratory symptoms generally indicate of the presence of pulmonary NTM diseases, and chest radiography, along with a sputum examination, are essential for its diagnosis. Because NTM are ubiquitous environmental organisms, a positive culture from a minimum of two separate expectorated sputum samples are required to make a diagnosis. The repertoire of effective drugs for treatment is considerably limited, indicating the need for long-term management with multiple drugs. Establishing a treatment regimen with high therapeutic efficacy and safety is an important issue for the future.
Topics: Humans; Lung; Mycobacterium Infections, Nontuberculous; Mycobacterium avium Complex; Nontuberculous Mycobacteria; Radiography
PubMed: 33840690
DOI: 10.2169/internalmedicine.4361-19 -
Applied Microbiology and Biotechnology Apr 2022Nontuberculous mycobacterium (NTM) infections are increasing in the USA and have a high cost burden associated with treatment. Thus, it is necessary to understand what...
Nontuberculous mycobacterium (NTM) infections are increasing in the USA and have a high cost burden associated with treatment. Thus, it is necessary to understand what changes could be contributing to this increase in NTM disease rate. Water samples from 40 sites were collected from around the USA. They represented three water types: groundwater disinfected with chlorine and surface water disinfected with chlorine or monochloramine. Two methods, culture and qPCR, were used to measure M. avium and M. intracellulare. Heterotrophic bacteria and NTM counts were also measured. M. avium and M. intracellulare were molecularly detected in 25% (73/292) and 35% (102/292) of samples. The mean concentrations of M. avium and M. intracellulare were 2.8 × 10 and 4.0 × 10 genomic units (GU) L. The Northeast sites had the highest sample positively rate for both M. avium and M. intracellulare. The highest NTM counts and M. avium concentrations were observed in the surface water treated with chloramine. Geographic location and source water/disinfectant type were observed to significantly influence M. avium and M. intracellulare occurrence rates. These studies can help improve public health risk management by balancing disinfectant treatments and diverse microbial loads in drinking water. KEY POINTS: • M. avium (MA) culture rate increased significantly: 1% (1999) to 13%. • Culture versus qPCR method: 13% vs 31% for MA and 6% vs 35% for MI. • The results of each method type tell two different stories of MA and MI occurrence.
Topics: Chlorine; Disinfectants; Drinking Water; Mycobacterium avium; Mycobacterium avium Complex
PubMed: 35298694
DOI: 10.1007/s00253-022-11849-7 -
Scientific Reports Nov 2023The prevalence of Mycobacterium avium complex-pulmonary disease (MAC-PD) has become a growing concern worldwide, and current treatments involving macrolides...
The prevalence of Mycobacterium avium complex-pulmonary disease (MAC-PD) has become a growing concern worldwide, and current treatments involving macrolides (clarithromycin [CLR] or azithromycin), ethambutol, and rifampicin have limited success, highlighting the need for better therapeutic strategies. Recently, oxazolidinone drugs have been identified as novel anti-tuberculosis drugs effective against drug-resistant M. tuberculosis. However, the effects of these drugs against MAC are still controversial due to limited data. Here, we first evaluated the intracellular anti-MAC activities of two oxazolidinone drugs, linezolid (LZD) and delpazolid (DZD), against 10 macrolide-susceptible MAC strains and one macrolide-resistant M. avium strain in murine bone marrow-derived macrophages (BMDMs) and found that both drugs demonstrated similar potential. The synergistic efficacies with CLR were then determined in a chronic progressive MAC-PD murine model by initiating a 4-week treatment at 8 weeks post-infection. Upon assessment of bacterial burdens and inflamed lesions, oxazolidinone drugs exhibited no anti-MAC effect, and there was no significant difference in the synergistic effect of CLR between LZD and DZD. These findings suggest that oxazolidinone drugs inhibit intracellular bacterial growth, even against macrolide-resistant MAC, but their clinical application requires further consideration.
Topics: Humans; Mice; Animals; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Oxazolidinones; Anti-Bacterial Agents; Antitubercular Agents; Clarithromycin; Macrolides; Lung Diseases
PubMed: 37996500
DOI: 10.1038/s41598-023-48001-y -
International Archives of Allergy and... 2023Cervical scrofulous lymphadenitis due to Mycobacterium avium complex (MAC) in immunocompetent adults is a rare disease. The presence of MAC infections demands meticulous...
INTRODUCTION
Cervical scrofulous lymphadenitis due to Mycobacterium avium complex (MAC) in immunocompetent adults is a rare disease. The presence of MAC infections demands meticulous clinical evaluation of patients along with detailed phenotypic and functional evaluation of their immune system including next-generation sequencing (NGS) analyses of target genes.
METHODS
Exact clinical histories of the index patients both suffering from retromandibular/cervical scrofulous lymphadenitis were obtained along with phenotypic and functional immunological evaluations of leukocyte populations followed by targeted NGS-based sequencing of candidate genes.
RESULTS
Immunological investigations showed normal serum immunoglobulin and complement levels, but lymphopenia, which was caused by significantly reduced CD3+CD4+CD45RO+ memory T-cell and CD19+ B-cell numbers. Despite normal T-cell proliferation to a number of accessory cell-dependent and -independent stimuli, the PBMC of both patients elaborated clearly reduced levels of a number of cytokines, including IFN-γ, IL-10, IL-12p70, IL-1α, IL-1β, and TNF-α upon TCR-dependent T-cell stimulation with CD3-coated beads but also superantigens. The IFN-γ production deficiency was confirmed for CD3+CD4+ helper and CD4+CD8+ cytotoxic T cells on the single-cell level by multiparametric flow cytometry irrespective of whether PMA/ionomycin-stimulated whole blood cells or gradient-purified PBMC was analyzed. In the female patient L1, targeted NGS-based sequencing revealed a homozygous c.110T>C mutation in the interferon-γ receptor type 1 (IFNGR1) leading to significantly reduced receptor expression on both CD14+ monocytes and CD3+ T cells. Patient S2 presented with normal IFNGR1 expression on CD14+ monocytes but significantly reduced IFNGR1 expression on CD3+ T cells, despite the absence of detectable homozygous mutations in the IFNGR1 itself or disease-related target genes. Exogenous addition of increasing doses of IFN-γ resulted in proper upregulation of high-affinity FcγRI (CD64) on monocytes from patient S2, whereas monocytes from patient L1 showed only partial induction of CD64 expression after incubation with high doses of IFN-γ.
CONCLUSION
A detailed phenotypic and functional immunological examination is urgently required to determine the cause of a clinically relevant immunodeficiency, despite detailed genetic analyses.
Topics: Adult; Humans; Female; Mycobacterium avium Complex; Leukocytes, Mononuclear; Mycobacterium avium-intracellulare Infection; Cytokines; Lymphadenitis
PubMed: 37279717
DOI: 10.1159/000530844 -
Molecules (Basel, Switzerland) Oct 2022We evaluated the anti-mycobacterial effect of a flavonoid 5,7-dihydroxy-2-(4-hydroxyphenyl) 4-chromen-4-one () and two pyrimidines,...
We evaluated the anti-mycobacterial effect of a flavonoid 5,7-dihydroxy-2-(4-hydroxyphenyl) 4-chromen-4-one () and two pyrimidines, 4-hydroxy-2-dimethylamino-5-nitroso-6-aminopyrimidine () and 2-chloro-5--nonylpyrimidine () in vitro against (, H37Ra) and , using a Microplate Alamar Blue Assay (MABA). The effects of the compounds - in combination with first- and second-line anti-TB drugs isoniazid, rifampicin, cycloserine, and clarithromycin on the growth of and were also evaluated in in vitro assays. As a single agent, compounds and exhibited modest activity while compound was the most effective against and . When compounds - were evaluated at lower than 50% of their inhibitory concentrations in a two-drug combination with isoniazid or rifampicin, they showed additive to synergistic interactions. This inhibitory effect was improved when each of the three compounds was tested together in a three-drug combination with two of the first-line anti-TB drugs. Compounds - also demonstrated strong synergistic interaction in combination with cycloserine and clarithromycin in inhibiting the growth of and , respectively. This study demonstrated that compounds - have potential to be developed as effective anti-TB agents with combined use.
Topics: Antitubercular Agents; Clarithromycin; Cycloserine; Drug Combinations; Flavonoids; Humans; Isoniazid; Microbial Sensitivity Tests; Mycobacterium avium; Mycobacterium tuberculosis; Pyrimidines; Rifampin; Tuberculosis
PubMed: 36235249
DOI: 10.3390/molecules27196714