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Microbiology Spectrum Aug 2023Tuberculosis (TB) is an ongoing threat to public health, and furthermore, the incidence of infections by nontuberculous mycobacteria (NTM), whose symptoms are not...
Tuberculosis (TB) is an ongoing threat to public health, and furthermore, the incidence of infections by nontuberculous mycobacteria (NTM), whose symptoms are not distinguishable from TB, is increasing globally, thus indicating a need for accurate diagnostics for patients with suspected mycobacterial infections. Such diagnostic strategies need to include two steps, (i) detecting the mycobacterial infections and, if the case is an NTM infection, (ii) identifying the causative NTM pathogen. To eliminate a false-positive TB diagnosis for a host vaccinated by the bacillus Calmette-Guérin (BCG) strain of Mycobacterium bovis, a new target specific for M. tuberculosis species was selected, together with the species-specific targets for the six dominant NTM species of clinical importance, i.e., M. intracellulare, M. avium, M. kansasii, M. massiliense, M. abscessus, and M. fortuitum. Using sets of primers and probes, a two-step real-time multiplex PCR method was designed. The diagnostic performance was assessed by using a total of 1,772 clinical specimens from patients with suspected TB or NTM infection. A total of 69.4% of M. tuberculosis and 28.8% of NTM infections were positive for the primary step of the real-time PCR corresponding to the culture within 10 weeks, and mycobacterial species of 75.5% of the NTM-positive cases were identified by the secondary step. The two-step method described herein presented promising results and similar diagnostic sensitivity and specificity to commercially available real-time PCR kits for detecting TB and NTM infections. The method also enabled the identification of mycobacterial species in three-quarters of NTM infection cases, thus providing a better treatment strategy. Tuberculosis (TB) is an ongoing threat to public health. In addition, infection by nontuberculous mycobacteria (NTM) is a nonnegligible issue for global public health, with increasing incidences. Since the antimicrobial treatment strategy needs to be differed by the causative pathogen, a rapid and accurate diagnostic method is necessary. In this study, we developed a two-step molecular diagnostic method using clinical specimens of TB and NTM infection-suspected patients. The diagnostic power of the new method using the novel target was similar to the widely used TB detection kit, and, among the NTM-positive specimens, three-quarters of the NTM species were able to be identified. This simple and powerful method will be useful as it is, and it could be applied easily to a point-of-care diagnostic apparatus for better application to patients, especially those living in developing countries.
Topics: Humans; Real-Time Polymerase Chain Reaction; Tuberculosis; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Mycobacterium tuberculosis; Mycobacterium bovis
PubMed: 37378523
DOI: 10.1128/spectrum.01606-23 -
Annali Dell'Istituto Superiore Di Sanita 2023Nontuberculous mycobacteria (NTM) are environmental mycobacteria which may cause pulmonary and extrapulmonary diseases. These organisms are difficult to treat due to...
INTRODUCTION
Nontuberculous mycobacteria (NTM) are environmental mycobacteria which may cause pulmonary and extrapulmonary diseases. These organisms are difficult to treat due to their intrinsic drug-resistance. In Italy, no major nationwide study on NTM epidemiology and drug susceptibility was performed.
METHODS
Data on the epidemiology of 7,469 NTM clinical isolates identified in Italy in 2016-2020 and on the minimum inhibitory concentrations (MICs) of 1,506 of these strains were analysed.
RESULTS
Overall, 63 species were identified in 42 hospital laboratories located in 16 out of 20 regions, with Mycobacterium avium complex (MAC) being the most frequently isolated, followed by M. gordonae, M. xenopi, M. abscessus. The MICs of 12 drugs for MAC, M. xenopi, M. kansasii, M. abscessus, M. fortuitum and M. chelonae were interpreted for clinical significance (susceptible, intermediate, resistant) based on the guidelines published by the Clinical and Laboratory Standards Institute in November 2018.
CONCLUSIONS
Our data are in line with other nationwide studies and may be of value for further update of microbiological and clinical guidelines.
Topics: Humans; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Microbial Sensitivity Tests; Italy
PubMed: 37337988
DOI: 10.4415/ANN_23_02_06 -
Antibiotics (Basel, Switzerland) Apr 2023Tuberculosis (TB) remains a major health problem worldwide, and the emergence of multi-resistant strains to first-line drugs has become the biggest obstacle to its...
Tuberculosis (TB) remains a major health problem worldwide, and the emergence of multi-resistant strains to first-line drugs has become the biggest obstacle to its treatment. On the other hand, the incidence of non-tuberculous mycobacteria (NTM) in humans has increased remarkably in recent years. The search for new and better treatments against mycobacterial infections is a constant at the global level. Hence, in this study, we propose to investigate the antimycobacterial effect of the extracts and major compounds of against clinical isolates of and non-tuberculous mycobacteria: , , , and . To determine the antimycobacterial activity, a microdilution assay was used to establish the minimum inhibitory concentration (MIC) of the different strains of . The methanolic extract presented the best activity against , inhibiting ten of the twelve strains analyzed at a concentration < 2500 µg/mL; meanwhile, the hexanic extract presented the best activity against non-tuberculous mycobacteria (NTM) by inhibiting eight of the ten strains studied at ≤625 µg/mL. Moreover, there is a strong positive correlation between the antimycobacterial activity of pulegone and the hexanic extract against non-tuberculous strains, so this compound could serve as a predictability marker against these types of microorganisms.
PubMed: 37237736
DOI: 10.3390/antibiotics12050833 -
Acta Microbiologica Et Immunologica... Jun 2023Mycobacterium fortuitum is a clinically important species among nontuberculous mycobacteria (NTM). Treatment of diseases caused by NTM is challenging. The aim of this...
Frequency of mutations in erm(39) related to clarithromycin resistance and in rrl related to linezolid resistance in clinical isolates of Mycobacterium fortuitum in Iran.
Mycobacterium fortuitum is a clinically important species among nontuberculous mycobacteria (NTM). Treatment of diseases caused by NTM is challenging. The aim of this study was identification of drug susceptibility and detection of mutations in erm(39) related to clarithromycin resistance and in rrl related to linezolid resistance in clinical isolates of M. fortuitum in Iran. In the study, 328 clinical NTM isolates were subjected to identification based on rpoB and 15% of isolates were assigned to M. fortuitum. Minimum inhibitory concentration for clarithromycin and linezolid was determined by E-test. Altogether 64% of M. fortuitum isolates showed resistanc to clarithromycin and 18% of M. fortuitum isolates showed resistance to linezolid. PCR and DNA sequencing were performed in erm(39) and in rrl genes for detection of mutations related to clarithromycin and linezolid resistance, respectively. Sequencing analysis revealed (84.37%) single nucleotide polymorphisms in the erm(39). A total 55.55% of M. fortuitum isolates harbored an A→G, 14.81% harbored an C→A, 29.62% harbored an G→T mutation in erm(39) at position 124, 135, 275. Seven strains harbored point mutation in the rrl gene either at T2131C or at A2358G. Our findings showed M. fortuitum isolates have become a serious problem with high-level antibiotic resistance. The existence of drug resistance to clarithromycin and linezolid indicates more attention to the study of drug resistance in M. fortuitum.
Topics: Clarithromycin; Linezolid; Mycobacterium fortuitum; Iran; Anti-Bacterial Agents; Nontuberculous Mycobacteria; Mutation; Microbial Sensitivity Tests; Drug Resistance, Bacterial
PubMed: 37224008
DOI: 10.1556/030.2023.02020 -
Microbial Drug Resistance (Larchmont,... Jul 2023There is a scarcity of data regarding the antimicrobial susceptibility testing profiles of nontuberculous mycobacterial (NTM) in Israel and other Middle Eastern...
There is a scarcity of data regarding the antimicrobial susceptibility testing profiles of nontuberculous mycobacterial (NTM) in Israel and other Middle Eastern countries. We aimed to describe the antimicrobial susceptibility profiles of NTM in Israel. A total of 410 clinical isolates of NTM, identified to the species level using matrix-assisted laser desorption ionization-time of flight mass spectrometry or gene sequencing, were included. Minimum inhibitory concentrations for slowly growing mycobacteria (SGM) and rapidly growing mycobacteria (RGM) for 12 and 11 drugs were determined using the Sensititre SLOMYCOI and RAPMYCOI broth microdilution plates, respectively. complex (MAC) was the most frequently isolated species ( = 148; 36%), followed by ( = 93; 23%), group ( = 62; 15%), ( = 27; 7%), and ( = 22; 5%) accounting together for 86% of isolates. The most active agents against SGM were amikacin (98%/85%/100%) and clarithromycin (97%/99%/100%), followed by moxifloxacin (25%/10%/100%) and linezolid (3%/6%/100%) for MAC, , and , respectively. For RGM, the most active agents were amikacin (98%/100%/88%) followed by linezolid (48%/80%/100%) and clarithromycin (39%/28%/94%) for group, , and , respectively. These findings can assist in guiding the treatment of NTM infections.
Topics: Humans; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Linezolid; Anti-Bacterial Agents; Amikacin; Clarithromycin; Israel; Microbial Sensitivity Tests
PubMed: 37219996
DOI: 10.1089/mdr.2023.0024 -
Journal of Infection and Chemotherapy :... Sep 2023The prevalence of nontuberculous mycobacteria (NTM) infections is increasing worldwide. Although NTM can affect extrapulmonary organs, studies on the clinical...
INTRODUCTION
The prevalence of nontuberculous mycobacteria (NTM) infections is increasing worldwide. Although NTM can affect extrapulmonary organs, studies on the clinical characteristics of extrapulmonary NTM are rare.
METHODS
We retrospectively analyzed patients who were newly diagnosed with NTM infections at Hiroshima University Hospital between 2001 and 2021 to investigate species distribution, infected sites, and risk factors of extrapulmonary NTM compared to pulmonary NTM.
RESULTS
Of the 261 NTM infections, 9.6% and 90.4% had extrapulmonary and pulmonary NTM, respectively. The mean ages of patients with extrapulmonary and pulmonary NTM were 53.4 and 69.3 years, 64.0% and 42.8% were male, 36.0% and 9.3% received corticosteroids, 20.0% and 0% had acquired immune deficiency syndrome (AIDS), and 56.0% and 16.1% had any immunosuppressive conditions, respectively. Younger age, corticosteroid use, and AIDS were associated with extrapulmonary NTM. In pulmonary NTM, Mycobacterium avium complex (MAC) accounted for 86.4% of NTM species, followed by M. abscessus complex (4.2%), whereas in extrapulmonary NTM, M. abscessus complex, MAC, M. chelonae, and M. fortuitum accounted for 36.0%, 28.0%, 12.0%, and 8.0%, respectively. Compared to pulmonary NTM, extrapulmonary NTM were significantly more likely to be rapid-growing mycobacteria (RGM) (56.0% vs. 5.5%). The most common sites of infection were the skin and soft tissues (44.0%), followed by the blood (20.0%), tenosynovium, and lymph nodes (12.0%).
CONCLUSION
Younger age and immunosuppressive conditions are associated with extrapulmonary NTM, with a higher prevalence of RGM in extrapulmonary NTM than in pulmonary NTM. These results provide a better understanding of extrapulmonary NTM.
Topics: Humans; Male; Middle Aged; Aged; Female; Retrospective Studies; Acquired Immunodeficiency Syndrome; Japan; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Mycobacterium avium Complex; Pneumonia
PubMed: 37209842
DOI: 10.1016/j.jiac.2023.05.013 -
South African Journal of Botany :... Jul 2023Tuberculosis (TB) is currently rated as the 13th leading cause of mortality and the second leading cause of death after COVID-19, and above AIDS. Existing challenges...
Tuberculosis (TB) is currently rated as the 13th leading cause of mortality and the second leading cause of death after COVID-19, and above AIDS. Existing challenges relating to the development of multidrug-resistant strains and dangerous side effects of currently used drugs add impetus to the search for additional TB treatments. Hence, interest has grown in the use of medicinal plants as a source of bioactive preparations with efficacy against TB-causing organisms, and also with the ability to ameliorate the negative effects of TB drugs. This study aimed to evaluate the antimycobacterial and hepatoprotective potentials of extracts and isolated flavonoid compounds from invasive Test organisms used were pathogenic and H37RV, and the fast-growing and . The selectivity index (SI) values of the test substances were determined through cytotoxicity assays to promote these extracts and compounds as leads for the development of effective and safe anti-tubercular drugs. The antimycobacterial activity was evaluated using a serial microdilution method, and the SI was calculated from the 50% lethal concentrations calculated from cytotoxicity tests. Hepatoprotective activity was determined using HepG2 liver cells treated with rifampicin as a toxin. The extracts and compounds had a range of antimycobacterial activity with minimum inhibitory concentration (MIC) values ranging from 0.031 to 2.5 mg/mL. Two flavonoid compounds, 5,7,4'-trimethoxy flavanone and 5‑hydroxy-3,7,4'-trimethoxyflavone showed promising antimycobacterial potential, and minimal toxicity was observed, as most SI values were higher than 1. The flavonoid compound 5,7,4'-trimethoxy flavanone had the highest SI (6.452), which was against H37RV. The HepG2 cells were reduced to 65% due to toxicity by rifampicin, however, the flavonoid compounds were able to improve cell viability to between 81 and 89% at different concentrations tested. Results obtained indicate that may serve as a lead for the development of safe and effective antimycobacterial and hepatoprotective drugs.
PubMed: 37206481
DOI: 10.1016/j.sajb.2023.05.002 -
Molecular epidemiology of nontuberculous mycobacteria isolated from tuberculosis-suspected patients.AMB Express May 2023It is a growing problem around the world to deal with nontuberculous mycobacteria infection (NTM), but its clinical significance is still largely unknown. This study...
It is a growing problem around the world to deal with nontuberculous mycobacteria infection (NTM), but its clinical significance is still largely unknown. This study aims to investigate the epidemiology of NTM infections from various clinical samples and determine their clinical significance. From December 2020 to December 2021, 6125 clinical samples were collected. In addition to phenotypic detection, genotypic detection through multilocus sequence typing (hsp65, rpoB, and 16S rDNA genes) and sequencing was also conducted. Records of patients were consulted for clinical information, such as symptoms and radiological findings. Of the 6,125 patients, 351 (5.7%) were positive for acid-fast bacteria (AFB). Out of 351 AFB, 289 (82.3%) and 62 (17.7%) subjects were identified as M. tuberculosis complex (MTC) and NTM strains, respectively. Isolates of Mycobacterium simiae and M. fortuitum were the most frequent, followed by isolates of M. kansasii and M. marinum. We also isolated M. chelonae, M. canariasense, and M. jacuzzii, which are rarely reported. Symptoms (P = 0.048), radiographic findings (P = 0.013), and gender (P = 0.039) were associated with NTM isolates. M. Fortuitum, M. simiae, and M. kansasii presented with bronchiectasis, infiltration, and cavitary lesions most frequently, while cough was the most common symptom. In conclusion, Mycobacterium simiae and M. fortuitum were presented in seventeen and twelve NTM isolates from the collected samples. There is evidence that NTM infections in endemic settings may contribute to the dissemination of various diseases and the control of tuberculosis. In spite of this, further research is needed to evaluate the clinical significance of NTM isolates.
PubMed: 37202495
DOI: 10.1186/s13568-023-01557-4 -
Orthopaedic Surgery Jun 2023Periprosthetic joint infection (PJI) caused by non-tubercular mycobacteria (NTM) is uncommon but catastrophic. However, conclusive clinical data on PJI caused by NTM are... (Review)
Review
OBJECTIVE
Periprosthetic joint infection (PJI) caused by non-tubercular mycobacteria (NTM) is uncommon but catastrophic. However, conclusive clinical data on PJI caused by NTM are lacking. In this case series and systematic review, the clinical manifestations, diagnosis, and management of NTM PJI are summarized and analyzed.
METHODS
From 2012 to 2020, we retrospectively analyzed consecutive PJI cases caused by NTM in our institution. A literature review was also conducted from January 2000 to December 2021, utilizing the PubMed, MEDLINE, Cochrane Library, and EMBASE databases to identify all reported NTM-induced PJI cases. The clinical characteristics, demographics, pathogen identification, treatment protocols, and prognosis of NTM PJI were summarized and analyzed.
RESULTS
In this retrospective analysis, seven patients infected with NTM following total joint arthroplasty at our institution were included, including six cases of PJI caused by NTM and one case of septic arthritis (SA) caused by NTM. There were six men and one woman, and their average age was 62.3 years. The average interval between TJA and PJI onset was 4 months. The preoperative serological markers, including the mean ESR (51 mm/h), CRP (4.0 mg/dL), fibrinogen (5.7 g/L), and D-dimer (1.1 g/L), were increased. Six patients underwent staged revision surgery, and one patient with SA received antibiotic-loaded bone cement beads to treat the infection. After an average of 33 months of observation following surgical intervention, none of the patients showed any symptoms of infection recurrence. From 2000 to 2021, 68 patients with NTM PJI were found in 39 studies in the published literature. Reinfections occurred within 1 year after arthroplasty in more than half (53.2%) of the patients. M. fortuitum and M. abscesses were the most prevalent rapidly growing mycobacteria (RGM) in all PJI patients, whereas Mycobacterium avium intracellulare (MAC) was the most prevalent slowly growing mycobacterium (SGM). The corresponding antibiotics were amikacin and ethambutol. The rate of culture-negative without specific clinical symptoms was as high as 36.4% (12/33), while 45% (18/40) utilized additional diagnostic techniques such as NGS. A final clinical follow-up record was available for 59 patients (86.7%; mean follow-up period, 29 months), and 10.1% of patients failed to respond to treatment.
CONCLUSION
Orthopaedic surgeons should consider NTM in patients with negative routine cultures who are at risk for Mycobacterium infection. Treatment options rely on the accurate result of microbiologic identification and drug sensitivity testing, and to achieve this, it may be necessary to send multiple culture specimens, extend the culture time, and change the culture medium. Every effort should be made to identify NTM and its various subtypes through modern diagnostic tools if necessary.
Topics: Male; Female; Humans; Middle Aged; Arthroplasty, Replacement, Knee; Retrospective Studies; Arthroplasty, Replacement, Hip; Mycobacterium; Arthritis, Infectious; Prosthesis-Related Infections
PubMed: 37154097
DOI: 10.1111/os.13661 -
Pathogens (Basel, Switzerland) Apr 2023Over the last 30 years, the number of invasive turtle species living in the wild has significantly increased in Poland. This proliferation carries many threats, which...
Over the last 30 years, the number of invasive turtle species living in the wild has significantly increased in Poland. This proliferation carries many threats, which mainly include the displacement of native species of animals from their natural habitats. Turtles can also be reservoirs for pathogens, including bacteria from the genus. In order to confirm or rule out the presence of acid-fast mycobacteria in the population of invasive turtle species, samples from carapace, plastron, internal organs and mouth cavity swabs from 125 animals were tested. Twenty-eight mycobacterial strains were isolated in culture, which were classified as atypical following multiplex-PCR reactions. The GenoType Mycobacterium Common Mycobacteria (CM) test, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, PCR-restriction fragment length polymorphism (PRA)- and DNA sequencing were used to identify the species of isolates. Of the 28 strains, 11 were identified as , 10 as , 3 as ssp. , 2 as and 1 each of and . The results of the research will also strengthen the understanding that these animals can be vectors for pathogens when living in the wild.
PubMed: 37111456
DOI: 10.3390/pathogens12040570