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Infection and Drug Resistance 2023China has seen a drastic increase in the incidence of non-tuberculous mycobacteria (NTM) infection, which is a notable public health issue. Due to a lack of reliable...
BACKGROUND
China has seen a drastic increase in the incidence of non-tuberculous mycobacteria (NTM) infection, which is a notable public health issue. Due to a lack of reliable epidemiological surveillance information, there is a need to gather accurate epidemiological and surveillance data, which can help clinicians effectively treat NTM patients. Moreover, drug susceptibility testing for NTM is not frequently performed in China. This retrospective study, therefore, determined the prevalence and resistance characteristics of NTM to provide a reference to control the NTM epidemic.
METHODS
Sputum, alveolar lavage fluid, and other respiratory specimens were collected from 3025 patients with suspected pulmonary tuberculosis attending The Second Affiliated Hospital of Hainan Medical University from January 2014 to December 2021. Strain identification and species distribution of NTM were performed by DNA chip technology and gene sequencing, and the drug resistance of NTM isolates was evaluated by calculating the minimum inhibitory concentration through antimicrobial susceptibility testing for NTM.
RESULTS
From 2014 to 2021, 373 strains of NTM were isolated and identified from respiratory specimens of 3025 suspected tuberculosis patients. Except in 2014, NTM-infected patients accounted for more than 10% of suspected tuberculosis patients in other years. The median age of patients with NTM infection was 62.0 years (53.0, 71.0), and the male-to-female ratio among these patients was 0.79:1. Among culture-positive strains, 12.3% (373/3040; 95% CI 11.1-13.4%) were identified as NTM comprising forty species of NTM. The forty species of NTM included 23 slow-growing mycobacteria (SGM) and 17 rapidly-growing mycobacteria (RGM). Among the NTM isolates, 58.7% (219/373; 95% CI 53.7-63.7%) were SGM and 41.3% (154/373; 95% CI 36.3-46.3%) were RGM. complex(MAC)(41.3%; 95% CI 36.3-46.3%) and complex (MABC)(33.2%; 95% CI 28.4-38.0%) were the most frequently detected species, followed by Complex (11.8%; 95% CI 8.5-15.1%), group (5.1%; 95% CI 2.9-7.3%), and others. Drug sensitivity test results showed that most of the NTM isolates were susceptible to amikacin and clarithromycin with a drug resistance rate of less than 10%. However, clarithromycin could induce drug resistance, followed by linezolid and moxifloxacin, and their drug resistance rate was less than 50%.
CONCLUSION
During 2014-2021, the number of NTM isolates detected in the respiratory specimens of the study patients in The Second Affiliated Hospital of Hainan Medical University increased year by year. is the most common pathogenic NTM species, and there is a high incidence of NTM infection on Hainan Island. Our findings might be of great importance for diagnosing and treating this patient population in Hainan.
PubMed: 36721630
DOI: 10.2147/IDR.S396050 -
Frontiers in Cellular and Infection... 2022Infections caused by non-tuberculosis mycobacteria are significantly worsening across the globe. M. fortuitum complex is a rapidly growing pathogenic species that is of...
INTRODUCTION
Infections caused by non-tuberculosis mycobacteria are significantly worsening across the globe. M. fortuitum complex is a rapidly growing pathogenic species that is of clinical relevance to both humans and animals. This pathogen has the potential to create adverse effects on human healthcare.
METHODS
The MF GZ001 clinical strain was collected from the sputum of a 45-year-old male patient with a pulmonary infection. The morphological studies, comparative genomic analysis, and drug resistance profiles along with variants detection were performed in this study. In addition, comparative analysis of virulence genes led us to understand the pathogenicity of this organism.
RESULTS
Bacterial growth kinetics and morphology confirmed that MF GZ001 is a rapidly growing species with a rough morphotype. The MF GZ001 contains 6413573 bp genome size with 66.18 % high G+C content. MF GZ001 possesses a larger genome than other related mycobacteria and included 6156 protein-coding genes. Molecular phylogenetic tree, collinearity, and comparative genomic analysis suggested that MF GZ001 is a novel member of the M. fortuitum complex. We carried out the drug resistance profile analysis and found single nucleotide polymorphism (SNP) mutations in key drug resistance genes such as rpoB, katG, AAC(2')-Ib, gyrA, gyrB, embB, pncA, blaF, thyA, embC, embR, and iniA. In addition, the MF GZ001strain contains mutations in iniA, iniC, pncA, and ribD which conferred resistance to isoniazid, ethambutol, pyrazinamide, and para-aminosalicylic acid respectively, which are not frequently observed in rapidly growing mycobacteria. A wide variety of predicted putative potential virulence genes were found in MF GZ001, most of which are shared with well-recognized mycobacterial species with high pathogenic profiles such as M. tuberculosis and M. abscessus.
DISCUSSION
Our identified novel features of a pathogenic member of the M. fortuitum complex will provide the foundation for further investigation of mycobacterial pathogenicity and effective treatment.
Topics: Animals; Humans; Middle Aged; Microbial Sensitivity Tests; Phylogeny; Drug Resistance, Bacterial; Mycobacteriaceae
PubMed: 36683685
DOI: 10.3389/fcimb.2022.1056007 -
Italian Journal of Dermatology and... Dec 2022
Topics: Humans; Mycobacterium fortuitum; Hair Removal; Skin Diseases, Bacterial
PubMed: 36651205
DOI: 10.23736/S2784-8671.22.07206-1 -
Diagnostic Microbiology and Infectious... Mar 2023Antimicrobial susceptibility testing for rapidly growing mycobacteria (RGM) is uncommon or only performed in large reference laboratories. Here we developed a cumulative...
Antimicrobial susceptibility testing for rapidly growing mycobacteria (RGM) is uncommon or only performed in large reference laboratories. Here we developed a cumulative antibiogram for 14 RGM using the largest sample size to date (N = 3860). All RGM showed 82% to 100% susceptibility to amikacin. Mycobacterium abscessus showed low percentages of susceptibility to most antimicrobials; of antimicrobials without interpretations, the minimum inhibitory concentration-90 for clofazimine was low (≤0.5mg/L). All three subspecies had ≤2.6% rrl resistance mutations, however intact erm(41) was detected in 70% to100% of M. abscessus abscessus and bolletii. Mycobacterium chelonae had a similar susceptibility pattern to M. abscessus subsp. massiliense and Mycobacterium immunogenum except that it was susceptible to tobramycin (87%). Mycobacterium fortuitum complex and similar organisms showed higher frequency of susceptibility to fluoroquinolones, beta-lactams, linezolid, and trimethoprim/sulfamethoxazole. Although relatively small published RGM antibiograms showed substantial variance, a comprehensive antibiogram can help influence treatment and monitoring patterns of resistance.
Topics: Humans; United States; Nontuberculous Mycobacteria; Anti-Bacterial Agents; Mycobacterium; Mycobacterium Infections, Nontuberculous; Amikacin; Microbial Sensitivity Tests
PubMed: 36610383
DOI: 10.1016/j.diagmicrobio.2022.115882 -
PLoS Neglected Tropical Diseases Dec 2022Nontuberculous mycobacterial (NTM) lung infections are a major public health concern. Diagnosis of NTM-pulmonary disease (NTM-PD) is difficult because its clinical,...
BACKGROUND
Nontuberculous mycobacterial (NTM) lung infections are a major public health concern. Diagnosis of NTM-pulmonary disease (NTM-PD) is difficult because its clinical, microbiological, and radiological features resemble to those of pulmonary tuberculosis (TB), leading to misdiagnosis. Identification at the species level is essential for diagnosis and determination of therapy, which is currently not performed routinely in Indonesian laboratories.
METHODOLOGY AND PRINCIPAL FINDINGS
From January 2020 to May 2021, 94 NTM isolates were collected from three TB referral centers in Java Province. Species were identified using matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS). Tests were performed to determine antibiotic susceptibility, biofilm formation ability, sliding motility characteristics, and the ability to adhere to and invade pneumocytes. After identifying the species of all the isolates, we found nine groups of NTMs: M. fortuitum group 51% (48/94), M. abscessus 38.3% (36/94), M. intracellulare 3.1% (3/94), M. neoaurum 2.1% (2/94), M. chelonae 1.1% (1/94), M. gordonae 1.1% (1/94), M. szulgai 1.1% (1/94), M. mucogenicum 1.1% (1/94), and M. arupense 1.1% (1/94). Amikacin was the most effective antibiotic against M. fortuitum group and M. abscessus. The M. fortuitum group was significantly better at forming biofilms than M. abscessus, but both had the same sliding motility capability. The ability of the M. fortuitum group to adhere to and invade pneumocytes was better than that of M. abscessus, with the number isolates of the M. fortuitum group capable of superior adhesion and invasion to that of M. abscessus.
CONCLUSIONS/SIGNIFICANCE
This study shows that M. fortuitum group and M. abscessus were the most common NTM found in Java, Indonesia. The M. fortuitum group and M. abscessus were the most susceptible to amikacin; therefore, this was the empirical treatment of choice. The ability to form biofilms is directly proportional to the ability to adhere to and invade pneumocytes but not to the susceptibility profile or sliding motility characteristics.
Topics: Humans; Nontuberculous Mycobacteria; Indonesia; Amikacin; Mycobacterium Infections, Nontuberculous; Anti-Bacterial Agents
PubMed: 36574422
DOI: 10.1371/journal.pntd.0011007 -
Microbial Biotechnology Apr 2023Identification of Nocardia and Mycobacterium species by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) is still a...
Identification of Nocardia and Mycobacterium species by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) is still a challenging task that requires both suitable protein extraction procedures and extensive databases. This study aimed to evaluate the VITEK MS Plus system coupled with updated RUO (v4.17) and IVD (v3.2) databases for the identification of Nocardia spp. and Mycobacterium spp. clinical isolates. Sample preparation was carried out using the VITEK MS Mycobacterium/Nocardia kit for protein extraction. From 90 Nocardia spp. isolates analysed, 86 (95.6%) were correctly identified at species or complex level using IVD and 78 (86.7%) using RUO. Only two strains were misidentified as other species pertaining to the same complex. Among the 106 non-tuberculous Mycobacterium clinical isolates tested from a liquid culture medium, VITEK MS identified correctly at species or complex level 96 (90.6%) isolates in the IVD mode and 89 (84.0%) isolates in the RUO mode. No misidentifications were detected. Although the IVD mode was unable to differentiate members of the M. fortuitum complex, the RUO mode correctly discriminated M. peregrinum and M. septicum. The robustness and accuracy showed by this system allow its implementation for routine identification of these microorganisms in clinical laboratories.
Topics: Nocardia; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Mycobacterium; Culture Media; Nontuberculous Mycobacteria
PubMed: 36541026
DOI: 10.1111/1751-7915.14146 -
Animals : An Open Access Journal From... Nov 2022Mycobacteriosis is an important disease that affects captive and wild aquatic fish. Syngnathids are susceptible to infection by non-tuberculous mycobacteria. The aim of...
Mycobacteriosis is an important disease that affects captive and wild aquatic fish. Syngnathids are susceptible to infection by non-tuberculous mycobacteria. The aim of this study was to describe clinical signs, and macroscopic and histological lesions in 25 syngnathids and the molecular characterization of the causative mycobacteria. Clinical presentation ranged from sudden death to non-specific signs, including anorexia, poor body condition, weight loss and marked dyspnea with increased respiratory effort and rate. Gross lesions were mostly ulcers on the tail and small white nodules in the liver, coelomic cavity and inside the eye. The most affected organs were gills, liver, intestine and coelomic mesentery. Microscopic lesions consisted of areas of multifocal to diffuse granulomatous inflammation and bacterial emboli with numerous intralesional acid-fast bacilli. Epithelioid cells, multinucleated giant cells, lymphocytes and fibrous connective tissue, which are commonly observed in granulomatous inflammation, were not observed here. In the real-time PCR, , and common primers, spp. were detected in 4, 7 and 14 individuals, respectively. In addition, this is the first description of mycobacteriosis found in .
PubMed: 36496780
DOI: 10.3390/ani12233259 -
Microbiology Spectrum Feb 2023Infections caused by rapidly growing mycobacteria (RGM) have increased globally. Chemotherapy against these infections is challenging due to the minimal antimicrobial...
Infections caused by rapidly growing mycobacteria (RGM) have increased globally. Chemotherapy against these infections is challenging due to the minimal antimicrobial choices available. The main aim of this study was to evaluate the susceptibilities of four tetracyclines against different RGM species. The MICs of eravacycline (ERC), omadacycline (OMC), sarecycline (SAC), and tigecycline (TGC) against the reference strains of 27 RGM species and 121 RGM clinical isolates were determined by microtiter plate assay. The minimum bactericidal concentrations (MBCs) and cytotoxicities of these antibiotics were also tested. Except for SAC, the other three tetracyclines had MICs of ≤0.5 μg/mL against all 27 RGM reference strains. ERC generally presented the lowest MICs, with MICs against the clinical isolates of Mycobacterium abscessus subsp. , Mycobacterium abscessus subsp, and Mycobacterium fortuitum of 0.25 μg/mL, 0.25 μg/mL, and 0.06 μg/mL, respectively. TGC and OMC also showed equivalent inhibitory activities against the isolates, while the TGC MICs for M. abscessus subsp. , M. abscessus subsp, and M. fortuitum were lower than or equal to the OMC MICs (1, 1, and 0.25 μg/mL versus 1, 2, and 2 μg/mL). In addition, the MICs of three of the antibiotics for each species were always 2-fold lower than the corresponding MICs. MBC and cytotoxicity assays indicated that all four tetracycline antibiotics tested were bacteriostatic agents with low toxicity to the THP-1 cell line. Tetracycline antibiotics are efficacious in RGM infection treatment, with omadacycline showing the best promise for clinical application due to its potent antimicrobial activity, safety, and convenient administration route. The global rise in antibiotic-resistant nontuberculous mycobacteria has prompted the urgent need for new antimicrobials, especially oral antibiotics. Currently, adverse effects have limited the use of tetracycline-class antibiotics, particularly tigecycline (TGC), in the treatment of rapidly growing mycobacteria (RGM). However, several new tetracycline-class antibiotics might overcome the limitations of TGC. We assessed the antibiotic susceptibilities of four tetracyclines (eravacycline, omadacycline, sarecycline, and tigecycline) against reference RGM strains and clinical isolates of different RGM species. We showed that three of these antibiotics (tigecycline, eravacycline, and omadacycline) might be efficacious in M. abscessus subsp. , M. abscessus subsp. , and M. fortuitum treatment. Furthermore, omadacycline was more promising for clinical application for M. abscessus infections as an oral drug, whereas sarecycline, which had the best safety parameters, should be considered a potential antibiotic for M. abscessus infections caused by susceptible strains. Our work underscores the possible clinical applications of tetracycline-class antibiotics in the treatment of RGM infections.
Topics: Humans; Tigecycline; Tetracycline; Tetracyclines; Anti-Bacterial Agents; Mycobacterium; Mycobacterium abscessus; Microbial Sensitivity Tests; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous
PubMed: 36475850
DOI: 10.1128/spectrum.03238-22 -
Antimicrobial Agents and Chemotherapy Dec 2022Mycobacterial pathogens, including nontuberculous mycobacteria (NTM) and Mycobacterium tuberculosis, are pathogens of significant worldwide interest owing to their...
Mycobacterial pathogens, including nontuberculous mycobacteria (NTM) and Mycobacterium tuberculosis, are pathogens of significant worldwide interest owing to their inherent drug resistance to a wide variety of FDA-approved drugs as well as causing a broad range of serious infections. Identifying new antibiotics active against mycobacterial pathogens is an urgent unmet need, especially those antibiotics that can bypass existing resistance mechanisms. In this study, we demonstrate that gepotidacin, a first-in-class triazaacenapthylene topoisomerase inhibitor, demonstrates potent activity against M. tuberculosis and M. fortuitum, as well as against other clinically relevant NTM species, including fluoroquinolone-resistant M. abscessus. Furthermore, gepotidacin exhibits concentration-dependent bactericidal activity against various mycobacterial pathogens, synergizes with several drugs utilized for their treatment, and reduces bacterial load in macrophages in intracellular killing assays comparably to amikacin. Additionally, M. fortuitum ATCC 6841 was unable to generate resistance to gepotidacin . When tested in a murine neutropenic M. fortuitum infection model, gepotidacin caused a significant reduction in bacterial load in various organs at a 10-fold lower concentration than amikacin. Taken together, these findings show that gepotidacin possesses a potentially new mechanism of action that enables it to escape existing resistance mechanisms. Thus, it can be projected as a potent novel lead for the treatment of mycobacterial infections, particularly for NTM, where present therapeutic interventions are extremely limited.
Topics: Animals; Mice; Amikacin; Mycobacterium Infections, Nontuberculous; Anti-Bacterial Agents; Nontuberculous Mycobacteria; Mycobacterium tuberculosis; Neutropenia; Microbial Sensitivity Tests
PubMed: 36445129
DOI: 10.1128/aac.00564-22