Treatment Of Nontuberculous Mycobacteria Infection Research Articles

Prescription habits and drugs accessibility for the treatment of non-tuberculous mycobacteria infections in Italy: a multicentric survey from the IRENE study group

Prescription habits and drugs accessibility for the treatment of non-tuberculous mycobacteria infections in Italy: a multicentric survey from the IRENE study group

Analysis of Clinical Isolation Characteristics of Nontuberculous Mycobacteria and Drug Sensitivity of Rapidly Growing Mycobacteria in the General Hospital of Guangzhou, China.

The clinical distribution characteristics of nontuberculous mycobacteria (NTM) in general hospital were explored to guide the clinical diagnosis and treatment of NTM infection. Samples with positive mycobacterium culture in the First Affiliated Hospital of Guangzhou Medical University were collected and identified through PCR. Phenotypic drug sensitivity experiments were conducted on 44 Mycobacteroides abscessus isolated from clinical departments with broth microdilution method, and rrl, rrs and erm (41) genes associated with drug resistance were detected. From September 2020 to July 2023, 314 mycobacterium-positive isolates were separated from patients in the First Affiliated Hospital of Guangzhou Medical University, with 147 (46.8%) NTM isolates were included in our study. The samples were respiratory tract specimens mainly, with 64% bronchoalveolar lavage fluid. Of 144 cases identified, samples were from 133 patients (60 males and 73 females; gender ratio of 0.82:1). NTM was mainly isolated from the people aged 40 and above, especially females (χ2 = 10.688, P = 0.014). M. abscessus (61, 42.36%), M. intracellulare (35, 24.31%) were the two most NTMs in this hospital. Clinical strains of M. abscessus exhibited high resistance to antibiotics, except for cefoxitin (31.8%), linezolid (25.0%), amikacin (0%), and clarithromycin (18.2%). Among 8 strains of M. abscessus with clarithromycin acquired resistance, just 4 strains (50.0%) showed mutations (A2270G, A2271G) in rrl gene, but a new mutation (C2750T) was detected in 1 strain. Among 14 strains of M. abscessus with clarithromycin-induced resistance, 13 (93.0%) strains had T28 erm (41) gene and 1 (7.0%) strain had C28 erm (41) gene. M. avium-intracellulare complex was gradually becoming predominant strain in Guangzhou area. The resistant situation of M. abscessus in general hospital had shown severe. Potential mutation in rrl gene associated with clarithromycin acquired resistance of M. abscessus were found, but drug-resistant mechanism remained unclear.

Sudapyridine (WX-081) antibacterial activity against Mycobacterium avium, Mycobacterium abscessus, and Mycobacterium chelonae in vitro and in vivo.

Due to the rapidly increased cases globally, non-tuberculous mycobacteria (NTM) disease has become a significant public health problem. NTM accounted for 11.57% of all mycobacterial isolates in China, with a high detection rate of Mycobacterium abscessus, Mycobacterium avium, and Mycobacterium chelonae during 2000-2019. Treatment of NTM infection is often challenging, as natural resistance to most antibiotics is quite common among different NTM species. Hence, identifying highly active anti-NTM agents is a priority for potent regimen establishment. The pursuit of new drugs to treat multidrug-resistant tuberculosis may also identify some agents with strong activity against NTM. Sudapyridine (WX-081) is a structural analog of bedaquiline (BDQ), which was developed to retain the anti-tuberculosis efficacy but eliminates the severe side effects of BDQ. This study initially evaluated the antimicrobial activity of this novel compound against M. avium, M. abscessus, and M. chelonae in vitro, in macrophages and mice, respectively.

Plasmid-mediated drug resistance in mycobacteria: the tip of the iceberg?

Macrolides, such as clarithromycin, are crucial in the treatment of nontuberculous mycobacteria (NTM). NTM are notoriously innately drug resistant, which has made the dependence on macrolides for their treatment even more important. Not surprisingly, resistance to macrolides has been documented in some NTM, including Mycobacterium avium and Mycobacterium abscessus, which are the two NTM species most often identified in clinical isolates. Resistance is mediated by point mutations in the 23S ribosomal RNA or by methylation of the rRNA by a methylase (encoded by an erm gene). Chromosomally encoded erm genes have been identified in many of the macrolide-resistant isolates, but not in Mycobacterium chelonae. Now, Brown-Elliott et al. (J Clin Microbiol 61:e00428-23, 2023, https://doi.org/10.1128/JCM.00428-23) describe the identification of a new erm variant, erm(55), which was found either on the chromosome or on a plasmid in highly macrolide-resistant clinical isolates of M. chelonae. The chromosomal erm(55) gene appears to be associated with mobile elements; one gene is within a putative transposon and the second is in a large (37 kb) insertion/deletion. The plasmid carrying erm(55) also encodes type IV and type VII secretion systems, which are often linked on large mycobacterial plasmids and are hypothesized to mediate plasmid transfer. While the conjugative transfer of the erm(55)-containing plasmid between NTM has yet to be demonstrated, the inferences are clear, as evidenced by the dissemination of plasmid-mediated drug resistance in other medically important bacteria. Here, we discuss the findings of Brown-Elliott et al., and the potential ramifications on treatment of NTM infections.

In Vitro Activity of the Sudapyridine (WX-081) against Non-Tuberculous Mycobacteria Isolated in Beijing, China.

Sudapyridine (WX-081) is a structural analog of bedaquiline (BDQ), which shows an anti-tuberculosis activity but, unlike BDQ, did not prolong QT interval (QT) in animal model studies. This study evaluated the antimicrobial activity of this novel drug against non-tuberculous mycobacteria (NTM). Fifty reference strains of different mycobacterial species, and 132 NTM clinical isolates from four commonly isolated NTM species were recruited. The microplate alamarBlue assay was performed to determine the MIC of WX-081 and BDQ. Cytotoxicity assay was performed for both drugs using the THP-1 cells, and the minimum bactericidal concentrations (MBCs) of both drugs against the reference strains of five selected NTM species were also determined. All the tested reference strains had MICs lower than 0.5 μg/mL, with the majority having MICs far below 0.1 μg/mL for WX-081. The epidemiological cut-offs of WX-081 ranged from 0.0156 μg/mL to 0.25 μg/mL against commonly isolated NTM, and this value was comparable with that of BDQ. The MBC/MIC ratios suggest a bacteriostatic activity for both drugs against the five selected NTM species. Cytotoxicity assays indicated that THP-1 cells had nearly 100% viability when exposed to WX-081 for 24 h below 4 μg/mL, 200- to 300-fold the MICs of Mycobacterium intracellulare, Mycobacterium avium, and Mycobacterium kansasii. WX-081 has a strong antimicrobial activity against different NTM species with low cytotoxicity and therefore has the potential to be used for treating NTM infections. IMPORTANCE Due to the rapidly increased cases globally, non-tuberculous mycobacteria (NTM) disease has become a significant public health problem. Over 200 species or subspecies of NTM have been reported, whereas pulmonary diseases in humans are caused mainly by M. avium complex (MAC), M. kansasii, and M. abscessus. Treatment of NTM infection is often challenging as natural resistance to most antibiotics is quite common among different NTM species. Hence, identifying highly active anti-NTM agents is a priority for potent regimen establishment. The pursuit of new drugs to treat multidrug-resistant-tuberculosis (MDR-TB) may also identify some agents with strong activity against NTM. Sudapyridine (WX-081) is a structural analog of bedaquiline (BDQ), which was developed to retain the antituberculosis efficacy but eliminate the severe side effect of BDQ. This study initially evaluated the antimicrobial activity of this novel drug against non-tuberculous mycobacteria (NTM).

Treating nontuberculous mycobacteria in children with cystic fibrosis: a multicentre retrospective study

BackgroundRespiratory infection with nontuberculous mycobacteria (NTM) in children with cystic fibrosis (CF) has increased in prevalence. The condition is difficult to diagnose and treatments are complex with limited evidence to...

494: Antibiotic alternative for the treatment of nontuberculous mycobacteria infections in cystic fibrosis

494: Antibiotic alternative for the treatment of nontuberculous mycobacteria infections in cystic fibrosis

Tedizolid vs Linezolid for the Treatment of Nontuberculous Mycobacteria Infections in Solid Organ Transplant Recipients

BackgroundTreatment options for nontuberculous mycobacteria (NTM) infections are limited by the pathogen’s intrinsic resistance profile and toxicities. Tedizolid and linezolid display in vitro activity against NTM species. However, safety data and treatment outcomes are limited in the solid organ transplant (SOT) population.MethodsThis was a single-center retrospective cohort study of adult SOT recipients receiving linezolid or tedizolid for an NTM infection from January 1, 2010, to August 31, 2019. The primary outcome compared the hematologic safety profiles of tedizolid vs linezolid. We also described nonhematological adverse drug events (ADEs) and therapy discontinuation rates. In an exploratory analysis, we assessed symptomatic microbiologic and clinical outcomes in those receiving tedizolid or linezolid for at least 4 weeks.ResultsTwenty-four patients were included (15 tedizolid, 9 linezolid). No differences were identified comparing the effects of tedizolid vs linezolid on platelet counts, absolute neutrophil counts (ANCs), and hemoglobin over 7 weeks using mixed-effects analysis of variance models. ANC was significantly decreased in both groups after 7 weeks of therapy (P = .04). Approximately 20% of patients in each arm discontinued therapy due to an ADE. Seven of 12 (58%) and 2 of 3 (67%) patients were cured or clinically cured with tedizolid- and linezolid-containing regimens, respectively.ConclusionsThis study suggests no significant safety benefit of tedizolid over linezolid for the treatment of NTM infections in SOT recipients. Tedizolid or linezolid-containing regimens demonstrated a potential benefit in symptomatic and microbiologic improvement. Larger cohorts are needed to further delineate the comparative role of linezolid and tedizolid for the treatment of NTM infections in SOT recipients.

Identification of Nontuberculous Mycobacteria in Patients with Pulmonary Diseases in Gyeongnam, Korea, Using Multiplex PCR and Multigene Sequence-Based Analysis.

Background Nontuberculous mycobacteria (NTM) are widely present in environments, such as soil and water, and have recently been recognized as important pathogenic bacteria. The incidence of NTM-related infections is steadily increasing. As the diagnosis and treatment of NTM infection should be distinguished from tuberculosis, and the treatment should be specific to the species of NTM acquired, accurate species identification is required. Methods In this study, two-step multiplex PCR (mPCR) and multigene sequence-based analysis were used to accurately identify NTM species in 320 clinical isolates from Gyeongsang National University Hospital (GNUH). In particular, major mycobacterial strains with a high isolation frequency as well as coinfections with multiple species were diagnosed through two-step mPCR. Multigene sequencing was performed to accurately identify other NTM species not detected by mPCR. Variable regions of the genes 16S rRNA, rpoB, hsp65, and 16S-23S rRNA internal transcribed spacer were included in the analysis. Results Two-step mPCR identified 234 (73.1%) cases of M. intracellulare, 26 (8.1%) cases of M. avium subsp. avium, and 13 (4.1%) cases of M. avium subsp. hominissuis infection. Additionally, 9 (2.8%) M. fortuitum, 9 (2.8%) M. massiliense, 2 (0.6%) M. abscessus, and 4 (1.2%) M. kansasii isolates were identified. Coinfection was identified in 7 (2.2%) samples. The sixteen samples not classified by two-step mPCR included 6 (1.9%) cases of M. chimaera, 4 (1.3%) M. gordonae, 1 (0.3%) M. colombiense, 1 (0.3%) M. mageritense, and 1 (0.3%) M. persicum identified by sequence analysis. Conclusions The results of this study suggest a strategy for rapid detection and accurate identification of species using two-step mPCR and multigene sequence-based analysis. To the best of our knowledge, this study is the first to report the identification of NTM species isolated from patients in Gyeongnam/Korea.

Successful desensitization to clarithromycin and moxifloxacin for the treatment of nontuberculous mycobacteria infection

Successful desensitization to clarithromycin and moxifloxacin for the treatment of nontuberculous mycobacteria infection

Non-Tuberculous Mycobacteria: Seven-Year Experience of a Tertiary Hospital.

Non-tuberculous mycobacteria are ubiquitous organisms. Precise determination of infection numbers is difficult, sincereporting them to public health departments is frequently not mandatory; furthermore, isolating a non-tuberculous mycobacteria doesnot necessarily translate into disease. The aims of this study were to ascertain non-tuberculous mycobacteria data of a tertiary hospital,determine the incidence and approach to colonization versus disease, and the incidence of predisposing comorbidities. Retrospective study in a tertiary hospital, involving patients with positive cultural exam for non-tuberculousmycobacteria in any biological sample, from 2010 to 2017. A total of 125 non-tuberculous mycobacteria isolates was identified, corresponding to 96 patients. Of these, 57.4% were male(n = 54); median age was 65 years (interquartile range = [50 - 82]). From these, 60.7% (n = 57) had some degree of immunosuppression,most frequently due to malignant tumour (49.0%) or HIV infection (39.2%). It was found that 29 patients (31.0%) had structuralrespiratory tract changes. Colonization was defined in 65.6% of patients (n = 63). While 71.0% of non-tuberculous mycobacteria infectionswere pulmonary, the remaining 29.0% presented as disseminated. According to available clinical records, 60.6% (n = 20) of thepresumably infected patients fulfilled American Thoracic Society diagnostic criteria for non-tuberculous mycobacteria disease. Several cases of non-tuberculous mycobacteria infection in this study presented as life-threatening, multi-systemic disease,highlighting the importance of accurate diagnosis and timely treatment. Other cases of presumed infection might instead havecorresponded to colonization, possibly resulting in futile therapy. While there are diagnostic criteria for treatment of non-tuberculous mycobacteria infections, no such guidelines existto assess colonization. One of the most challenging aspects remains the correct differentiation between colonization and early-stageinfection.

Differential Identification of Mycobacterial Species Using High-Resolution Melting Analysis.

Infections caused by non-tuberculous mycobacteria (NTM) is increasing wordwide. Due to the difference in treatment of NTM infections and tuberculosis, rapid species identification of mycobacterial clinical isolates is necessary for the effective management of mycobacterial diseases treatment and their control strategy. In this study, a cost-effective technique, real-time PCR coupled with high-resolution melting (HRM) analysis, was developed for the differentiation of Mycobacterial species using a novel rpoBC sequence. A total of 107 mycobacterial isolates (nine references and 98 clinical isolates) were subjected to differentiation using rpoBC locus sequence in a real-time PCR-HRM assay scheme. From 98 Mycobacterium clinical isolates, 88 species (89.7%), were identified at the species level by rpoBC locus sequence analysis as a gold standard method. M. simiae was the most frequently encountered species (41 isolates), followed by M. fortuitum (20 isolates), M. tuberculosis (15 isolates), M. kansassi (10 isolates), M. abscessus group (5 isolates), M. avium (5 isolates), and M. chelonae and M. intracellulare one isolate each. The HRM analysis generated six unique specific groups representing M. tuberculosis complex, M. kansasii, M. simiae, M. fortuitum, M. abscessus–M. chelonae group, and M. avium complex. In conclusion, this study showed that the rpoBC-based real-time PCR followed by HRM analysis could differentiate the majority of mycobacterial species that are commonly encountered in clinical specimens.

Analysis of distribution characteristics of clinical isolates of nontuberculous mycobacteria in a general hospital

Objective To investigate the current prevalence of nontuberculous mycobacteria (NTM) in Shanghai, and to study the distribution characteristics of NTM clinical isolates, which may help to improve the diagnostic level of NTM and provide guidance for effective prevention and treatment of NTM infection. Methods Culture-positive isolates of clinical mycobacteria were collected from 2008 to 2013 in Huashan Hospital affiliated to Fudan University. All isolates were heat inactivated, and the genomic DNA was extracted and the species were identified by comprehensive comparative analysis of 16S rDNA, hsp65 and rpoB target genes sequencing. Results From January 2008 to December 2013, the overall mycobacterial culture-positive rate was 4.1% (411/10 015). After excluding the repeated isolates, a total of 253 culture-positive mycobacteria isolates were collected for the species identification. By genes sequencing analysis, 140 isolates were identified as mycobacterium tuberculosis complex (MTBc), 102 NTM and 11 Nocardias, accounting for 55.3%, 40.3% and 4.4%, respectively. Positive rate of NTM isolates had an increasing trend from 25.0% in 2008 to 42.7% in 2013, reaching a highest rate of 54.9% in 2012. In further analysis of 102 NTM isolates, 16 species were identified. Among them, 28 were M. abscesses, 18 strains of M. marinum, 17 strains of M. avium-intracellulare complex and 10 strains of M. fortuitum, accounted for 27.5%, 17.6%, 16.7% and 9.8%, respectively. Conclusions Both of the isolation number and isolation rate of NTM in the general hospital are increasing. NTM related cases are also increasing in recent years, which mainly caused by M. abscess, M. marinum, M. avium-intracellulare complex and M. fortuitum. Key words: Nontuberculous mycobacterium; Target gene sequencing; Species identification; Distribution type

Medical Management for the Treatment of Nontuberculous Mycobacteria Infection of the Parotid Gland: Avoiding Surgery May Be Possible.

Infection with nontuberculous mycobacteria (NTM) is uncommon in the head and neck; therefore there is no clear consensus on treating these infections. Our objective was to report our experience with a unique case of NTM infection of the parotid in an immunocompetent patient, in order to determine appropriate management through our experience with this pathology. A 57-year-old man, known for numerous comorbid diseases, presented to our institution complaining of right parotid swelling and pain. A computed tomography (CT) of the neck showed a multiloculated collection in the inferior portion of the right parotid gland, compatible with abscess formation. This abscess was drained by interventional radiology (IR) but required repeat drainage twice due to lack of initial improvement. He was treated with several antibiotics as culture results initially indicated Gram-positive bacilli and then Mycobacterium species, with final identification by a reference laboratory as Mycobacterium abscessus. Imipenem was initiated with amikacin and clarithromycin. His infection clinically and radiologically resolved after 5 months of antibiotherapy. In our case, the patient improved following intravenous antibiotic therapy. Our experience demonstrates that appropriate antibiotherapy can lead to resolution of Mycobacterium abscessus infection in the parotid without the risks associated with surgical intervention.

US Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis

Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause chronic pulmonary infection, particularly in individuals with pre-existing inflammatory lung disease such as cystic fibrosis (CF). Pulmonary disease caused by...

Non-tuberculous mycobacteria in cystic fibrosis

Non-tuberculous mycobacteria (NTM) are environmental organisms found in soil and water throughout the world that can cause chronic lung infection, usually in the context of structural lung disease or immunodeficiency.1 There is considerable evidence that rates of NTM infection are increasing in patients with Cystic Fibrosis (CF).2 In contrast to Mycobacterium tuberculosis, NTM do not seem to be transmissible from person to person nor re-activate following latent infection.3 Observed increases in NTM infection in CF patients are therefore likely to reflect increased exposure and/or increased susceptibility to infection. This review aims to summarize the epidemiology, diagnosis and treatment of NTM infection in CF patients focusing on the two most common mycobacterial groups causing disease: the M. avium-intracellulare complex (MAC) and the M. abscessus complex (MABSC).

Nontuberculous Mycobacteria in Solid Organ Transplant Recipients

Nontuberculous Mycobacteria in Solid Organ Transplant Recipients

Infección por Mycobacterium kansasii tras el trasplante hepático

Infections are one of the leading causes of morbidity and mortality in solid organ transplant recipients because of treatment with immunosuppressive agents. Infections due to nontuberculous mycobacteria (NTM) are infrequent but may be a major cause of morbidity. Treatment is associated with therapeutic limitations due to drug interactions with immunosuppressive agents and enhanced toxicity. Treatment of NTM infection most commonly involves surgery, reducing the doses of immunosuppressive medications and/or therapy with antimycobacterial medications The American Thoracic Society recommends isoniazid, rifampicin, and ethambutol. The current duration for treatment of pulmonary disease caused by Mycobacterium kansasii is 18 months. We describe the case of an immunosuppressed liver transplant recipient with poor outcome due to acute cholangitis who also developed concomitant infection with an uncommon organism, M. kansasii, in the late posttransplantation period.

Nontuberculous Mycobacterial Pulmonary Infections in Non-HIV Patients

Nontuberculous mycobacteria (NTM) are ubiquitous organisms with nearly 100 different species found in soil and water. The fatty-acid and wax-rich impermeable cell wall of the mycobacteria allow for adherence to solid substrates such as pipes and leaves, allowing the organism to persist despite treatment with common disinfectants. Mycobacteria can cause infection in both humans and animals. It is difficult to assess the incidence or prevalence of NTM disease due to multiple factors. Nontuberculous mycobacteria infection may be difficult to differentiate from colonization, and when NTM infection is diagnosed, it is not a reportable disease. Furthermore, some species such as Mycobacterium gordonae may be a contaminant. Nontuberculous mycobacteria infection is not a communicable disease, although health care-associated outbreaks have been reported, associated with a single facility or procedure. While the nontuberculous infection may affect other organs, the most common site is the lung, and the most common species is Mycobacterium avium complex, commonly referred to as MAC infection. An increasing occurrence of MAC has been reported, especially in certain populations such as middle-aged or elderly thin women, patients with chronic lung disease, human immunodeficiency virus infection, and cystic fibrosis. An association of NTM infection with gastroesophageal reflux disease has also been noted. The clinical presentation often includes chronic productive cough. Other less common symptoms include dyspnea and hemoptysis. With increased use of computed tomography and high-resolution computed tomography, patterns of MAC pulmonary infection have been described. Recently, the American Thoracic Society has outlined guidelines for the diagnosis and management of NTM infection. Treatment of NTM infection requires at least 3 effective drugs for a minimum of 12 months after sputum conversion to negative cultures. Surgical therapy may be considered for localized disease which has failed medical management. In this article, the clinical presentation, radiographic features, diagnostic evaluation, and management are discussed.

Micobactérias não-tuberculosas: diversidade das espécies no estado de São Paulo

O gênero Mycobacterium é constituído por espécies do complexo M. tuberculosis e outras denominadas micobactérias não-tuberculosas (MNT). Até o momento, mais de cem MNT foram descritas. Os objetivos deste estudo foram avaliar a diversidade das espécies de MNT identificadas no estado de São Paulo, no período de 1991 a 1997, que antecedeu a expansão da terapia anti-retroviral, e determinar a freqüência dos casos que atenderam alguns critérios bacteriológicos para o diagnóstico das infecções causadas pelas MNT. MATERIAL E MÉTODOS: Foram analisadas 1.892 cepas isoladas de sítios estéreis e não-estéreis de 1.248 pacientes atendidos no estado de São Paulo. RESULTADOS: Do total de pacientes, 1.199 (96,1%) tiveram suas cepas identificadas e 3,9% apresentaram resultados não-conclusivos. As dez espécies encontradas foram o complexo M. avium (MAC), M. kansasii, M. chelonae, M. fortuitum, M. szulgai, M. xenopi, M. marinum, M. gordonae, M. terrae e M. nonchromogenicum. Quarenta e sete (7,8%) casos pulmonares tiveram diagnóstico confirmado pelo isolamento da mesma espécie em três ou mais amostras e 67 (34%) pacientes tiveram o diagnóstico bacteriológico confirmado por isolamento em sítios estéreis. CONCLUSÕES: As espécies de MNT mais freqüentemente isoladas no estado de São Paulo foram MAC e M. kansasii. Uma publicação nacional com recomendações para diagnóstico e tratamento dessas infecções seria fundamental para a conduta correta no diagnóstico e no tratamento de micobacterioses.