Rare Nontuberculous Mycobacteria Research Articles

Successful treatment of Keratitis caused by Mycobacterium chelonae and an overview of previous cases in Europe

Introduction and purposeMycobacterium (M.) chelonae is responsible for a half of relatively rare nontuberculous mycobacteria (NTM) keratitis. We report a case of M. chelonae keratitis in a woman following sclerocorneal suture extraction after cataract surgery.ResultsA 70-year-old woman presented with a red eye and corneal infiltration of her left eye six weeks following sclerocorneal suture extraction after an elective cataract surgery in another institute. She complained of a sharp, cutting pain and photophobia. Since initial corneal scrapes and conjunctival swabs proved no pathogen using culture and PCR methods, non-specific antibiotics and antifungal agents were administered. As keratitis was complicated by an inflammation in the anterior chamber and vitreous, samples of the vitreous fluid were sent for microbiologic examination. DNA of Epstein-Barr virus (EBV) was repeatedly detected. Since the intrastromal abscess had formed, corneal re-scrapings were performed and M. chelonae was detected using culture, MALDI-TOF MS and PCR methods. Therapy was changed to a combination of oral and topical clarithromycin, intravitreal, topical and intracameral amikacin, and oral and topical moxifloxacin. The successful therapy led to stabilization. The optical penetrating keratoplasty was performed and no signs of the infection recurrence were found.ConclusionsThe diagnosis of nontuberculous mycobacterial keratitis is difficult and often delayed. An aggressive and prolonged antimicrobial therapy should include systemic and topical antibiotics. Surgical intervention in the form of corneal transplantation may be required in the active and nonresponsive infection. In the presented case this was necessary for visual rehabilitation due to scarring.

Shedding light on Mycobacterium chelonae and its cutaneous intrusion: A case report

Background: Mycobacterium chelonae, a rapidly proliferating nontuberculous mycobacterium, is renowned for instigating diverse infections, notably those affecting the integumentary system. Despite its pervasive presence in the environment, its propensity for pathogenicity in human hosts often eludes recognition. In this case report, we endeavor to provide a thorough exposition encompassing the epidemiological characteristics, clinical presentations, diagnostic modalities, and therapeutic strategies pertinent to Mycobacterium chelonae infections, with particular emphasis on its manifestations in skin and soft tissues. Case Description: We describe the case of an immunocompromised patient with a history of rheumatoid arthritis that presented with a four-month history of erythematous nodules that started from her left hand and later extended up that arm. A diagnosis was not made until mycobacterial cultures grew Mycobacterium Chelonae. Patient was treated with a six-month course of antibiotics, including tigecycline and azithromycin, which resulted in a significant reduction of her cutaneous lesions. Conclusion: This report discusses the presentation, diagnosis, and treatment of Mycobacterium. Chelonae, a rare nontuberculous mycobacterium that presented as a skin infection in an immunocompromised patient. Early recognition followed by treatment with appropriate antibiotics is crucial in reducing to its spread to disseminated infections.

MYCOBACTERIUM SHIMOIDEI: A RARE NONTUBERCULOUS INFECTION IN A US PATIENT

MYCOBACTERIUM SHIMOIDEI: A RARE NONTUBERCULOUS INFECTION IN A US PATIENT

Mycobacterium paragordonae is an emerging pathogen in human pulmonary disease: clinical features, antimicrobial susceptibility testing and outcomes

ABSTRACT Objectives: Mycobacterium paragordonae (MPG) is an emerging and less common type of Non-tuberculous mycobacteria (NTM) and we know little about its characteristics and prognosis, hence we constructed this retrospective cohort study. Methods: MPG was identified using MALD-TOF MS, multi-target combined gene sequencing and WGS. Clinical information was collected, antimicrobial susceptibility testing was measured using the SLOMYCO panel, and optimal growth temperature testing was measured using Lowenstein-Jensen medium. Results: Eight MPGs were isolated from 1730 NTMs (0.46%); the mean age of MPG pulmonary disease (MPG-PD) patients was 42.38 ± 9.92 years, 37.5% were male, and the average BMI was 18.4 ± 0.51 kg/m2. All patients had the symptoms of cough and sputum and CT images mainly presented in patchy or streaky shadows, MPG grew at 25°C, 30°C and 37°C, and the optimal growth temperature is 37°C. MPGs were sensitive to clarithromycin, rifabutin, amikacin, linezolid, moxifloxacin, cotrimoxazole and ciprofloxacin, two isolates were resistant to rifampicin. Two patients had follow up information, their imaging remained stable during the follow-up. Conclusions: MPG-PD is a rare NTM disease and is more likely to develop in middle-aged, female, and low BMI patients. The patients present with no specific features within the symptoms as well as the CT imaging. The optimal growth temperature of MPG is at 37°C, MPG-PD has excellent sensitivity to drugs recommended by CLSI and presents with a stable disease.

Trends and Species Diversity of Non-tuberculous Mycobacteria Isolated From Respiratory Samples in Northern China, 2014-2021.

BackgroundPulmonary non-tuberculous mycobacteria (NTM) infection has become a public health concern in China and around the world. The objective of this study was to describe the longitudinal changes in the frequency and diversity of NTM in northern China.MethodsWe retrospectively analyzed data on mycobacterium species in Beijing Chest Hospital from January 2014 to December 2021. The isolates were identified to species level by targeted DNA sequencing.ResultsAfter excluding duplicates, 1,755 NTM strains were analyzed, which were from 27 provinces in China over 8 years. Among all mycobacteria, the proportion of NTM increased each year, from 4.24% in 2014 to 12.68% in 2021. Overall, 39 different NTM species were identified, including 23 slow growing mycobacteria (SGM) and 16 rapid growing mycobacteria (RGM). The most common species were M. intracellulare (51.62%), M. abscessus (22.22%), M. kansasii (8.32%), M. avium (7.75%) and M. fortuitum (2.05%). The number of NTM species identified also increased each year from 9 in 2014 to 26 in 2021. Most species showed stable isolation rates over the years; however, the proportion of M. avium increased from 3.85 to 10.42% during the study period. Besides, 81 non-mycobacteria strains, including Gordonia (21 isolates), Nocardia (19 isolates) and Tsukamurella (17 isolates), etc., were also discovered.ConclusionThe proportion of NTM and species diversity increased considerably in northern China from 2014 to 2021. M. intracellulare was the most common NTM isolated among respiratory specimens, followed by M. abscessus and M. kansasii. Rare NTM species and non-mycobacteria pathogens also need attention.

High Prevalence of Nontuberculous Mycobacteria in Cystic Fibrosis Patients in Tropical French Reunion Island.

Reunion Island is a French overseas department located in a tropical area, where cystic fibrosis incidence is high. Cystic fibrosis (CF) patients are at risk of developing nontuberculous mycobacteria (NTM) infection. Epidemiologic studies are lacking in Reunion Island. From 2002 to 2015, a retrospective review was performed in university hospitals on Reunion Island. All CF patients having at least 1 positive NTM isolate were included. Clinical, radiologic, and microbiologic data were collected from patient records. Fifty-one CF patients were included. The overall estimated prevalence of NTM was 26.4% in total CF population and 36.9% in patients over 12 years of age. Mycobacterium abscessus and Mycobacterium avium were the most frequently identified species found in 31 patients (60.8%) and 14 patients (27.4%), respectively. A rare NTM species: Mycobacterium simiae was found in 4 patients (7.8%). Twenty-nine patients (56.9%) met the American Thoracic Society (ATS) criteria for infection. They were more likely younger with a low body mass index and more frequently infected by Mycobacterium abscessus (22/29). The overall prevalence of NTM in tropical Reunion Island is 3 times higher than in metropolitan France. A different environmental exposure in a tropical climate or risk factors related to cystic fibrosis or its treatment in Reunion patients could explain it.

Rare species in the structure of acid-resistent members of the order Actinomycetales isolated from clinical material.

The article presents data on the structure of acid-resistant members of the order Actinomycetales and rare species that have been isolated and identified using various methods. The study included strains of non-tuberculous mycobacteria (NTM) isolated from clinical material during examination for tuberculosis in the period from 2016 to 2019. The total number of samples with signs of NTMs growth that were included in the study was 316 samples. Primary isolation on Levenshtein-Jensen, Finn II, and MGIT media and NTMs identification by DNA-hybridization. All strains that were not identified prior to the species and culture, identified as microorganisms with a high G+C content (High GC GR +) were re-identified using a MALDI-ToF Microflex LT mass spectrometer (Bruker®). By the method of DNA-hybridization, 188 strains isolated by NTM were successfully identified to form 58.5% of all selected cultures. Among the selected species, representatives of slowly growing NTMs (M. avium complex, M. gordonae, M. kansasii) predominated, which amounted to 67.0% of all NTM strains identified to the species. Among the cultures for which DNA hybridization failed to carry out acceptable identification, predominantly NTMs were found, among which M. gordonae, M. avium, M. kansasii dominated. A number of NTMs were represented by rare species: M. iranicum and M. pseudoshottsii. Among this group of microorganisms, other acid-resistant aerobic actinomycetes were isolated, including those of potential clinical significance: Gordonia spp., Tsukamurella spp., Rhodococcus spp., Nocardia spp. When identifying cultures containing high concentrations of G+C, the maximum number of microbial associations was revealed, including those consisting of two types of NTMs (M. monacense + M. flavescens, M. avium + M. kansasii), as well as associations of M. gordonae with staphylococci. The same group included rare NTM species: M. fredericbergense, M. szulgai, M. malmoense, M. bohemicum, M. septicum, as well as representatives of the genera Nocardia, Gordonia, Tsukamurella.

A global update on rare non-tuberculous mycobacteria in humans: epidemiology and emergence.

Non-tuberculous mycobacteria (NTM) have evolved as an emerging group of pathogens globally. Due to the pitfalls in identification, the majority of them are not familiar or remain 'rare' to clinicians and microbiologists. In available literatures, a consolidated global data analysis is non-existent on rarely encountered NTM. A systematic review and meta-analysis have been carried out on 100 rare NTM species, which are possibly identified only by DNA sequencing methods, to establish their global epidemiology, emergence and clinical relevance. Articles published in English from 1956 to 2018 reporting rare NTM species were searched in MEDLINE, Scopus, Ovid and Embase. A total of 447 articles matched the selection criteria, and 1670 rare NTM cases were identified from 52 countries. The majority of the incidences were reported from North America (33.4%), followed by Europe (23.8%) and Asia (20.8%). Of 100 species, 43 were defined as emerging species, with 1351 (80.9%) new incidence cases globally. In total, 87 species caused clinically relevant pulmonary and extrapulmonary diseases. Interestingly, some NTM species showed significant geographic predominance, such as M. conceptionense to South Korea, M. shinjukuense to Japan; M. arupense and M. nonchromogenicum to the United States and M. riyadhense to Saudi Arabia. Rare NTM species mainly caused pulmonary infection (67.1%), while extrapulmonary infections generally comprised mycobacteremia and skin/soft tissue infections. In conclusion, the majority of rarely encountered NTM species are now well-established pathogens with valid clinical implications. The emergence of these rare pathogens warrants immediate local and international follow-ups. Their increasing clinical and pathological significance should not be disregarded.

The clinical significance of Mycobacterium triplex.

Mycobacterium triplex is a slow-growing nontuberculous mycobacteria (NTM) and is a rare cause of human disease. The pathogenicity, natural history and spectrum of disease is unknown. The aim of this study was to review the clinical features, outcomes and drug susceptibility testing (DST) of all M. triplex isolates in Queensland, Australia to guide management of this rare NTM infection in the future. This retrospective study included all patients who isolated M. triplex in Queensland, Australia from the 1st January 2000 to 31st December 2016. Clinical information was obtained from medical records to determine the clinical significance of isolates, natural history of disease and treatment outcomes. DST was performed on 15 isolates. Forty-three patients (21 male) had positive cultures for M. triplex. Thirty-nine patients had isolates from pulmonary specimens and 17 (43.6%) met the American Thoracic Society criteria for NTM lung disease. Six patients with pulmonary infection received antimicrobial therapy with 5 patients demonstrating treatment success. Four patients had localised extrapulmonary disease and were cured with surgical management ± antimicrobial therapy. DST suggests 93% of isolates are susceptible to macrolides. This is the largest case series of M. triplex isolates and confirms it is a rare human pathogen. Extrapulmonary disease responded well to surgical management. Treatment of M. triplex pulmonary disease is challenging, and the optimal antimicrobial regimen is unknown. However, the DST data suggests macrolide resistance is rare and macrolides should be included in treatment regimens.

High-Quality Draft Genome Sequences of Rare Nontuberculous Mycobacteria Isolated from Surfaces of a Hospital

Nontuberculous mycobacteria (NTM), some of which had multidrug-resistant profiles, were isolated from a tertiary care hospital setting. Although most NTM are nonpathogenic, contamination of hospital surfaces by these opportunistic pathogens poses a health risk to vulnerable inpatients. These high-quality NTM draft genomes are fundamental for future genetic and epidemiological studies.

Mycobacterium lentiflavum as the main cause of lymphadenitis in pediatric population

IntroductionCervical lymphadenitis is the most common nontuberculous mycobacteria (NTM) infection in immunocompetent children, mainly in those under 5 years. For many years Mycobacterium lentiflavum (M. lentiflavum) has been considered a rare NTM causing lymphadenitis. MethodsA restrospective study was performed in pediatric patients with microbiologically confirmed NTM cervical lymphadenitis at the Niño Jesús Hospital in Madrid during 2009–2016. ResultsDuring the period studied, 28 cases of cervical lymphadenitis were recorded. In 23 (82.14%) and in 5 (17.85%) cases, M. lentiflavum and Mycobacterium avium were isolated, respectively. In those patients infected with M. lentiflavum, the most frequent location was sub-maxilar (43.47%); 15 (65.21%) were boys, global median age was 30.8 months and all cases showed a satisfactory evolution. ConclusionWe propose that M. lentiflavum should be considered an important emergent pathogen cause of cervical lymphadenitis in the pediatric population.

Clinical, Radiological, and Microbiological Characteristics of Mycobacterium simiae Infection in 97 Patients.

Mycobacterium simiae is a rare species of slow-growing nontuberculous mycobacteria (NTM). From 2002 to 2017, we conducted a retrospective study that included all patients with NTM-positive respiratory samples detected in two university hospitals of the French overseas department of Reunion Island. We recorded the prevalence of M. simiae in this cohort, as well as the clinical, radiological, and microbiological features of patients with at least 1 sample positive for M. simiae In our cohort, 97 patients (15.1%) were positive for M. simiae Twenty-one patients (21.6%) met the American Thoracic Society (ATS) criteria for infection. M. simiae infection was associated with bronchiectasis, micronodular lesions, and weight loss. Antibiotic susceptibility testing was performed for 60 patients, and the isolates were found to have low susceptibility to antibiotics, except for amikacin, fluoroquinolones, and clarithromycin. Treatment failed for 4 of the 8 patients treated for M. simiae infection. Here, we describe a specific cluster corresponding to a large cohort of patients with M. simiae, a rare nontuberculous mycobacterium associated with low pathogenicity and poor susceptibility to antibiotics.

The first Saudi Arabian national inventory study revealed the upcoming challenges of highly diverse non-tuberculous mycobacterial diseases.

BackgroundIncidences of nontuberculous mycobacteria (NTM) causing pulmonary and extrapulmonary diseases are reportedly increasing globally and the current epidemiologic situation in Saudi Arabia remains unclear. To study such trend, we carried out a nationwide systematic epidemiological study focusing on NTM diseases for the first time in the country.Methods/Principle findingsA nationwide collection of NTM isolates with clinical and demographical data was conducted for a period of 24 months. Primary species identification was carried out by line probe assays followed by sequencing of 16S rRNA, 16S-23S ITS region, rpoB and hsp65 genes. The laboratory findings were comprehensively analysed against demographical and clinical data. A total of 527 isolates were enrolled with a higher proportion of Saudi citizens (76.5%), elderly (>60 years) patients (34.2%), and male gender (65.3%) respectively. Overall, 75.1% isolates were pulmonary origin with a proven clinical significance of 44.7%. In total, 34 NTM species including 17 rare species were identified, in addition to 8 ‘undefined’ isolates. M.simiae (22.6%), M.fortuitum (18.1%) and M.abscessus (17.8%) were predominant species. Interestingly, 27 new cases of clinically relevant M.riyadhense were also noticed (Primary data on emergence of rare NTM species and M.riyadhense has been recently reported). Results showed, rare clinical events such as mycobacteremia, cecum abscess, peritonitis and ascites caused by M.wolinskyi, M.holsaticum, M.duvalii and M.monacence respectively. Diabetes mellitus (P value-0.04) and previous history of tuberculosis (P value- 0.001) were identified as independent risk factors associated with NTM diseases.Conclusions/SignificanceNTM disease spectrum and pathogen diversity is an emerging challenge to any nation, including Saudi Arabia. Therefore, more priorities will be given to NTM’s with an immediate initiative to develop diagnostic infrastructures and disease management plans.

Mycobacterium lentiflavum como causa principal de linfadenitis en población pediátrica

IntroductionCervical lymphadenitis is the most common nontuberculous mycobacteria (NTM) infection in immunocompetent children, mainly in those under 5years. For many years Mycobacterium lentiflavum (M. lentiflavum) has been considered a rare NTM causing lymphadenitis. MethodsA restrospective study was performed in pediatric patients with microbiologically confirmed NTM cervical lympahdenitis at the Niño Jesús Hospital in Madrid during 2009-2016. ResultsDuring the period studied, 28 cases of cervical lymphadenitis were recorded. In 23 (82.14%) and in 5 (17,85%) cases, M. lentiflavum and Mycobacterium avium were isolated, respectively. In those patients infected with M. lentiflavum, the most frequent location was sub-maxilar (43.47%); 15 (65.21%) were boys, global median age was 30,8 months and all cases showed a satisfactory evolution. ConclusionWe propose that M. lentiflavum should be considered an important emergent pathogen cause of cervical lymphadenitis in the pediatric population.

Emerging pathology: Pulmonary disease caused by Mycobacterium xenopi - a challenge in clinical practice

Introduction. Human nontuberculous mycobacteria (NTM) or environmental mycobacteria related disease is on increase. Risk factors are unclear and associations are observed in relation to climate differences, population density, or host susceptibility. With availability of molecular techniques for NTM identification, we faced emergence of NTM pulmonary cases. The work is an invitation more to colleagues to enroll the rare NTM cases into large study group. Case report. During an episode of productive cough and fever in a 73-year-old HIV-negative man smoker with minimal sequellae of pulmonary tuberculosis, sputum smears were acid fast bacilli positive on direct microscopy. The L?wenstein- Jensen culture results were positive with 20, 30 and 50 colonies, and molecular identification confirmed Mycobacterium xenopi (M. xenopi). Standard chest radiography showed no signs of active lesions. Examination was completed with bronchoscopy and thorax multi-slice computed tomography (MSCT). Cavitary lesions in the apico-posterior part of the left upper lobe (LUL) were detected. Under treatment (rifampicin, ethambutol, clarithromycin) sputum conversion was achieved, but irregular cavitation in the LUL remained at MSCT after 6 and after 12 months with signs of minimal regression. Patient?s general condition only mildly improved and asthenia remained. Observed risk factors were previous pulmonary disease, tobacco smoking, malnutrition and prolonged emotional stress. Conclusion. M. xenopi related pulmonary disease, difficult to cure and with uncertain prognosis, is a challenge in clinical practice. Since treatment is still controversial, more randomized clinical trials are needed. Current international multicentre approach might be a good option for a larger sample size and development of new guide.

Emergence of Rare Species of Nontuberculous Mycobacteria as Potential Pathogens in Saudi Arabian Clinical Setting.

BackgroundClinical relevance of nontuberculous mycobacteria (NTM) is increasing worldwide including in Saudi Arabia. A high species diversity of NTM’s has been noticed in a recent study. However, the identification in diagnostic laboratories is mostly limited to common species. The impact of NTM species diversity on clinical outcome is so far neglected in most of the clinical settings.Methodology/Principal FindingsDuring April 2014 to September 2015, a nationwide collection of suspected NTM clinical isolates with clinical and demographical data were carried out. Primary identification was performed by commercial line probe assays. Isolates identified up to Mycobacterium species level by line probe assays only were included and subjected to sequencing of 16S rRNA, rpoB, hsp65 and 16S-23S ITS region genes. The sequence data were subjected to BLAST analysis in GenBank and Ez-Taxon databases. Male Saudi nationals were dominated in the study population and falling majorly into the 46–59 years age group. Pulmonary cases were 59.3% with a surprising clinical relevance of 75% based on American Thoracic Society guidelines. Among the 40.7% extra-pulmonary cases, 50% of them were skin infections. The identification revealed 16 species and all of them are reporting for the first time in Saudi Arabia. The major species obtained were Mycobacterium monascence (18.5%), M. cosmeticum (11.1%), M. kubicae (11.1%), M. duvalli (7.4%), M.terrae (7.4%) and M. triplex (7.4%). This is the first report on clinical relevance of M. kubicae, M. tusciae, M.yongonense, M. arupense and M.iranicum causing pulmonary disease and M. monascence, M. duvalli, M. perigrinum, M. insubricum, M. holsaticum and M. kyorinense causing various extra-pulmonary diseases in Saudi Arabia. Ascites caused by M. monascence and cecum infection by M. holsaticum were the rarest incidents.Conclusions/SignificanceTo the first time in the country, clinical significance of various rare NTM’s are well explored and the finding warrants a new threat to the Saudi Arabian clinical settings.

Frequency and clinical implications of the isolation of rare nontuberculous mycobacteria.

BackgroundTo date, more than 125 species of nontuberculous mycobacteria (NTM) have been identified. In this study, we investigated the frequency and clinical implication of the rarely isolated NTM from respiratory specimens.MethodsPatients with NTM isolated from their respiratory specimens between July 1, 2010 and June 31, 2012 were screened for inclusion. Rare NTM were defined as those NTM not falling within the group of eight NTM species commonly identified at our institution: Mycobacterium avium, M. intracellulare, M. abscessus, M. massiliense, M. fortuitum, M. kansasii, M. gordonae, and M. peregrinum. Clinical, radiographic and microbiological data from patients with rare NTM were reviewed and analyzed.ResultsDuring the study period, 73 rare NTM were isolated from the respiratory specimens of 68 patients. Among these, M. conceptionense was the most common (nine patients, 12.3%). The median age of the 68 patients with rare NTM was 68 years, while 39 of the patients were male. Rare NTM were isolated only once in majority of patient (64 patients, 94.1%). Among the four patients from whom rare NTM were isolated two or more times, only two showed radiographic aggravation caused by rare NTM during the follow-up period.ConclusionsMost of the rarely identified NTM species were isolated from respiratory specimens only once per patient, without concomitant clinical aggravation. Clinicians could therefore observe such patients closely without invasive work-ups or treatment, provided the patients do not have decreased host immunity towards mycobacteria.

The first case of pulmonary disease caused by Mycobacterium septicum in China

Mycobacterium septicum is a rapidly growing Mycobacterium (RGM) that rarely causes pulmonary disease globally. We describe a case of M. septicum pulmonary disease, which to our knowledge is the first reported in China. The isolates were identified as M. septicum and were susceptible in vitro to amikacin, ciprofloxacin, ofloxacin, levofloxacin, kanamycin, and sulfamethoxazole.

A rifampicin-resistant Mycobacterium marinum infection in a newly diagnosed HIV-1 individual

Mycobacterium marinum is a rare non-tuberculous mycobacterium known commonly to cause fish tank granuloma. It is found in aquatic surroundings and is common in healthy individuals. We report a case and review the literature in an immunocompromised HIV-1 individual with a first reported case of a rifampicin-resistant M. marinum organism in the literature.

A Case ofMycobacterium szulgaiLung Disease in Patient with Healed Tuberculosis

Mycobacterium szulgai is a rare nontuberculous mycobacterium found in Korea. It is an opportunistic pathogen and is usually isolated from patients with a history of alcoholism, chronic pulmonary disease, or an immunocompromising condition. We present here a case of M. szulgai isolated from a patient with a history of pulmonary tuberculosis. A 54-year-old man was admitted with dyspnea and febrile sensation. He had a history of pulmonary tuberculosis which occurred 30 years earlier and treatment with anti-tuberculosis medication. His chest computed tomography scan showed cavitary consolidation in both upper lungs. A sputum acid-fast bacilli (AFB) smear was positive and anti-tuberculous medication was started. However, a polymerase chain reaction for mycobacterium tuberculosis was negative and anti-tuberculous medication was stopped. M. szulgai was isolated on 3 separate sputum and bronchial wash fluid AFB cultures. He was treated with clarithromycin, rifampicin, and ethambutol. After 1 month, a sputum AFB smear and culture became negative and no additional M. szulgai were isolated during a 16-month treatment.