Nontuberculous Mycobacteria Isolates Research Articles

Attenuated tuberculin skin test responses associated with Mycobacterium intracellulare sputum colonization in an adolescent TB prevalence survey in Western Kenya

IntroductionExposure to Non-tuberculous Mycobacteria (NTM) varies regionally and may partly explain the disparate outcomes of BCG vaccination and tuberculosis (TB) susceptibility. MethodsWe examined NTM sputum colonization, associations with clinical characteristics, and tuberculin skin test (TST) responses in an adolescent TB prevalence survey. ResultsAmong 5004 adolescents screened, 2281 (45.5 %) were evaluated further. TB and NTM prevalence rates were 0.3 % and 8.0 %, respectively. Among 418 NTM isolates, 103 were unidentifiable, and 315 (75 %) comprised 15 species, the most frequent being M. intracellulare (MAC) (108, 26 %), M. scrofulaceum (96, 23 %) and M. fortuitum (51, 12 %). “NTM colonized” adolescents had less frequent chronic cough and night sweats (adjusted odds ratio [aOR] 0.62, 95 % confidence interval [CI] 0.44-0.87and aOR 0.61, CI 0.42–0.89 respectively), and lower TST induration (median 11 mm (interquartile range [IQR] 0–16) vs 13 mm (IQR 6–17; p = 0.006)) when compared to “NTM not colonized” participants. MAC, but not M. scrofulaceum or M. fortuitum, was associated with decreased TST induration (median 7.5 mm (IQR 0–15) vs 13 mm (IQR 6–17) among “MAC colonized” vs “not colonized”, p = 0.001). ConclusionWe observed high NTM prevalence rates with species-specific associations with TST induration, consistent with a model of species-dependent heterologous immunity among mycobacteria.

In vitro activity of gepotidacin and comparator antimicrobials against isolates of nontuberculous mycobacteria (NTM).

Novel antimicrobials are needed to treat rising nontuberculous mycobacteria (NTM) infections. Using standard broth microdilution methods, 68 NTM isolates were tested against gepotidacin, a new, first-in-class, oral triazaacenaphthylene bacterial topoisomerase inhibitor. MICs varied (0.25 to >64 µg/mL) with the lowest being M. fortuitum complex (0.25-8 µg/mL), M. mucogenicum complex (1-2 µg/mL), M. kansasii (0.25-8 µg/mL), and M. marinum (4-16 µg/mL). Testing greater numbers of some species is suggested to better understand gepotidacin activity against NTM.

Efficacy of SPR720 in murine models of non-tuberculous mycobacterial pulmonary infection.

Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is increasing worldwide, with Mycobacterium avium complex (MAC) and Mycobacterium abscessus as the predominant pathogens. Current treatments are poorly tolerated and modestly effective, highlighting the need for new treatments. SPR719, the active moiety of the benzimidazole prodrug SPR720, inhibits the ATPase subunits of DNA gyrase B, a target not exploited by current antibiotics, and therefore, no cross-resistance is expected with standard-of-care (SOC) agents. To evaluate the in vitro activity of SPR719 against MAC and M. abscessus clinical isolates, including those resistant to SOC agents, and in vivo efficacy of SPR720 in murine non-tuberculous mycobacteria (NTM) pulmonary infection models. NTM isolates were tested for susceptibility to SPR719. Chronic C3HeB/FeJ and severe combined immunodeficient murine models of pulmonary infection were used to assess efficacy of SPR720 against MAC and M. abscessus, respectively. SPR719 was active against MAC (MIC90, 2 mg/L) and M. abscessus (MIC90, 4 mg/L) clinical isolates. Efficacy of SPR720 was demonstrated against MAC pulmonary infection, both as a monotherapy and in combination with SOC agents. SPR720 monotherapy exhibited dose-dependent reduction in bacterial burden, with the largest reduction observed when combined with clarithromycin and ethambutol. Efficacy of SPR720 was also demonstrated against M. abscessus pulmonary infection where monotherapy exhibited a dose-dependent reduction in bacterial burden with further reductions detected when combined with SOC agents. In vitro activity of SPR720 against common NTM pathogens and efficacy in murine infections warrant the continued clinical evaluation of SPR720 as a new oral option for the treatment of NTM-PD.

Non-Tuberculous Mycobacterial isolates from Panama: A retrospective 5-year analysis (2017-2021)

BackgroundThe genus Mycobacterium includes well-known bacteria such as M. tuberculosis causing tuberculosis and M. leprae causing leprosy. Additionally, various species collectively termed non-tuberculous mycobacteria (NTM) can cause infections in humans and animals, affecting individuals across all age groups and health conditions. However, information on NTM infection prevalence in Panama is limited. MethodsThis study conducted a retrospective analysis of clinical records from 2017 to 2021, specifically focusing on patients with NTM isolates. Data were categorized by variables like sex, age, HIV status, and sample source. ResultsAmong the 4430 clinical records analyzed, 698 were linked to patients with NTM isolates. Of these patients, 397 were male, and 301 were female. Most female patients with NTM isolates (n = 190) were aged >45 to 85 years, while most male patients (n = 334) fell in the >25 to 75 years age group. A noteworthy proportion of male patients (n = 65) were aged 25–35 years. A significant age difference between male (median [min-max] = 53 years [3–90]) and female (median [61 years [6–94]) patients was observed (p < 0.001). Regarding HIV status, 77 positive individuals were male, and 19 were female (p < 0.001). Most samples (n = 566) were sputum samples, with additional pulmonary-associated samples such as broncho-alveolar lavage, tracheal secretions, and pleural fluid samples. Among extrapulmonary isolates (n = 48), sources included catheter secretions, intracellular fluids, peritoneal fluid, blood cultures, cerebrospinal fluid, bone marrow samples, and capillary transplant lesions. Specifically, the analysis identified the pathogenic microorganisms responsible for mycobacteriosis in Panama during the specific period 2017–2021, as M. fortuitum (34.4%), M. intracellulare (20.06%), and M. abscessus (13.75%), respectively. ConclusionsThis study highlights the growing public health concern of NTM infections in Panama. The research provides valuable insights into the prevalence and distribution of NTM species in the country, offering a foundation for the development and implementation of effective prevention and control strategies for NTM infections in Panama.

In vitro and ex vivo activity of the fluoroquinolone DC-159a against mycobacteria.

Antimicrobial resistance is a global health problem. In 2021, it was estimated almost half a million of multidrug-resistant tuberculosis (MDR-TB) cases. Besides, non-tuberculous mycobacteria (NTM) are highly resistant to several drugs and the emergence of fluoroquinolone (FQ) resistant M. tuberculosis (Mtb) is also a global concern making treatments difficult and with variable outcome. The aim of this study was to evaluate the activity of the FQ, DC-159a, against Mtb and NTM and to explore the cross-resistance with the currently used FQs.A total of 12 pre-extensively drug-resistant (XDR) Mtb, 2 XDR, 36 fully drug susceptible strains and 41 NTM isolates were included to estimate the in vitro activity of DC-159a, moxifloxacin (MOX) and levofloxacin (LX), using minimal inhibitory and bactericidal concentration (MIC and MBC). The activity inside the human macrophages and pulmonary epithelial cells were also determined.DC-159a was active in vitro and ex vivo against mycobacteria. Besides, it was more active than MOX/LX. Moreover, no cross-resistance was evidenced between DC-159a and LX/MOX as DC-159a could inhibit Mtb and MAC strains that were already resistant to LX/MOX.DC-159a could be a possible candidate in new therapeutic regimens for MDR/ XDR-TB and mycobacterioses cases.

Five-year species distribution and antimicrobial susceptibility of non-tuberculous mycobacteria in Malaysia, 2018-2022.

Introduction. Non-tuberculous Mycobacteria (NTM) is a group of mycobacteria distinct from the Mycobacterium tuberculosis complex. They can cause opportunistic infections, especially in immunocompromised individuals.Gap Statement. Over the last few years, there has been a growing concern regarding the distribution and antimicrobial resistance of NTM in Malaysia. however, a comprehensive study to fully grasp the NTM situation has yet to be conducted.Aim. This study aimed to investigate the species distribution and antimicrobial susceptibility patterns of NTM isolated from clinical samples in Malaysia from 2018 to 2022.Methodology. A retrospective analysis was conducted on NTM isolates obtained from various clinical specimens over a span of five years. The isolates were identified using phenotypic and molecular techniques, and antimicrobial susceptibility profiles for clinically significant isolates were determined using minimum inhibitory concentration.Results. The study revealed a diverse distribution of NTM species in Malaysia, with Mycobacteroides abscessus complex and Mycobacterium avium complex emerging as the most predominant. Furthermore, the antimicrobial susceptibility patterns showed varying degrees of resistance to commonly used antibiotics, highlighting the significance of treatment tailored to susceptibility testing results.Conclusion. This study provides valuable perspective into the epidemiology of NTM in Malaysia. The information gained from this study should prove useful for empirically treating serious NTM infections prior to species identification and the availability of antimicrobial susceptibility testing results.

Non-tuberculous mycobacteria hybridisation profiles in the GenoType MTBDRplus assay: experience from a diagnostic routine of a high-throughput laboratory.

Introduction. Disease caused by non-tuberculous mycobacteria (NTM) is an emergent problem. Because NTM pulmonary disease and tuberculosis (TB) have similar clinical presentations, many cases of NTM may be misdiagnosed as TB before laboratory identification of the NTM species.Hypothesis/Gap Statement. Clinical laboratories should always perform differentiation between Mycobacterium tuberculosis complex (MTBC) and NTM to guide patients' correct treatment.Aim. To describe the characteristics and to identify mycobacterial isolates presumptively classified as MTBC by macroscopic characteristics in culture media that tested negative in GenoType MTBDRplus.Methodology. All cultures from February 2019 to December 2021 showing MTBC macroscopic characteristics were processed by GenoType MTBDRplus. MTBC-negative cultures underwent species identification by immunochromatography, line probe assays and PRA-hsp65. Patients' data were obtained from Brazilian surveillance systems.Results. Only 479 (3.1%) of 15 696 isolates presumptively identified as MTBC were not confirmed by GenoType MTBDRplus and were then subjected to identification. A total of 344 isolates were shown to be NTM, of which 309 (64.5%) and 35 (7.3%) were identified to the species and genus levels, respectively. Of the 204 NTM isolates with MTBC characteristics, the most frequent species were M. fortuitum (n=52, 25.5%), M. abscessus complex (MABC; n=27, 13.2%) and M. avium complex (MAC; n=26, 12.7%). Regarding the GenoType MTBDRplus results from NTM isolates, there were diverse hybridisation profiles with rpoB gene's different wild-type (WT) probes. Seventy-six (16.1%) of the 473 patients were classified as having NTM disease, the most frequent being MAC (n=15, 19.7%), MABC (n=13, 17.1%), M. kansasii (n=10, 13.2%) and M. fortuitum (n=6, 7.9%).Conclusion. Because the signs and symptoms of pulmonary TB are similar to those of pulmonary mycobacteriosis and treatment regimens for TB and NTM are different, identifying the disease-causing species is paramount to indicate the correct management. Thus, in the laboratory routine, when an isolate presumptively classified as MTBC is MTBC-negative, it is still essential to perform subsequent identification.

NONTUBERCULOUS MYCOBACTERIA DIVERSITY IN KARST WATERS AND BIOFILMS IN BULGARIAN CAVES

Background: Nontuberculous Mycobacteria (NTM) are emerging pathogens causing opportunistic infections in humans and animals. Their distribution in the waters and caves of Bulgaria is poorly studied. Climatic changes are associated with changes in the amplitudes of ambient and water temperature, as well as changes in the amount of precipitation which play an essential role in the creation of reservoirs of some types of NTM in the environment. Material and Methods: We optimized the methods for successful isolation of environmental NTM and then used molecular genetic methods for identification. Results: A total of 235 samples (karst water, sediments, soil, bat guano) were collected in some caves of the following karst regions: 203 in Vratsa Karst area, 204 in Ponor Karst area, 205 in Bezdenski area and 303 in Karst and caves of Bosnek region. Primary isolation of mycobacteria by Löwenstein–Jensen at room temperature was more successful than on liquid media at 37°C. We identified NTM in 10% (n=24) from these materials. Diverse NTM included: M. chelonae (n=3), M. gordonae (n=2), M. intermedium (n=3), M. scrofulaceum (n=1), M. szulgai (n=4), M. fortuitum group (n=4), NTM mix culture (n=5), M. terrae complex (n=1), Mycobacterium sp. (n=1). Rapidly growing NTM (M. chelonae, M. fortuitum group) were the most common. The isolates belonged to group of environmental saprophytes (Risk group 1) and potential pathogens (Risk group 2). Conclusions: We successfully implemented a procedure for decontamination and isolation of NTM from the environment. For the first time in the country, NTM species were identified in biofilms, karst waters, soil and bat guano within caves. The presence of NTM in cave ecosystems represents a potential source for human infection.

In vitro susceptibility of nontuberculous mycobacteria in China

ObjectivesThis study aimed to measure the prevalence of resistance to antimicrobial agents, and explore the risk factors associated with drug resistance by using nontuberculous Mycobacteria (NTM) isolates from China.MethodsA total of 335 NTM isolates were included in our analysis. Broth dilution method was used to determine in vitro drug susceptibility of NTM isolates.ResultsClarithromycin (CLA) was the most potent drug for Mycobacterium intracellulare (MI). The resistance rate of 244 MI isolates to CLA was 21%, yielding a minimum inhibitory concentrations (MIC)50 and MIC90 of 8 and 64 mg/L, respectively. 51% of 244 MI isolates exhibited resistance to amikacin (AMK). For 91 Mycobacterium abscessus complex (MABC) isolates, 6 (7%) and 49 (54%) isolates were categorized as resistant to CLA at day 3 and 14, respectively. The resistance rate to CLA for Mycobacterium abscessus subspecies abscessus (MAA) was dramatically higher than that for Mycobacterium abscessus subspecies massiliense (MAM). Additionally, the percentage of patients presenting fever in the CLA-susceptible group was significantly higher than that in the CLA-resistant group.ConclusionsOur data demonstrate that approximate one fifth of MI isolates are resistant to CLA. We have identified a higher proportion of CLA-resistant MAA isolates than MAM. The patients caused by CLA-resistant MI are at low risk for presenting with fever relative to CLA-susceptible group.

NONTUBERCULOUS MYCOBACTERIA - CURRENT RISK IN BULGARIA

Background: Nontuberculous mycobacteria (NTM) are generally free-living and have a potential to cause opportunistic infection. More than 190 species of NTM have been identified (http://www.bacterio.net/mycobacterium.html), up to 60 species of them are pathogenic. The distribution is geographically specific for some species and others are cosmopolitan. Understanding their diversity has practical value for the treatment and management of NTM disease. Except for isolated reports, there is no accurate information about NTM spread among Bulgarian patients. Material and Methods: We retrospectively analysed the data on the NTM isolated from patients throughout the country for the period from January 2010 to December 2017. Identification to the species level was done by Line Probe Assay (LPA). Results: 586 NTM strains were identified. We calculated the rate of NTM isolation in Bulgaria and NTM disease incidence by applying microbiological criteria defined by the American Thoracic Society (ATS). As a result, the laboratory isolation rate amounted to 1/100 000 people for the period, and when applying only the ATS criteria, the prevalence of NTM disease was 0,23 per 100 000 people. In both cases, we reported that NTM   disease incidence remains low as compared to tuberculosis, though with an increasing  trend. The prevalence of NTM varied significantly between northern and southern Bulgaria, as well as between the capital and the rest of the country's regions. Conclusions: Slow growing NTM species predominate in Bulgaria but rapidly growing ones have isolation levels higher than the average for Europe and closer to that of Asian countries. Given the demographic situation in Bulgaria and the changing climatic factors, NTM infections need special attention.

Isolation of potential zoonotic Mycobacterium spp. from diseased freshwater angelfish (Pterophyllum scalare) from an aquarium.

Nontuberculous mycobacteria infection is one of the most common chronic bacterial diseases in ornamental aquarium fish and appears to be directly related to stressful husbandry practices. Furthermore, it also represents zoonotic potential. Here we present the isolation and characterization of non-tuberculous mycobacteria from diseased freshwater angelfish (Pterophyllum scalare) in São Paulo, Brazil. Nine discarded breeding females with signs of disease were evaluated. The fish exhibited lethargy, loss of appetite, cachexia, skin ulcers, and exophthalmia. At necropsy, four fishes presented macroscopic granulomas in the spleen. Mycobacterium chelonae, M. fortuitum, M. gordonae, M. intracellulare and M. peregrinum were isolated and identified by hsp65 PCR restriction analysis. Histopathological analysis revealed microscopic lesions compatible with mycobacteriosis, and Mycobacterium bacillus were observed by Ziehl-Neelsen stain. Notably, all Mycobacterium species identified in this study have already been reported in human patients; therefore, diseased animals may be a source of infection for people who handle fish and aquariums.

Fluorescent nanodiamond immunosensors for clinical diagnostics of tuberculosis.

Fluorescent nanodiamonds (FNDs) are carbon nanoparticles containing a dense ensemble of nitrogen-vacancy defects as color centers. These centers have exceptional photostability and unique quantum properties, making them useful for ultrasensitive biosensing applications. This work employed FNDs conjugated with antibodies as magneto-optical immunosensors for tuberculosis (TB) diagnostics using competitive spin-enhanced lateral flow immunoassay (SELFIA). ESAT6 (6-kDa early secretory antigenic target) of Mycobacterium tuberculosis is a clinical marker of TB. We evaluated the assay's performance using the recombinant ESAT6 antigen and its antibodies noncovalently coated on FNDs. A detection limit of ∼0.02 ng mL-1 was achieved with the lateral flow membrane strip pre-structured with a narrow channel of 1 mm width. Adopting a cut-off value of 24.0 ng mm-1 for 100-nm FNDs on the strips, the method detected 49 out of 50 clinical samples with Mycobacterium tuberculosis complexes. In contrast, none of the assays for 10 clinical samples with non-tuberculous mycobacteria (NTM) isolates exhibited the presence of ESAT6. These results suggest that the SELFIA platform is applicable for TB detection and can differentiate TB from NTM infections, which also affect the human respiratory system. The FND-enabled immunosensing techniques are versatile and promising for early detection of TB and other diseases, opening a new avenue for biomedical applications of carbon-based nanomaterials.

Non-Tuberculous Mycobacteria Infections based on 16S rRNA detections in patients with Suspected Chronic Tuberculosis at a Tertiary Referral Hospital in Indonesia

This study identified non-tuberculous mycobacteria (NTM) isolates from the clinical respiratory specimen of patients suspected of chronic tuberculosis at a tertiary referral hospital in Indonesia. In this study, 20 clinical non-tuberculous mycobacteria (NTM) isolates were obtained from respiratory samples examined in the tuberculosis section of the Clinical Microbiology laboratory at Dr Soetomo General Hospital. The isolates were identified using TB Ag MPT 64 (SD Bioline) and targeting 16S rRNA genes sequence for analysis at the species level. Data on clinical features were collected and chest radiographs were evaluated. The highest bacterium found in the isolates was Mycobacterium kansasii (12 strains, 60%.), followed by Mycobacterium gordonae (2 strains, 5%), Mycobacterium parascofulaceum (2 strains, 5%), Mycobacterium avium (1 strain, 2.5%), Mycobacterium simiae (1 strain, 2.5%). Mycobacterium abcessus (1 strain, 2.5%), and Mycobacterium paraterrae (1 strain, 2.5%). Males dominated patients with Mycobacterium kansasii. Clinical symptoms include cough, dyspneu, hemoptysis, chest pain, and sweats. Half of the patients had a history of previous tuberculosis and other comorbid diabetes mellitus. Non-tuberculous mycobacteria (NTM) species identified were dominated by Mycobacterium kansasii. The predominance of non-tuberculous mycobacteria (NTM) species from clinical respiratory can be a reference to determine prudent treatment for patients in high-burden TB countries.

Prospective healthcare-associated links in transmission of nontuberculous mycobacteria among people with cystic fibrosis (pHALT NTM) study: Rationale and study design.

Healthcare-associated acquisition and transmission of nontuberculous mycobacteria (NTM) among people with cystic fibrosis (pwCF) has been described, and remains a concern for both patients and providers. This report describes the design of a prospective observational study utilizing the standardized epidemiologic investigation toolkit for healthcare-associated links in transmission of NTM among pwCF. This is a parallel multi-site study of pwCF who have infections with respiratory NTM isolates and receive healthcare within a common CF Care Center. Participants have a history of one or more NTM positive airway cultures and have been identified as having NTM infections suggestive of a possible outbreak within a single Center, based on NTM isolate genomic analysis. Participants are enrolled in the study over a 3-year period. Primary endpoints are identification of shared healthcare-associated source(s) among pwCF in a Center, identification of healthcare environmental dust and water biofilm NTM isolates that are genetically highly-related to respiratory isolates, and identification of common home of residence watersheds among pwCF infected with clustered isolates. Secondary endpoints include characterization of healthcare-associated transmission and/or acquisition modes and settings as well as description of incidence and prevalence of healthcare-associated environmental NTM species/subspecies by geographical region. We hypothesize that genetically highly-related isolates of NTM among pwCF cared for at the same Center may arise from healthcare sources including patient-to-patient transmission and/or acquisition from health-care environmental dust and/or water biofilms. This study design utilizes a published, standardized, evidence-based epidemiologic toolkit to facilitate confidential, independent healthcare-associated NTM outbreak investigations within CF Care Centers. This study will facilitate real-time, rapid detection and mitigation of healthcare-associated NTM outbreaks to reduce NTM risk, inform infection prevention and control guidelines, and characterize the prevalence and origin of NTM outbreaks from healthcare-associated patient-to-patient transmission and/or environmental acquisition. This study will systematically characterize human disease causing NTM isolates from serial collection of healthcare environmental dust and water biofilms and define the most common healthcare environmental sources harboring NTM biofilms. ClinicalTrials.gov NCT05686837.

Isolation and characterization of nontuberculous mycobacteria in drinking water of Monterrey, Mexico

Isolation and characterization of nontuberculous mycobacteria in drinking water of Monterrey, Mexico

2584. Predictors of Clinically Significant Infection in Patients with Mycobacterium simiae Isolated from Respiratory Samples: a Retrospective Study from a Tertiary Care Center in Lebanon

Abstract Background Mycobacterium simiae is a rare slow-growing, non-tuberculous mycobacterium (NTM). It is predominant in Middle Eastern countries like Israel, Iran and Lebanon and is the most isolated NTM spp. at our institution (40%). Little is known about its reservoirs, pathogenesis, risk factors and indications for treatment. Methods We retrospectively studied patients with respiratory cultures showing M. simiae at the American University of Beirut Medical Center (AUBMC) over 19 years. We used the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) criteria to define NTM lung disease. Samples were cultured at AUBMC using Lowenstein-Jensen media and the BacT/ALERT system. NTM isolates were referred for speciation and susceptibility testing at Mayo Clinic, MN, USA. Results We identified 72 isolates from 66 patients. Most were obtained from sputum samples (57.6%), the rest from bronchoalveolar lavages (BAL). Acid-fast bacilli smear was positive in 27% of samples with no difference between sputum and BAL. The median age of patients was 64 years and 51.5% were females. Bronchiectasis (34.5%), chronic obstructive pulmonary disease (27.3%) and immunosuppression (33.3%) were common (Table 1). As per the ATS/IDSA criteria, 67.9% of patients had NTM lung disease. The most common symptoms were cough (83.3%) and sputum production (74.5%). All patients except 2 had abnormal findings on CT imaging like nodules (58.5%), tree in bud aspect (45.3%) and bronchiectasis (24.5%). Among those, 55.6% had abnormal CT findings preceding the M. simiae isolation. Bronchiectasis was more common in those who satisfied the ATS/IDSA criteria versus those who did not (38.9% vs 20.0%). Otherwise, we found no significant differences between both groups (Table 2). Treatment was given to 88.9% of patients who satisfied the NTM lung disease and 42.1% of those who did not (p&amp;lt; 0.001) with a median duration of 12 months. Of those with available follow-up, relapse was reported in 24% of cases. Characteristics of patients with M. simiae isolated from respiratory samples. BMI, body mass index, COPD, chronic obstructive pulmonary disease, AFB, acid-fast bacilli. *Median(Interquartile range) **Composite variable including hematologic malignancy, solid organ malignancy, hematopoietic transplantation, solid organ transplant, chronic steroids treatment, and active chemotherapy. Clinical and radiological differences between patients with M. simiae lung disease and those colonized according to the ATS/IDSA criteria. BMI, body mass index, COPD, chronic obstructive pulmonary disease. *Median (Interquartile range) Conclusion M. simiae is a significant cause of NTM lung disease at our institution with a high rate of relapse. Further research is required to understand its geographic restriction, predisposing factors, and identify patients at risk for clinically significant infection. Disclosures Souha S Kanj, MD, Gilead: Advisor/Consultant|Menarini: Advisor/Consultant|MSD: Advisor/Consultant|Pfizer: Advisor/Consultant

1868. Epidemiology of Healthcare Facility-Associated Nontuberculous Mycobacteria at a 10-Hospital Network

Abstract Background Numerous studies have reported that rates of nontuberculous mycobacteria (NTM) infections are increasing. However, data on the epidemiology of healthcare facility-associated (HCFA) NTM are sparse. We performed a multicenter longitudinal study to analyze the epidemiology of NTM at a network of U.S. academic hospitals. Methods We retrospectively analyzed data on positive cultures for NTM obtained from 2012-2020 at a network of 10 U.S. academic hospitals and associated clinics (Table). Variables analyzed included NTM species, specimen source, and hospital admission status. A unique NTM episode was defined as a patient’s first positive culture for a particular NTM species and specimen source category (pulmonary vs. extrapulmonary). Episodes linked to isolates obtained on day 3 or later of hospitalization were considered to represent hospital-onset (HO) NTM. Seven hospitals contributed at least 12 months of baseline data prior to January 2014, and within this closed cohort, trends of NTM incidence rates were estimated with log regression. Characteristics of a 10-hospital network that performed retrospective culture-based NTM surveillance from 2012-2020. Results Across the 10-hospital network, 24,376 total NTM isolates were identified during 19,248,137 patient-days of surveillance; 12,847 (53%) isolates represented unique NTM episodes. Of these episodes, 3,044 (24%) were HO-NTM, which were most commonly caused by M. avium complex (n=1,466, 48%), M. abscessus complex (n=397, 13%), and M. chelonae-M. immunogenum (n=348, 11%). For 595 (20%) HO episodes, specimen source was extrapulmonary. Individual hospital incidence rates of HO-NTM were highly variable with a median rate of 1.1 episodes per 10,000 patient-days (range, 0.4 – 5.5 episodes) (Table). For the 7-hospital closed cohort, the HO-NTM incidence rate decreased from 2.3 to 1.4 episodes per 10,000 patient-days from 2014 to 2020 (incidence rate ratio, 0.6; 95% CI, 0.5-0.7; P &amp;lt; .0001) (Figure 1). Trend analysis estimated that the rate of HO-NTM decreased by 10% per year (95% CI, 8-12%; P &amp;lt; .0001) (Figure 2). Incidence rates of NTM episodes observed from 2014-2020 at a 7-hospital cohort. Admitted epsiodes consisted of episodes that were hospital-onset (HO) or not HO. Log regression model of hospital-onset NTM incidence rates from 2014-2020 within a 7-hospital cohort. The fit plot displays predicted values with 95% confidence limits and observed rates. Conclusion Network HO-NTM incidence rates decreased from 2014-2020, but rates varied substantially at individual hospitals. These results provide comprehensive data on HCFA-NTM isolation, including rates that can serve as external benchmarks. Given hospital variability, NTM surveillance at the individual hospital level is paramount. Disclosures Arthur W. Baker, MD, MPH, Insmed: Grant/Research Support|Medincell: Advisor/Consultant Ricardo M. La Hoz, MD, Takeda: Advisor/Consultant Melissa B. Miller, PhD, BioFire: Advisor/Consultant|BioFire: Honoraria|Cantata Bio: Grant/Research Support|Luminex Molecular Diagnostics: Advisor/Consultant|Luminex Molecular Diagnostics: Honoraria|MiraVista Diagnostics: Advisor/Consultant|MiraVista Diagnostics: Honoraria|QIAGEN: Advisor/Consultant|QIAGEN: Grant/Research Support|QIAGEN: Honoraria David J. Weber, MD, MPH, BD: Advisor/Consultant|Germitic: Advisor/Consultant|GSK: DSMB|PDI: Advisor/Consultant|Pfizer: Advisor/Consultant|Wellair: Advisor/Consultant Barbara D. Alexander, MD, F2G Pharmaceuticals: Advisor/Consultant|HealthTrackRx: Advisor/Consultant|HealthTrackRx: Board Member|Leadiaint: Grant/Research Support|Merck: Advisor/Consultant|Scynexis: Grant/Research Support|Thermofisher: Advisor/Consultant Jason E. Stout, MD, MHS, AN2 pharmaceuticals: Grant/Research Support

Disruption of nontuberculous mycobacteria biofilms induces a highly vulnerable to antibiotic killing phenotype

ObjectivesStructural or mucus hypersecretory pulmonary diseases such as cystic fibrosis (CF), wherein viscous mucus accumulates and clearance functions are impaired, predispose people to lung infection by inhaled bacteria that form biofilm aggregates. Nontuberculous mycobacteria (NTM), primarily Mycobacterium abscessus and Mycobacterium avium, are the growing cause of these lung infections and are extremely challenging to treat due to antibiotic recalcitrance. Better therapeutic approaches are urgently needed. We developed a humanized monoclonal antibody (HuTipMab) directed against a biofilm structural linchpin, the bacterial DNABII proteins, that rapidly disrupts biofilms and generates highly vulnerable newly released bacteria (NRel). MethodsHuTipMab's ability to recognize HupB, NTM's DNABII homologue was determined by ELISA. Relative ability of HuTipMab to disrupt biofilms formed by lab-passaged and clinical isolates of NTM was assessed by CLSM. Relative sensitivity of NTM NRel to antibiotic killing compared to when grown planktonically was evaluated by plate count. ResultsHuTipMab recognized HupB and significantly disrupted NTM biofilms in a time- and dose-dependent manner. Importantly, NTM NRel of lab-passaged and clinical isolates were now highly sensitive to killing by amikacin and azithromycin. ConclusionsIf successful, this combinatorial treatment strategy would empower existing antibiotics to more effectively kill NTM newly released from a biofilm by HuTipMab and thereby both improve clinical outcomes and perhaps decrease length of antibiotic treatment for people that are NTM culture-positive.

Trends in the Antibiotic Resistance of Non-Tuberculous Mycobacteria in Iran: A Systematic Review and Meta-Analysis.

Non-tuberculous mycobacteria (NTM) infections have been continuously increasing as major concerns of public health in Iran. Because innate resistance of NTM species, the treatment of these infections is difficult task, but until now resistance pattern of NTM and suitable regimens are not determined. We systematically searched the relevant studies in PubMed, Scopus, and Embase (Until Dec 2022). All statistical analyses were carried out using the statistical package R. Eleven studies included in the analysis were performed in 6 provinces and investigated 1223 NTM clinical species. The majority of the studies originated in Tehran. Among the first-line anti-TB drugs, almost all NTM species were highly resistant to first-line anti-TB drugs. No significant difference in the isoniazid resistance rate was found in the slow or rapid-growing species and Runyon's classification of NTM isolates. A decreased in the prevalence of ciprofloxacin, clarithromycin, and moxifloxacin resistance were showed in during 2013-2022 years. Most investigated antibiotics have a minor effect on NTM species and a steady increase of resistance has been seen in last few years then, need more-effective alternative regimens is clear.

Epidemiology of Nontuberculous Mycobacteria in Tuberculosis suspects, Southwest of China, 2017-2022.

This study summarizes the epidemiological characteristics, species distribution, and drug sensitivity of clinical nontuberculous mycobacteria (NTM) isolates at the Public Health Clinical Center of Chengdu, China, from January 2017 to December 2022. We retrospectively analyzed data from patients with clinically isolated NTM strains. Chi-square analysis assessed the rate of Mycobacterium strain isolation over 6 years. The number of samples tested for Mycobacterium tuberculosis (MTB) and/or NTM increased each year, while MTB detection decreased and NTM detection rose significantly each year (P=0.03). The average age of NTM patients was 51 ± 17.53 years, with a 14.1% HIV infection rate. The predominant isolates were Mycobacterium avium-intracellulare (MAC) and M. chelonae/M. abscessus, with 96.4% of cases being of Han ethnicity. Amikacin, moxifloxacin, and clarithromycin were effective against M. avium and M. intracellulare; linezolid, amikacin, and cefoxitin were effective against M. chelonae/M. abscessus. Over 90% of NTM cases originated from the respiratory tract. The NTM isolation rate in Southwest China has risen in recent years, primarily among elderly patients with a high HIV co-infection rate. The main NTM isolates were MAC and M. chelonae/M. abscessus. Amikacin, moxifloxacin, clarithromycin, and linezolid exhibited strong antibacterial activity against SGM, while amikacin and linezolid displayed relatively better antibacterial activity against RGM. The prevalence of NTM infection may be positively associated with regional economic development and health conditions.