Nontuberculous Mycobacteria Infection Research Articles

Cystic Fibrosis Carrier States Are Associated With More Severe Cases of Bronchiectasis.

People with cystic fibrosis (CF) are at increased risk for bronchiectasis, and several reports suggest that CF carriers may also be at higher risk for developing bronchiectasis. The purpose of this study was to determine if CF carriers are at risk for more severe courses or complications of bronchiectasis. Using MarketScan data (2001-2021), we built a cohort consisting of 105 CF carriers with bronchiectasis and 300 083 controls with bronchiectasis but without a CF carrier diagnosis. We evaluated if CF carriers were more likely to be hospitalized for bronchiectasis. In addition, we examined if CF carriers were more likely to be infected with Pseudomonas aeruginosa or nontuberculous mycobacteria (NTM) or to have filled more antibiotic prescriptions. We considered regression models for incident and rate outcomes that controlled for age, sex, smoking status, and comorbidities. The odds of hospitalization were almost 2.4 times higher (95% CI, 1.116-5.255) for CF carriers with bronchiectasis when compared with non-CF carriers with bronchiectasis. The estimated odds of being diagnosed with a Pseudomonas infection for CF carriers vs noncarriers was about 4.2 times higher (95% CI, 2.417-7.551) and 5.4 times higher (95% CI, 3.398-8.804) for being diagnosed with NTM. The rate of distinct antibiotic fill dates was estimated to be 2 times higher for carriers as compared with controls (95% CI, 1.735-2.333), and the rate ratio for the total number of days of antibiotics supplied was estimated as 2.8 (95% CI, 2.290-3.442). CF carriers with bronchiectasis required more hospitalizations and more frequent administration of antibiotics as compared with noncarriers. Given that CF carriers were also more likely to be diagnosed with Pseudomonas and NTM infections, CF carriers with bronchiectasis may have a phenotype more resembling CF-related bronchiectasis than non-CF bronchiectasis.

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.

Multiple intracellular pathogen infections with ocular pathologies associated with adult-onset immunodeficiency due to anti-interferon-γ autoantibodies: a case report

BackgroundAutoantibodies against interferon-γ (IFN-γ) can inhibit IFN-γ-dependent signal transducer and activator of transcription 1 phosphorylation and thus increase the risk of infection with intracellular pathogens, such as Talaromyces marneffei (TM), nontuberculous mycobacteria (NTMs), and Mycobacterium tuberculosis (TB). Here, we report a rare case of triple infection caused by TM, NTM, and TB in a human immunodeficiency virus–negative patient.Case presentationA middle-aged female was admitted to our hospital after experiencing recurrent rash, cough, and expectoration for 4 months. She was successively diagnosed with NTM, TM, and TB infections without conventional immunosuppression-associated factors. However, after effective anti-infective treatment, the patient was confirmed to have allergic conjunctivitis and was successfully treated with corticosteroids and immunosuppressants. The most conspicuous characteristics were recurrent infection and immune disorders.ConclusionsHigh-titer anti-IFN-γ autoantibodies are strongly associated with severe and disseminated infections, such as NTM, TM, and TB. It is characterized by persistently high degree of inflammation and high immunoglobin levels.

Survey of Mycobacterium spp. in Eurasian Badgers (Meles meles) in Central Italy.

A survey to determine the presence of Mycobacterium spp. in the Abruzzo and Molise regions was conducted by testing samples from 124 badgers found dead or road-killed during the 2013-2021 period. Head lymph nodes were collected from all carcasses, as well as mediastinal lymph nodes from 20 of them, for bacteriological and molecular tests; tissues were inoculated onto a set of solid egg-based Lowenstein-Jensen media and in a liquid culture system (BACTEC) and were analyzed by polymerase chain reactions (PCRs). Organs and lymph nodes from 31 carcasses were collected for histological tests. During post-mortem examinations, macroscopic lesions consistent with a Mycobacterium tuberculosis complex (MTBC) and with nontuberculous mycobacteria (NTM) infections were not detected. Mycobacteria were isolated from four animals (3.22%). M. avium subsp. avium was isolated by head lymph nodes from two badgers (1.61%), M. avium subsp. paratuberculosis (0.80%) from one, and Mycobacterium spp. from another (0.80%). The significance of nontuberculous mycobacteria (NTM) in wildlife hosts in the absence of clinical signs and gross pathology has yet to be assessed. The most critical aspect came from isolates belonging to the Mycobacterium avium complex infection in wildlife due to the possible interference with tuberculin skin tests in cattle.

Investigating cutaneous tuberculosis and nontuberculous mycobacterial infections a Department of Dermatology, Beijing, China: a comprehensive clinicopathological analysis.

Cutaneous tuberculosis (CTB) and nontuberculous mycobacteria (NTM) infections present considerable diagnostic and therapeutic challenges. This study aims to provide a comprehensive clinicopathological analysis of CTB and NTM infections. We conducted a retrospective analysis of 103 patients diagnosed with cutaneous tuberculosis (CTB) and nontuberculous mycobacteria (NTM) infections at a Beijing dermatology department from January 2000 to January 2024. Demographic, clinical, histological, and laboratory finding data were collected. Diagnostic methods and histopathological examination were recorded. Treatment regimens and outcomes were reviewed. Descriptive statistics were used to summarize demographic and clinical data, and continuous variables expressed as means and standard deviations (SD), and categorical variables as frequencies and percentages. Statistical analyses were conducted using SPSS version 25.0. The cohort included 103 patients (40.8% males and 59.2% females), with a mean age of 51.86 years. Common clinical manifestations included nodules (97.1%), erythema (74.8%), and plaques (68.9%). Histological examination revealed hyperkeratosis (68.9%), parakeratosis (23.3%), and extensive neutrophil infiltration (95.1%) were observed. Acid fast bacteria (AFB) stains and nucleic acid tests exhibited respective positivity rates of 39.6% and 52.3%, respectively. Most patients were treated with a combination of three drugs; 77.1% of patients showed improvement, with the cure rate for CTB being 20.0%. This study highlights the diverse clinical and histological presentations of CTB and NTM infections, emphasizing the need for comprehensive diagnostic approaches. The variability in treatment regimens reflects the complex management of these infections. The implementation of advanced molecular techniques and standardized treatment protocols is imperative for enhancing diagnostic precision and therapeutic outcomes.

Employing Multicolor Melting Curve Analysis to Rapidly Identify Non-Tuberculous Mycobacteria in Patients with Bronchiectasis: A Study from a Pulmonary Hospital in the Fuzhou District of China, 2018-2022.

Non-tuberculous mycobacteria (NTM) infection is common in bronchiectasis, with rising incidence globally. However, investigation into NTM in bronchiectasis patients in China remains relatively limited. This work aimed to identify and understand the features of NTM in bronchiectasis patient in Fuzhou district of China. The pulmonary samples were collected from 281 bronchiectasis patients with suspected NTM infection in Fuzhou, 2018-2022. MPB64 antigen detection was employed for the preliminary evaluation of NTM. Further NTM identification was realized using gene chip and gene sequencing. Among 281 patients, 172 (61.21%) patients were NTM-positive (58.72%) according to MPB64 antigen detection, with females (58.72%) outnumbering males (41.28%) and the highest prevalence in the age group of 46-65 years. In total, 47 NTM single infections and 3 mixed infections (1 Mycobacterium tuberculosis complex-M. intracellulare, 1 M. avium-M. intracellulare, and 1 M. abscessus-M. intracellulare) were identified through multicolor melting curve analysis (MMCA), which was compared with gene sequencing results. Both methods suggested Mycobacterium (M.) intracellulare, M. abscessus, and M. avium as the primary NTM species affecting bronchiectasis patients. M. intracellulare and M. abscessus were more frequent in females than males with the highest prevalence in the age group of 46-65 years according to MMCA. This research provides novel insights into the epidemiological and clinical features of NTM in bronchiectasis patients in Southeastern China. Significantly, M. intracellulare, M. abscessus, and M. avium were identified as the major NTM species, contributing to a better understanding and management of bronchiectasis accompanied by NTM infection.

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.

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.

Prevalence of nontuberculous mycobacteria and the emergence of rare species in Henan Province, China.

Nontuberculous mycobacteria (NTM) is a large group of mycobacteria other than the Mycobacterium tuberculosis complex and Mycobacterium leprae. Epidemiological investigations have found that the incidence of NTM infections is increasing in China, and it is naturally resistant to many antibiotics. Therefore, studies of NTM species in clinical isolates are useful for understanding the epidemiology of NTM infections. The present study aimed to investigate the incidence of NTM infections and types of NTM species. Of the 420 samples collected, 285 were positive for M. tuberculosis, 62 samples were negative, and the remaining 73 samples contained NTM, including 35 (8.3%) only NTM and 38 (9%) mixed (M. tuberculosis and NTM). The most prevalent NTM species were Mycobacterium intracellulare (30.1%), followed by Mycobacterium abscessus (15%) and M. triviale (12%). M. gordonae infection was detected in 9.5% of total NTM-positive cases. Moreover, this study reports the presence of Mycobacterium nonchromogenicum infection and a high prevalence of M. triviale for the first time in Henan. M. intracellulare is the most prevalent, accompanied by some emerging NTM species, including M. nonchromogenicum and a high prevalence of M. triviale in Henan Province. Monitoring NTM transmission and epidemiology could enhance mycobacteriosis management in future.

Congenital Pulmonary Airway Malformation with Suspected Nontuberculous Mycobacterium Infection.

Congenital Pulmonary Airway Malformation with Suspected Nontuberculous Mycobacterium Infection.

Disseminated Nontuberculous Mycobacterium Infection During Treatment of Multiple Myeloma: A Case Report and Review of the Literature.

Multiple myeloma (MM) is a plasma B-cell malignancy characterized by immune dysfunction, with infection representing a major complication. Bacteria, including Streptococcus pneumoniae, are common pathogens in patients with MM, but reports on infections with nontuberculous mycobacteria (NTM) have been limited. We herein report a case of disseminated NTM infection in a patient with MM undergoing treatment with immunomodulatory drugs. At the diagnosis, the patient showed lymphocytopenia and was treated with clarithromycin, rifampicin, and ethambutol; however, culture positivity persisted, and the patient died. The possibility of NTM infection should be considered in cases of unexplained deterioration of the MM patient's general condition.

An Atypical Etiology for Granulomatous Mediastinal Lymphadenopathy in an Immunocompetent Adult Male

Abstract Nontuberculous mycobacteria (NTM) are widely distributed microorganisms that have the potential to cause severe illness in humans, especially those with compromised immune systems. In adults, the disease mainly manifests as chronic pulmonary disease. Few case reports are available on lymphadenopathy caused by nontubercular mycobacterium in children, primarily affecting the cervical lymph nodes. However, it is exceptionally rare for an immunocompetent adult to develop mediastinal lymphadenopathy due to NTM infection. We present a case of posttubercular fibrocavitary lung disease with mediastinal adenopathy in an immunocompetent male. The initial clinical suspicion was the reactivation of tuberculosis. However, the cultures from the mediastinal node aspirate obtained by Endo Bronchial Ultra Sound guided Trans Bronchial Needle Aspiration (EBUS-TBNA) and the bronchoalveolar lavage showed growth of nontubercular mycobacterium. Our literature search only revealed a case report discussing mediastinal lymphadenopathy associated with NTM in an immunocompetent individual.

Intracellular iron accumulation facilitates mycobacterial infection in old mouse macrophages

Aging has a significant impact on the immune system, leading to a gradual decline in immune function and changes in the body’s ability to respond to bacterial infections. Non-tuberculous mycobacteria (NTM), also known as atypical mycobacteria or environmental mycobacteria, are commonly found in soil, water, and various environmental sources. While many NTM species are considered opportunistic pathogens, some can cause significant infections, particularly in individuals with compromised immune systems, such as older individuals. When mycobacteria enter the body, macrophages are among the first immune cells to encounter them and attempt to engulf mycobacteria through a process called phagocytosis. Some NTM species, including Mycobacterium avium (M. avium) can survive and replicate within macrophages. However, little is known about the interaction between NTM and macrophages in older individuals. In this study, we investigated the response of bone marrow–derived macrophage (BMMs) isolated from young (5 months) and old (25 months) mice to M. avium serotype 4, one of the main NTM species in patients with pulmonary NTM diseases. Our results demonstrated that BMMs from old mice have an increased level of intracellular iron and are more susceptible to M. avium serotype 4 infection compared to BMMs from young mice. The whole-cell proteomic analysis indicated a dysregulated expression of iron homeostasis–associated proteins in old BMMs regardless of mycobacterial infection. Deferoxamine, an iron chelator, significantly rescued mycobacterial killing and phagolysosome maturation in BMMs from old mice. Therefore, our data for the first time indicate that an intracellular iron accumulation improves NTM survival within macrophages from old mice and suggest a potential application of iron-chelating drugs as a host-directed therapy for pulmonary NTM infection in older individuals.

Bedaquiline for treatment of non-tuberculous mycobacteria (NTM): a systematic review and meta-analysis.

Non-tuberculous mycobacteria (NTM) infections are increasing in incidence and associated mortality. NTM are naturally resistant to a variety of antibiotics, complicating treatment. We conducted a literature assessment on the efficacy of bedaquiline in treating NTM species in vitro and in vivo (animal models and humans); meta-analyses were performed where possible. Four databases were searched using specific terms. Publications were included according to predefined criteria. Bedaquiline's impact on NTM in vitro, MICs and epidemiological cut-off (ECOFF) values were evaluated. A meta-analysis of bedaquiline efficacy against NTM infections in animal models was performed. Culture conversion, cure and/or relapse-free cure were used to evaluate the efficacy of bedaquiline in treating NTM infection in humans. Fifty studies met the inclusion criteria: 33 assessed bedaquiline's impact on NTM in vitro, 9 in animal models and 8 in humans. Three studies assessed bedaquiline's efficacy both in vitro and in vivo. Due to data paucity, an ECOFF value of 0.5 mg/mL was estimated for Mycobacterium abscessus only. Meta-analysis of animal studies showed a 1.86× reduction in bacterial load in bedaquiline-treated versus no treatment within 30 days. In humans, bedaquiline-including regimens were effective in treating NTM extrapulmonary infection but not pulmonary infection. Bedaquiline demonstrated strong antibacterial activity against various NTM species and is a promising drug to treat NTM infections. However, data on the genomic mutations associated with bedaquiline resistance were scarce, preventing statistical analyses for most mutations and NTM species. Further studies are urgently needed to better inform treatment strategies.

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.

Development and Evaluation of an NTM-IGRA to Guide Pediatric Lymphadenitis Diagnosis.

Diagnosis of nontuberculous mycobacteria (NTM) infections remains a challenge. In this study, we describe the evaluation of an immunological NTM-interferon (IFN)-γ release assay (IGRA) that we developed using glycopeptidolipids (GPLs) as NTM-specific antigens. We tested the NTM-IGRA in 99 samples from pediatric patients. Seventy-five were patients with lymphadenitis: 25 were NTM confirmed, 45 were of unknown etiology but compatible with mycobacterial infection and 5 had lymphadenitis caused by an etiologic agent other than NTM. The remaining 24 samples were from control individuals without lymphadenitis (latently infected with M. tuberculosis , uninfected controls and active tuberculosis patients). Peripheral blood mononuclear cells were stimulated overnight with GPLs. Detection of IFN-γ producing cells was evaluated by enzyme-linked immunospot assay. NTM culture-confirmed lymphadenitis patient samples had a significantly higher response to GPLs than the patients with lymphadenitis of unknown etiology but compatible with mycobacterial infection ( P < 0.001) and lymphadenitis not caused by NTM ( P < 0.01). We analyzed the response against GPLs in samples from unknown etiology lymphadenitis but compatible with mycobacterial infection cases according to the tuberculin skin test (TST) response, and although not statistically significant, those with a TST ≥5 mm had a higher response to GPLs when compared with the TST <5 mm group. Stimulation with GPLs yielded promising results in detecting NTM infection in pediatric patients with lymphadenitis. Our results indicate that the test could be useful to guide the diagnosis of pediatric lymphadenitis. This new NTM-IGRA could improve the clinical handling of NTM-infected patients and avoid unnecessary misdiagnosis and treatments.

2729. Clinical characteristics, treatment and outcomes of infections among adult-onset immunodeficiency with anti-interferon (IFN)-γ autoantibodies patients: A single-center 10-year review from tertiary care hospital in Thailand

Abstract Background Adult-onset immunodeficiency (AOI) with anti-interferon (IFN)-γ autoantibodies is an acquired immunodeficiency syndrome increasingly recognized in East and Southeast Asia. Antibody against IFN- γ or its receptor is the main pathophysiology leading to opportunistic infections especially mycobacterial, dimorphic fungal or Salmonella infection. However, clinical information of infectious complications in this patient population remains scarce. Methods A retrospective study was conducted in Buddhachinaraj hospital, Phitsanuloke, Thailand. We collected data on demographic, infectious complications, treatment and outcomes in patients with AOI with anti-IFN-γ autoantibodies who presented to our center between March 2013 and February 2023. All patients were diagnosed by elevation of anti-IFN- γ antibody level in serum more than 1.0. Results A total of 35 patients. 54.3% were men with a median age of 58 years (IQR 14-63). Lymphadenopathy was the most common initial presentation (57%), followed by prolonged fever (40%), cough (11%) and skin lesions (11%). Lymph node involvement was found in 80% while 31% and 11% had intra-abdominal abscess and osteomyelitis. Organisms were identified in 21 patients (60%). Mycobacterial infections were found in 19 patients (90%) which the main etiologic agent was Mycobacterium abscessus (43%). Six patients (28%) had evidence of mycobacterial infection but were unable to specified. Histoplasma capsulatum was found in 2 patients (9%). Another 14 patients (40%) were presumptive treated as non-tuberculous mycobacterium (NTM) infection without retrieving specific organism. All patients were treated with antimicrobial agents according to identified causative organism. Fourteen patients with presumptive NTM infection were empirically treated with combination antibiotics. Median time of treatment was 24 months (IQR 12-35). Seven patients (20%) experienced relapse after antimicrobial discontinuation requiring retreatment. Three patients (6%) had died at median duration of 4 months from diagnosis. Conclusion AOI with (IFN)-γ autoantibodies should be considered in patient whom suspected mycobacterium or fungal infection among non-HIV patients. Diagnosis and treatment are challenge and recurrent infection is common. Disclosures All Authors: No reported disclosures

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

2200. The Antibiotic Steward's Nightmare: Long-Term Antibiotics in An Infectious Disease Practice

Abstract Background The effects of long-term antibiotic use, including the frequency of recurrent infections and new-onset resistant infections, are not fully understood. The role of antibiotics in the disruption of the gut microbiota has been well-described, impacting insulin susceptibility and lipid deposition. Prolonged antibiotic use may have potential to be implicated in obesity, diabetes, and hyperlipidemia. There may also be an effect on the incidence of secondary infections with new organisms, the frequency of breakthrough infections from the index organism, and the selection for resistant infections. Methods This retrospective study evaluated 78 patients seen at an outpatient infectious disease practice. Inclusion criteria were patients with prescription of an oral antibiotic for 90 or more consecutive days between 9/1/18 and 12/31/2019, who utilize a health system pharmacy. Data was collected from patient charts at baseline prior to antibiotic initiation, and at time of most recent follow up after the initiation of antibiotic. Results Cephalexin (37.2%), azithromycin (34.6%) and amoxicillin (12.8%) were the most common antibiotics prescribed. Mean patient age was 69.4 years. Indications for antibiotic use included NTM infections (34.6% of cases), prosthetic joint infections (21.8%), recurrent UTIs (10.3%), and prosthetic valve infection (7.7%). 23.4% of patients experienced breakthrough infection with the index organism, while 21.8% experienced new, unrelated infection during follow-up, of which 52.9% had a resistant organism isolated. Mean BMI at baseline was 26.9, and BMI at follow-up was 27.3. The difference between baseline and follow-up BMI was not statistically significant (p=0.177). A1C, LDL, and cholesterol rose from baseline to follow-up, but did not reach statistical significance. Conclusion Patients on long-term antibiotics had a numerical increase in BMI, A1C, LDL, and cholesterol values following initiation, but those increases were not statistically significant. Recurrence of infection and emergence of resistance was common. The small sample size and limitation of studying patients from one practice within one health system pharmacy are limitations of the study. Further studies with larger sample sizes and comparative groups by diagnosis are needed. Disclosures All Authors: No reported disclosures

A Comparative Study on the Mechanism of Delayed-Type Hypersensitivity Mediated by the Recombinant Mycobacterium tuberculosis Fusion Protein ESAT6-CFP10 and Purified Protein Derivative

While purified protein derivative (PPD) is commonly used as skin diagnostic reagent for tuberculosis (TB) infection, it cannot distinguish effectively Bacillus Calmette–Guérin (BCG) vaccination from Mycobacterium tuberculosis (MTB) complex and nontuberculous mycobacteria infection. The new skin reagent ESAT6-CFP10 (EC) has favorable sensitivity and specificity, which can overcome limitations associated with PPD. At present, EC skin test reactions are mainly characterized by erythema, while PPD mainly causes induration. We conducted a comparative study on the potential differences between EC-induced erythema and PPD-induced induration using a guinea pig model. The size of EC-dependent erythema was similar to that of PPD-induced induration, and an inflammatory response characterized by the infiltration of monocytes, macrophages and lymphocytes, as well as tissue damage, appeared at the injection site. The lymphocytes included CD4+ T and CD8+ T cells, which released IFN-γ as the main cytokine. Both EC erythema and PPD induration could lead to increased levels of acute-phase proteins, and the differential pathways were similar, thus indicating that the main induced immune pathways were similar. The above results indicated that erythema produced by EC could generate the main delayed-type hypersensitivity (DTH) response characteristic of PPD induration, thereby suggesting that erythema might also have a certain diagnostic significance and provide a possible theoretical basis for its use as a diagnostic indicator for detecting MTB infection.