The goal of this observational study is to support U.S. healthcare centers in determining if they may have an NTM outbreak among patients receiving care at the healthcare center. The study applies a standardized, reproducible outbreak investigation approach across diverse healthcare settings. This study focuses on patients with NTM isolates suspected to be part of an outbreak, receiving care at a specific U.S. healthcare center.

The main questions it aims to answer are:

Can application of a standardized epidemiologic investigation framework support evaluation of whether clustered NTM infections may be consistent with healthcare-associated exposure? Are respiratory NTM isolates genetically related to environmental NTM isolates identified within healthcare settings or shared home water sources?

Researchers will compare clinical, epidemiologic, molecular, and infection prevention data from suspected NTM isolates to determine whether patterns are consistent with healthcare-associated transmission or acquisition.

Participants (healthcare centers and selected patients) will:

• Implement a standardized epidemiologic investigation using the Healthcare-Associated Links in Transmission of Nontuberculous Mycobacteria (HALT-NTM) toolkit
• Submit available respiratory and environmental NTM isolates for molecular comparison, when applicable
• Optionally collect dust and water biofilm samples within the healthcare setting
• Complete a survey to provide home address history for watershed mapping, when clustered infections are identified

This study is a parallel multi-site study of people cared for in a healthcare center who are identified with highly similar respiratory nontuberculous mycobacteria (NTM) isolates. All study activities described herein are optional and conducted at the discretion of each participating site.

This is an outbreak investigation and involves no more than minimal risk, which is commensurate with those inherent in the actual or expected care of a patient with pulmonary NTM. No samples will be collected from the identified participants outside of routine clinical care. As with any research study, there is a potential risk of breach of individual patient confidentiality. Linked to the samples will be clinical data, specifically NTM culture results and designation of NTM disease status, as well as data captured routinely in the course of clinical care. There is no additional testing required for this protocol beyond what is recommended for standard care, and no additional research visits beyond normally scheduled clinic visits.

The Transmission and Acquisition of Nontuberculous Mycobacteria Outbreak Investigation (TrANsMIt) study is designed to provide resources to systematically collect data to perform an outbreak investigation on people in a suspected healthcare-associated NTM outbreak. Respiratory NTM isolates will undergo WGS to identify infections that are highly related and falling into clusters in order to determine if the source of NTM infection may be a healthcare-associated outbreak. The investigators integrated clinical and epidemiological research methods to adapt a CDC standardized, and validated Healthcare-Associated Infection Outbreak Investigation Toolkit to retrospectively collect data for suspected healthcare-associated NTM outbreak investigations. Through consultation with subject matter experts and scientific literature review, the investigators modified the CDC Healthcare-Associated Infection Outbreak Investigation Abstraction Form, designed to be utilized in local investigations of common healthcare-associated infections to develop the Healthcare-associated links in transmission of NTM (HALT NTM) study Outbreak Investigation Abstraction Toolkit. The HALT NTM Toolkit is a Health Insurance Portability and Accountability Act (HIPAA) compliant, web-based, branching logic questionnaire that uses integrated clinical and epidemiological research methods to perform an epidemiologic investigation to identify overlaps in space and time with mapping of visits and source(s) of care among patients with highly similar NTM isolates in a Center. Additionally, the Toolkit assesses detailed Center-specific IP&C measures utilized the healthcare system. Utilizing the HALT NTM toolkit, the TrANsMit study facilitates a standardized, stepwise process by which healthcare centers perform an internal epidemiologic evaluation of patients identified as part of an NTM cluster. Since clustered NTM isolates could originate from a shared healthcare source, dust and water biofilms from the healthcare environment are collected. NTM are recovered, identified, and sequenced as described to determine if the respiratory NTM strain genotype is similar to those recovered from the healthcare environment. Through a collaborative agreement, TrANsMIt is available to U.S. healthcare centers to conduct a standardized, independent, confidential NTM outbreak investigation.

Inclusion Criteria:

• Male or female participant of any age who has a history of NTM or a first positive NTM culture collected as part of routine clinical care from expectorated sputum, induced sputum and/or bronchoalveolar lavage.

Exclusion Criteria:

• No NTM respiratory culture

Male or female participant of any age who has a history of respiratory NTM or a first positive NTM culture collected as part of routine clinical care from expectorated sputum, induced sputum and/or bronchoalveolar lavage.

There is a plan to make de-identified IPD and related data dictionaries available. All IPD will be made available upon reasonable request. Requests will be reviewed to ensure alignment with the original informed consent and applicable ethical and regulatory requirements.

De-identified IPD and supporting documentation will become available 6 months after publication and will remain available for a period of 3 years thereafter.

Access to de-identified IPD will be granted to qualified researchers upon reasonable request. Requests must include a methodologically sound research proposal and will be reviewed for consistency with the original informed consent, ethical considerations, and applicable regulatory requirements.

Prior to data release, approval by the University of North Carolina at Chapel Hill (UNC) and execution of a UNC Data Use Agreement (DUA) will be required. Data will be shared only after confirmation that all required institutional approvals and agreements are fully executed. Requests should be directed to the corresponding author.