During IDWeek 2024 in Los Angeles, California, US, case studies highlighted the current methods for detecting and preventing nontuberculous mycobacteria (NTM) outbreaks.
NTM refers to infection with a group of bacteria within the Mycobacterium genus, which excludes Mycobacterium tuberculosis (tuberculosis) and Mycobacterium leprae (leprosy). NTM are ubiquitous in the environment, particularly within water, soil, and dust. Exposure to NTM occurs daily, but it does not result in an infection for most healthy individuals. Conversely, NTM are opportunistic pathogens that are responsible for causing infections in patients with pre-existing health conditions or compromised immune systems. The most frequently observed types of NTM infections are pulmonary and disseminated. According to GlobalData, prevalent cases of pulmonary NTM are expected to increase by approximately 7.2% in the seven major pharmaceutical markets (7MM: US, Germany, France, Italy, Spain, UK, and Japan) during 2023–2033. Likewise, prevalent cases of disseminated NTM and other NTM infections are expected to increase by approximately 7.4% and 8.7%, respectively, over this period.
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One method for detecting and characterising NTM outbreaks that was presented by the US Centers for Disease Control and Prevention (CDC) involves utilising epidemiology and genomics. Historically, healthcare-associated NTM outbreaks have undergone epidemiological investigations, especially if the outbreak is caused by the same species of NTM among patients who may be linked geographically or temporally. In these instances, researchers and healthcare workers may look for commonalities between patients through chart reviews or formal epidemiological case-control studies. However, the addition of a genomic investigation utilises whole genome sequencing (WGS) of healthcare-associated infection isolates to link an outbreak back to a particular source, such as the environment or a contaminated product. Genomic investigations are thought to be especially helpful for NTM outbreaks, as WGS may be the only method that is granular enough to distinguish a common source outbreak versus NTMs that are normally circulating in the environment. This has been evidenced by a 2020 study by Labuda and colleagues, published in Clinical Infectious Diseases, in which 52 patients at an oncology clinic developed NTM bloodstream infections. WGS of the isolates identified a novel species of NTM and determined the source of the outbreak to be contaminated saline flushes.
Regarding the prevention of NTM outbreaks within hospital settings, water management is of utmost importance. As discussed in a 2023 study by Klompas and colleagues, published in Annals of Internal Medicine, NTM are water-avid pathogens that are commonly associated with hospital-acquired infections. Following the detection of Mycobacteroides abscessus in four cardiac surgery patients within the same hospital, an in-depth investigation led hospital staff to conclude that the infections were potentially attributable to mycobacteria found within ice and water machines. Prevention objectives should typically include operating building water systems in ways that prevent hazardous conditions from occurring and preventing opportunistic premise plumbing pathogens (OPPPs) that are found within water systems from infecting patients. Strategies for improving the treatment of hospital water systems include increasing water heater temperatures to 130°F or greater, monitoring chlorine levels, using copper for water pipes, and avoiding sources of stagnant water. Other mitigation strategies can include installing water filters, avoiding aerosolisation of nonsterile water from devices onto sterile fields, minimising or eliminating the use of unfiltered tap water altogether, and protecting patients who are most at risk of infection.
Post-outbreak management was also discussed at the conference, with a focus on the typical courses of treatment for NTM patients. For example, tobramycin was highlighted as being the best option for patients infected with Mycobacteroides chelonae and carbapenems such as imipenem were highlighted as being the best option for Mycobacterium fortuitum infections. The majority of the drugs currently used to treat NTM infections are used off-label. However, several novel late-stage pipeline products are in development specifically for the treatment of NTM infections. One such product is Paratek Pharmaceuticals’ omadacycline, which was highlighted during the presentation. Omadacycline is currently in a Phase II trial for the treatment of M. abscessus infections, and a data readout can be expected within the next few weeks.
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