Extrapulmonary Nontuberculous Mycobacteria Infections in Hospitalized Patients

United States, 2009-2014

Emily E. Ricotta; Jennifer Adjemian; Rebekah A. Blakney; Yi Ling Lai; Sameer S. Kadri; D. Rebecca Prevots


Emerging Infectious Diseases. 2021;27(3):845-852. 

In This Article


Using the Cerner Health Facts EHR database, we found that the annual prevalence of extrapulmonary NTM overall was stable over time and that SST NTM infections increased significantly, which could result from the increased number of patients taking immunosuppressive drugs (20% of patients in this cohort) or increased cosmetic procedures (e.g., tattooing, pedicures).[10,11] Although population-based studies have found a lower and stable prevalence of extrapulmonary NTM, it is possible that the higher prevalence we found results from patients having more severe infections that necessitate testing, increasing the chances of diagnosing this disease.[4,11]

NTM infections varied by geographic region in prevalence, infection type, and mycobacterial species. Specifically, prevalence of extrapulmonary NTM was higher among hospitalized patients in the South, Midwest, and Northeast than in the West, although these high rates resulted from disseminated infection in the South versus a more even distribution of SST infections in other regions. Recent studies of extrapulmonary NTM in the United States have focused on specific geographic locations. In Oregon, Shih et al.[12] and Henkle et al.[4] analyzed all extrapulmonary NTM cases identified via statewide laboratory-based active surveillance efforts and estimated incidence rates to be 1.1–1.5 cases/100,000 persons/year, with only one third of those patients hospitalized.[12] These estimates are substantially lower than those reported in North Carolina,[13] where a similar surveillance-based study estimated the prevalence among residents of 3 counties to be ≈3 cases/100,000 persons. The differences in prevalence estimates between Oregon and North Carolina similarly reflect the regional differences that we observed; prevalence was higher in southern than in western states. The geographic variations in prevalence of extrapulmonary NTM cases that we found are also similar to what has been shown in US population–level pulmonary NTM studies,[8,14,15] that residents of southern states are at increased risk for NTM lung disease, particularly among high-risk groups such as persons with cystic fibrosis.[15–17] Differences by geographic region are largely associated with environmental factors, such as greater amounts of water on land and in the lower level atmosphere,[14–16] which probably contributes to increased environmental abundance of mycobacteria. In addition to higher levels of exposure to mycobacteria, studies have identified that these high-risk areas also tend to have a higher proportion of rapidly growing NTM species relative to MAC or other mycobacteria,[7,15,17] which can result in more severe disease with limited effective treatment options.[3]

Among extrapulmonary NTM cases, mycobacteria species also varied greatly by infection source and underlying condition. Although MAC infections were most frequent across all types of extrapulmonary NTM cases, in certain regions rapidly growing NTM play a substantial role in causing disease. Nearly all patients with HIV had MAC; those with a history of cancer were more likely to have rapidly growing NTM. Given that species of rapidly growing NTM, particularly M. abscessus and M. fortuitum, which were the most prevalent species in this study, are typically more challenging to treat than MAC, these findings have implications for the clinical management of these patients with complex infections and medical conditions. Co-infections were common among patients with extrapulmonary NTM, and ≥1 other pathogen was isolated from nearly half of all patients. Co-infections may complicate treatment-related decisions, particularly if mycobacteria, which are typically slow growing, are detected after other pathogens and are not treated with appropriate antimicrobial drug therapy.

Because we evaluated ≈9 million unique persons from 275 hospitals across the United States, we were able to identify key epidemiologic patterns for what is otherwise a very rare disease with limited population-level data. Because our analysis included only hospitalized patients, we probably overestimated the true incidence of extrapulmonary NTM disease in the general population by selecting for generally sicker patients with more severe underlying disease. We may have missed less severe SST infections that did not require extensive treatment or hospital intervention. Because the hospitals included here represent only those that use the Cerner Health Facts system, this study does not include patients at other facilities, which may also affect our incidence calculations. Similarly, not captured here were surgeries, procedures, or prior medical events that occurred in other facilities, which may be associated with risk, infection type, and outcome. However, these limitations would be applied systematically to the entire study population and therefore would probably not alter the geographic or temporal patterns that we found.

Overall, extrapulmonary NTM disease remains rare with relatively stable incidence rates for disseminated NTM infections and modestly increased rates for SST infections. In similar studies assessing pulmonary NTM, rates appear to be steadily increasing in the general population and among high-risk groups such as persons with cystic fibrosis.[8,17] Patients with extrapulmonary NTM typically include persons with HIV, other underlying immunodeficiencies, histories of surgical procedures, or other unique exposures that increase the risk for infection. In addition, we found that species variability is associated with geographic region; rapidly growing NTM are more prevalent in the southern United States than in other regions. Given the added treatment challenges that exist for these patients with often-complex conditions, knowledge of key trends and risks by patient-level factors and geographic location is critical for improving clinical outcomes and determining sources of infections that may be common to patients with pulmonary and extrapulmonary NTM.