Mycobacterium gordonae: the canary in the coal mine?

Introduction

Several nontuberculous mycobacteria (NTM) species are rarely associated with clinical disease, despite being isolated from respiratory samples. The most common of these less pathogenic NTM is Mycobacterium gordonae (M. gordonae), often considered a contaminant (1) as it is frequently recovered from laboratory faucets, pipelines and freshwater (2). Pseudo-outbreaks have been reported, implicating contaminated tap water or ice, topical anesthetics, and medications (3). Symptomatic infection is quite rare, usually occurring in severely immunocompromised patients.

Patients with bronchiectasis are at greater risk of infection by pathogenic NTM species including Mycobacterium avium complex (MAC) and Mycobacterium abscessus (M. abscessus) than the general population (4). We theorized that isolation of less pathogenic NTM, such as M. gordonae, would also be associated with bronchiectasis, reasoning that defects in airway host defense (5) that increase risk for pathogenic NTM might also increase the likelihood of colonization with less pathogenic NTM. We further theorized that colonization with a less pathogenic NTM might indicate a degree of host defense impairment that could be a marker for increased risk of developing infection by more pathogenic NTM. Accordingly, we performed a retrospective study to investigate these questions.

Methods

We used records from the University of Connecticut mycobacteriology laboratory to identify isolates of M. gordonae between May 2^nd, 2010 and October 18^th, 2022. We then performed a retrospective chart review to delineate characteristics, comorbid medical conditions of patients from whom M. gordonae was isolated, and past and future isolation of any other NTM.

Further analysis was conducted on patients with M. gordonae from May 2^nd, 2018 to October 18^th 2022, the period during which we had access to diagnosis codes (an electronic health record was implemented on May 2, 2018), to assess for an association between isolation of M. gordonae and the presence of bronchiectasis. ICD-10 codes identifying patients with bronchiectasis included J47.0, J47.1 and J47.9. Fisher’s exact test was utilized to determine the association of M. gordonae with the presence of bronchiectasis. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the institutional review board of UConn Health (IRB No. 22X-243-1) on March 8^th, 2022. Individual consent for this retrospective analysis was waived.

Results

M. gordonae was isolated 35 times from 31 patients with bronchiectasis and 39 times from 26 patients without bronchiectasis. Baseline patient characteristics, the respiratory specimen type and indication for mycobacterial culture are shown in Table 1.

Among the 31 bronchiectasis patients who grew M. gordonae, 11 (35.5%) had previously grown a pathogenic NTM and 5 (16.1%) subsequently grew a pathogenic NTM. Overall, 14 (45.2%) grew one or more pathogenic NTM either before or after growing M. gordonae (23 total positive isolates; 20 MAC and 3 M. abscessus or “M. chelonae/abscessus”). Among 155 patients with bronchiectasis who never had isolation of M. gordonae, 45 (29.0%) grew pathogenic NTM at some point during their course (P=0.09 compared to patients who grew M. gordonae). Six patients (19.4%) of those who grew M. gordonae grew MAC at least twice, therefore meeting American Thoracic Society criteria for MAC lung disease (6), while 25 patients among the 155 (16.1%) non-M. gordonae cohort met ATS criteria for NTM lung disease. Among the 26 patients without bronchiectasis who grew M. gordonae, 1 (4%) had previous isolation of MAC and 1 (4%) subsequently grew MAC. Table 2 summarizes prior and subsequent growth of pathogenic NTM from patients who grew M. gordonae.

Between May 2^nd, 2018 and October 18^th 2022, among 1,346 mycobacterial cultures, 394 (29.3%) were from patients with bronchiectasis and 952 (70.7%) from patients without bronchiectasis. Among the 394 cultures from patients with bronchiectasis, 17 (4.3%) grew M. gordonae. Among the 952 cultures from patients without bronchiectasis, 16 (1.7%) grew M. gordonae (P=0.007). When considered at the patient level, there remained a statistically significant increased rate of M. gordonae isolation among patients with bronchiectasis. Among 754 unique patients who had mycobacterial cultures sent, 168 patients had bronchiectasis and 586 patients did not have bronchiectasis. Of the 168 patients with bronchiectasis, 12 (7.1%) had at least one mycobacterial culture that grew M. gordonae. Of the 586 patients without bronchiectasis, 13 (2.2%) had at least one mycobacterial culture that grew M. gordonae (P<0.001).

One of the 57 patients who grew M. gordonae was felt to have infection necessitating treatment. This patient was a 39-year-old male with history of psoriatic arthritis and sarcoidosis on adalimumab who presented with chronic productive cough found to have bilateral pulmonary nodules and thoracic lymphadenopathy. Expectorated mycobacterial culture on July 11^th, 2016 grew M. gordonae. He was treated for approximately 5 months with rifampin and ethambutol but failed to follow-up to complete treatment.

Discussion

The link between bronchiectasis and pathogenic NTM species including MAC and M. abscessus is well established. United States Medicare data demonstrated NTM pulmonary disease being 50 to 75 times more prevalent in patients with bronchiectasis than those without (7). An association between less pathogenic NTM including M. gordonae and bronchiectasis has not previously been investigated.

Our study describes the largest cohort of patients with isolation M. gordonae from respiratory specimens to date. There are limited data to which our results can be compared to, as literature regarding M. gordonae is largely limited to rare case reports or case series of infection mostly in immunocompromised patients, although case reports of infection in immunocompetent patients do exist (8).

While isolation of M. gordonae has previously been thought to almost always represent specimen or solution contamination, or oropharyngeal exposure to contaminated water without pulmonary relevance (6,9), our finding of a higher likelihood of isolating M. gordonae in patients with bronchiectasis than other types of lung disease suggest that it could be a marker for underlying impaired local airway host defense such as seen in bronchiectasis (5), even when not pathogenic.

We also found a high rate (45.2%) of positive cultures for more pathogenic NTM among the patients who grew M. gordonae. This prevalence is much higher than the 10% reported in a meta-analysis of the prevalence of NTM in bronchiectasis (10). We had limited statistical power to detect an increased risk of isolation of pathogenic NTM in patients who had M. gordonae versus those who did not have M. gordonae, therefore an increased risk of isolating pathogenic NTM in these patients cannot be ruled out, given the P value approaching significance for this outcome (P=0.09).

Our study has some limitations. It is a single center study. Patients with bronchiectasis were probably more likely to have mycobacterial cultures given its association with NTM lung disease, but this would not explain the rate of M. gordonae isolation in our culture-level analysis (as opposed to a patient-level analysis). While the association of M. gordonae with other NTM could be subject to confounding by indication (mycobacterial cultures more likely to be sent in patients with suspected NTM disease), most of the M. gordonae isolates were from samples sent for routine bronchiectasis surveillance.

Conclusions

In summary, isolation of M. gordonae occurs more commonly in patients with bronchiectasis, and therefore, in many cases is likely not the result of specimen contamination or solely oropharyngeal exposure; rather its isolation likely reflects the impaired local airway host defenses seen in patients with bronchiectasis. Although the difference did not reach statistical significance, we cannot rule out the possibility that isolation of M. gordonae in patients with bronchiectasis is a marker of increased risk of isolation of pathogenic NTM.

Acknowledgments

Funding: None.

Footnote

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1648/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1648/coif). C.L.D. reports institutional contracts from AN2, Bugworks, Insmed, Iuvabis, Paratek, Cystic Fibrosis Foundation, FDA, PCORI, and NIH; reports consulting fees from Genentech, and Pfizer; reports participation in the data safety monitoring committees of Otsuka, Bill and Melinda Gates Foundation, and Lilly; reports participation in the advisory boards of AN2, Astrazeneca, Hyfe, Insmed, MannKind, Matinas Biopharma, Nob Hill, Paratek, Spero, and Zambon. These activities are outside of the submitted work. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the institutional review board of UConn Health (IRB No. 22X-243-1). Individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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