Clinical, Radiological, and Microbiological Characteristics of Mycobacterium simiae Infection in 97 Patients

DISCUSSION

To the best of our knowledge, this is the largest cohort of patients with clinical isolates of M. simiae reported in the literature to date (4, 6, 7, 15). Reunion Island is a French overseas department located in the Indian Ocean, with a population estimated in 2016 to be more than 850,000 (Institut National de la Statistique et des Etudes Economiques, https://www.insee.fr/fr/statistiques/2018922). Medical care in Reunion Island is similar to that offered in metropolitan France. The incidence of tuberculosis in Reunion Island is similar to that in metropolitan France, being around 8 cases/100,000 inhabitants per year. Except for a few private laboratories that send respiratory samples to metropolitan France for NTM identification, most mycobacterial samples are referred to one of the two university laboratories on the island (St. Pierre and St. Denis). Moreover, even if patients are initially tested in private laboratories, the majority of those found to be infected with mycobacteria are referred to one of the two university hospital centers in Reunion Island. Although our study was not exhaustive, we estimated a high incidence of NTM in Reunion Island, i.e., approximately 5 cases/100,000 inhabitants per year, about 5 times the incidence observed in metropolitan France. The cystic fibrosis prevalence in Reunion Island is similar to that in metropolitan France, but the NTM prevalence in cystic fibrosis patients is 3 times higher in Reunion Island than it is in metropolitan France (16). M. simiae was common in our cohort, accounting for 15.1% of all patients with NTM isolates, a rate 15 times higher than that observed in metropolitan France (17). We hypothesize that the tropical climate, with high water temperatures, explains the high incidence of NTM, and especially of M. simiae, in Reunion Island (18). NTM species have indeed been found to be common in other tropical regions, such as in Hawaii, as reported by Adjemian et al. (19). High vapor pressure and household proximity to water have also been reported to be associated with NTM infections among cystic fibrosis patients (20–22). Another explanatory factor for the high incidence of NTM may be contamination of water supplies with M. simiae, a finding that was previously reported in a study conducted in Texas (5).

Underlying diseases were common among our patients with M. simiae. The main general predisposing factor was immunodepression, with HIV infection affecting 4.1% of patients who were positive for M. simiae and 25% of patients who were treated for M. simiae infection. Other general predisposing factors were diabetes mellitus and alcohol abuse. Unfortunately, tobacco status and occupational exposure were not clearly reported in our data sources. Wood smoke exposure was common in Reunion Island until the early 1980s, due to cooking habits, but it is rarely notified or quantified in medical reports. Non-cystic fibrosis bronchiectasis was the most prevalent local predisposing factor, affecting 49.5% of our cohort patients and 71.4% of those who met the ATS criteria for infection. In multivariate analysis, the rate of bronchiectasis was significantly higher in patients who met the ATS criteria for M. simiae infection. Our conclusions are limited, however, as bronchiectasis diagnosis and NTM isolation were often performed simultaneously, making it difficult to determine whether bronchiectasis was a predisposing factor for or a consequence of M. simiae infection. Preexisting bronchiectasis was documented for only 2 of the 6 patients treated for M. simiae infection.

Our study confirms the low pathogenicity of M. simiae in humans; 21.6% of our cohort patients met the ATS criteria for infection, but only 8.2% (8 patients) received treatment. In the Texas study, only 6 (10%) of the 62 patients with M. simiae isolates had definite infections (4). Similarly, Rynkiewicz et al. (23) found in their study that only 2 of 23 patients with M. simiae isolates (9%) had true M. simiae infections. In a study conducted in the Netherlands, van Ingen et al. (7) found 28 patients with clinical isolates of M. simiae, among whom only 8 (21%) met the ATS criteria for infection and only 6 received treatment (7). While the appropriateness of gastric aspiration for the diagnosis of M. simiae pulmonary infection may be debated, it did not affect the proportion of infected patients in our cohort.

As reported elsewhere (7, 15), clinical signs of infection among our cohort patients were mostly respiratory symptoms such as productive cough. Our study confirms the findings of van Ingen et al. (7), with patients who lost weight being significantly more likely to meet the ATS diagnostic criteria.

Micronodular lesions were the most common radiological findings and were associated with ATS criteria for M. simiae in the multivariate analysis. Cavitary lesions were present in 25.8% of our cohort patients, compared with studies that reported cavitary lesions in 3% to 15% of patients (11, 15). Unlike in the study by van Ingen et al. (7), cavitary lesions were not associated with ATS criteria for infection in our cohort. We found cavitary lesions in 5 of the 8 treated patients, suggesting more cavitary lesions with M. simiae disease than with Mycobacterium avium complex (MAC) species.

In vitro drug susceptibility testing showed a natural multidrug resistance profile. As in the study by van Ingen et al. (7), we found most strains to be resistant to rifampin, ethambutol, and isoniazid. However, unlike van Ingen et al. (7), we found susceptibility to amikacin, fluoroquinolones, and clarithromycin to be significant. While previous studies showed M. simiae strains to be susceptible to clofazimine and cycloserine (7, 24), susceptibility to these antibiotic agents was not tested in our study.

The treatment regimens administered to our patients included macrolides, rifampin, ethambutol, moxifloxacin, clofazimine, and amikacin. Treatment decisions were more frequent for infected patients with positive smears. Responses to treatment were poor, as 3 of 7 patients who completed the treatment regimen experienced failure or relapse. These results, however, are better than those reported in the literature; van Ingen et al. (7) found that treatment was successful for only 1 of 3 patients in their study, and 14 of 18 patients with AIDS in the Texas study by Al-Abdely et al. (25) died within 6 months, with no response to antibiotics.

This study has several limitations. The retrospective nature of the analysis is clearly a weakness. Despite being the largest study to date, the small numbers of evaluated patients and events might have resulted in a lack of power. The small number of respiratory samples from patients who did not meet the ATS criteria for infection is another limitation of our study, as it suggests that some patients were misclassified due to missing microbiological data.

The data reported here reflect common medical practice, which may also be viewed as a limitation. The conclusions of this double-center study cannot be extrapolated to institutions outside Reunion Island, especially with regard to the choice of antibiotics. While single-center studies are useful to reveal local ecological patterns, larger studies can help to uncover regional and global trends that are not apparent in smaller studies.

In Reunion Island, M. simiae isolates are common but are associated with low pathogenicity. In vitro susceptibility to antibiotics is low, and clinical responses to treatment are poor. Further studies are needed to explore the impact of the environment on NTM isolates in this specific region.