Nontuberculous mycobacteria in patients of a specialty hospitalABSTRACT
The incidence and clinical characteristics of NTM diseases in Brazil remain relatively unknown. The present study describes the diagnosis of NTM isolates, the clinical presentation and treatment outcomes. We analyzed NTM isolates in patients of a tertiary hospital in the Southeast region of Brazil, from January 2008 to July 2019. The ATS/IDSA criteria for diagnosis and treatment of these patients was applied. Mycobacterium kansasii were identified in 13/113 (11.5%) patients. In 59/113 (52.2%) patients who met the ATS criteria for disease, 29/59 (49.1%) received treatment, and 22/29 (75.8%) were cured. The major species identified was M. kansasii. The most frequent symptoms among the treated patients were dyspnea and cough, and the proportion of cured patients was high.
Mycobacteria; Sample; Diagnostic; Treatment
INTRODUCTION
Nontuberculous mycobacteria (NTM) are a large and diverse group comprising more than 190 species and subspecies1. They colonize different environments such as soil, surfaces, and drinking water1,2. Reports of human disease caused by NTM have increased worldwide over the last two decades, with those of the Mycobacterium abscessus complex, M. avium complex (MAC), and M. kansasii frequently reported as being of greatest clinical importance2,3.
NTM transmission is predominantly through the inhalation of aerosols and dust particles, contaminated water or soil, or aspiration of the gastric contents. Because many NTM are present in the environment, detection in nonsterile biological materials, such as sputum or urine, can be due to contamination or colonization, not necessarily implying disease4,5.
Despite its low pathogenicity in humans, NTM disease more frequently displays predisposing factors, such as silicosis, bronchiectasis, chronic obstructive pulmonary disease, human immunodeficiency virus (HIV) infection, and immunosuppressive diseases4,5.
Extrapulmonary NTM infections, particularly the disseminated disease, usually develop in people with congenital or acquired immunodeficiencies (e.g., PLHIV)6, but can also be associated with medical or cosmetic procedures that expose a wound to sources contaminated with mycobacteria6.
The difficulty of applying a uniform diagnostic criteria, imprecise characterization of pathogens, the lack of clinical reference data, and unknown proportion of people living with HIV (PLHIV) are important factors that hinder the proper evaluation of the epidemiological situation and NTM disease. In addition to these factors, diagnosis and drug sensitivity results delay the expensive treatment. Undesirable adverse drug effects also pose a problem, particularly relevant in low middle income countries2,3,5.
In Brazil, there are few studies on NTM infection; its prevalence and geographically variable species are still not well known7.
In 2007, the American Thoracic Society (ATS), in conjunction with the Infectious Diseases Society of America (IDSA), described the treatment criteria for patients with NTM4. These criteria were updated in 20205. The treatment generally includes at least three drugs administered for ≥12 months, depending on the species and severity of the disease5.
Thus, this study aims to evaluate NTM isolates, apply the ATS/IDSA criteria for diagnosis and treatment, and analyze the clinical data and outcomes in patients who received treatment at a specialty hospital.
MATERIALS AND METHODS
This study included analyses of patients with NTM isolates from inpatients and outpatients at a tertiary hospital at the Universidade Federal de Minas Gerais (UFMG). The data were collected between January 2008 and July 2019. All patients, with at least one positive sample from any part of the body with NTM, were eligible. However, only those who met the 2007 ATS/IDSA criteria – in the case of sputum at least two samples were required with identification of the same species4, ≥ 18 years old with isolates of NTM or Mycobacterium sp. – answered a standardized questionnaire survey and had their medical records reviewed, which included clinical, mycobacteriological and radiological data, such as age, sex, symptoms, and comorbidities. For the diagnosis of infection by extrapulmonary NTM, clinical, mycobacteriological and imaging data were analyzed4,5. Cure criteria was defined according to van Ingen et al.8.
Identification tests were performed using phenotypic methods9 or enzyme restriction analysis of the hsp-65 gene (PRA-hsp65)8 at the Fundacao Ezequiel Dias (FUNED). A drug susceptibility test was not conducted in this study. The nomenclatures of the genera, species, and subspecies were verified in the list of Prokaryotic Names with Standing in Nomenclature10,11.
The treated patients were administered aminoglycosides for 2–3 months depending on the severity and presence or absence of pulmonary cavity, rifampin, ethambutol, macrolides (clarithromycin or azithromycin), and isoniazid. The latter was not prescribed when MAC was identified. The treatment duration for pulmonary and extrapulmonary diseases ranged from 12 to 18 months4.
Data collected from the questionnaires were analyzed using SPSS Statistical Software (version 22.0, IBM, Armonk, NY, USA). Descriptive analyses were performed using the Statistical Analysis Software (version 9.4, SAS Institute Inc., Cary, NC, USA).
The UFMG Research Ethics Committee approved the study protocol under Nº 2.843.437 (CAAE 93672218.8.0000.5149).
RESULTS
We obtained 506 clinical samples from 113 patients, 129 of which were positive for NTM or Mycobacterium sp., with an annual average of 10 patients. Of these, 59 patients met the disease criteria and 29 received treatment (Figure 1).
Of the 506 samples, 333 (65.8%) were sputum, 106 (20.9%) urine, 21 (4.2%) bronchoalveolar lavage, 14 (2.8%) tracheal aspirate, 10 (2%) liquor, 9 (1.7%) biopsies, 5 (1%) pleural liquid, 5 (1%) blood and 3 (0.5%) secretions. Of 113 NTM patients, M. kansasii, M. fortuitum, M. gordonae, and M. intracellulare were identified in 69 (61.1%) and Mycobacterium spp. in 44 (38.9%) patients. The cases of M. gordonae occurred in patients with an underlying predisposition (n=2) and transplant recipients (n=1) (Table 1). Although the pleural fluid and blood were not positive for mycobacteria, the samples isolated from other sites were positive.
Species of Nontuberculous Mycobacteria in 113 patients attended at the tertiary hospital of the Universidade Federal de Minas Gerais from 2008 to 2019.
Among 113 with NTM isolates, 59 (52.2%) patients met the disease criteria: 29 (49.1%) received treatment for pulmonary or extrapulmonary forms (Table 1). Of 20/29 (68.9%) patients who received treatment, NTM species was identified. Treatment was not instituted for other patients (n=30), as they were lost to follow-up. Among the 29 patients treated for NTM, 24 (82.8%) presented the pulmonary form (Table 2) and clinical characteristics (Table 3).
The NTM species of the patients treated with or without comorbidity are described in Table 4. The outcomes of the 29 patients who underwent treatment were as follows: 22 (75.8%) were cured, four (13.7%) died from NTM infection (M. intracellulare; n=2, M. avium subsp. avium; n=1, and M. chimera; n=1), and three (10.3%) were lost to follow-up. Serious adverse reactions were not observed. One patient with corneal lesion was previously described in another article11.
DISCUSSION
Based on these results, in addition to identifying the high proportion of cured patients among the treated ones, it is important to identify patients with NTM disease as per the ATS/IDSA criteria.
The largest number of NTM are identified in the Southeast and South regions, which may be due to the increase in laboratory coverage and greater investment in laboratory techniques for diagnosis6. Our study identified the majority of the species (61.1%).
Efforts have been made in recent years by researchers at FUNED-MG to increase and improve the identification of NTM. Some studies report that the drug susceptibility testing have great value in guiding therapy, particularly when tested for aminoglycosides, rifampicin, and ethambutol, in addition to genotypic tests to detect mutations responsible for drug resistance5,11,12. Microbiological diagnosis, even if insufficient, is essential for the diagnosis of an infection. To achieve this, it is essential to correctly identify NTM’s species4,5.
Diseases caused by NTM are emerging worldwide, a fact that has been related to the improvement of diagnostic methods, population aging, and the presence of associated immunosuppressive diseases such as HIV infection, pulmonary sequelae, and smoking. Moreover, iatrogenic and nosocomial infections caused by NTM are becoming more frequent, as are breast implant surgeries and ophthalmologic surgical procedures to correct refraction problems1,13. Importantly, the awareness of medical professionals regarding these diseases has also increased6.
In our study, the pulmonary form was the most frequent, as described in other studies6,13, associated with main preconditions like HIV/AIDS, organ transplantation, cystic fibrosis, TB sequelae, and being a current or former smoker, which corresponded to the profile of patients attended to in a tertiary hospital.
The signs and symptoms of the pulmonary form (most frequent) are similar to those of pulmonary TB. Patients with such symptoms may be inadequately treated for TB, since it is often only considered when there is treatment failure for TB and the patient is in a more advanced stage of the disease. Thus, the diagnosis requires a high index of suspicion and combined efforts of microbiologists and physicians14.
Some studies have reported that MAC and M. kansasii are the most common pathogens that cause lung diseases1,6. However, M. kansasii, M. chimera, M. fortuitum, and M. intracellulare are the main species with respect to disease criteria and indications for treatment. These differences in results are probably due to geographic differences15.
M. gordonae is commonly found in the environment and clinical laboratories and is almost always considered non-pathogenic. However, M. gordonae causes infections, particularly in patients with an underlying predisposition or immunosuppression, such as Acquired Immunodeficiency Syndrome (AIDS), undergoing peritoneal dialysis in transplant recipients5. Our study-enrolled patients had an underlying predisposition and were immunosuppressed.
Few studies have described the prevalence of NTM in the extrapulmonary form; however, these differences in involvement may be due to environmental influences and the dynamics of the disease12,16.
In some NTM cases that are treated as TB, the patient may positively respond to treatment, since drugs are effective in some NTM species, as for M. kansasii, which responds effectively to treatment even in the absence of macrolides4,5,6.
In a study conducted in Brazil, the authors described that the cure rate of patients with MAC was 60.7%, whereas that of those infected with M. kansasii was 73.3%17. Regardless of species, the cure rate was higher (75.8%) in patients treated during this study.
The application of the “Recommendations for the diagnosis and treatment of diseases caused by nontuberculous mycobacteria” in Brazilian reference health units may contribute to greater success in the treatment of NTM.
This study had limitations in terms of the follow-up and outcomes of patients who did not undergo treatment.
CONCLUSION
We conclude that the major species identified in this study was M. kansasii. The most frequent symptoms of the patients who underwent treatment were dyspnea, coughing, sputum, and loss of appetite, and the proportion of cured patients was high among the treated patients.
ACKNOWLEDGMENTS
We are also grateful to the Graduate Program in Health Sciences, Tropical Medicine, and Infectology of the Universidade Federal de Minas Gerais (UFMG) School of Medicine, the Brazilian Office for the Advancement of Higher Education, the Brazilian National Council for Scientific and Technological Development, the Foundation for the Support of Research in the Minas Gerais State, UFMG President’s Office for Research, the Brazilian Tuberculosis Research Network, and the Bacterial and Fungal Diseases Service Laboratory, Ezequiel Dias Foundation of Minas Gerais State.
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Publication Dates
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Publication in this collection
30 June 2023 -
Date of issue
2023
History
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Received
3 Jan 2023 -
Accepted
22 May 2023
