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Non-Tuberculous Mycobacteria: Epidemiological Pattern in a Reference Laboratory and Risk Factors Associated with Pulmonary Disease

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Non-Tuberculous Mycobacteria: Epidemiological Pattern in a Reference Laboratory and Risk Factors Associated with Pulmonary Disease Epidemiol. Infect. (2017), 145, 515–522. © Cambridge University Press 2016 doi:10.1017/S0950268816002521 Non-tuberculous mycobacteria: epidemiological pattern in a reference laboratory and risk factors associated with pulmonary disease J. MENCARINI1,C.CRESCI2, M. T. SIMONETTI3,C.TRUPPA1, G. CAMICIOTTOLI2,4,M.L.FRILLI4,P.G.ROGASI5,S.VELOCI1, 2,4 3,6,7 1,5 M. PISTOLESI ,G.M.ROSSOLINI ,A.BARTOLONI AND F. BARTALESI5* 1 Infectious Diseases Unit, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy 2 Pneumology Unit, Careggi Hospital, Florence, Italy 3 Tuscany Regional Reference Centre for Mycobacteria, Microbiology and Virology Unit, Careggi Hospital, Florence, Italy 4 Section of Respiratory Medicine, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy 5 Unit of Infectious and Tropical Diseases, Careggi Hospital, Florence, Italy 6 Section of Microbiology, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy 7 Department of Medical Biotechnologies, University of Siena, Siena, Italy Received 8 April 2016; Final revision 7 October 2016; Accepted 9 October 2016; first published online 2 November 2016 SUMMARY The diseases caused by non-tuberculous mycobacteria (NTM), in both AIDS and non-AIDS populations, are increasingly recognized worldwide. Although the American Thoracic Society published the guidelines for diagnosis of NTM pulmonary disease (NTM-PD), the diagnosis is still difficult. In the first part of the study, we collected data on NTM isolates in the Mycobacteriology Laboratory of Careggi Hospital (Florence, Italy) and analysed the epidemiological data of NTM isolates. Then, to analyse the risk factors associated to NTM-PD, we studied the presence of ATS/IDSA criteria for NTM-PD in patients who had at least one positive respiratory sample for NTM and were admitted to the Infectious Disease Unit and the Section of Respiratory Medicine. We selected 88 patients with available full clinical data and, according to ATS/IDSA criteria, classified 15 patients (17%) as NTM-PD cases and 73 as colonized patients (83%). When comparing colonized and NTM-PD patients we did not find significant differences of age, gender and comorbidity. We observed that Mycobacterium avium and M. intracellulare were statistically associated with NTM-PD (P = 0·001) whereas M. xenopi was statistically associated with colonization. Although the number of studied patients is limited, our study did not identify risk factors for NTM-PD that could help clinicians to discriminate between colonization and disease. We underline the need of close monitoring of NTM-infected patients until the diagnosis is reasonably excluded. Further larger prospective studies and new biological markers are needed to identify new useful tools for the diagnosis of NTM-PD. Key words: Mycobacteria, respiratory infections. * Author for correspondence: Dr F. Bartalesi, Infectious and Tropical Disease Unit, Careggi Hospital, Largo Brambilla 3, 50134, Florence, Italy. (Email: [email protected]) Downloaded from https://www.cambridge.org/core. IP address: 170.106.40.40, on 28 Sep 2021 at 00:27:40, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms. https://doi.org/10.1017/S0950268816002521 516 J. Mencarini and others INTRODUCTION to clarifying the application of those criteria in clinical Non-tuberculous mycobacteria (NTM) are environ- practice and to describing our local epidemiology. We fi mental organisms residing in soil and water, with identi ed patients with positive specimens from the low pathogenicity to humans. Over recent decades, Infectious Disease Unit and the Section of the isolation of NTM, and the disease caused by Respiratory Medicine and collected their medical NTM in both AIDS and non-AIDS populations records to classify the patients by the presence of the ATS/IDSA criteria for NTM-PD. have been increasingly reported worldwide [1–3]. This rise is certainly due to the increase in number and quality of mycobacteriology laboratories, and MATERIALS AND METHODS the improvement of laboratory techniques, as well as to the advent of AIDS in the 1980s. However, there Data collection are probably other factors that can justify this trend, We retrospectively reviewed the database of the myco- such as the larger number of immunocompromised bacteria isolated in a mycobacteriology laboratory patients surviving today, rising life expectancy and (Tuscany Regional Reference Centre for Mycobacteria, the availability of computed tomography scanning Careggi Hospital, Florence, Italy) for the period from [4, 5]. January 2011 to December 2012. We excluded 349 myco- NTM disease and its pattern of presentation are bacteria of the Mycobacterium tuberculosis complex and related to the interactions between species-specific viru- 32 NTM isolated from non-respiratory specimens. lence factors and host factors. Although generally Finally, we identified a total of 554 NTM isolated from NTM virulence is low, it may differ between species respiratory samples [sputum, bronchoalveolar lavage and some strains might demonstrate different virulence (BAL), pleural effusion]. We analysed the epidemio- [6–8]. Regarding the host, pre-existing structural lung logical data of NTM isolates, considering also the demo- disease [tuberculosis, cystic fibrosis, chronic obstructive graphic characteristic (age, sex, geographical origin) of pulmonary disease (COPD), silicosis and other the patients with positive specimens. In the second part pneumoconiosis], alcoholism, smoking, oesophageal of our study, among the patients with NTM isolates, reflux and alterations of innate or acquired immunity we selected those admitted to the Infectious Disease are acknowledged risk factors for development of Unit and the Section of Respiratory Medicine who had NTM pulmonary disease (NTM-PD) [9, 10]. full clinical data available. For each patient we collected The NTM infection’s clinical presentation is non- clinical and radiological information from clinical specific and in the clinical setting it is not easy to dis- records. We define a ‘NTM-PD case’ as a patient fulfilling tinguish environmental contamination with transient ATS/IDSA diagnostic criteria (clinical, microbiological colonization from pulmonary disease. In order to and radiological criteria) in the absence of other pulmon- standardize the definition for NTM-PD and to reach ary infections. We compared clinical data between a more accurate diagnosis, in 2007 the American patients definedasNTM-PDcasesandasNTM-PD Thoracic Society, in collaboration with the Infectious colonized, to identify potential risk factors associated Disease Society of America (ATS/IDSA), published with NTM-PD. guidelines for the diagnosis, treatment and prevention of NTM disease. In this guideline, it is specified that the diagnosis of NTM-PD requires the presence of Laboratory diagnosis respiratory symptoms, radiological features, microbio- Specimens were decontaminated using a standard N- logical criteria and the exclusion of other diagnoses [11]. acetyl-L-cysteine-NaOH method. A rhodamine-auramine The clinical relevance of NTM species could differ stain method was utilized to analyse specimens for acid- by region or setting and some authors suggest modu- fast bacilli. Cultures were performed on liquid and solid lation of diagnostic criteria according to clinical rele- medium at 35–37 °C. As liquid medium, a non- vance of each species [9, 12]. radiometric automated system (BATECT™ MGIT™ Considering the complexity of the NTM-PD diag- 960, Becton Dickinson, USA) was used to detect myco- nosis, due to the difficulty in applying ATS/IDSA cri- bacterial growth; solid media (Lowenstein–Jensen) were teria in different settings, we collected data on NTM observed weekly for up to 2 months. Positive cultures isolates in the mycobacteriology laboratory of our were microscopically confirmed and identified to differen- hospital over 2 years, with the aim of contributing tiate M. tuberculosis complex from NTM using a rapid Downloaded from https://www.cambridge.org/core. IP address: 170.106.40.40, on 28 Sep 2021 at 00:27:40, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms. https://doi.org/10.1017/S0950268816002521 NTM and pulmonary disease 517 immunochromatographic test to detect MTbc-specific Table 1. Microbiological date of the 554 NTM isolated MPT64 antigen (MGIT TB identification test). A further from respiratory sample in the years 2011–2012 differentiation up to species level was performed using commercially available molecular genetic methods (line Variable Samples, n (%) ® probe assay): Hain GenoType MTBC for differentiation Isolation sources of the M. tuberculosis complex and Hain GenoType® Sputum 372 (67·1) Mycobacterium CM (Hain Lifescience GmbH, Bronchoalveolar lavage 113 (20·5) Germany) for non-tuberculous more common mycobac- Bronchial aspirated 66 (11·9) Pleural fluid 3 (0·5) teria. Another Hain kit was used to identify some uncom- Species identification ® mon species (GenoType Mycobacterium AS, Hain Mycobacterium xenopi 219 (39·5) Lifescience GmbH) [13]. In some cases a further sequen- Mycobacterium avium complex 216 (38·9) cing of specific genetic targets was needed in order to dif- M. chimaera 100 (46·3) ferentiate species between a complex (e.g. M. avium M. avium 78 (36·1) M. intracellulare 37 (17·1) complex) or a group (e.g. M. fortuitum group) or to detect M. bouchedurhonense 1 (0·5) some infrequently encountered
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