Genetic diversity and drug resistance of Mycobacterium avium in Italy

Mycobacterium avium complex is responsible for most of the human-associated nontuberculous mycobacteria infections. M. avium is classified into 4 subspecies, each endowed with specific pathogenetic and host range characteristics; among these, M. avium subsp. hominissuis (MAH), that is usually isolated from human and swine sources, is an important pathogen that causes infections in the respiratory tract, lymph node, and, occasionally, soft tissue of immunocompetent patients; moreover, it causes disseminated diseases in patients with human immunodeficiency virus infection. In Italy, as in many other countries worldwide, MAH is the most common cause of nontuberculous mycobacteria infection and the incidence of MAH infections is increasing. In the present study, we determined the VNTR-based genetic diversity of a collection of 71 MAH human strains isolated from 2010 to 2016 in order to estimate the genetic relationships among MAH isolates in our setting. Moreover, we performed the clarithromycin susceptibility test in order to investigate whether there was any association between the VNTR pattern and the minimal inhibitory concentration (MIC) of clarithromycin. The VNTR analysis revealed 24 distinct VNTR patterns; of these, 16 patterns were unique, while 8 patterns were shared by 2 or more isolates, thus yielding 8 clusters including a total of 55 isolates. Our results showed that most MAH isolates displayed a close genetic relationship, indicating that the MAH genotypes are quite homogeneous in our geographical area. Such genotypic stability of the MAH strain population circulating in our region supports the hypothesis of the presence of possible local sources of infection and transmission pathways at the local level. Clarithromycin showed strong antimicrobial activity against MAH isolates, as indicated by the high proportion (94.4%) of susceptible strains. No significant association between VNTR genotype and MIC of clarithromycin was found; moreover, due to the small number of resistant isolates, it was not easy to evaluate the correlation between VNTR genotypes and clarithromycin susceptibility. Further investigations on larger collections of MAH strains of human, animal and environmental origin, are needed both to define the correlation between genotypes and clinical features or drug resistance and to clarify the sources of infection and the specific transmission pathways of our region, in order to achieve a better control of MAH infection.