Title : Study of a Non-TB Mycobacterium Cohort in a NHS District General Hospital
Abstract:
Introduction:
Non-TB mycobacterium (NTM) infections are relatively rare but increasingly prominent, with a rising incidence in both the United Kingdom and Europe. The commonest species is Mycobacterium avium intracellulare (MAI), usually associated with chronic lung diseases. Most data comes from tertiary referral centers, which introduces selection bias. Therefore, we conducted a retrospective cohort study in an NHS District General Hospital (DGH), with an aim to identify underlying characteristics of an unselected population. Our patients displayed varying disease courses, from indolent to disseminated. We were interested to find an association between interferon-gamma pathway defects and disseminated NTM in some cases.
Method:
Retrospective cohort study conducted by reviewing electronic medical records. Inclusion criteria: adults with NTM growth in sputum. Exclusion criteria: paediatric patients and incomplete records.
Results:
61 patients had a coded diagnosis of NTM between 2016 - 2019. 57 of these had complete data records, included in our final analysis. Average age was 64 years, with equivocal number of male and female patients. The commonest causative organism was MAI - 50.9% of our cohort. The second-commonest organism was Mycobacterium chimaera (MC) - 14% (n=8). 39 patients underwent thoracic CT imaging. NTM lesions were predominantly in the upper lobes; 7 were bi-apical. 11 patients (19.3%) had pre-existing immunodeficiency; 3 of whom suffered severe or disseminated disease – all required intravenous treatment with Amikacin. Each of these patients had a deficiency in the interferon-gamma pathway. An association between deficiency of this cytokine and susceptibility to NTM infections is emerging, with several cases reports associating it with disseminated disease. Pre-existing pulmonary conditions were present in 46 patients (80.7%) - 19 of whom had bronchiectasis and 17 had COPD. 2 patients had lung cancer. Prior inhaled corticosteroids (ICS) use represented 42.1% of our population (n=24); Fluticasone was the commonest. 25 patients underwent treatment, 12 whom are on lifelong or continuing antibiotics. Average length of treatment was 26 months for those who completed a finite course. 11 patients achieved complete resolution of their NTM, whether treated or untreated.
Conclusion:
This study of a general population of British patients with NTM provided several interesting findings. The prevalence on MC was surprisingly higher than expected – 14% compared to 6% reported average. Although several publications associate MC with cardiac surgery and heater-cooler systems, none of our patients had a history of this. High prevalence in our cohort was likely due to increasing recognition of MC as a separate sub-species of Mycobacterium avium complex.
Immunodeficiency predisposed to more severe disease. Importantly, we found an association between disseminated disease requiring IV aminoglycosides and deficient interferon-gamma pathways. A few published case reports have made such an association and understanding of how interferon-gamma is involved in destroying NTM infections is emerging.
A significant proportion of our cohort had underlying respiratory diseases such as COPD and bronchiectasis – many of these patients were established with ICS. The commonest ICS was Fluticasone; this steroid has been associated with NTM previously. We are interested to investigate whether particular steroid inhalers predispose to NTM.
