NTM MAC is Difficult to Treat
Treatment options for NTM MAC
Non-tuberculous mycobacteria (NTM) are a group of bacteria, capable of causing lower respiratory tract infections (LRTIs).1 These are pathogens that affect both immunocompromised and immunocompetent patients. The incidence and prevalence of NTM pulmonary disease (NTM-PD) are increasing worldwide, and rapidly becoming a major public health problem.2 Most patients with NTM-PD require a multi-drug treatment for a prolonged period of time as 12 months of sputum culture negativity is required for treatment to be classified as a success, meaning the burden to both the healthcare system, and the patient are very significant.2 3 Mycobacterium avium complex (MAC) is the most common cause of NTM-PD worldwide.4
The decision to start treatment for NTM-PD is often not easy, and requires careful analysis of risks and benefits for each individual patient.2 So how do you know when, or if, to treat a patient presenting with NTM-PD?
What are the guideline recommendations for treatment?
To prevent the emergence of macrolide-resistant MAC strains, which are associated with increased mortality, it is important that patients receive a multidrug regimen as the first line treatment.5 6 The British Thoracic Society (BTS) recommends the following antibiotic regimens for the treatment of NTM MAC pulmonary disease.3
None of the drugs in these regimens are licensed in Europe for NTM-PD and so use of these drugs for this condition is “off-label”. There is limited data to support these recommendations, in terms of both suggested regimen and duration of therapy. Much of the guidelines are based on expert opinion and small numbers of patients studied in trials.
What are the implications of delayed treatment?
Despite the BTS guidelines, around half of patients in primary care do not receive guideline-based therapy, and around 14% of patients do not receive treatment at all.7 Patients may decide not to initiate treatment due to the side effects from the multi-drug therapy outweighing the severity of the symptoms associated with NTM-PD. A delay in commencing NTM-PD therapy can lead to severe consequences and disease progression. Of 40 patients with untreated nodular bronchiectatic MAC pulmonary disease, 97.5% experienced radiologic deterioration over an average of 6 years, after receiving no early interventional treatment due to minimum symptoms.8 Other studies, involving larger numbers of patients, investigating radiographic changes in MAC pulmonary disease patients have shown that persistent culture positivity and cavitary disease are associated with greater radiographic progression.9 10 Furthermore, it has been shown that NTM MAC patients who do not receive treatment have a significantly higher mortality rate, compared with NTM MAC patients who do receive treatment.11 Additionally, a delay in diagnosis and the subsequent treatment of NTM-PD can lead to a decline of lung function, a worsening of symptoms such as chronic cough, fatigue, malaise and fever, and a decrease in health-related quality of life for patients.12 13 14 15
Even with set guideline recommendations from the BTS for both treatment and testing, a significant number of patients are either misdiagnosed or not diagnosed at all, due to variable rates of testing and symptoms similar in nature to underlying lung disease.15 16 17 18 19
NTM MAC – is it a difficult decision to treat?
Treatment for NTM can be lengthy and challenging due to the fact it varies according to species and the fact there are limited treatment options. Treatment is further complicated by potential toxicity and discouraging outcomes.2 The decision to initiate treatment is influenced by the severity of NTM-PD, the risk of progressive NTM-PD, the presence of comorbidity and the goals of treatment, as well as patient preference.3 Whilst diagnosis of NTM MAC pulmonary disease does not always require immediate initiation of treatment, an understanding of the potential for progression is important.4
The duration and toxicity of antimicrobial therapy must be considered for each patient. It is often appropriate to observe a patient’s clinical course before embarking on therapy.3 The important side effects and substantial toxicity associated with some of the therapies recommended by guidelines for use in the treatment of NTM-PD suggest that there is a significant trade-off involved in undertaking medical treatment.14
Patients are considered treatment failures or to have refractory disease if they have not had a response (microbiologic, clinical or radiographic) after 6 months of appropriate therapy or achieved conversion of sputum to culture negative status after 12 months of appropriate therapy.6 3 Refractory patients face many more treatment challenges than treatment naïve patients, with current choices for effective treatment being sparse.5 20
The recommended treatment for NTM MAC can be lengthy and complicated,2 with guidance suggesting continuing treatment for 12 months after negative sputum culture conversion needed for culture clearance.4 Guidelines recommend initiating a multi-drug regimen as first line treatment to prevent the emergence of antibiotic resistant strains of MAC.5 6 Moreover, a delay in commencing treatment for NTM-PD can lead to a worsening of symptoms and a decline in lung function.12 13 14 The decision to initiate treatment must be made based on the potential risks and benefits of therapy for individual patients.