US Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis

Abstract

Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause chronic pulmonary infection, particularly in individuals with pre-existing inflammatory lung disease such as cystic fibrosis (CF). Pulmonary disease caused by NTM has emerged as a major threat to the health of individuals with CF but remains difficult to diagnose and problematic to treat. In response to this challenge, the US Cystic Fibrosis Foundation (CFF) and the European Cystic Fibrosis Society (ECFS) convened an expert panel of specialists to develop consensus recommendations for the screening, investigation, diagnosis and management of NTM pulmonary disease in individuals with CF. Nineteen experts were invited to participate in the recommendation development process. Population, Intervention, Comparison, Outcome (PICO) methodology and systematic literature reviews were employed to inform draft recommendations. An anonymous voting process was used by the committee to reach consensus. All committee members were asked to rate each statement on a scale of: 0, completely disagree, to 9, completely agree; with 80% or more of scores between 7 and 9 being considered 'good' agreement. Additionally, the committee solicited feedback from the CF communities in the USA and Europe and considered the feedback in the development of the final recommendation statements. Three rounds of voting were conducted to achieve 80% consensus for each recommendation statement. Through this process, we have generated a series of pragmatic, evidence-based recommendations for the screening, investigation, diagnosis and treatment of NTM infection in individuals with CF as an initial step in optimising management for this challenging condition.

Keywords: Bacterial Infection; Cystic Fibrosis.

Figure 1

A suggested algorithm for the investigation of individuals with clinical suspicion of NTM-PD (AFB, acid-fast bacilli; CF, cystic fibrosis; FEV₁, forced expiratory volume in 1 s; HRCT, high-resolution CT; NTM-PD, non-tuberculous mycobacteria pulmonary disease).

Figure 2

Typical treatment schedules for individuals with CF with Mycobacterium abscessus or MAC pulmonary disease. (A) M. abscessus treatment is divided into an initial intensive phase with an oral macrolide (preferably azithromycin) and intravenous amikacin with one or more additional intravenous antibiotics (tigecycline, imipenem, cefoxitin) for 3–12 weeks (depending on severity of infection, response to treatment, and the tolerability of the regimen), followed by a continuation phase of oral macrolide (preferably azithromycin) and inhaled amikacin with 2–3 additional antibiotics (minocycline, clofazimine, moxifloxacin, linezolid). Antibiotic choices should be guided but not dictated by drug susceptibility testing. Baseline and interval testing for drug toxicity is essential (B). MAC treatment (for clarithromycin-sensitive disease) should be with a daily oral macrolide (preferably azithromycin), rifampin and ethambutol. An initial course of injectable amikacin or streptomycin should be considered in the presence of (i) AFB smear positive respiratory tract samples, (ii) radiological evidence of lung cavitation or severe infection and (iii) systemic signs of illness. Baseline and interval testing for drug toxicity is essential (AFB, acid-fast bacilli; CF, cystic fibrosis; HRCT, high-resolution CT; MAC, Mycobacterium avium complex).