Management of Non-Tuberculous Mycobacteria in Individuals with Cystic Fibrosis
Publication Date: December 13, 2015
Last Updated: March 14, 2022
Recommendation Statements
The CF Foundation and the ECFS recommend that the potential for cross-infection of non-tuberculous mycobacteria (NTM) (particularly Mycobacterium abscessus complex [MAC]) between individuals with CF should be minimised by following national infection control guidelines.
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The CF Foundation and the ECFS recommend that cultures for NTM be performed annually in spontaneously expectorating individuals with a stable clinical course.
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The CF Foundation and the ECFS recommend that, in the absence of clinical features suggestive of NTM pulmonary disease, individuals who are not capable of spontaneously producing sputum do not require screening cultures for NTM.
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The CF Foundation and the ECFS recommend that culture and smears for AFB from sputum should be used for NTM screening.
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The CF Foundation and the ECFS recommend against the use of oropharyngeal swabs for NTM screening.
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The CF Foundation and the ECFS recommend that culture and smears for AFB from sputum, induced sputum, bronchial washings or bronchoalveolar lavage samples can be used to evaluate individuals with CF suspected to have NTM pulmonary disease.
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The CF Foundation and the ECFS recommend against the routine use of transbronchial biopsies to detect NTM in individuals with CF suspected to have NTM pulmonary disease.
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The CF Foundation and the ECFS recommend against the use of oropharyngeal swabs to perform diagnostic smears and cultures in individuals with CF suspected to have NTM pulmonary disease.
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The CF Foundation and the ECFS recommend that respiratory tract samples should be cultured using both solid and liquid media.
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The CF Foundation and the ECFS recommend that the incubation duration for NTM cultures should be for a minimum of 6 weeks.
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The CF Foundation and the ECFS recommend that an NTM culture should be processed within 24 h of collection to optimise the detection of NTM in respiratory samples. If a delay in processing is anticipated, refrigeration of samples is advised.
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The CF Foundation and the ECFS recommend that respiratory tract samples should be decontaminated using the standard N-acetyl L-cysteine, NALC, (0.5%)–NaOH (2%) method.
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The CF Foundation and the ECFS recommend that, if a sample remains contaminated with Gram-negative bacteria after standard NALC-NaOH decontamination, it should be further treated with either 5% oxalic acid or 1% chlorhexidine.
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The CF Foundation and the ECFS recommend against the use of non-culture-based methods for detecting NTM in respiratory tract samples.
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The CF Foundation and the ECFS recommend that all NTM isolates from individuals with CF should undergo molecular identification.
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The CF Foundation and the ECFS recommend that all NTM isolates from individuals with CF should be identified to the species level, except for M. intracellulare, M. avium and M. chimaera, where identification can be limited to MAC, and M. abscessus complex, which should be subspeciated.
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The CF Foundation and the ECFS recommend that for MAC, clarithromycin susceptibility testing should be performed on an isolate recovered prior to initiation of treatment. Clarithromycin susceptibility testing should also be performed on subsequent isolates if the patient
(a) fails to culture convert after 6 months of NTM treatment
(b) recultures MAC after initial culture conversion while on NTM treatment or
(c) recultures MAC after completion of NTM treatment.
(b) recultures MAC after initial culture conversion while on NTM treatment or
(c) recultures MAC after completion of NTM treatment.
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The CF Foundation and the ECFS recommend that for M. abscessus complex, susceptibility testing should include at least clarithromycin, cefoxitin and amikacin (and preferably also tigecycline, imipenem, minocycline, moxifloxacin and linezolid).
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The CF Foundation and the ECFS recommend that drug susceptibility testing should be performed in accordance with CLSI guidelines.
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The CF Foundation and the ECFS recommend that ATS/IDSA criteria for the diagnosis of NTM pulmonary disease should be used in individuals with CF (ATS/IDSA 2007 Statement).
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The CF Foundation and the ECFS recommend that other CF pathogens and comorbidities should be considered as potential contributors to a patient's symptoms and radiological features when determining the clinical significance of NTM-positive cultures.
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The CF Foundation and the ECFS recommend that NTM treatment should be considered for individuals with CF who have ATS/IDSA defined NTM pulmonary disease.
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The CF Foundation and the ECFS recommend that individuals receiving azithromycin as part of their CF medical regimen who have a positive NTM culture should not continue azithromycin treatment while evaluation for NTM disease is underway as azithromycin monotherapy may lead to resistance. A macrolide agent may be included in a multidrug treatment regimen if criteria are met for NTM disease.
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The CF Foundation and the ECFS recommend that treatment of M. abscessus complex pulmonary disease should involve an intensive phase followed by a continuation phase.
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The CF Foundation and the ECFS recommend that the intensive phase should include a daily oral macrolide (preferably azithromycin) in conjunction with 3–12 weeks of intravenous amikacin and one or more of the following: intravenous tigecycline, imipenem or cefoxitin, guided but not dictated by drug susceptibility testing. The duration of intensive phase therapy should be determined by the severity of infection, the response to treatment and the tolerability of the regimen.
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The CF Foundation and the ECFS recommend that the continuation phase should include a daily oral macrolide (preferably azithromycin) and inhaled amikacin, in conjunction with 2–3 of the following additional oral antibiotics: minocycline, clofazimine, moxifloxacin and linezolid, guided but not dictated by drug susceptibility testing.
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The CF Foundation and the ECFS recommend that individuals with M. abscessus complex pulmonary disease should be managed in collaboration with experts in the treatment of NTM and CF, as drug intolerance and drug-related toxicity occur frequently, and changes in antibiotic therapy are often required.
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The CF Foundation and the ECFS recommend that monotherapy with a macrolide or other antimicrobial should never be used in the treatment of M. abscessus complex pulmonary disease.
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The CF Foundation and the ECFS recommend the same antibiotic regimen for treatment of all species within the MAC.
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The CF Foundation and the ECFS recommend that clarithromycin-sensitive MAC pulmonary disease should be treated with a daily oral antibiotic regimen containing a macrolide (preferably azithromycin), rifampin and ethambutol.
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The CF Foundation and the ECFS recommend against the use of intermittent (three times per week) oral antibiotic therapy to treat MAC pulmonary disease.
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The CF Foundation and the ECFS recommend that monotherapy with a macrolide or other antimicrobial agent should never be used in the treatment of MAC pulmonary disease.
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The CF Foundation and the ECFS recommend that an initial course of intravenous amikacin should be considered for the treatment of MAC pulmonary disease in the presence of one or more of the following:
- AFB smear positive respiratory tract samples
- Radiological evidence of lung cavitation or severe infection
- Systemic signs of illness
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The CF Foundation and the ECFS recommend that clarithromycin-resistant MAC pulmonary disease should be managed in collaboration with experts in the treatment of NTM and CF.
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The CF Foundation and the ECFS recommend that individuals with CF receiving NTM treatment should have expectorated or induced sputum samples sent for NTM culture every 4–8 weeks throughout the entire course of treatment to assess the microbiological response.
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The CF Foundation and the ECFS recommend that a schedule for detecting drug toxicity (including hearing loss, visual loss, renal impairment and liver function test abnormalities) should be set in place at the time of NTM treatment initiation and implemented throughout treatment based on the specific drugs prescribed.
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The CF Foundation and the ECFS recommend that an HRCT scan of the lungs should be performed shortly before starting NTM treatment and at the end of NTM treatment to assess the radiological response.
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The CF Foundation and the ECFS recommend that NTM antibiotic therapy should be prescribed for 12 months beyond culture conversion (defined as three consecutive negative cultures, with the time of conversion being the date of the first of the three negative cultures) as long as no positive cultures are obtained during those 12 months.
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The CF Foundation and the ECFS recommend that individuals who fail to culture convert despite optimal NTM therapy may benefit from long-term suppressive antibiotic treatment.
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The CF Foundation and the ECFS recommend that, when amikacin is given intravenously or when streptomycin is given intravenously or intramuscularly, serum levels should be monitored and dosing adjusted to minimise ototoxicity and nephrotoxicity.
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The CF Foundation and the ECFS recommend against routinely obtaining serum levels of other anti-mycobacterial drugs. However, absorption of oral medications is often reduced in CF. Therefore use of therapeutic drug monitoring should be considered for individuals failing to improve despite taking recommended drug regimens or for those on concomitant medications with significant interactions with NTM drugs.
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The CF Foundation and the ECFS recommend against the use of interferon γ as adjuvant therapy for NTM pulmonary disease in individuals with CF.
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The CF Foundation and the ECFS recommend that vitamin D should be supplemented according to national CF care guidelines.
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The CF Foundation and the ECFS recommend that lung resection should only be considered under extraordinary circumstances and in consultation with experts on the treatment of NTM and CF.
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The CF Foundation and the ECFS recommend that all individuals with CF being considered for lung transplantation should be evaluated for NTM pulmonary disease.
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The CF Foundation and the ECFS recommend that the presence of current or previous respiratory tract samples positive for NTM should not preclude individuals being considered for lung transplantation.
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The CF Foundation and the ECFS recommend that individuals with CF who have NTM pulmonary disease and are being evaluated for transplantation should start treatment prior to transplant listing.
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The CF Foundation and the ECFS recommend that individuals with CF receiving NTM treatment with sequential negative cultures may be eligible for transplant listing.
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The CF Foundation and the ECFS recommend that individuals with CF who have completed treatment for NTM pulmonary disease with apparent eradication of the organism may be eligible for transplant listing.
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The CF Foundation and the ECFS recommend that the presence of persistent M. abscessus complex or MAC infection despite optimal therapy is not an absolute contraindication to lung transplant referral.
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Recommendation Grading
Overview
Title
Management of Non-Tuberculous Mycobacteria in Individuals with Cystic Fibrosis
Authoring Organization
Cystic Fibrosis Foundation
Publication Month/Year
December 13, 2015
Last Updated Month/Year
August 1, 2023
Supplemental Implementation Tools
Document Type
Consensus
External Publication Status
Published
Country of Publication
US
Inclusion Criteria
Female, Male, Adolescent, Adult, Child, Infant, Older adult
Health Care Settings
Emergency care, Hospital
Intended Users
Respiratory therapist, epidemiology infection prevention, nurse, nurse practitioner, physician, physician assistant
Scope
Counseling, Management
Diseases/Conditions (MeSH)
D003550 - Cystic Fibrosis, D009165 - Mycobacterium Infections, Nontuberculous
Keywords
cystic fibrosis, Non-tuberculous mycobacteria, chronic pulmonary infection
Source Citation
Floto RA, Olivier KN, Saiman L, et alUS Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosisThorax 2016;71:i1-i22.