British Thoracic Society guidelines for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD)

SeCTion 4: WhaT iS The evidenCe for TranSmiSSion of nTm BeTWeen individualS?recommendation ► Adequate infection control policies need to be implemented in both inpatient and outpatient settings to minimise risks of person-to-person transmission of Mycobacterium abscessus in individuals with cystic fibrosis (CF).(Grade B) SeCTion 5: hoW Should The lung diSeaSe aTTriBuTaBle To nTm infeCTion Be defined?recommendation ► In the absence of robust evidence to support an alternative definition and due to the clinical and research benefits of having a uniform definition, use of the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) 2007 definition of non-tuberculous mycobacterial (NTM) pulmonary disease is recommended 1 (see Box 1).(Grade D) good practice point 3 The management of coexisting lung conditions/ infections should be optimised before ascribing clinical decline to NTM-pulmonary disease. BTS guidelineSeCTion 12a: WhaT anTiBioTiC regimen Should Be uSed To TreaT maC-pulmonary diSeaSe?recommendations ► Clarithromycin-sensitive MAC-pulmonary disease should be treated with rifampicin, ethambutol and clarithromycin or azithromycin using an intermittent (three times per week) or daily oral regimen.The choice of regimen should be based on the severity of disease (as defined in table 3) and treatment tolerance.(Grade D) ► An intermittent (three times per week) oral antibiotic regimen should not be used in individuals with severe MAC-pulmonary disease (as defined in table 3) or in individuals with a history of treatment failure.(Grade D) ► An injectable aminoglycoside (amikacin or streptomycin) should be considered in individuals with severe MAC-pulmonary disease (as defined in table 3).(Grade D) ► Clarithromycin-resistant MAC-pulmonary disease should be treated with rifampicin, ethambutol and isoniazid or a quinolone, and consider an injectable aminoglycoside (amikacin or streptomycin).(Grade D) ► Nebulised amikacin may be considered in place of an injectable aminoglycoside when intravenous/intramuscular administration is impractical, contraindicated or longer term treatment with an aminoglycoside is required for the treatment of MAC-pulmonary disease.(Grade D) ► Macrolide monotherapy or macrolide/quinolone dual therapy regimens should not be used for the treatment of MAC-pulmonary disease.(Grade D) ► Antibiotic treatment for MAC-pulmonary disease should continue for a minimum of 12 months after culture conversion.(Grade D) good practice points 3 Individuals with clarithromycin-resistant MAC-pulmonary disease should be managed in collaboration with a physician experienced in managing NTM-pulmonary disease.3 Individuals with a history of treatment intolerance or treatment failure should be managed in collaboration with a physician experienced in managing NTM-pulmonary disease.SeCTion 12B: WhaT anTiBioTiC regimen Should Be uSed To TreaT M. kansasii-pulmonary diSeaSe?recommendations ► Rifampicin-sensitive M. kansasii-pulmonary disease should be treated with rifampicin, ethambutol and isoniazid or a macrolide (clarithromycin or azithromycin) using a daily oral regimen.(Grade D) ► Rifampicin-resistant M. kansasii-pulmonary disease should be treated with a three-drug regimen guided, but not dictated by, drug susceptibility test results using a daily oral regimen.(Grade D) ► Antibiotic treatment for M. kansasii-pulmonary disease should continue for a minimum of 12 months after culture conversion.(Grade D) good practice points 3 Individuals with rifampicin-resistant M. kansasii-pulmonary disease should be managed in collaboration with a physician experienced in managing NTM-pulmonary disease.3 Individuals with a history of treatment intolerance or treatment failure should be managed in collaboration with a physician experienced in managing NTM-pulmonary disease.SeCTion 12C: WhaT anTiBioTiC regimen Should Be uSed To TreaT M. MalMoense-pulmonary diSeaSe?recommendations ► M. malmoense-pulmonary disease should be treated with rifampicin, ethambutol and a macrolide (clarithromycin or azithromycin) using a daily oral regimen.(Grade D) ► An injectable aminoglycoside (amikacin or streptomycin) should be considered in individuals with severe M. malmoense-pulmonary disease (ie, acid-fast bacilli (AFB) smear-positive respiratory tract samples, radiological evidence of lung cavitation/severe infection or severe symptoms/signs of systemic illness).(Grade D) ► Nebulised amikacin may be considered in place of an injectable aminoglycoside when intravenous/intramuscular administration is impractical, contraindicated or longer term treatment with an aminoglycoside is required in the treatment of M. malmoense-pulmonary disease.(Grade D) ► Antibiotic treatment for M. malmoense-pulmonary disease should continue for a minimum of 12 months after culture conversion.(Grade D) good practice points 3 Individuals with a history of treatment intolerance or treatment failure should be managed in collaboration with a physician experienced in managing NTM-pulmonary disease.SeCTion 12d: WhaT anTiBioTiC regimen Should Be uSed To TreaT M. xenopi pulmonary diSeaSe?recommendations ► M. xenopi-pulmonary disease should be treated with a fourdrug regimen (where tolerated) comprising rifampicin, ethambutol and a macrolide (clarithromycin or azithromycin), with either a quinolone (ciprofloxacin or moxifloxacin) or isoniazid.(Grade D) ► An injectable aminoglycoside (amikacin or streptomycin) should be considered in individuals with severe M. xenopi-pulmonary disease (ie, AFB smear positive respiratory tract samples, radiological evidence of lung cavitation/ severe infection or severe symptoms/signs of systemic illness).(Grade D) ► Nebulised amikacin may be considered in place of an injectable aminoglycoside when intravenous/intramuscular administration is impractical, contraindicated or longer term treatment with an aminoglycoside is required in the treatment of M. xenopi-pulmonary disease.(Grade D) ► Antibiotic treatment for M. xenopi-pulmonary disease should continue for a minimum of 12 months after culture conversion.(Grade D) good practice point 3 Individuals with a history of treatment intolerance or treatment failure should be managed in collaboration with a physician experienced in managing NTM-pulmonary disease.SeCTion 12e: WhaT anTiBioTiC regimen Should Be uSed To TreaT M. abscessus-pulmonary diSeaSe?recommendations BTS guideline Therapeutic drug monitoring recommendations ► Therapeutic drug monitoring (other than for aminoglycosides) should not be performed routinely in individuals' prescribed antibiotic therapy for NTM-pulmonary disease.(Grade D) ► When aminoglycosides are administered, serum levels and the serum creatinine must be monitored and aminoglycoside dosing adjusted according to local policies.(Grade D) good practice point 3 Therapeutic drug monitoring can be considered in individuals in whom gastrointestinal malabsorption, drug-drug interactions or suboptimal adherence may be adversely affecting treatment response.monitoring for drug toxicity recommendations ► When aminoglycosides are administered serum levels and the serum creatinine must be monitored and aminoglycoside dosing adjusted according to local policies.(Grade D) ► Audiometry should be considered before starting aminoglycosides and intermittently during treatment (frequency according to perceived risk and symptoms).Patients should be informed to stop aminoglycoside treatment immediately and to inform the prescriber if they develop tinnitus, vestibular disturbance or hearing loss.(Grade D) ► Assess visual acuity and colour vision before starting ethambutol and advise patients to stop treatment immediately and inform the prescriber if changes in visual acuity or colour vision occur.(Grade D) ► Serum ethambutol levels should be measured in patients with renal dysfunction.(Grade D) good practice points 3 The frequency/type of toxicity monitoring required during NTM treatment is dependent on the drug regimen.Treatment-related adverse events and suggested toxicity monitoring protocols are outlined in the NTM antibiotic treatment monograph (section 18). 3 Audiometry should be considered before starting azithromycin or clarithromycin and intermittently during treatment (frequency according to perceived risk and symptoms) and advise individuals to stop treatment immediately and inform the prescriber if they develop tinnitus, vestibular disturbance or hearing loss.3 Perform an ECG before, and 2 weeks after, starting drugs (such as azithromycin or clarithromycin) that are known to prolong the QT interval.SeCTion 15: are There differenCeS in ouTCome BeTWeen paTienTS WiTh nTm-pulmonary diSeaSe TreaTed in SpeCialiST verSuS non-SpeCialiST Care SeTTingS?recommendation ► Individuals with NTM-pulmonary disease should be managed in collaboration with a physician experienced in managing NTM-pulmonary disease.(Grade D) SeCTion 16: WhaT iS The role of Surgery in The TreaTmenT of nTm-pulmonary diSeaSe?recommendations ► The role of lung resection surgery in the management of NTM-pulmonary disease should be considered at the time of diagnosis and revisited in individuals who develop refractory disease.(Grade D) ► Lung resection surgery for NTM-pulmonary disease may be indicated in individuals with localised areas of severe disease.(Grade D) ► Lung resection surgery for NTM-pulmonary disease should only be performed following expert multidisciplinary assessment in a centre experienced in managing individuals with NTM-pulmonary disease.(Grade D) ► Individuals with NTM-pulmonary disease should be established on antibiotic treatment prior to lung resection surgery and should continue treatment for 12 months after culture conversion.(Grade D). ► Following resection of a solitary NTM nodule in an individual with no other features of NTM-pulmonary disease, antibiotic treatment is not usually required.(Grade D) good practice points 3 Individuals with NTM-pulmonary disease in whom lung resection surgery is being considered should have a comprehensive assessment of cardiopulmonary status in line with current guidance for lung cancer resection.3 Nutritional status should be optimised prior to lung resection surgery.