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Surgery in nontuberculous mycobacteria pulmonary disease

Mimi Lu, Dominic Fitzgerald, Jonathan Karpelowsky, Hiran Selvadurai, Chetan Pandit, Paul Robinson, Ben J. Marais
Breathe 2018 14: 288-301; DOI: 10.1183/20734735.027218
Mimi Lu
1Dept of Respiratory Medicine, The Children's Hospital at Westmead, Sydney, Australia
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  • For correspondence: Mimi.lu1@health.nsw.gov.au
Dominic Fitzgerald
1Dept of Respiratory Medicine, The Children's Hospital at Westmead, Sydney, Australia
2Discipline of Child and Adolescent Health, Sydney Medical School, University of Sydney, Sydney, Australia
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Jonathan Karpelowsky
2Discipline of Child and Adolescent Health, Sydney Medical School, University of Sydney, Sydney, Australia
3Dept of Paediatric Surgery, The Children's Hospital at Westmead, Sydney, Australia
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Hiran Selvadurai
1Dept of Respiratory Medicine, The Children's Hospital at Westmead, Sydney, Australia
2Discipline of Child and Adolescent Health, Sydney Medical School, University of Sydney, Sydney, Australia
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Chetan Pandit
1Dept of Respiratory Medicine, The Children's Hospital at Westmead, Sydney, Australia
2Discipline of Child and Adolescent Health, Sydney Medical School, University of Sydney, Sydney, Australia
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Paul Robinson
1Dept of Respiratory Medicine, The Children's Hospital at Westmead, Sydney, Australia
2Discipline of Child and Adolescent Health, Sydney Medical School, University of Sydney, Sydney, Australia
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  • ORCID record for Paul Robinson
Ben J. Marais
2Discipline of Child and Adolescent Health, Sydney Medical School, University of Sydney, Sydney, Australia
4Dept of Infectious Diseases, The Children's Hospital at Westmead, Sydney, Australia
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Tables

  • Table 1

    Common adverse effects of antibiotics used to treat NTM infections in patients with CF#

    Antibiotic (delivery route)Common adverse effectsSuggested monitoring
    Amikacin (intravenous; intramuscular)¶Nephrotoxicity
    Auditory-vestibular toxicity (tinnitus, high-frequency hearing loss)
    Trough levels
    Serum creatinine
    Amikacin (nebulisation)¶None described
    Azithromycin (oral)+Nausea, vomiting, diarrhoea
    Auditory-vestibular toxicity
    Prolonged QTc
    Symptoms
    Audiology
    ECG
    Bedaquiline (oral)¶Headaches, dizziness, joint aches
    Prolonged QTc
    Liver enzyme derangement
    Symptoms
    ECG
    LFT
    Cefoxitin (intravenous)¶Fever, rash
    Eosinophilia, anaemia, leukopenia, thrombocytopenia
    Interference with serum creatinine measurement
    Symptoms
    FBC
    Clofazimine (oral)¶Discoloration of skin or sclera
    Enteropathy (can mimic pancreatic insufficiency), nausea and vomiting
    Symptoms
    Ethambutol (oral)+Optic neuritisSymptoms, colour vision and acuity
    Imipenem (intravenous)¶Nausea, vomiting, diarrhoea
    Hepatitis
    Symptoms
    LFT
    Linezolid (oral)¶Anaemia, leukopenia, thrombocytopenia
    Peripheral neuropathy, optic neuritis
    FBC
    Symptoms/clinical
    Minocycline (oral)¶Photosensitivity, skin discolouration
    Nausea, vomiting, diarrhoea
    Vertigo
    Symptoms
    Moxifloxacin (oral)¶Nausea, vomiting, diarrhoea
    Insomnia, agitation, anxiety
    Tendonitis
    Photosensitivity
    Prolonged QTc
    Symptoms
    ECG
    Rifabutin (oral)+Leukopenia, anterior uveitis (when combined with clarithromycin), flu-like symptoms (polyarthralgia or myalgia)Symptoms
    FBC
    Rifampicin (oral)+Orange discolouration of bodily fluids, fever, chills, nausea, vomiting, diarrhoea
    Hepatitis
    Thrombocytopenia
    Renal failure
    Increased drug metabolism
    Symptoms
    LFT
    FBC
    EUC
    Streptomycin (intravenous, intramuscular)¶NephrotoxicityTrough levels, serum creatinine
    Tigecycline (intravenous)¶Nausea, vomiting, diarrhoea
    Pancreatitis
    Hypoproteinaemia, bilirubinaemia
    Symptoms
    Serum amylase, lipase
    LFT plus albumin

    LFT: liver function test; FBC: full blood count; EUC: electrolytes, urea and creatinine; QTc: corrected QT interval. #: based on United States CF Foundation (USCF) and European CF society (ECFS) consensus recommendations [46]; ¶: primarily used for Mycobacterium abscessus complex; +: primarily used for MAC. Reproduced from [10] with permission.

    • Table 2

      Overview of patient characteristics in NTM lung surgery studies performed to date

      First author 
[ref.]Study year(s), 
locationPatients 
nMedian (range) 
age yearsFemales %NTM speciesLung involvement and/or comorbidities
      Studies without clarithromycin
       Elkadi [23]1962–1973 Missouri, USA4848 (20–72)33%M. kansasii 54%
      M. intracellulare 42%
      Rapid grower 2%
      Lung cavities 77%
       Pomerantz [36]1983–1990 Colorado, USA3850 (33–39)68%MAC 87%
      M. kansaii 3%
      M. chelonae 3%
      M. xenopi 3%
      Previous lobectomy 18%
      Previous TB 8%
      Bronchopleural fistula 8%
      Chest radiation 8%
       Ono [35]1991–1996 Wakayama, Japan850 (36–72)50%MAC 100%Cigarette smoker 25%
      Bronchiectasis, 25%
      Previous TB 25%
      Sjögren's syndrome 13%
       Nelson [38]1989–1997 Texas, USA28Mean±sd 50±1125%MAC 100%Almost all were smokers
      67% >20% below weight standard
      No immunocompromised
       Shiraishi [34]1979–1996 Tokyo, Japan3350 (30–69)48%MAC 100%Cigarette smoker 97%
      Bronchiectasis 21%
      Cavity 64%; nodule 3%
      Previous TB 9%
      Pneumonia 9%
      Studies incorporating clarithromycin
       Shiraishi [28]1993–2001 Kyoto, Japan2156 (27–67)48%MAC 100%Bronchiectasis 10%
      Cavity 76%; nodule 10%
      Destroyed lung 5%
      No immunocompromised
       Shiraishi [29]1983–2002 Tokyo, Japan1157 (43–69)73%MAC 91%
      M. abscessus 9%
      Multiple cavities 55%
      Destroyed lung 46%
      Bilateral disease 36%
      No immunocompromised
       Watanabe [39]1990–2005 Tokyo, Japan2254 (30–77)68%MAC 100%Bronchiectasis predominant 64%
      Cavitary predominant 36%
      No immunocompromised
       Mitchell [43]1983–2006 Colorado, USA23654 (23–77)83%MAC 80%
      M. abscessus 14%
      Focal bronchiectasis 55%
      Cavitary lung disease 29%
      Mixed pattern 9%
      Prior thoracic surgery 20%
       Koh [40]2002–2007 Seoul, Korea2345 (24–66)70%MAC 43%
      M. abscessus 52%
      M. xenopi 4%
      Cavities 70%
      Bronchiectasis 30%
      No immunocompromised
       van Ingen [19]2000–2009 Holland852 (41–59)25%MAC 88%
      M. xenopi 12%
      Cavitary 62%
      Mixed pattern 25%
      Bronchiectasis 13%
      No immunocompromised
       Yu [30]2004–2009 Colorado, USA12859 (34–81)96%MAC 88%
      M. abscessus or chelonae 10%
      Bronchiectasis 95%
      Cigarette smoker 16%
      Cavitary disease 3%
      Mixed pattern 2%
      Prior thoracic procedure 10%
       Jarand [41]#2001–2008
      Alberta, Canada
      24Mean±sd 57.7±11.183%M. abscessus 100%Localised bronchiectasis 86%
      Coexisting/previous MAC 54.2%
      Cavitary disease 37%
      Previous smokers 23%
      Previous TB 8.3%
       Shiraishi [31]2007–2011 Tokyo, Japan6050 (20–72)68%MAC 92%
      M. abscessus 5%
      M. gordonae 2%
      M. xenopi 2%
      Bronchiectasis 48%
      Cavities 42%
      Cigarette smoker 18%
      Mixed pattern 7%
      Diabetes mellitus 6.7%
       Asakura [37]1994–2015 Yokohama, Japan12560 (IQR 49–66)

      53%MAC 80%
      M. intracellulare 8%
      M. abscessus 5%
      M. kansasii 3%
      Others 5%
      Cavities 70%; nodules 98%
      Bronchiectasis 89%
      Cigarette smoker 29%
      Old TB 26%,
      COPD 10%
      Diabetes mellitus 10%

      M. kansasii: Mycobacterium kansasii; M. intracellulare: Mycobacterium intracellulare; M. chelonae: Mycobacterium chelonae; M. xenopi: Mycobacterium xenopi; M. abscessus: Mycobacterium abscessus; M. gordonae: Mycobacterium gordonae; IQR: interquartile range; COPD: chronic obstructive pulmonary disease. #: compared combined antibiotic and surgical treatment with antibiotic treatment alone.

      • Table 3

        Indication, type and complications of surgery performed for pulmonary NTM disease

        First author [ref.]Patients nSurgical indicationsType of surgeryHospital stayComplications
        Studies without clarithromycin
         Elkadi [23]

        48Medical treatment failureLobectomy 67%
        Segmentectomy 21%
        Pneumonectomy 6%
        Wedge resection 4%
        Extrapleural plombage 2%
        2.4–4 months#Total=13%
         Bronchopleural fistula 4%
         Wound dehiscence 4%
         Infection 2%
         Haemorrhage 2%
         Pomerantz [36]

        38Localised disease with complicationsLobectomy 59%
        Pneumonectomy 41%
        Both (7%)
        Not reportedTotal=50%
         Bronchopleural fistula 21%¶
         Prolonged air leak 11%
         Respiratory failure 5%
         Wound dehiscence 3%
         Pericardial effusion 3%
         Horner's syndrome 3%
         Ono [35]

        8Medical treatment failure Persistent symptomsLobectomy 75%
         +partial resection 25%
        Not reportedNone reported
         Nelson [38]28Medical treatment failure
        Significantly destroyed lung
        Severe haemoptysis
        Partial resection 71%
        Pneumonectomy 29%
        Not reportedTotal=32%
         Bronchopleural fistula 4%
         Prolonged air leak 14%
         Atelectasis requiring bronchoscopy 4%
         Severe post-thoracotomy pain 4%
         Death due to post-operative MI 4%
         Shiraishi [34]33Symptomatic localised diseaseLobectomy 79%
        Segmentectomy 15%
        Pneumonectomy 3%
        Wedge resection 3%
        Not reportedTotal=18%
         Bronchopleural fistula 3%
         Residual pleural space 15%
        Studies incorporating clarithromycin
         Shiraishi [28]21Medical treatment failure or drug intoleranceLobectomy 76%
         Two lobes 5%
        Pneumonectomy 14% (90% right sided)
        Not reportedTotal=29%
         Bronchopleural fistula 10%
         Prolonged air leak 4%
         Residual pleural space 10%
         Pneumonia 4%
         Shiraishi [29]11Multiple cavities or total lung destructionPneumonectomy 100%Not reportedTotal=45%
         Bronchopleural fistula 27%
         Empyema 9%
         ARDS 9%
         Watanabe [39]22Medical treatment failure
        Persistent symptoms
        Lobectomy 64% +
         Two lobes 5%+
        Partial lung resection 27%+
        Segmentectomy 18%+
        Wedge resection 27%+
        Multiple resections 45%
        Not reportedTotal=9%
         Residual pleural space 5%
         Home oxygen for 2 months 5%
         Mitchell [43]236Medical treatment failure
        Focal persistent lung damage
        Lobectomy 48%
        Segmentectomy 21%
        Pneumonectomy 17%
        Mixed procedures 15%
        Not reportedTotal=19%
         Bronchopleural fistula 4%
         Prolonged air leak 4%
         Respiratory failure/pneumonia 3%
         Post-operative bleeding 2%
         Wound dehiscence 1%
         ARDS 1%
         Atrial fibrillation 4%
         Koh [40]23Medical treatment failure 48%
        Remaining cavity relapse risk 35%
        Persistent symptoms 17%
        Lobectomy 70%
         Two lobes 9%
         Two sides 13%
        Segmentectomy 13%
        Pneumonectomy 17%
        9 days (IQR 6–15 days)Total=35%
         Bronchopleural fistula 9%
         Prolonged air leak 9%
         Pneumonia 13%
         Wound dehiscence 4%
         Pneumonectomy syndrome 4%
         van Ingen [19]8Treatment failure
        Infected destroyed lung
        Lobectomy 63%
         Two lobes 13%
        Wedge resection 13%
        Pneumonectomy 25%
        Not reportedTotal=63%
         Pneumothorax 38%
         Atelectasis requiring bronchoscopy 13%
         Respiratory distress 13%
         Pneumonia 13%
         Yu [30]134Localised disease ±cavitation
        Medical treatment failure
        Persistent symptoms
        Lobectomy 100%
         Middle 59%
         Lingulectomy 41%
        3 days (1–15 days)Total=8%
         Prolonged air leak 4%
         Wound infection 1%
         Atelectasis 1%
         Pleural effusion 1%
         Atrial fibrillation 1%
         Jarand [41]24Localised bronchiectasis 86%
        Cavitary disease 37%
        Haeptysis 11%
        Lobectomy 83%
        Pneumonectomy 21%
        Segmentectomy 10%
        Wedge resection 3%
        Not reportedTotal=25%
         Haemorrhage 4%
         Bronchopleural fistulae 4%
         Wound infection 4%
         Brachial plexus injury 4%
         Frozen shoulder 4%
         Respiratory failure/death 4%
         Shiraishi [31]60Medical treatment failure 87%
        Persistent symptoms 10%
        Secondary infection 3%
        Lobectomy 90%
         Two lobes 5%
        Segmentectomy 7%
        Pneumonectomy 2%
        Wedge resections 3%
        Not reportedTotal=12%
         Prolonged air leak 6%
         Atelectasis 3%
         Respiratory failure 1%
         Haemorrhage 1%
         Atrial fibrillation 1%
         Asakura [37]125Medical treatment failure 56%
        Cavities; severe bronchiectasis 29%
        Persistent symptoms 15%
        Lobectomy 88%
         Two lobes 10%
        Pneumonectomy 25%
        Segmentectomy 11%
        Wedge resection 2%
        Not reportedTotal=22%
         Bronchopulmonary fistula 6%
         Bronchopleural fistula 2%
         Prolonged air leak 1%
         Wound dehiscence 1%
         Pneumonia or empyema 7%
         Bronchial stenosis 1%
         Diaphragmatic hernia 1%
         Left atrial rupture 1%

        MI: myocardial infarction; ARDS: acute respiratory distress syndrome. #: patients were kept in hospital until sputum conversion; ¶: 15% of bronchopleural fistula occurred post-right pneumonectomy; +: primarily as 45% of this cohort had multiple resections.

        • Table 4

          Pre- and post-surgical treatment with sputum clearance, relapse and mortality (early and total)

          First author [ref.]Patients nNTM speciesPre-surgery antibiotics
          % on antibiotics; duration; macrolide; % sputum clearance
          Post-surgery antibiotics
          % on antibiotics; duration
          Follow up duration#,¶Sputum conversion immediately post-surgeryRelapseMortality early and total
          Studies without clarithromycin
           Elkadi [23]48M. kansasii 54%
          M. intracellulare 42%
          Rapid grower 2%
          100%; 1–22 months; no clarithromycin;
          54%
          Up to 9 months or until sputum conversionNot reported85.4%
          With additional antibiotics 100%
          Not reportedNone
          and
          None
           Pomerantz [36]38MAC 87%
          M. kansaii 2.6%
          M. chelonae 2.6%
          M. xenopi 2.6%
          100%; 3 months; no clarithromycin;
          32%
          Not reportedNot reportedNot reportedNot reported2.6%
          and
          21%
           Ono [35]8MAC 100%62.5%; 8.1 months (1–30 months); no clarithromycin;
          12.5%
          Nil treatment post-operatively20 months# (4–56)100%13% 6 monthsNone
          and
          None
           Nelson [38]28MAC 100%100%; 1 year (1–6 years); 61% had clarithromycin;
          50%
          100%; up to 12 months39 months#>90% 3 months after surgery: 93% (of those alive)4% 2 years7%
          and
          14%+
           Shiraishi [34]33MAC 100%85%; 8 months (1–64 months); 
4% had clarithromycin;
          35%
          91%; 13 months (1–96 months)(1–18 years)94%3% 5 years
          12% 10 years
          None
          and
          6%
          Studies incorporating clarithromycin
           Shiraishi [28]21MAC 100%100%; 11 months (2.2–29.1); 100% on clarithromycin;
          38%
          90%; 6–12 months35 months¶ (6–99)100%10% 2 yearsNone
          and
          None
           Shiraishi [29]11MAC 91%
          M. abscessus 9%
          100%; 57 months 
(13–109 months); 100% had clarithromycin;
          Not reported
          64%; 6–24 months2 years¶ (0.6–17)100%9% 2 yearsNone
          and
          18%
           Watanabe [39]22MAC 100%100%; 17 months (2–37 months); 82% on clarithromycin;
          80%§
          100%; 6–35 months46 months¶ (6–164)90%
          100% after antimicrobials
          Not reportedNone
          and
          None
           Mitchell [43]236MAC 80%
          M. abscessus 14%
          100%; 2–6 months;
          57% negative sputum prior surgery
          Not reportedNot reported100%Not reported2.6%
          and
          2.6%
           Koh [40]23MAC 43%
          M. abscessus 52%
          M. xenopi 4%
          87%; 7.5 months (5–17 months);100% on clarithromycin;
          26%
          97%; 12 months (6–26 months)14 months¶ (IQR 6–11)100% (in 1–2 months)Not reportedNone
          and
          9%
           van Ingen [19]8MAC 87.5%
          M. xenopi 12.5%
          100%; 22 months;
          Not reported
          50%; 9 months19 months#88%0% 19 months12.5%
          and
          12.5%
           Yu [30]128MAC 88%
          M. abscessus or chelonae 10%
          100%; at least 2–3 months;
          Not reported
          100%; duration not reported23 months# (0–70)84%
          97% sputum negative at final follow up at 34 months
          7% 17 monthsNone
          and
          None
           Jarand [41]24M. abscessus 100%100%; uncertain; % macrolide uncertain;
          71%
          100%; duration not separately reported for surgery group34 months (2–82)#Uncertain
          Overall 65%
          Never converted or relapsed 35%Uncertain
          and
          17%
           Shiraishi [31]60MAC 92%
          M. abscessus 5%
          M. gordonae 1.6%
          M. xenopi 1.6%
          100%; 14.2 months (3.3–75.2); 100% clarithromycin;
          Not reported
          100%; at least 12 months post-surgery or post-sputum conversion34 months¶ (13–70)100%3%
          34 months
          None
          and
          None
           Asakura [37]125MAC 80%
          M. Intracellulare 8%
          M. abscessus 5%
          M. kansasi 3%
          Others 5%
          94% treatment before and after surgery; 7 months (IQR 6–18 months); 82% clarithromycin;
          Not reported
          94% (before and after);
          7 months (IQR 6–18 months)
          7.1 years¶ (IQR 3.5–10.3)91%5% 1 year
          10% 3 years
          15% 5 years
          20% 19 years
          4%
          and
          4%

          #: mean; ¶: median (range); +: 2 patients (7%) suffered late deaths due to unrelated causes; §: only those (5 out of 25) who did not sputum convert were referred on for surgical treatment and joined 17 other patients from another hospital to make up to 22 patients in the cohort.

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          Surgery in nontuberculous mycobacteria pulmonary disease
          Mimi Lu, Dominic Fitzgerald, Jonathan Karpelowsky, Hiran Selvadurai, Chetan Pandit, Paul Robinson, Ben J. Marais
          Breathe Dec 2018, 14 (4) 288-301; DOI: 10.1183/20734735.027218

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          Surgery in nontuberculous mycobacteria pulmonary disease
          Mimi Lu, Dominic Fitzgerald, Jonathan Karpelowsky, Hiran Selvadurai, Chetan Pandit, Paul Robinson, Ben J. Marais
          Breathe Dec 2018, 14 (4) 288-301; DOI: 10.1183/20734735.027218
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          • Article
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