Tables
- Table 1
Common adverse effects of antibiotics used to treat NTM infections in patients with CF#
Antibiotic (delivery route) Common adverse effects Suggested monitoring Amikacin (intravenous; intramuscular)¶ Nephrotoxicity
Auditory-vestibular toxicity (tinnitus, high-frequency hearing loss)Trough levels
Serum creatinineAmikacin (nebulisation)¶ None described Azithromycin (oral)+ Nausea, vomiting, diarrhoea
Auditory-vestibular toxicity
Prolonged QTcSymptoms
Audiology
ECGBedaquiline (oral)¶ Headaches, dizziness, joint aches
Prolonged QTc
Liver enzyme derangementSymptoms
ECG
LFTCefoxitin (intravenous)¶ Fever, rash
Eosinophilia, anaemia, leukopenia, thrombocytopenia
Interference with serum creatinine measurementSymptoms
FBCClofazimine (oral)¶ Discoloration of skin or sclera
Enteropathy (can mimic pancreatic insufficiency), nausea and vomitingSymptoms Ethambutol (oral)+ Optic neuritis Symptoms, colour vision and acuity Imipenem (intravenous)¶ Nausea, vomiting, diarrhoea
HepatitisSymptoms
LFTLinezolid (oral)¶ Anaemia, leukopenia, thrombocytopenia
Peripheral neuropathy, optic neuritisFBC
Symptoms/clinicalMinocycline (oral)¶ Photosensitivity, skin discolouration
Nausea, vomiting, diarrhoea
VertigoSymptoms Moxifloxacin (oral)¶ Nausea, vomiting, diarrhoea
Insomnia, agitation, anxiety
Tendonitis
Photosensitivity
Prolonged QTcSymptoms
ECGRifabutin (oral)+ Leukopenia, anterior uveitis (when combined with clarithromycin), flu-like symptoms (polyarthralgia or myalgia) Symptoms
FBCRifampicin (oral)+ Orange discolouration of bodily fluids, fever, chills, nausea, vomiting, diarrhoea
Hepatitis
Thrombocytopenia
Renal failure
Increased drug metabolismSymptoms
LFT
FBC
EUCStreptomycin (intravenous, intramuscular)¶ Nephrotoxicity Trough levels, serum creatinine Tigecycline (intravenous)¶ Nausea, vomiting, diarrhoea
Pancreatitis
Hypoproteinaemia, bilirubinaemiaSymptoms
Serum amylase, lipase
LFT plus albuminLFT: 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), location Patients n Median (range) age years Females % NTM species Lung involvement and/or comorbidities Studies without clarithromycin Elkadi [23] 1962–1973 Missouri, USA 48 48 (20–72) 33% M. kansasii 54%
M. intracellulare 42%
Rapid grower 2%Lung cavities 77% Pomerantz [36] 1983–1990 Colorado, USA 38 50 (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, Japan 8 50 (36–72) 50% MAC 100% Cigarette smoker 25%
Bronchiectasis, 25%
Previous TB 25%
Sjögren's syndrome 13%Nelson [38] 1989–1997 Texas, USA 28 Mean±sd 50±11 25% MAC 100% Almost all were smokers
67% >20% below weight standard
No immunocompromisedShiraishi [34] 1979–1996 Tokyo, Japan 33 50 (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, Japan 21 56 (27–67) 48% MAC 100% Bronchiectasis 10%
Cavity 76%; nodule 10%
Destroyed lung 5%
No immunocompromisedShiraishi [29] 1983–2002 Tokyo, Japan 11 57 (43–69) 73% MAC 91%
M. abscessus 9%Multiple cavities 55%
Destroyed lung 46%
Bilateral disease 36%
No immunocompromisedWatanabe [39] 1990–2005 Tokyo, Japan 22 54 (30–77) 68% MAC 100% Bronchiectasis predominant 64%
Cavitary predominant 36%
No immunocompromisedMitchell [43] 1983–2006 Colorado, USA 236 54 (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, Korea 23 45 (24–66) 70% MAC 43%
M. abscessus 52%
M. xenopi 4%Cavities 70%
Bronchiectasis 30%
No immunocompromisedvan Ingen [19] 2000–2009 Holland 8 52 (41–59) 25% MAC 88%
M. xenopi 12%Cavitary 62%
Mixed pattern 25%
Bronchiectasis 13%
No immunocompromisedYu [30] 2004–2009 Colorado, USA 128 59 (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, Canada24 Mean±sd 57.7±11.1 83% 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, Japan 60 50 (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, Japan 125 60 (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 n Surgical indications Type of surgery Hospital stay Complications Studies without clarithromycin Elkadi [23]
48 Medical treatment failure Lobectomy 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]
38 Localised disease with complications Lobectomy 59%
Pneumonectomy 41%
Both (7%)Not reported Total=50%
Bronchopleural fistula 21%¶
Prolonged air leak 11%
Respiratory failure 5%
Wound dehiscence 3%
Pericardial effusion 3%
Horner's syndrome 3%Ono [35]
8 Medical treatment failure Persistent symptoms Lobectomy 75%
+partial resection 25%Not reported None reported Nelson [38] 28 Medical treatment failure
Significantly destroyed lung
Severe haemoptysisPartial resection 71%
Pneumonectomy 29%Not reported Total=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] 33 Symptomatic localised disease Lobectomy 79%
Segmentectomy 15%
Pneumonectomy 3%
Wedge resection 3%Not reported Total=18%
Bronchopleural fistula 3%
Residual pleural space 15%Studies incorporating clarithromycin Shiraishi [28] 21 Medical treatment failure or drug intolerance Lobectomy 76%
Two lobes 5%
Pneumonectomy 14% (90% right sided)Not reported Total=29%
Bronchopleural fistula 10%
Prolonged air leak 4%
Residual pleural space 10%
Pneumonia 4%Shiraishi [29] 11 Multiple cavities or total lung destruction Pneumonectomy 100% Not reported Total=45%
Bronchopleural fistula 27%
Empyema 9%
ARDS 9%Watanabe [39] 22 Medical treatment failure
Persistent symptomsLobectomy 64% +
Two lobes 5%+
Partial lung resection 27%+
Segmentectomy 18%+
Wedge resection 27%+
Multiple resections 45%Not reported Total=9%
Residual pleural space 5%
Home oxygen for 2 months 5%Mitchell [43] 236 Medical treatment failure
Focal persistent lung damageLobectomy 48%
Segmentectomy 21%
Pneumonectomy 17%
Mixed procedures 15%Not reported Total=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] 23 Medical 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] 8 Treatment failure
Infected destroyed lungLobectomy 63%
Two lobes 13%
Wedge resection 13%
Pneumonectomy 25%Not reported Total=63%
Pneumothorax 38%
Atelectasis requiring bronchoscopy 13%
Respiratory distress 13%
Pneumonia 13%Yu [30] 134 Localised disease ±cavitation
Medical treatment failure
Persistent symptomsLobectomy 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] 24 Localised bronchiectasis 86%
Cavitary disease 37%
Haeptysis 11%Lobectomy 83%
Pneumonectomy 21%
Segmentectomy 10%
Wedge resection 3%Not reported Total=25%
Haemorrhage 4%
Bronchopleural fistulae 4%
Wound infection 4%
Brachial plexus injury 4%
Frozen shoulder 4%
Respiratory failure/death 4%Shiraishi [31] 60 Medical treatment failure 87%
Persistent symptoms 10%
Secondary infection 3%Lobectomy 90%
Two lobes 5%
Segmentectomy 7%
Pneumonectomy 2%
Wedge resections 3%Not reported Total=12%
Prolonged air leak 6%
Atelectasis 3%
Respiratory failure 1%
Haemorrhage 1%
Atrial fibrillation 1%Asakura [37] 125 Medical treatment failure 56%
Cavities; severe bronchiectasis 29%
Persistent symptoms 15%Lobectomy 88%
Two lobes 10%
Pneumonectomy 25%
Segmentectomy 11%
Wedge resection 2%Not reported Total=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 n NTM species Pre-surgery antibiotics
% on antibiotics; duration; macrolide; % sputum clearancePost-surgery antibiotics
% on antibiotics; durationFollow up duration#,¶ Sputum conversion immediately post-surgery Relapse Mortality early and total Studies without clarithromycin Elkadi [23] 48 M. kansasii 54%
M. intracellulare 42%
Rapid grower 2%100%; 1–22 months; no clarithromycin;
54%Up to 9 months or until sputum conversion Not reported 85.4%
With additional antibiotics 100%Not reported None
and
NonePomerantz [36] 38 MAC 87%
M. kansaii 2.6%
M. chelonae 2.6%
M. xenopi 2.6%100%; 3 months; no clarithromycin;
32%Not reported Not reported Not reported Not reported 2.6%
and
21%Ono [35] 8 MAC 100% 62.5%; 8.1 months (1–30 months); no clarithromycin;
12.5%Nil treatment post-operatively 20 months# (4–56) 100% 13% 6 months None
and
NoneNelson [38] 28 MAC 100% 100%; 1 year (1–6 years); 61% had clarithromycin;
50%100%; up to 12 months 39 months# >90% 3 months after surgery: 93% (of those alive) 4% 2 years 7%
and
14%+Shiraishi [34] 33 MAC 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 yearsNone
and
6%Studies incorporating clarithromycin Shiraishi [28] 21 MAC 100% 100%; 11 months (2.2–29.1); 100% on clarithromycin;
38%90%; 6–12 months 35 months¶ (6–99) 100% 10% 2 years None
and
NoneShiraishi [29] 11 MAC 91%
M. abscessus 9%100%; 57 months (13–109 months); 100% had clarithromycin;
Not reported64%; 6–24 months 2 years¶ (0.6–17) 100% 9% 2 years None
and
18%Watanabe [39] 22 MAC 100% 100%; 17 months (2–37 months); 82% on clarithromycin;
80%§100%; 6–35 months 46 months¶ (6–164) 90%
100% after antimicrobialsNot reported None
and
NoneMitchell [43] 236 MAC 80%
M. abscessus 14%100%; 2–6 months;
57% negative sputum prior surgeryNot reported Not reported 100% Not reported 2.6%
and
2.6%Koh [40] 23 MAC 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 reported None
and
9%van Ingen [19] 8 MAC 87.5%
M. xenopi 12.5%100%; 22 months;
Not reported50%; 9 months 19 months# 88% 0% 19 months 12.5%
and
12.5%Yu [30] 128 MAC 88%
M. abscessus or chelonae 10%100%; at least 2–3 months;
Not reported100%; duration not reported 23 months# (0–70) 84%
97% sputum negative at final follow up at 34 months7% 17 months None
and
NoneJarand [41] 24 M. abscessus 100% 100%; uncertain; % macrolide uncertain;
71%100%; duration not separately reported for surgery group 34 months (2–82)# Uncertain
Overall 65%Never converted or relapsed 35% Uncertain
and
17%Shiraishi [31] 60 MAC 92%
M. abscessus 5%
M. gordonae 1.6%
M. xenopi 1.6%100%; 14.2 months (3.3–75.2); 100% clarithromycin;
Not reported100%; at least 12 months post-surgery or post-sputum conversion 34 months¶ (13–70) 100% 3%
34 monthsNone
and
NoneAsakura [37] 125 MAC 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 reported94% (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 years4%
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.
Vol 14 Issue 4
Table of Contents
Surgery in nontuberculous mycobacteria pulmonary disease
