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Evidence for answers

• Symptoms in this patient could suggest an issue with environmental allergy, although the history does not detail any pets, or issue relating to her environment specifically.
• Cough and oppressive thoracic pain could also suggest asthma but there is not enough information about personal and family history.
• The lack of expectorated sputum suggests that a lung infection may not be the issue at this point, but we do not have an overview of her respiratory condition.

Evidence for answers

• The patient is an ex-smoker and has a persistent cough leading to the suspicion of COPD; however, she does not have a typical history of COPD with progressive and increasing breathlessness, expectorated sputum or frequent chest infections.
• On the other hand, whilst test for pylori infection was negative, she has a mild hiatus hernia and respiratory symptoms, still suggestive of a GERD-related cough. GERD can be a risk factor for non-cystic fibrosis bronchiectasis (NCFBE) although she is relatively young at 54-years-of-age.
• A pulmonologist might at this point have ordered a CT scan and ruled out COPD and/or NCFBE.

Evidence for answers

• The prescription of macrolides in bronchiectasis patients should be carefully considered; in particular an ECG, hearing tests and repeated sputum cultures should be performed in order to screen for contraindications to macrolides use and to rule out NTM infections that should never be treated with monotherapy (macrolides only)
• In patients with persistent cough and bronchiectasis, the risk of NTM infection has to be considered and inhaled corticosteroids are not indicated.
• In consideration of the long-term clinical history of cough and increasing dyspnea and high risk of NTM a referral to a pulmonologist with expertise in respiratory infections is desirable.

Evidence for answers

• Lung function tests are recommended to assess all chronic respiratory disease in order to decide the appropriate therapy
• A diagnosis of bronchiectasis has been done having compatible symptoms and radiological signs (bronchiectatic nodules on thoracic CT scan, along with persistent cough and wheeze)¹
• In this patient the presence of an intractable cough and dyspnea are also suggestive of non-tuberculous mycobacterial pulmonary disease (NTM-PD), other key diagnostic symptoms for NTM-PD include underlying lung disease, weight loss, fatigue and fever.² An active NTM infection should be ruled out by repeated sputum cultures as suggested by the 2020 International guideline.³ 
• Inhaled corticosteroids should not be initiated when NTM are suspected due to increased risk of disease spread.

Evidence for answers

• Guidelines for NTM-PD published in 2020,¹ indicate that in patients who meet the diagnostic criteria for NTM-PD treatment with antimicrobial therapy should be initiated over a ‘watch and wait’ approach. However, the decision to treat needs to consider the infecting NTM species and individual patient wishes. In one study in patients with MAC-PD disease progression was evident in 97.5% of patients who were untreated over 6 years.²
• If treatment is delayed patients should still receive training on techniques such as airway clearance and vaccination (e.g. influenza) to control sputum and related symptoms and prevent respiratory infection.³
• Once NTM infection is identified, patients with MAC or kansasii should undergo antimicrobial susceptibility testing.¹ For MAC patients should be tested for macrolide and amikacin susceptibility.¹
• Once a decision to treat MAC-PD has been made patients without cavities or severe disease should be treated with macrolide containing triple therapy.¹ Ideally, the macrolide should be azithromycin.
• The guideline recommended treatment regimen for MAC-PD is azithromycin 250–500 mg/day ethambutol 15 mg/kg/day, rifampicin 10 mg/kg/day (or 450 mg or 650 mg/day).¹ For patients with nodular bronchiectatic disease for intermittent dosing three times a week (azithromycin 500 mg/day, ethambutol 25 mg/kg/day, rifampicin 600 mg/day).¹

Evidence for answers

• The presence of fungi in sputum culture of CF patients does not always requires treatment. In this patient fungal chronic infection had been described since 2009. Treatment for Scedosporium apiospermum in patients with CF is suggested for those for whom symptoms of infection are not responding to antibacterial therapy, or growth of Scedosporium apiospermum is persistently noted in culture.¹ However, Scedosporium apiospermum is known to be highly resistant to many antifungals and so voriconazole is used in preference to other candidates. In this patient voriconazole caused hallucinations, and whilst it is not known if she is resistant to other anti-fungals, unless her Scedosporium apiospermum infection is considered to be driving her symptoms, it would be sensible to treat the kansasii infection first.
• The recent sputum culture did not show increased bacterial load by Pseudomonas and /or Staphylococcus aureus. In specialised CF units quantitative cultures are typically requested in order to better investigate correlation between clinical status and microbiological findings. Additionally, the impact of eventual antibiotic therapies has to be considered to interpret sputum cultures.
• In young CF patients adherence to treatment^2,3 can be inconsistent and should always be assessed as a result; however in this case there is insufficient information to understand clearly the adherence in this patient.
• As this patient has demonstrated culture positivity for kansasii, treatment of this infection should be the focus, as isolation of M. kansasii is considered to always be indicative of active disease.

References:

1. Noni M et al. Mycoses 2017;9:594–99.
2. Quittner AL et al. Curr Opin Pulm Med. 2016 ;22(2):187–91.
3. Goldbeck L et al. Cochrane Database Syst Rev. 2014 Jun 18;2014(6):CD003148.

Evidence for answers

M. kansasii is an aggressive virulent form of non-tuberculous mycobacteria (NTM). Aggressive therapy for M. kansasii pulmonary disease (MK-PD) is recommended as it is associated with a high risk of mortality.¹

In a study of 109 patients with MK-PD 64% had radiographic progression within 1 year and a 1-year mortality rate of 43% with a median survival of only 71 days.¹

Factors considered to be prognostic for radiographic progression include acid-fast smear grade ≥3, plus CLOUD factors; fibroCavitary disease, Leucocyte count >9,000 μL, Old age (>65 years), pUre M. kansasii in sputum (no other mycobacterium identified) and no presence of Diabetes mellitus.¹

Guidelines published in 2020 for NTM-PD recommend that treatment for M. kansasii is implemented after first culture positivity and that before treatment patients should be tested for rifampicin susceptibility.²

References:

1. Liu C-J et al. Resp Med 2019;151:19–26
2. Daley CL et al. Eur Respir J 2020;56:2000535 

Evidence for answers

As described in the 2020 International guideline:

• in patients with rifampicin-susceptible kansasii pulmonary disease, we suggest a regimen of rifampicin, ethambutol, and either isoniazid or macrolide
• neither parenteral amikacin nor streptomycin should be used routinely for treating patients with kansasii pulmonary disease.

Ongoing medications

Omeprazole 20 mg b.i.d.

Polyethylene glycol plus mineral salts 13.8g b.i.d.

Pancreatin 25,000 8 capsules over 24 hours

Multivitamin/minerals 1 capsule every 24 hours

Calcium carbonate and Vitamin D 1/2 (500 mg calcium carbonate [25 mEq Calcium equivalent] and 400 IU Vitamin D)

Calcifediol (Vitamin D3) 266 μg/1.5 mL ampoule (oral liquid administration)

Inhaled olodaterol/tiotropium 2.5/2.5 μg 2 puffs in 24 hours

Inhaled salbutamol 0.1 mg 2 puffs

Acetylcysteine 600 mg

Inhaled hypertonic saline/hyaluronic acid b.i.d.

Lactobacillus 1.5g daily

Newly prescribed medications

Daily

Oral azithromycin 500 mg/day

Oral rifampicin 300 mg b.i.d.

Oral ethambutol 400 mg b.i.d.

On alternate days

Inhaled colistin 1,662,600 IU

Oral amikacin 500 mg/day

Guidelines published in 2020 for NTM-PD recommend that treatment for M. kansasii should be rifampicin based and given the uncertain value of isoniazid, macrolides are increasingly included.¹ The guideline recommends a multi-drug regimen of rifampicin, ethambutol and either isoniazid or macrolide. In this case, as this is the first isolation of M. kansasii and she demonstrates susceptibility to clarithromycin (and therefore azithromycin) inclusion of a macrolide would be appropriate. Guidelines do not recommend the addition of amikacin or streptomycin when a rifampicin-based triple therapy including ethambutol and a macrolide or isoniazid can be used.¹ In this patient additional antibiotics of inhaled colistin and oral amikacin 500 mg/day are included with a view to targeting the Pseudomonas infection including MDR strains. Inhaled colistin is recommended in patients with CF or bronchiectasis and Pseudomonas infection.^2,3 New infections with Pseudomonas in patients with CF are likely to progress to chronic infection which is associated with worsening lung function, so prompt therapy is indicated.³

References:

1. Daley CL et al. Eur Respir J 2020;56:2000535
2. Polverino E et al. Eur Respir J 2017;50:1700629
3. Castellani C et al. J Cyst Fibros 2018;17:153–78

Evidence for answers

In this patient, the CT scan shows:

• bilateral bronchiectasis with wall thickening in upper lobes, with centrilobular lingula micronodules
• air trapping
• appearance of a new cavitary nodular lesion in the upper right lobe
• distal mucous plugging

Radiographical presentation of M. kansasii can be extremely diverse and so monitoring for disease or treatment success must also include sputum mycobacterial culture.¹ A study in patients with M. kansasii suggests that patients have a high level of unilateral cavitation and a higher likelihood of right upper lobe disease.² An early study indicated that the appearance of pleural effusion of adenopathy is rare;³ and this is supported by more recent data.²

References:

1. Cattachmanchi A et al. Chest 2008;133:875–80
2. Matveychuk A et al. Resp Med 2012;106:1472–77
3. Christensen EE et al. Am J Roentgenol 1978;131:985–93

Evidence for answers

Rifampicin is not recommended on alternate days in presence of cavitary disease.¹ Inhaled antibiotics are directed at reducing bacterial load of Pseudomonas aeruginosa. In this patient, bronchodilator treatment was optimised as it had previously been established and maintained over many years. Patient adherence is crucial in the management of NTM pulmonary infection; given that the CT scan showed a new nodular lesion at upper right lobe the need to continue appropriate therapy is confirmed.

References:

1. Daley CL et al. Eur Respir J 2020;56:2000535