NTM Infection Flashcards
What specific monitoring is required with NTM drugs?
Ethambutol, Amikacin, Macrolides
Ethambutol requires baseline visual testing (acuity and colour vision)
Aminoglycosides e.g amikacin need hearing assessment. Stop immediately if tinnitus, balance problems or hearing loss
Macrolides require baseline ECG and repeat 2 weeks after starting (QTc prolongation)
If NTM infection becomes sputum negative, for how long should treatment continue?
Minimum 12 months after negative sputum sample.
How should patients that are unable to expectorate sputum be followed up?
CT scans followed by CT-directed bronchial washings should be performed after 6 months and 12 months of commencing treatment
Is NTM infection a contraindication to lung transplant?
No- can still be referred for assessment.
Should be treated prior to listing to either eradicate or lower bacterial load
Current/previous M.abscessus need counselling for high postoperative risk of disseminated disease requiring extensive treatment
Progression despite optimal NTM treatment is likely to be a contraindication
What is Lady Windermere syndrome?
A pattern of Mycobacterium Avium Complex (MAC) infection. Often seen in elderly, white women with no smoking history or underlying lung disease. May have pectus excavatum and mitral valve prolapse. Classically middle lobe/lingula bronchiectasis. Named after an Oscar Wilde character.
Name some risk factors for NTM acquisition
Gastro-oesophageal reflux
Rheumatoid arthritis
Low vitamin D
Low BMI
Malnutrition
Underlying lung disease
PPIs
What are the clinical criteria for diagnosing NTM infection?
BOTH are required
1: Pulmonary symptoms with nodular/cavitatory opacities on CXR or CT showing multifocal bronchiectasis with multiple small nodules
2: Exclusion of other diagnoses
What are the microbiological criteria for diagnosing NTM infection?
1: NTM positive culture grown from sputum on at least 2 separate samples
OR
2: NTM isolated on at least 1bronchial wash or BAL
OR
3: Transbronchial/lung biopsy with granulomatous features/AFB positive and positive culture for NTM or one or more positive sputum cultures or washes
What is the chance of developing NTM pulmonary disease after a single positive culture?
Between 4 and 14%. Hence the need to acquire at least 2 positive sputum results.
What is the best method of microscopic detection of NTM in respiratory samples?
Auramine-phenol staining.
More sensitive than the Ziehl-Neelsen method
What gene in M.abscessus infection can be linked to inducible macrolide resistance?
erm41 gene
Present fully in M. a. abscessus but only partially in M. a. massiliense meaning massiliense more likely to be treatable with macrolide-based regimens
When should macrolide susceptibility be tested in MAC treatment?
1: Prior to commencing therapy
2: If failure to culture convert after 6-12 months of treatment
3: If MAC recultured after culture conversion whilst still on treatment
4: If MAC re-cultured after treatment cessation
Macrolide resistance is associated with poorer treatment outcomes and needs augmented treatment
Should also test for amikacin sensitivity
What is the recommended treatment regimen for non-severe MAC infection?
Rifampicin 600mg 3x weekly
Ethambutol 25mg/kg 3x weekly
AND
Azithromycin 500mg 3x weekly
OR Clarithromycin 500mg BD 3x weekly
Minimum 12 months after sputum conversion
What is the recommended treatment regimen for severe Mycobacterium Avium Complex (MAC) infection?
Severe if smear positive or evidence of cavitation/severe infection or significant systemic symptoms
Rifampicin 600mg OD
Ethambutol 15mg/kg OD
AND
Clarithromycin 500mg BD OR Azithromycin 250mg OD
AND
Consider IV/nebulised amikacin for up to 3 months when commencing on treatment
If MAC is found to be macrolide resistant, what is the appropriate treatment regimen?
Rifampicin 600mg OD
Ethambutol 15mg/kg OD
AND
Moxifloxacin 400mg OD OR Isoniazid 300mg OD (+pyridoxine 10mg)
PLUS
Consider up to 3 months of treatment with IV or nebulised amikacin
If treating M. Kansasii infection, what must be considered and what is the usual treatment regimen?
Need to test for rifampicin resistance. Rifampicin-sensitive M. Kansasii has faster conversion rate and lower relapse
Rifampicin 600mg OD
Ethambutol 15mg/kg OD
AND
Isoniazid 300mg OD (+pyridoxine 10mg) OR Macrolide (Clarithromycin 500mg BD OR Azithromycin 250mg OD)
What is the recommended treatment regimen for M. Malmoense infection?
Any additions if severe infection?
Treatment with ethambutol, rifampicin and macrolide:
Rifampicin 600mg OD
Ethambutol 15mg/kg OD AND
Clarithromycin 500mg BD OR Azithromycin 250mg OD
If severe infection then consider up to 3 months of IV amikacin or nebulised amikacin
Severe disease is AFB smear positive or progression of cavitation/marked systemic symptoms
Remember acuity and colour visual testing required before ethambutol
What is the recommended treatment regimen for M. xenopi pulmonary disease?
Usually requires a FOUR drug regimen:
Rifampicin 600mg OD
Ethambutol 15mg/kg OD
Macrolide (Clarithro/Azithro daily)
AND
Moxifloxacin 400mg OD or Isoniazid 300mg OD (+pyridoxine 10mg)
Consider IV/nebulised amikacin if severe disease
How is culture conversion defined in the treatment of NTM infection?
Culture conversion requires 3 consecutive negative mycobacterium cultures over a period of over MINIMUM 3 MONTHS. The time of conversion is subsequently classed as the date of the first negative sample.
A single negative culture from CT-directed bronchial washings can be used instead in patients unable to expectorate.
How often should sputum samples be sent in patients on NTM treatment? What are the recommendations if not expectorating?
Sputum should be sent every 4-12 weeks whilst on treatment
If progression suspected but samples negative then should consider CT-directed bronchial wash
For patients unable to expectorate, CT scan followed by CT-directed bronchial was should be performed at 6 months and 12 months after starting treatment.
What is the mimimum (and extended) sensitivity testing recommended in M. abscessus infection?
Minimum: Clarithromycin, cefoxitime and amikacin
Also recommended for tigecycline, imipenem, doxycycline, minocycline, moxifloxacin, co-trimoxazole linezolid and clofazimine
What is the initial phase treatment for M.abscessus infection? What is the suggested duration?
Requires a combination of oral and IV antibiotics. Need to test if clarithromycin sensitive or inducible macrolide resistance:
1: IV amikacin 15mg/kg OD or 3x weekly
2: IV tigecycline 50mg BD
3: IV Imipenem 1g BD
AND 4: PO clarithromycin or azithromycin where tolerated
Treatment for at least 1 month
What is the continuation phase treatment for M.abscessus infection (macrolide sensitive)?
1: Nebulised Amikacin AND
2: PO clarithromycin OR Azithromycin
AND any 1-3 of the following:
PO moxifloxacin 400mg OD
PO minocycline 100mg BD
PO co-trimoxazole 960mg BD
PO linezolid 600mg 1-2x daily
PO clofizamine 50-100mg daily
What is the continuation phase treatment for M.abscessus with macrolide resistance? And responsible gene mutation?
23 S ribosomalRNA point mutation
Nebulised amikacin PLUS 2-4 of:
PO moxifloxacin 400mg OD
PO minocycline 100mg BD
PO co-trimoxazole 960mg BD
PO linezolid 600mg 1-2x daily
PO clofizamine 50-100mg daily