Non-tuberculous mycobacterial pulmonary disease, cystic fibrosis patients RHC

The CF Foundation and the ECFS recommend that ¹

• cultures for NTM be performed annually in spontaneously expectorating individuals with a stable clinical course. [Recommendation 2]
• in the absence of clinical features suggestive of NTM pulmonary disease, individuals who are not capable of spontaneously producing sputum do not require screening cultures for NTM [Recommendation 3]
• culture and smears for AFB from sputum should be used for NTM screening.
• when being investigated for potential NTM-PD, individuals should discontinue drugs liable to compromise NTM culture (such as macrolides, fluoroquinolones, aminoglycosides, co-trimoxazole, linezolid and doxycycline) prior to sputum sample collection. In the case of azithromycin, intracellular accumulation within phagocytes may require a washout period of 2 weeks or more to allow for drug clearance . For this reason prescribed azithromycin should be stopped for 2 weeks prior to AFB screening. [Recommendation 4]

Patients are defined as having NTM-Pulmonary Disease ( NTM-PD)  if they meet clinical and radiological criteria : ⁴

• Positive cultures from two or more separate expectorated sputum samples, or from a single BAL.
• Radiological evidence of NTM specific changes on HRCT
• Clinical / FEV1 decline despite optimum treatment of other CF organisms/ morbidities

There is considerable overlap between the clinical and radiological presentation of NTM and CF as well as between NTM and infection by other CF pathogens.  While some patients with persistent NTM in sputum have declining clinical and radiographic parameters, this is not true of all patients.

 In identifying which patients require NTM treatment, it is essential that initially all non-mycobacterial organisms are optimally treated. Starting treatment should be a senior medical  consensus decision based on the risks and benefits of treatment for each individual patient, tailored according to the specific species of NTM .³

M. ABSCESSUS

Treatment of CF NTM-PD due to M. abscessus includes a 3 week Intensive (Induction) Phase followed by a Continuation Phase until the patient has been clear of the organism for > 12 months ^1;2;3

RHC INDUCTION PHASE 

The CF Foundation and the ECFS recommend that the intensive phase should include a daily oral macrolide (preferably azithromycin) in conjunction with 3–12 weeks of intravenous amikacin and one or more of the following: intravenous tigecycline, imipenem or cefoxitin, guided but not dictated by DST. The duration of intensive phase therapy should be determined by the severity of infection, the response to treatment and the tolerability of the regimen. Recommendation 25

DURATION 3 WEEKS ^{1; 2;3}

RHC CONTINUATION PHASE ^{1; 2 ; 3}

The CF Foundation and the ECFS recommend that the continuation phase should include a daily oral macrolide (preferably azithromycin) and inhaled amikacin, in conjunction with 2–3 of the following additional oral antibiotics: minocycline, clofazimine, moxifloxacin and linezolid, guided but not dictated by DST. [Recommendation 26]

DURATION –Until respiratory samples are clear of M. Abscessus for < 12 months

PATIENTS ON CONTINUATION PHASE  M. ABSCESSUS TREATMENT WHO PRESENT WITH  RESPIRATORY EXACERBATIONS OR WHO REQUIRE REGULAR IV ANTIBIOTICS COURSES

Following the IV Induction Phase, patients who present with a respiratory exacerbation or who receive regular IV antibiotics courses should be prescribed IV antibiotics which are targeted to the patient’s M abscessus . Additional IV or oral antibiotics may also be required to cover other current  CF pathogens. 

Where IV Imipenem + Amikacin are prescribed, Nebulised Amikacin is stopped for the duration of the IV course. All other Continuation Phase drugs are continued.

Duration – 2 weeks extended if clinically indicated. ²

M. AVIUM /INTRACELLULARE ( MAC) TREATMENT

Initial therapy should be triple oral therapy as listed below ³ . 

Criteria for IV therapy - one or more of ⁴ :

• AFB smear positive respiratory tract samples
• Radiological evidence of lung cavitation or severe infection
• Systemic signs of illness

Patients who are unwell should begin by having 2 weeks intravenous therapy with amikacin and a second intravenous antibiotic   (discuss with Microbiologist). 

As with M. abscessus, eradication would be considered successful  when sputum samples are free of M. Avium for a 1 year period. ^3;4