Information for health care professionals - Non-tuberculous mycobacteria
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Information for health care professionals

Non-tuberculous mycobacteria

The problem

The significance of NTM airway infection in CF depends on the context and the type of NTM. Single isolates in child with mild stable lung disease may not require treatment. Repeated positive cultures, especially when associated with unexplained decline in lung function, new radiographic abnormailites or recurrent fever, should be treated. Response to treatment is variable.

Infection with NTM can adversely affect outcome of lung transplantation, particularly infection with M. abscessus. Vigorous efforts should be made to treat and eradicate this infection if transplantation is being considered. Persitent infection with M. abscessus is a contraindication to transplantation in some units, but not at Great Ormond Street.

NTM infection if it does occur is usually with M. avium complex (M. avium and M. intracellulare) or M. abscessus, although infection with several other strains (such as M. fortuitum, M. kansaii and M. chelonae) can occur. M.abscessus is particularly troublesome.

The prevalence of NTM (defined as 3 positive cultures over a 12 month period) is between 3-5% in pre-adolescent children. The prevalence increases with age to above 30% in older adult patients.

In most children the clinical impact of non-abscessus NTM infection is difficult to determine. M. abscessus airway infection is associated with an increase in the annual rate of decline of lung function.

Long term azithromycin therapy is associated with NTM macrolide resistance which makes treatment of possible future NTM infection more difficult. Children and adults treated with long term macrolides should have regular cultures for NTM.

Diagnosis

Annual screening on sputum culture for NTM infection is recommended for all children with CF and NTM cultures are always requested at annual review for children of all ages. We also recommend sending sputum for NTM in all children during exacerbations needing ivs, and in all children with unexplained loss of lung function. If these children are unable to produce sputum, they may require bronchoscopy. NTM do not seem to grow from cough swabs, even when they are known to be present on sputum samples. We do not therefore send cough swabs for NTM culture.

The decision to treat NTM depends on which NTM is present and the impact of that infection. Standard criteria for treatment includes 3 positive airway samples over a 12 month period. If there is doubt about treatment, a CT scan may help. Treatment will be recommended on the basis of a single positive sample collected at bronchoscopy in children with deteriorating lung function who have suspicious CT changes. This is particularly true for M. abscessus.

Mycobacterium abscessus treatment

Treatment is of M. abscessus is complex. BTS guidelines were published in 2017. Treatement involves an initial iv phase followed by 12-18 months of oral and nebulised treatment. We usually use 4 weeks initial treatment with iv amikacin, iv imepenem, iv tigecycline (or cefoxitin for children under 12y), followed by maintenance with oral moxifloxacin Oral clofazimine and oral linezolid. AND nebulised amikacin - and use this treatment for 18 months. Minocycline (in the over 12s) or cotrimoxazole (in the under 12s) are alternative oral medications. For Abscessus that is macrolide sensitive, long term azithromycin should also be used. Clofazimine leads to pink to brownish-black skin discoloration (resembling sun-tanning) within 1-4wks in 75-100% of patients. It gradually disappears within 6-12 months after stopping treatment. Linezolid can cause myelosuppression, and requires weekly FBC monitoring for he first 2 months, and then monthly thereafter. It can also cause optic neuritis and color vison testing needs to be done 3 monthly. Hearing testing should be 3 monthly. In addition, we normally repeat the ivs every 3 months, for 2 weeks at a time, for 12 months. Amikacin is toxic, so hearing and renal function need to be monitored. See relevant sections for doses. Eradication is reported to be achieved in 60% of (adult) patients with this approach.

If subsequent sputum samples become negative for M. abscessus, the patient should still be regarded as a potential carrier from the date of the first negative sample for a total of at least twelve months. A minimum of 4x negative sputum samples is required during this twelve-month period, with the final negative sample at least twelve months after the first negative sample. For instances where sputum cannot be obtained a negative BAL off treatment would suffice.

If M.abscessus does not clear after 18 months of treatment, it may be necessary to rationalise the nebulised and oral treatments. iv treatment for exacerbations would need to cover M. abscessus.

Other NTM treatment

Other forms of NTM are treated with a combination of oral clarithromycin, rifampicin and ethambutol taken for 12-18 months can be effective. Combinations of macolides and ciprofloxacin alone can lead to resistance.