Excerpt from European CF conference 2013 - Dr. Ken Olivier
Special Symposium: ECFS/CFF Guidelines for the Management of NTM in CF
Treatment of Mycobacterium; Ken Olivier MD
Talk from the 36th European Cystic Fibrosis Congress; June 12-15, 2013;
Dangerous emerging pathogens like nontuberculous mycobacteria (NTM) have magnified the relevance of careful screening in individuals with cystic fibrosis (CF). Identifying asymptomatic those who are positive for NTM gives clinicians the chance to segregate them appropriately and intervene early. Two discussions from the Special Symposium on ECFS/CFF Guidelines for the Management of NTM in CF focused on the pressing issues of diagnosis and treatment of NTM in CF.
According to Charles Haworth, MD, Director of the Cambridge Centre for Lung Infection at Papworth Hospital, Cambridge, UK, in his presentation on Diagnosing NTM, it is vital to screen all patients for NTM, especially when concerns arise about patient-to-patient transmission. Screening involves performing cultures and smears for acid-fast bacilli from sputum. Induced sputum or bronchoalveolar lavage (BAL) samples; oropharyngeal swabs are not recommended on three separate days and processing the samples within 24 hours to optimize detection. The United States Cystic Fibrosis Foundation recommends yearly cultures in spontaneously expectorating patients with stable clinical courses.
The American Thoracic Society/ Infectious Diseases Society of America (ATS/IDSA) definition of NTM pulmonary disease includes characteristic symptoms: two or more positive sputum samples of the same NTM or one positive lavage, radiology studies consistent with NTM infections and appropriate exclusion of other diagnoses. Shared characteristics of NTM and P. aeruginosa (PA) infection, such as cough, sputum, fever, and malaise, may obscure diagnosis, along with nonspecific radiology. Bacterial overgrowth with PA, inhibitory effects of antibiotics such as azithromycin, mixed cultures with M. abscessus and M. avium
and distinguishing treatment failure from reinfection, can also make microbiologic findings confusing.
Should clinical suspicion of NTM pulmonary disease arise, clinicians are urged to first withhold azithromycin for 2 weeks, as monotherapy can cause resistance. If a patient meets the ATS criteria, the clinician must decide whether to start treatment or observe the patient. A symptomatic patient may require immediate treatment, and if the treatment aim is to eradicate the organism, it should be started early. To prevent progression, however, in patients with a small chance of clearing the organism (eradication), a watch and wait policy would be warranted. Furthermore, finding the balance between under- and overtreatment can be challenging, Dr. Haworth said.
In his Treatment of Mycobacterium presentation, Ken Olivier, MD, of the Laboratory of Clinical Infectious Diseases, NIAID, Bethesda, Maryland, USA, noted that M. abscessus infections require a treatment regimen consisting of an intensive phase followed by a continuation phase. The intensive phase should include a daily oral macrolide, preferably azithromycin, with 3-12 weeks of IV amikacin, plus one or more of the following intravenous drugs, guided but not dictated by susceptibility tests: tigecycline, imipenem, or cefoxitin. The duration of the intensive phase should be determined by the severity of infection, response to treatment, and tolerability of regimen.
The continuation phase should include a daily oral macrolide (azithromycin) and inhaled amikacin, with the primary goal of limiting the toxicity of IV amikacin. This phase should also include two or three of the following oral antibiotics guided but not dictated by susceptibility tests: minocycline, clofazimine, moxifloxacin, linezolid,
M. avium complex may be easier to treat, using daily oral macrolide (preferably azithromycin), rifampin, and ethambutol, for clarithromycin-sensitive M. avium complex. For milder disease, the clinician may choose an intermittent regimen (three times a week). The treatment regimen for cavitary M. avium complex pulmonary disease includes an initial course of IV amikacin.
Monitoring NTM treatment for a therapeutic response and toxicity is as follows: expectorated or induced sputum samples should be sent for NTM culture every 4-8 weeks to assess the microbiologic response. Sputum conversion is expected to occur between 3-6 months for the majority of patients. A schedule for detecting drug toxicity based on the specific drugs prescribed should be in place at the time of NTM treatment initiation and continued throughout treatment.
Antibiotic therapy for NTM should be prescribed for 12 months beyond culture conversion, which is defined as three consecutive negative cultures with the time of conversion set at the date of the first of the three negative cultures, and no positive cultures during the 12-month period. Patients who fail to culture convert despite optimal NTM therapy may benefit from long-term suppressive antibiotic treatment.
A CT scan of the lungs should be performed shortly before starting NTM treatment and at the end of NTM treatment to assess the radiologic response.
All individuals with CF being considered for lung transplantation should be evaluated for NTM pulmonary disease. Current or previous NTM positive respiratory cultures should not necessarily preclude evaluation for lung transplantation.