Patients with cystic fibrosis or bronchiectasis and one form of Mycobacterium abscessus disease can be successfully treated with long-term oral macrolide monotherapy following short-term intravenous combination antibiotic therapy, a Korean research team has shown.
The M. abscessus complex is implicated in between a fifth and half of all cases of lung disease caused by nontuberculous mycobacteria (NTM). Though treatment is notoriously difficult and prolonged in all NTM lung disease, one subspecies of M. abscessus – M. massiliense – lacks the active gene needed for developing resistance to macrolide-based antibiotics, making it potentially more readily treated.
In research published in CHEST, Won-Jung Koh, MD, of Samsung Medical Center and Sungkyunkwan University in Seoul, South Korea, and colleagues, sought to determine the optimal treatment protocol for patients with massiliense disease (Chest. 2016 Dec;150:1211-21). They identified 71 patients with massiliense disease who had initiated antibiotic treatment between January 2007 and December 2012. These patients were part of an ongoing prospective cohort study on NTM lung disease. The first 28 patients in the study were hospitalized for 4 weeks and treated with intravenous amikacin and cefoxitin along with oral clarithromycin and a fluoroquinolone. Following discharge these patients remained on the oral agents for 24 months.
Two years into the study, the protocol changed, and the next 43 patients were treated with a 2-week course of intravenous amikacin and cefoxitin along with the oral agents. In some patients, azithromycin, which came into use in Korea for NTM lung disease in 2011, replaced a fluoroquinolone. After discharge, all patients stayed on the oral macrolides (with seven also taking a fluoroquinolone) until their sputum cultures were negative for 12 months.
For the patients treated for 4 weeks, the response rates after 12 months of treatment were 89% for symptoms, 79% for computed tomography, and 100% for negative sputum cultures. In the patients treated for 2 weeks, they were 100%, 91%, and 91%, respectively. None of these differences between the two groups were statistically significant. Median total treatment duration, however, was significantly shorter – by nearly a year – in the 2-week plus macrolide monotherapy group than in the other group of patients (15.2 months vs. 23.9 months, P less than .001).
Acquired macrolide resistance developed in two patients in the group who received a 2-week course of intravenous amikacin and cefoxitin along with the oral agents, including one case of high-level clarithromycin resistance. Genotyping revealed reinfection with different strains of M. massiliense.
“[Oral] macrolide therapy after an initial 2-week course of combination antibiotics, rather than long-term parenteral antibiotics, might be effective in most patients with M. massiliense lung disease,” Dr. Koh and colleagues wrote, noting that their study’s nonrandomized single-site design was a limitation, and that multicenter randomized trials would be needed “to assess the efficacy” of the findings.
The Korean government funded Dr. Koh and colleagues’ study. None of the authors disclosed conflicts of interest.