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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[6]: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.
“In this study by Koh et al., it is gratifying that most patients had a favorable microbiologic outcome. It is also somewhat surprising that only two patients developed acquired macrolide resistant M. abscessus subsp massiliense isolates. While the absolute number is low, for those two individuals, the consequences of developing macrolide resistance are far from trivial. They have transitioned from having a mycobacterial infection that is relatively easy to treat effectively to a mycobacterial infection that is not,” David E. Griffith, MD, FCCP, and Timothy R. Aksamit, MD, FCCP, wrote in an editorial published in the December issue of CHEST (Chest. 2016 Dec;150[6];1177-8).
The authors noted that they “enthusiastically applaud and acknowledge the prolific and consistently excellent work done by the group in South Korea, but we cannot endorse the widespread adoption of macrolide monotherapy for” this patient group. “In our view, the risk/benefit balance of this approach does not favor macrolide monotherapy even though the majority of patients in this study were adequately treated.”
Dr. Griffith is professor of medicine at University of Texas Health Science Center, Tyler, and Dr. Aksamit is a consultant on pulmonary disease and critical care medicine at the Mayo Clinic, Rochester, Minn. They disclosed no conflicts of interest.
“In this study by Koh et al., it is gratifying that most patients had a favorable microbiologic outcome. It is also somewhat surprising that only two patients developed acquired macrolide resistant M. abscessus subsp massiliense isolates. While the absolute number is low, for those two individuals, the consequences of developing macrolide resistance are far from trivial. They have transitioned from having a mycobacterial infection that is relatively easy to treat effectively to a mycobacterial infection that is not,” David E. Griffith, MD, FCCP, and Timothy R. Aksamit, MD, FCCP, wrote in an editorial published in the December issue of CHEST (Chest. 2016 Dec;150[6];1177-8).
The authors noted that they “enthusiastically applaud and acknowledge the prolific and consistently excellent work done by the group in South Korea, but we cannot endorse the widespread adoption of macrolide monotherapy for” this patient group. “In our view, the risk/benefit balance of this approach does not favor macrolide monotherapy even though the majority of patients in this study were adequately treated.”
Dr. Griffith is professor of medicine at University of Texas Health Science Center, Tyler, and Dr. Aksamit is a consultant on pulmonary disease and critical care medicine at the Mayo Clinic, Rochester, Minn. They disclosed no conflicts of interest.
“In this study by Koh et al., it is gratifying that most patients had a favorable microbiologic outcome. It is also somewhat surprising that only two patients developed acquired macrolide resistant M. abscessus subsp massiliense isolates. While the absolute number is low, for those two individuals, the consequences of developing macrolide resistance are far from trivial. They have transitioned from having a mycobacterial infection that is relatively easy to treat effectively to a mycobacterial infection that is not,” David E. Griffith, MD, FCCP, and Timothy R. Aksamit, MD, FCCP, wrote in an editorial published in the December issue of CHEST (Chest. 2016 Dec;150[6];1177-8).
The authors noted that they “enthusiastically applaud and acknowledge the prolific and consistently excellent work done by the group in South Korea, but we cannot endorse the widespread adoption of macrolide monotherapy for” this patient group. “In our view, the risk/benefit balance of this approach does not favor macrolide monotherapy even though the majority of patients in this study were adequately treated.”
Dr. Griffith is professor of medicine at University of Texas Health Science Center, Tyler, and Dr. Aksamit is a consultant on pulmonary disease and critical care medicine at the Mayo Clinic, Rochester, Minn. They disclosed no conflicts of interest.
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[6]: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.
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[6]: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.
FROM CHEST
Key clinical point: A short course of intravenous antibiotics followed by oral macrolides may be effective at treating lung disease caused by the massiliense subspecies of M. abscessus.
Major finding: Of 43 patients receiving 2 weeks of combination antibiotics followed by a year of oral macrolides, 39 (91%) converted to negative sputum cultures before 12 months.
Data source: A prospective cohort study enrolling 71 patients at a single treatment center in Korea.
Disclosures: The Korean government sponsored the study and investigators disclosed no conflicts of interest.