Analysis of drug treatment outcome in clarithromycin-resistant Mycobacterium avium complex lung disease

Abstract

BackgroundAlthough the isolation of clarithromycin (CAM)-resistant Mycobacterium avium complex (MAC) indicates a poor treatment outcome and increased mortality, there have been only a few reports on drug treatment for CAM-resistant MAC lung disease. We aimed to reveal the effectiveness of the continuation of a macrolide and the use of a multidrug regimen in the treatment of CAM-resistant MAC lung disease.MethodsAmong patients with MAC pulmonary disease as defined by the 2007 criteria of the American Thoracic Society and the Infectious Diseases Society of America statement, those with CAM-resistant MAC (minimum inhibitory concentration ≥32 μg/ml) isolated, newly diagnosed and treated from January 2009 to June 2013 were analysed in this study. Effectiveness was measured based on culture conversion rate and improvement of radiological findings.ResultsThirty-three HIV-negative patients were analysed in this study. Twenty-six were treated with a regimen containing CAM or azithromycin (AZM), and 21 patients were treated with three or more drugs except macrolide. The median duration to be evaluated was 10.4 months after beginning the treatment regimen. Sputum conversion (including cases of inability to expectorate sputum) was achieved in 12 (36 %) patients. Radiological effectiveness improved in 4 (12 %) patients, was unchanged in 11 (33 %) patients and worsened in 18 (55 %) patients. In the multivariate analysis, CRP <1.0 mg/dl (p = 0.017, odds ratio 12, 95 % confidence interval (CI) 1.6–95) was found to be the only significant risk factor for radiological non-deterioration, and no significant risk factors for microbiological improvement were found.ConclusionsOur results suggested that continuation of macrolides or the addition of a new quinolone or injectable aminoglycoside to therapy with rifampicin and ethambutol would not improve clinical outcome after the emergence of CAM-resistant MAC. However, further prospective study is required to evaluate the precise clinical efficacy and effectiveness of these drugs.

Clinical Characteristics, Treatment Outcomes, and Resistance Mutations Associated with Macrolide-Resistant Mycobacterium avium Complex Lung Disease

“…However, a recently published study from Japan found that macrolide monotherapy or a two-drug regimen that included a macrolide were previously administered in only 18% and 12%, respectively, of patients with macrolide-resistant MAC-LD (15). The majority (60%) of patients had received adequate long-term combination therapies prior to the emergence of macrolide resistance (15).…”

“…An AFBpositive sputum smear at the time of detection of macrolide resistance was more frequently observed in patients with unfavorable outcomes. During the management of patients with MAC-LD, preventing the emergence of macrolide resistance is critical, because the development of such resistance is strongly associated with treatment failure and increased mortality (14,15). The first study on macrolide-resistant MAC-LD from the United States was published in 2006 and found that the major reasons (76%) for the development of macrolide resistance were initial macrolide monotherapy and the combination of a macrolide and a fluoroquinolone (14).…”

“…Because macrolides are key drugs for the treatment of MAC-LD, the development of macrolide resistance indicates a poor treatment outcome and increased mortality (14,15). However, there have been only two previous studies evaluating the risk factors, clinical characteristics, and treatment outcomes of macrolide-resistant MAC-LD, and the results are inconsistent, especially regarding the risk factors and optimal treatment modalities (14,15).…”

“…However, there have been only two previous studies evaluating the risk factors, clinical characteristics, and treatment outcomes of macrolide-resistant MAC-LD, and the results are inconsistent, especially regarding the risk factors and optimal treatment modalities (14,15). The aim of this study was to evaluate the clinical features and treatment outcomes of patients with macrolide-resistant MAC-LD, as well as the molecular characteristics of macrolide-resistant MAC isolates.…”

Lady Windermere syndrome

“…90 Treatment of patients with MAC pulmonary disease and macrolide resistance has low success rates with antibiotic therapy, and surgery is a possible treatment in these patients. 91,92 Two surgical studies using lobectomy and segmentectomy for isolated disease or disease not responding to several months of antibiotics showed that 92%-100% of patients underwent sputum conversion after surgery. 28,34 There was no operative mortality in these studies.…”