Long-term Follow-up of Mycobacterium avium Complex Lung Disease in Patients Treated With Regimens Including Clofazimine and/or Rifampin

Jarand, Julie; Davis, John P.; Cowie, Robert L.; Field, Stephen K.; Fisher, Dina

doi:10.1378/chest.15-0543

Cited by 121 publications

(73 citation statements)

References 34 publications

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“…A preliminary randomized study showed that the clinical efficacy of a daily two-drug regimen (CLR and EMB) was similar to that of a daily three-drug regimen (CLR, EMB, and RIF) for MAC-LD (39). In addition, the replacement of RIF with clofazimine and daily treatment with CLR or AZM, EMB, and clofazimine achieved similar treatment outcomes in patients with MAC-LD in two retrospective studies (40,41). Further clinical studies are warranted to evaluate these treatment options for MAC-LD.…”

Section: Discussionmentioning

confidence: 95%

Peak Plasma Concentration of Azithromycin and Treatment Responses in Mycobacterium avium Complex Lung Disease

Jeong

Jeon

Park

et al. 2016

Antimicrob Agents Chemother

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d Macrolides, such as azithromycin (AZM) and clarithromycin, are the cornerstones of treatment for Mycobacterium avium complex lung disease (MAC-LD). Current guidelines recommend daily therapy with AZM for cavitary MAC-LD and intermittent therapy for noncavitary MAC-LD, but the effectiveness of these regimens has not been thoroughly investigated. This study evaluated associations between microbiological response and estimated peak plasma concentrations (C max ) of AZM. The AZM C max was measured in patients receiving daily therapy (250 mg of AZM daily, n ‫؍‬ 77) or intermittent therapy (500 mg of AZM three times weekly, n ‫؍‬ 89) for MAC-LD and daily therapy for Mycobacterium abscessus complex LD (MABC-LD) (250 mg of AZM daily, n ‫؍‬ 55). The AZM C max was lower with the daily regimen for MAC-LD (median, 0.24 g/ml) than with the intermittent regimen for MAC-LD (median, 0.65 g/ml; P < 0.001) or daily therapy for MABC-LD (median, 0.53 g/ml; P < 0.001). After adjusting for confounding factors, AZM C max was independently associated with favorable microbiological responses in MAC-LD patients receiving a daily regimen (adjusted odds ratio [aOR], 1.58; 95% confidence interval [CI], 1.01 to 2.48; P ‫؍‬ 0.044) but not an intermittent regimen (aOR, 0.85; 95% CI, 0.58 to 1.23, P ‫؍‬ 0.379). With the daily AZM-based multidrug regimen for MAC-LD, a low AZM C max was common, whereas a higher AZM C max was associated with favorable microbiologic responses. The results also suggested that the addition of rifampin may lower AZM C max . When a daily AZM-based multidrug regimen is used for treating severe MAC-LD, such as cavitary disease, the currently recommended AZM dose might be suboptimal. (This study has been registered at ClinicalTrials.gov under identifier NCT00970801.)

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Section: Discussionmentioning

confidence: 95%

Peak Plasma Concentration of Azithromycin and Treatment Responses in Mycobacterium avium Complex Lung Disease

Jeong

Jeon

Park

et al. 2016

Antimicrob Agents Chemother

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“…though moxifloxacin or clofazimine can be effective for the treatment of macrolide-susceptible MAC-LD (38)(39)(40). In contrast, the combination of surgical resection and parenteral aminoglycoside was associated with favorable treatment outcomes in the treatment of macrolide-resistant MAC-LD (14), although surgical treatment may be associated with high complication rates (41,42).…”

Section: Discussionmentioning

confidence: 99%

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

Moon

Park

Kim

et al. 2016

Antimicrob Agents Chemother

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“…Despite a paucity of reliable studies, treatment against MAC strains resistant to clarithromycin should be initiated using medication that has not been previously used in the patient. The regimen should be composed of at least three or four antimycobacterials, including a parenteral aminoglycoside, high-dose ethambutol (6), rifabutin (3), fluoroquinolones acting against DNA gyrase and topoisomerase IV (27,28), and clofazimine (28,29). Although somewhat controversial, continuation of macrolide treatment, even at a lower dose, if well tolerated, may also be considered due to its broad mechanism of action.…”

Section: Discussionmentioning

confidence: 99%

PCR-Based Rapid Identification System Using Bridged Nucleic Acids for Detection of Clarithromycin-Resistant Mycobacterium avium-M. intracellulare Complex Isolates

et al. 2016

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The nontuberculous mycobacteria (NTM) cause miscellaneous disorders in humans, especially in the lungs, which present with a variety of radiological features. To date, knowledge of the pathogenic role of the Mycobacterium avium-intracellulare complex (MAC) in the human lung and the definitive criteria for initiating multidrug therapy are still lacking. However, there is little doubt that clarithromycin is the most efficacious drug among the various treatment regimens for lung NTM. In this study, with the use of a bridged nucleic acid (BNA) probe a detection system based on a real-time PCR (BNA-PCR) for the identification of the point mutations at position 2058 or 2059 in domain V of the 23S rRNA gene responsible for clarithromycin resistance was developed and has been assessed using MAC isolates from clinical samples. Out of 199 respiratory specimens, the drug susceptibility test demonstrated 12 strains resistant to clarithromycin, while the BNA-PCR showed 8 strains carrying the point mutation at position 2058 or 2059 of the 23S rRNA gene. This system revealed that there were mycobacterial strains resistant to clarithromycin which do not carry previously identified resistance genes. This paper documents a novel system for detecting clarithromycin-resistant strains and demonstrates that although these mutations are tacitly assumed to account for >90% of the reported resistant mutants, there is a significant fraction of resistant mutants that do not harbor these mutations. Therefore, unknown mechanisms affecting clarithromycin resistance remain to be elucidated. The nontuberculous mycobacteria (NTM) are ubiquitous microorganisms found in various environments. They are capable of causing miscellaneous disorders in humans, especially in the lungs, which present with a variety of radiological features. It is noteworthy that the prevalence of lung NTM is increasing throughout the world (1, 2). Whereas NTM diversity in clinical manifestations and geographic distribution has been well documented, Mycobacterium avium and Mycobacterium intracellulare, collectively referred to as the Mycobacterium avium-intracellulare complex (MAC), are frequently isolated from such patients in most countries (3).To date, knowledge of the pathogenic role of MAC strains in the human lung and the definitive criteria for initiating multidrug therapy are still lacking. However, there is little doubt that clarithromycin is the most efficacious drug among the various treatment regimens for lung NTM. Clarithromycin is a ribosome-targeting macrolide antibiotic that interacts with a bacterial 23S rRNA hairpin-like structure in domain II and the peptidyl transferase loop in domain V (4, 5). Additionally, clarithromycin is the only agent for which susceptibility testing has high clinical efficacy. Therefore, management of clarithromycin-resistant MAC isolates from advanced lung NTM is an emerging concern. It is worth noting that multidrug therapy containing clarithromycin as the key drug is now a mandatory implementation to prevent resistance.Other s...

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Long-term Follow-up of Mycobacterium avium Complex Lung Disease in Patients Treated With Regimens Including Clofazimine and/or Rifampin

Cited by 121 publications

References 34 publications

Peak Plasma Concentration of Azithromycin and Treatment Responses in Mycobacterium avium Complex Lung Disease

Peak Plasma Concentration of Azithromycin and Treatment Responses in Mycobacterium avium Complex Lung Disease

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

PCR-Based Rapid Identification System Using Bridged Nucleic Acids for Detection of Clarithromycin-Resistant Mycobacterium avium-M. intracellulare Complex Isolates

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