Antibiotic Treatment of <i>Mycobacterium abscessus</i> Lung Disease

Jeon, Kyeongman; Kwon, O Jung; Lee, Nam Yong; Kim, Bumjoon J.; Kook, Yoon Hoh; Lee, Seung-Heon; Park, Young Kil; Kim, Chang Ki; Koh, Won‐Jung

doi:10.1164/rccm.200905-0704oc

Cited by 298 publications

(203 citation statements)

References 39 publications

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“…NTM conversion after treatment was defined as having at least three consecutive negative NTM cultures over 1 year, consistent with current guidelines (23)(24)(25). Recurrence was defined as two consecutive positive cultures for the same NTM species after sputum conversion.…”

Section: Assessment Of Microbiologic Responsementioning

confidence: 99%

Clinical Significance of a First Positive Nontuberculous Mycobacteria Culture in Cystic Fibrosis

et al. 2014

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Rationale: Little is known about outcomes of infection with nontuberculous mycobacteria (NTM) in cystic fibrosis (CF) or about the significance of a positive NTM culture. Determining which patients are at risk for active NTM disease is clinically valuable.Objectives: To examine the clinical course of subjects with CF with an initial positive NTM culture and identify characteristics associated with active NTM disease.Methods: We performed a retrospective study of pediatric and adult subjects with CF with at least one positive NTM culture at the Colorado CF Center from 2000 to 2010.Measurements and Main Results: Mycobacterium avium complex was the first identified NTM in the majority of subjects (73%). The frequency of growing a second NTM species was 26% at 5 years. Clinical characteristics and distribution of NTM species between pediatric and adult subjects were similar except for differences in baseline FEV 1 (89% vs. 71%; P , 0.001) and coinfection with Pseudomonas aeruginosa (33% vs. 55%; P = 0.04). Over 60% of subjects had transient or persistent infection but not active NTM disease. Subjects who developed active NTM disease were distinguished from those with transient or persistent infection, respectively, by FEV 1 at the time of first positive NTM culture (72% vs. 84 or 86%; P = 0.02) and FEV 1 decline in the prior year (25.8%/yr vs. 20.7%/yr [P = 0.009] or 20.4%/yr [P = 0.001]). Conclusions:The majority of patients with CF with a first positive NTM culture do not progress to active disease. Lower lung function and accelerated lung function decline appear to be indicators of the significance of an initial positive NTM culture.

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Section: Assessment Of Microbiologic Responsementioning

confidence: 99%

Clinical Significance of a First Positive Nontuberculous Mycobacteria Culture in Cystic Fibrosis

et al. 2014

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“…bolletii. Their differentiation is of clinical interest, because subspecies differ in antibiotic resistance and treatment response in M. abscessus lung disease (1,2). Identification of the members of M. abscessus relies on sequencing of multiple genes (3,4).…”

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confidence: 99%

GenoType NTM-DR for Identifying Mycobacterium abscessus Subspecies and Determining Molecular Resistance

et al. 2016

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bWe studied the performance of a new line probe assay for identifying the subspecies and determining the macrolide and aminoglycoside resistance levels of 50 Mycobacterium abscessus isolates. Agreement of GenoType NTM-DR results with sequencing and phenotypic resistance results was 92% for subspecies identification and 98% for determining molecular and phenotypic resistance. The Mycobacterium abscessus complex is divided into three subspecies: M. abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. abscessus subsp. bolletii. Their differentiation is of clinical interest, because subspecies differ in antibiotic resistance and treatment response in M. abscessus lung disease (1, 2). Identification of the members of M. abscessus relies on sequencing of multiple genes (3, 4). Inducible macrolide resistance in M. abscessus is conferred by the presence of the inducible methylase Erm(41) (5, 6), whereas high-level clarithromycin resistance is attributed to mutations at position 2058 or 2059 in the peptidyltransferase-binding region of the 23S rRNA gene (rrl) (7). A single point mutation at position 1408 in rrs of the 16S rRNA gene is responsible for the high level of resistance against aminoglycosides, another category of first-line antibiotics (8).GenoType NTM-DR (Hain Lifescience, Nehren, Germany) is a new line probe assay that enables M. abscessus subspecies identification and the simultaneous determination of antibiotic resistance to macrolides and aminoglycosides of mutations at position 28 in erm(41) (5, 6), position 2058/2059 in rrl, and position 1408 in rrs. We studied the ability of this assay to characterize 50 M. abscessus isolates (28 M. abscessus subsp. abscessus isolates, 19 M. abscessus subsp. massiliense isolates, and 3 M. abscessus subsp. bolletii isolates). Furthermore, 4 Mycobacterium chelonae isolates were analyzed. M. chelonae is closely related to M. abscessus. The two species share the same biochemical features, have highly similar 16S rRNA sequences, and are frequently summarized as the M. chelonae/abscessus complex (9). Results of the GenoType NTM-DR assay were compared with the results of sequencing the hsp65, erm(41), rrl, rrs, and 16S rRNA genes, which were obtained previously (10) or sequenced within this study as described in reference 10. Additionally, molecular resistance results of all M. abscessus isolates were compared with results of phenotypic resistance to clarithromycin and amikacin published by Rueger et al. (10), who used the broth microdilution method in RAPMYCO Sensititre 96-well plates. According to the CLSI breakpoints, highlevel clarithromycin resistance was defined as an MIC of Ն8 g/ml on day 5, and inducible resistance was defined as an increase of the clarithromycin MIC from Յ2 g/ml on day 5 to Ն8 g/ml on day 14. Aminoglycoside resistance was defined as an amikacin MIC of Ն64 g/ml.Isolates were grown in mycobacterial growth indicator tube (MGIT) liquid medium (Becton, Dickinson and Company, Franklin Lakes, NJ, USA) at 37°C. GenoType NTM-DR was performed...

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“…Furthermore, recent research demonstrates that NTM is prevalent in CF populations globally (3)(4)(5)(6), with Mycobacterium avium complex (MAC) and Mycobacterium abscessus being the most commonly isolated species from patients with CF in the United States (1,7). After an NTM infection is established in the airways of persons with CF, eradication is difficult and often requires prolonged use of multidrug treatment regimens that include a macrolide (8,9), the only drugs for which in vitro susceptibility correlates with clinical outcomes and treatment response for NTM infections (8,10). However, macrolides are also increasingly used for the general management of CF because of their antiinflammatory properties (11), raising concerns over the potential development of macrolide-resistant NTM infections from long-term macrolide use.…”

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confidence: 99%

Epidemiology of Nontuberculous Mycobacterial Infections and Associated Chronic Macrolide Use among Persons with Cystic Fibrosis

Binder

Adjemian²,

Olivier³

et al. 2013

Am J Respir Crit Care Med

125

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Rationale: Persons with cystic fibrosis (CF) are at high risk of nontuberculous mycobacterial (NTM) infection, with treatment requiring prolonged multidrug regimens that include macrolides. Although macrolides, specifically azithromycin, are used in the management of patients with CF with chronic Pseudomonas, macrolide-resistant NTM infections are of growing concern. Objectives: To evaluate the relationship between chronic macrolide use and NTM infection among patients with CF included in the 2011 CF Patient Registry (CFPR). Methods: We performed a nested case-control study: incident NTM cases were persons aged more than 5 years with at least one positive culture for NTM in 2011. Controls were persons with negative cultures in 2010 and 2011. Measurements and Main Results: The 2011 CFPR included 27,112 patients; 5,403 (20%) were cultured for mycobacteria in 2010-2011 and met all inclusion criteria. Of these, 191 (4%) were NTMpositive in 2011 only (cases); 5,212 (96%) were NTM-negative in 2010 and 2011 (control subjects). Among the cases, 122 (64%) were culture-positive for Mycobacterium avium complex (MAC) and 69 (36%) for M. abscessus. Azithromycin use in 2010 was less frequently reported among MAC cases (57%; odds ratio ¼ 0.7, P , 0.05) and M. abscessus cases (51%; odds ratio ¼ 0.5, P , 0.01) than in control subjects (66%). Among adolescents and adults, patients with the greatest number of years on chronic macrolides were the least likely to develop incident NTM in 2011 (P , 0.01). Conclusions: Patients with incident NTM infections from either MAC or M. abscessus were less likely to have had chronic azithromycin treatment in the past year. However, because macrolide monotherapy may lead to macrolide resistance, routine screening for NTM should be considered for persons with CF. Keywords: macrolides; cystic fibrosis; nontuberculous mycobacteriaPersons with cystic fibrosis (CF) are at significantly greater risk of contracting nontuberculous mycobacterial (NTM) infections than the general population, with an estimated disease prevalence of 13-23% among all patients with CF (1, 2). Furthermore, recent research demonstrates that NTM is prevalent in CF populations globally (3-6), with Mycobacterium avium complex (MAC) and Mycobacterium abscessus being the most commonly isolated species from patients with CF in the United States (1, 7). After an NTM infection is established in the airways of persons with CF, eradication is difficult and often requires prolonged use of multidrug treatment regimens that include a macrolide (8, 9), the only drugs for which in vitro susceptibility correlates with clinical outcomes and treatment response for NTM infections (8, 10). However, macrolides are also increasingly used for the general management of CF because of their antiinflammatory properties (11), raising concerns over the potential development of macrolide-resistant NTM infections from long-term macrolide use.Macrolide-resistant pulmonary NTM infections in patients with CF are even more difficult to treat and have been associ...

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Antibiotic Treatment of Mycobacterium abscessus Lung Disease

Abstract: Standardized combination antibiotic therapy was moderately effective in treating M. abscessus lung disease. However, frequent adverse reactions and the potential for long-duration hospitalization are important problems that remain to be solved.

Cited by 298 publications

References 39 publications

Clinical Significance of a First Positive Nontuberculous Mycobacteria Culture in Cystic Fibrosis

Clinical Significance of a First Positive Nontuberculous Mycobacteria Culture in Cystic Fibrosis

GenoType NTM-DR for Identifying Mycobacterium abscessus Subspecies and Determining Molecular Resistance

Epidemiology of Nontuberculous Mycobacterial Infections and Associated Chronic Macrolide Use among Persons with Cystic Fibrosis

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