Detection and Assessment of Clarithromycin Inducible Resistant Strains Among Korean
            <i>Mycobacterium abscessus</i>
            Clinical Strains: PCR Methods

Lee, Seung Heon; Yoo, Hee Kyung; Kim, Seol Hee; Koh, Won Jung; Kim, Chang Ki; Park, Young Kil; Kim, Hee Jin

doi:10.1002/jcla.21702

Cited by 17 publications

(16 citation statements)

References 15 publications

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“…massiliense in our isolates, which appears to be more susceptible to macrolides than M. abscessus sensu stricto and M. bolletii [34]. This contrasts with previous studies describing constitutive macrolide resistance between 2.7% and 28.6% and inducible resistance in 65% to 68.8% of M. abscessus complex isolates [35–37]. …”

Section: Discussioncontrasting

confidence: 98%

Mycobacterium abscessus Complex Infections: A Retrospective Cohort Study

Sfeir

Walsh

Rosa

et al. 2018

Open Forum Infectious Diseases

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BackgroundInfections caused by Mycobacterium abscessus group strains are usually resistant to multiple antimicrobials and challenging to treat worldwide. We describe the risk factors, treatment, and clinical outcomes of patients in 2 large academic medical centers in the United States.MethodsA retrospective cohort study of hospitalized adults with a positive culture for M. abscessus in Miami, Florida (January 1, 2011, to December 31, 2014). Demographics, comorbidities, the source of infection, antimicrobial susceptibilities, and clinical outcomes were analyzed. Early treatment failure was defined as death and/or infection relapse characterized either by persistent positive culture for M. abscessus within 12 weeks of treatment initiation and/or lack of radiographic improvement.ResultsOne hundred eight patients were analyzed. The mean age was 50.81 ± 21.03 years, 57 (52.8%) were females, and 41 (38%) Hispanics. Eleven (10.2%) had end-stage renal disease, 34 (31.5%) were on immunosuppressive therapy, and 40% had chronic lung disease. Fifty-nine organisms (54.6%) were isolated in respiratory sources, 21 (19.4%) in blood, 10 (9.2%) skin and soft tissue, and 9 (8.3%) intra-abdominal. Antimicrobial susceptibility reports were available for 64 (59.3%) of the patients. Most of the isolates were susceptible to clarithromycin, amikacin, and tigecycline (93.8%, 93.8%, and 89.1%, respectively). None of the isolates were susceptible to trimethoprim/sulfamethoxazole, and only 1 (1.6%) was susceptible to ciprofloxacin. Thirty-six (33.3%) patients early failed treatment; of those, 17 (15.7%) died while hospitalized. On multivariate analysis, risk factors significantly associated with early treatment failure were disseminated infection (odds ratio [OR], 11.79; 95% confidence interval [CI], 1.53–81.69; P = .04), acute kidney injury (OR, 6.55; 95% CI, 2.4–31.25; P = .018), organ transplantation (OR, 2.37; 95% CI, 2.7–23.1; P = .005), immunosuppressive therapy (OR, 2.81; 95% CI, 1.6–21.4; P = .002), intravenous amikacin treatment (OR, 4.1; 95% CI, 0.9–21; P = .04), clarithromycin resistance (OR,79.5; 95% CI, 6.2–3717.1, P < .001), and presence of prosthetic device (OR, 5.43; 95% CI, 1.57–18.81; P = .008). Receiving macrolide treatment was found to be protective against early treatment failure (OR, 0.13; 95% CI, 0.002–1.8; P = .04).ConclusionsOur cohort of 108 M. abscessus complex isolates in Miami, Florida, showed an in-hospital mortality of 15.7%. Most infections were respiratory. Clarithromycin and amikacin were the most likely agents to be susceptible in vitro. Resistance to fluoroquinolone and trimethoprim/sulfamethoxazole was highly common. Macrolide resistance, immunosuppression, and renal disease were significantly associated with early treatment failure.

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Section: Discussioncontrasting

confidence: 98%

Mycobacterium abscessus Complex Infections: A Retrospective Cohort Study

Sfeir

Walsh

Rosa

et al. 2018

Open Forum Infectious Diseases

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“…abscessus with the macrolide-susceptible erm(41) C28 sequevar but also in M. abscessus subsp. abscessus with the intrinsically macrolide-resistant erm(41) T28 sequevar (15,18,19,30,31). In our study, of the 13 isolates with rrl mutations, 85% had the T28 sequevar and 15% had the C28 sequevar of erm(41).…”

Section: Discussionmentioning

confidence: 46%

Clinical Characteristics and Treatment Outcomes of Patients with Acquired Macrolide-Resistant Mycobacterium abscessus Lung Disease

Choi

Kim

et al. 2017

Antimicrob Agents Chemother

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Macrolide antibiotics are mainstays in the treatment of lung disease due to the complex. Although previous studies have reported development of acquired macrolide resistance in this species, limited data are available on the outcomes of lung disease due to macrolide-resistant subsp. This study evaluated the clinical features, treatment outcomes, and molecular characteristics of macrolide-resistant isolates of subsp. We performed a retrospective review of medical records and genetic analysis of clinical isolates from 13 patients who had acquired macrolide-resistant subsp. lung disease between November 2006 and March 2016. Eleven (85%) patients had the nodular bronchiectatic form of the disease, and two (15%) patients had the fibrocavitary form. When acquired macrolide resistance was detected, 10 (77%) patients were on antibiotic therapy for subsp. , and three (23%) patients were on therapy for lung disease due to other nontuberculous mycobacteria. The median treatment duration after detecting resistance was 24.0 months (interquartile range, 16.0 to 43.0 months). Treatment outcomes were poor, and final sputum culture conversion was achieved in only one (8%) patient, after resectional surgery. All 13 clinical isolates demonstrated point mutations at position 2058 ( = 10) or 2059 ( = 3) of the 23S rRNA gene, which resulted in acquired macrolide resistance. This study indicates that treatment outcomes are very poor after the development of acquired macrolide resistance in patients with subsp. lung disease. Thus, more effective measures are needed to prevent development and effectively treat macrolide-resistant subsp. lung disease.

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“…8006) harboring a point mutation 2059A>G in the rrl gene showed resistance to clarithromycin from day 3 through day 14 (MIC > 128 µg/ml). The presence of rrl mutations was reported in up to 30% of newly isolated strains in East Asia (16,35), whereas no rrl mutations were identified at the time of diagnosis in Spain (36). It has been reported that mutations in the rrl gene rapidly accumulate following clarithromycin use in monotherapy (3).…”

Section: Discussionmentioning

confidence: 99%

PCR amplification of the erm(41) gene can be used to predict the sensitivity of Mycobacterium�abscessus complex strains to clarithromycin

et al. 2019

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A worldwide increase in the Mycobacterium abscessus (M. abscessus) complex has been observed. Therefore, the aim of the present study was to investigate the diversity of the rrl and erm(41) genes, both of which are associated with macrolide sensitivity in the M. abscessus complex. The current study also examined the efficacy of mass spectrometry as an alternative to molecular testing to classify subspecies of the M. abscessus complex. A total of 14 strains of the M. abscessus complex were obtained, and based on conventional analyses using housekeeping genes, 57% were determined to be M. abscessus subsp. abscessus, 43% were M. abscessus subsp. massiliense, and none were identified as M. abscessus subsp. bolletii. However, depending on the strain, it was not always possible to distinguish between the subspecies by mass spectrometry. Consequently, PCR products for the rrl and erm(41) genes were directly sequenced. Overall, 7.1% of the strains were identified to have a rrl mutation, and 92.9% carried a T at position 28 of erm (41). Results presented here suggest that the principal cause of treatment failure for M. abscessus complex infections is inducible macrolide resistance encoded by the erm(41) gene. From a strictly pragmatic standpoint, the phenotypic function of a putative erm(41) gene is the most important piece of information required by clinicians in order to prescribe an effective treatment. Although PCR amplification of erm(41) is not sufficient to differentiate between the M. abscessus complex subspecies, PCR can be easily and efficiently used to predict the sensitivity of members of the M. abscessus complex to clarithromycin. PCR amplification of the erm(41) gene can be used to predict the sensitivity of Mycobacterium abscessus complex strains to clarithromycin

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Detection and Assessment of Clarithromycin Inducible Resistant Strains Among Korean Mycobacterium abscessus Clinical Strains: PCR Methods

Cited by 17 publications

References 15 publications

Mycobacterium abscessus Complex Infections: A Retrospective Cohort Study

Mycobacterium abscessus Complex Infections: A Retrospective Cohort Study

Clinical Characteristics and Treatment Outcomes of Patients with Acquired Macrolide-Resistant Mycobacterium abscessus Lung Disease

PCR amplification of the erm(41) gene can be used to predict the sensitivity of Mycobacterium�abscessus complex strains to clarithromycin

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