Phenotypic and molecular characterization of quinolone resistance in Mycobacterium abscessus subsp. bolletii recovered from postsurgical infections

Moura, Vinicius Calado Nogueira de; Silva, Marlei Gomes da; Gomes, Karen Machado; Coelho, Fábrice Santana; Sampaio, Jorge Luiz Mello; Mello, Fernanda Carvalho de Queiroz; Lourenço, Maria Cristina da Silva; Amorim, Efigênia de Lourdes Teixeira; Duarte, Rafael Silva

doi:10.1099/jmm.0.034942-0

Cited by 15 publications

(9 citation statements)

References 42 publications

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“…A mutation at codon 90 in gyrA gene was reported in clinical isolates of M. abscessus exhibiting high resistance to ciprofloxacin [51]. This observation contrasts with our genome analysis, which found no such mutations, suggesting that other mechanisms of resistance may be involved in high-level resistance to quinolones [52]. Accordingly, we found that M. abscessus mycobacteria encode qepA2, a plasmidic gene conferring quinolone resistance in gram-negative bacteria [53].…”

Section: Resultscontrasting

confidence: 59%

“…Also, M. abscessus genome encodes an erm(41) gene which mutations were reported to confer clarithromycin resistance [50]. In-vitro tests showed that M. massiliense clinical isolates could be distinguished from M. abscessus isolates for their susceptibility to ciprofloxacin [51] whereas M. bolletii isolates were reported to be resistant to all quinolones [52]. A mutation at codon 90 in gyrA gene was reported in clinical isolates of M. abscessus exhibiting high resistance to ciprofloxacin [51].…”

Section: Resultsmentioning

confidence: 99%

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Genome analysis reveals three genomospecies in Mycobacterium abscessus

Sassi

Drancourt

2014

BMC Genomics

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BackgroundMycobacterium abscessus complex, the third most frequent mycobacterial complex responsible for community- and health care-associated infections in developed countries, comprises of M. abscessus subsp. abscessus and M. abscessus subsp. bolletii reviously referred as Mycobacterium bolletii and Mycobacterium massiliense. The diversity of this group of opportunistic pathogens is poorly described.ResultsIn-depth analysis of 14 published M. abscessus complex genomes found a pan-genome of 6,153 proteins and core-genome of 3,947 (64.1%) proteins, indicating a non-conservative genome. Analysing the average percentage of amino-acid sequence identity (from 94.19% to 98.58%) discriminates three main clusters C1, C2 and C3: C1 comprises strains belonging to M. abscessus, C2 comprises strains belonging to M. massiliense and C3 comprises strains belonging to M. bolletii; and two sub-clusters in clusters C2 and C3. The phylogenomic network confirms these three clusters. The genome length (from 4.8 to 5.51-Mb) varies from 5.07-Mb in C1, 4.89-Mb in C2A, 5.01-Mb in C2B and 5.28-Mb in C3. The mean number of prophage regions (from 0 to 7) is 2 in C1; 1.33 in C2A; 3.5 in C2B and five in C3. A total of 36 genes are uniquely present in C1, 15 in C2 and 15 in C3. These genes could be used for the detection and identification of organisms in each cluster. Further, the mean number of host-interaction factors (including PE, PPE, LpqH, MCE, Yrbe and type VII secretion system ESX3 and ESX4) varies from 70 in cluster C1, 80 in cluster C2A, 74 in cluster C2B and 93 in clusters C3A and C3B. No significant differences in antibiotic resistance genes were observed between clusters, in contrast to previously reported in-vitro patterns of drug resistance. They encode both penicillin-binding proteins targeted by β-lactam antibiotics and an Ambler class A β-lactamase for which inhibitors exist.ConclusionsOur comparative analysis indicates that M. abscessus complex comprises three genomospecies, corresponding to M. abscessus, M. bolletii, and M. massiliense. The genomics data here reported indicate differences in virulence of medical interest; and suggest targets for the refined detection and identification of M. abscessus.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-359) contains supplementary material, which is available to authorized users.

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Section: Resultscontrasting

confidence: 59%

Section: Resultsmentioning

confidence: 99%

Genome analysis reveals three genomospecies in Mycobacterium abscessus

Sassi

Drancourt

2014

BMC Genomics

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“…These amino acid substitutions are different from those found in susceptible bacteria harboring a lysine at position 447 (Lys-447) and a serine at position 464 (Ser-464_ (Yoshida et al , 1991). These results are in accordance with other studies (Esfahani et al , 2016; de Moura et al , 2012; Guillemin et al , 1998; Guillemin et al , 1995;), showing that substitutions of amino acids at these positions are associated with acquired resistance to fluoroquinolones. It is hypothesized that the presence of these amino acids could decrease the interaction between the quinolone drug and the gyrase A and B subunit-DNA complex (Guillemin et al , 1998).…”

Section: Resultssupporting

confidence: 93%

Antibiograms and Molecular Characterization of Drug Resistance ofMycobacterium abscessuscomplex from Patients with Multidrug-Resistant Pulmonary Tuberculosis (MDR TB) Infection

2019

Preprint

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Mycobacterium massiliense 33 MAM. 42.9% MAB complex isolates were MDR. Macrolide resistant MAB and 34 MAM had T28 sequevar, showing functional erm(41) responsible for inducible 35 resistance. Unexpectedly, full length erm(41) was found in MAM. Therrl gene in these 36 isolates showed no point mutations, indicating T28 sequevar as cause of inducible 37 resistance. All fluoroquinolone resistant isolates showed Ala-83 in gyrA 38 fluoroquinolone resistant-dependent region (QRDR) and Arg-447 and Asn-464 39 in gyrB QRDR. These are associated with resistance to the drug. In the Philippines, one of the most common rapidly growing mycobacteria (RGM) from 43 patients with multiple drug resistant tuberculosis (MDR-TB) infection is M. abscessus 44 complex. This non-tuberculous Mycobacterium (NTM) species is usually found in TB 45 culture, either growing alongside with M. tuberculosis or after the patient has been 46 confirmed negative for pulmonary tuberculosis through direct sputum smear 47 microscopy (DSSM) and TB culture. Pulmonary diseases caused by the M. abscessus 48 complex are extremely hard to manage for these species are found to be resistant to 49 anti-tuberculous agents. Patients with M. abscessus infection do not receive appropriate 50 treatment for they are considered to have chronic TB and MDR-TB. As a result, 51 patients are prescribed a six-month anti-TB treatment which is not appropriate for M. 52 abscessus infections. Interestingly, there is no known study in the Philippines regarding 53 the antimicrobial resistance profile of M. abscessus complex. NTM studies are 54 overshadowed by pulmonary TB research studies and therefore, clinicians are not 55 guided on the treatment for NTM infections. Moreover, detection of NTM species 56 is not part of the routine procedure in the clinical microbiology laboratory. Treatment 57 failure to both first-line anti-TB drugs rifampicin and isoniazid is linked to infection 58 with multidrug-resistant M. tuberculosis (MDR-TB). Gler et al. (2012) showed very 59 high rates (83% to 97%) of MDR-TB infections in the Philippines in 2012. Because 60 MDR TB is often associated with the occurrence of M. abscessus complex in clinical 61 samples, the present study aimed to characterize local isolates of M. abscessus complex 62 from patients with multidrug-resistant pulmonary tuberculosis in terms of their 63 antimicrobial susceptibility profiles and determine the genetics of the antibiotic 101 Center of the Philippines from which these 20 isolates identified to be M. abscessus complex were taken. 102 103 Phenotypic characterization of Mycobacterium abscessus complex 104 Freshly grown 5 to 7-day old cultures of M. abscessus complex were subjected to 105 phenotypic characterization. Colony morphology was determined by observing the 106 colonies grown on Ogawa medium. There are two possible morphotypes of M.

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“…However, other rapidly growing mycobacteria species showed distinct susceptibilities to this class of antimicrobials and patterns of mutations, contrary to what has been traditionally defined, suggesting that other mechanisms of resistance, different from gyrA or gyrB mutations, may also be involved in resistance to high levels of quinolones [38]. …”

Section: Discussionmentioning

confidence: 99%

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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Phenotypic and molecular characterization of quinolone resistance in Mycobacterium abscessus subsp. bolletii recovered from postsurgical infections

Cited by 15 publications

References 42 publications

Genome analysis reveals three genomospecies in Mycobacterium abscessus

Genome analysis reveals three genomospecies in Mycobacterium abscessus

Antibiograms and Molecular Characterization of Drug Resistance ofMycobacterium abscessuscomplex from Patients with Multidrug-Resistant Pulmonary Tuberculosis (MDR TB) Infection

Mycobacterium abscessus Complex Infections: A Retrospective Cohort Study

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