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

2016 ◽  
Vol 60 (11) ◽  
pp. 6758-6765 ◽  
Author(s):  
Seong Mi Moon ◽  
Hye Yun Park ◽  
Su-Young Kim ◽  
Byung Woo Jhun ◽  
Hyun Lee ◽  
...  
Keyword(s):  
Lung Disease ◽  
Treatment Outcomes ◽  
Mycobacterium Avium ◽  
Macrolide Resistance ◽  
Clinical Isolates ◽  
23S Rrna ◽  
Molecular Characteristics ◽  
Rrna Gene ◽  
Resistance Mutations ◽  
Content Type

ABSTRACTMacrolide antibiotics are key components of the multidrug treatment regimen for treating lung disease (LD) due toMycobacterium aviumcomplex (MAC). Despite the emergence of macrolide resistance, limited data are available on macrolide-resistant MAC-LD. This study evaluated the clinical features and treatment outcomes of patients with macrolide-resistant MAC-LD and the molecular characteristics of the macrolide-resistant isolates. A retrospective review of the medical records of 34 patients with macrolide-resistant MAC-LD who were diagnosed between January 2002 and December 2014 was performed, along with genetic analysis of 28 clinical isolates. Nineteen (56%) patients had the fibrocavitary form of MAC-LD, and 15 (44%) had the nodular bronchiectatic form.M. intracellularewas the etiologic organism in 21 (62%) patients. Approximately two-thirds (22/34 [65%]) of the patients had been treated with currently recommended multidrug regimens that included macrolide, ethambutol, and rifamycin prior to the emergence of macrolide resistance, and none had been treated with macrolide monotherapy. The median duration of treatment after the detection of macrolide resistance was 23.0 months (interquartile range, 16.8 to 45.3 months). Treatment outcomes were poor after the development of macrolide resistance, with favorable treatment outcomes achieved in only five (15%) patients, including two patients who underwent surgical resection. One-, 3-, and 5-year mortality rates were 9, 24, and 47%, respectively. Molecular analysis of 28 clinical isolates revealed that 96% (27/28) had point mutations at position 2058 or 2059 of the 23S rRNA gene. Our analyses indicate that more effective therapy is needed to treat macrolide-resistant MAC-LD and prevent its development.

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

2017 ◽  
Vol 61 (10) ◽  
Author(s):  
Hayoung Choi ◽  
Su-Young Kim ◽  
Dae Hun Kim ◽  
Hee Jae Huh ◽  
Chang-Seok Ki ◽  
...  
Keyword(s):  
Lung Disease ◽  
Treatment Outcomes ◽  
Point Mutations ◽  
Mycobacterium Abscessus ◽  
Macrolide Resistance ◽  
Clinical Isolates ◽  
23S Rrna ◽  
Molecular Characteristics ◽  
Rrna Gene ◽  
Content Type

ABSTRACT Macrolide antibiotics are mainstays in the treatment of lung disease due to the Mycobacterium abscessus 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 Mycobacterium abscessus subsp. abscessus. This study evaluated the clinical features, treatment outcomes, and molecular characteristics of macrolide-resistant isolates of M. abscessus subsp. abscessus. We performed a retrospective review of medical records and genetic analysis of clinical isolates from 13 patients who had acquired macrolide-resistant M. abscessus subsp. abscessus 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 M. abscessus subsp. abscessus, 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 (n = 10) or 2059 (n = 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 M. abscessus subsp. abscessus lung disease. Thus, more effective measures are needed to prevent development and effectively treat macrolide-resistant M. abscessus subsp. abscessus lung disease.

scholarly journals Clinical Characteristics and Treatment Outcomes of Patients with Macrolide-Resistant Mycobacterium massiliense Lung Disease

2016 ◽  
Vol 61 (2) ◽  
Author(s):  
Hayoung Choi ◽  
Su-Young Kim ◽  
Hyun Lee ◽  
Byung Woo Jhun ◽  
Hye Yun Park ◽  
...  
Keyword(s):  
Antibiotic Therapy ◽  
Lung Disease ◽  
Treatment Outcomes ◽  
Mortality Rates ◽  
Macrolide Resistance ◽  
Clinical Isolates ◽  
23S Rrna ◽  
Rrna Gene ◽  
Content Type ◽  
Mycobacterium Massiliense

ABSTRACT Macrolide antibiotics are cornerstones in the treatment of Mycobacterium massiliense lung disease. Despite the emergence of resistance, limited data on macrolide-resistant M. massiliense lung disease are available. This study evaluated the clinical features and treatment outcomes of patients and the molecular characteristics of macrolide-resistant M. massiliense isolates. We performed a retrospective review of medical records and genetic analyses of clinical isolates from 15 patients who had macrolide-resistant M. massiliense lung disease between September 2005 and February 2015. Nine patients (60%) had the nodular bronchiectatic form of the disease, and six (40%) had the fibrocavitary form. Before the detection of macrolide resistance, three patients (20%) were treated with macrolide monotherapy, four (27%) with therapy for presumed Mycobacterium avium complex infections, and eight (53%) with combination antibiotic therapy for M. massiliense lung disease. The median treatment duration after the detection of resistance was 18.7 months (interquartile range, 11.2 to 39.8 months). Treatment outcomes were poor, with a favorable outcome being achieved for only one patient (7%), who underwent surgery in addition to antibiotic therapy. The 1-, 3-, and 5-year mortality rates were 7, 13, and 33%, respectively. Of the 15 clinical isolates, 14 (93%) had point mutations at position 2058 (n = 9) or 2059 (n = 5) of the 23S rRNA gene, resulting in macrolide resistance. Our study indicates that treatment outcomes are poor and mortality rates are high after the development of macrolide resistance in patients with M. massiliense lung disease. Thus, preventing the development of macrolide resistance should be a key consideration during treatment.

scholarly journals Prospective Evaluation of ResistancePlus MG, a New Multiplex Quantitative PCR Assay for Detection of Mycoplasma genitalium and Macrolide Resistance

2017 ◽  
Vol 55 (6) ◽  
pp. 1915-1919 ◽  
Author(s):  
S. N. Tabrizi ◽  
J. Su ◽  
C. S. Bradshaw ◽  
C. K. Fairley ◽  
S. Walker ◽  
...  
Keyword(s):  
Quantitative Pcr ◽  
Clinical Performance ◽  
Simultaneous Detection ◽  
Mycoplasma Genitalium ◽  
Macrolide Resistance ◽  
23S Rrna ◽  
Rrna Gene ◽  
Resistance Mutations ◽  
Content Type ◽  
Conventional Culture

ABSTRACT Mycoplasma genitalium is a significant pathogen for which first-line treatment is becoming less effective due to increased resistance to macrolides. As conventional culture and antimicrobial susceptibility testing is not feasible for routine detection of this pathogen, molecular markers such as detection of mutations in the 23S rRNA gene have been described to predict resistance. Recently, a novel multiplex quantitative PCR (qPCR) assay, ResistancePlus MG, has been described for the simultaneous detection of Mycoplasma genitalium and macrolide resistance. In the current study, the clinical performance of the assay was evaluated on 1,089 consecutive urine and anogenital swab samples in symptomatic and asymptomatic male and female patients. Overall, 6.0% were positive for M. genitalium , with 63.1% having macrolide resistance-associated mutations. Compared to the laboratory-validated qPCR method targeting the 16S rRNA gene and Sanger sequencing to determine 23S rRNA mutations, the sensitivity and specificity of M. genitalium detection were 98.5% and 100% and for detection of macrolide resistance mutations were 100.0% and 96.2%, respectively. This assay offers a considerable advantage in clinical settings for M. genitalium testing by making the results of macrolide resistance and mutation analyses simultaneously available, which is increasingly important with escalating macrolide resistance.

scholarly journals Ribosomal Mutations as the Main Cause of Macrolide Resistance in Campylobacter jejuni and Campylobacter coli

2011 ◽  
Vol 55 (12) ◽  
pp. 5939-5941 ◽  
Author(s):  
Mirva Lehtopolku ◽  
Pirkko Kotilainen ◽  
Marjo Haanperä-Heikkinen ◽  
Ulla-Maija Nakari ◽  
Marja-Liisa Hänninen ◽  
...  
Keyword(s):  
Macrolide Resistance ◽  
23S Rrna ◽  
Rrna Gene ◽  
Campylobacter Coli ◽  
Resistance Mutations ◽  
Content Type ◽  
Amino Acid Insertion ◽  
23S Rrna Gene ◽  
Ribosomal Protein L22 ◽  
Resistant Strains

ABSTRACTThe aim of this study was to examine macrolide resistance mutations inCampylobacterspecies. In 76 strains studied, point mutation A to G at position 2059 of the 23S rRNA gene was detected in 30 of the 33 erythromycin-resistant strains. An amino acid insertion in the ribosomal protein L22 was found in one resistant strain without a 23S rRNA mutation. The A2059G mutation is the main cause of macrolide resistance inCampylobacterspecies.

scholarly journals GenoType NTM-DR Performance Evaluation for Identification of Mycobacterium avium Complex and Mycobacterium abscessus and Determination of Clarithromycin and Amikacin Resistance

2019 ◽  
Vol 57 (8) ◽  
Author(s):  
Hee Jae Huh ◽  
Su-Young Kim ◽  
Hyang Jin Shim ◽  
Dae Hun Kim ◽  
In Young Yoo ◽  
...  
Keyword(s):  
Mycobacterium Avium ◽  
Drug Susceptibility ◽  
Rapid Identification ◽  
Drug Susceptibility Testing ◽  
Mycobacterium Abscessus ◽  
Clinical Isolates ◽  
Resistance Mutations ◽  
Content Type ◽  
Clarithromycin Resistance ◽  
Reference Strains

ABSTRACT We evaluated the GenoType NTM-DR (NTM-DR) line probe assay for identifying Mycobacterium avium complex (MAC) species and Mycobacterium abscessus subspecies and for determining clarithromycin and amikacin resistance. Thirty-eight reference strains and 145 clinical isolates (58 MAC and 87 M. abscessus isolates), including 54 clarithromycin- and/or amikacin-resistant strains, were involved. The performance of the NTM-DR assay in rapid identification was evaluated by comparison with results of multigene sequence-based typing, whereas performance in rapid detection of clarithromycin and amikacin resistance was evaluated by comparison with sequencing of the erm(41), rrl, and rrs genes and drug susceptibility testing (DST). The accuracies of MAC and M. abscessus (sub)species identification were 92.1% (35/38) and 100% (145/145) for the 38 reference strains and 145 clinical isolates, respectively. Three MAC strains other than M. intracellulare were found to cross-react with the M. intracellulare probe in the assay. Regarding clarithromycin resistance, NTM-DR detected rrl mutations in 52 isolates and yielded 99.3% (144/145) and 98.6% (143/145) concordant results with sequencing and DST, respectively. NTM-DR sensitivity and specificity in the detection of clarithromycin resistance were 96.3% (52/54) and 100% (91/91), respectively. The NTM-DR yielded accurate erm(41) genotype results for all 87 M. abscessus isolates. Regarding amikacin resistance, NTM-DR detected rrs mutations in five isolates and yielded 99.3% (144/145) and 97.9% (142/145) concordant results with sequencing and DST, respectively. Our results indicate that the NTM-DR assay is a straightforward and accurate approach for discriminating MAC and M. abscessus (sub)species and for detecting clarithromycin and amikacin resistance mutations and that it is a useful tool in the clinical setting.

Antimicrobial susceptibility and mechanisms of high-level macrolide resistance in clinical isolates of Moraxella nonliquefaciens

2014 ◽  
Vol 63 (2) ◽  
pp. 242-247 ◽  
Author(s):  
Shotaro Nonaka ◽  
Kosuke Matsuzaki ◽  
Tomoya Kazama ◽  
Hiroyuki Nishiyama ◽  
Yoko Ida ◽  
...  
Keyword(s):  
Antimicrobial Susceptibility ◽  
Ribosomal Proteins ◽  
Macrolide Resistance ◽  
Clinical Isolates ◽  
23S Rrna ◽  
Rrna Gene ◽  
Efflux System ◽  
Strong Activity ◽  
23S Rrna Gene ◽  
High Level

We investigated antimicrobial susceptibility and the molecular mechanism involved in conferring high-level macrolide resistance in 47 clinical isolates of Moraxella nonliquefaciens from Japan. Antimicrobial susceptibility was determined using Etest and agar dilution methods. Thirty-two erythromycin-non-susceptible strains were evaluated for the possibility of clonal spreading, using PFGE. To analyse the mechanism related to macrolide resistance, mutations in the 23S rRNA gene and the ribosomal proteins, and the presence of methylase genes were investigated by PCR and sequencing. The efflux system was examined using appropriate inhibitors. Penicillin, ampicillin, amoxicillin, cefixime, levofloxacin and antimicrobials containing β-lactamase inhibitors showed strong activity against 47 M. nonliquefaciens isolates. Thirty-two (68.1 %) of the 47 isolates showed high-level MICs to macrolides (MIC ≥128 mg l−1) and shared the A2058T mutation in the 23S rRNA gene. The geometric mean MIC to macrolides of A2058T-mutated strains was significantly higher than that of WT strains (P<0.0001). Thirty-two isolates with high-level macrolide MICs clustered into 30 patterns on the basis of the PFGE dendrogram, indicating that the macrolide-resistant strains were not clonal. In contrast, no common mutations of the ribosomal proteins or methylase genes, or overproduction of the efflux system were observed in A2058T-mutated strains. Moreover, of the 47 M. nonliquefaciens strains, 43 (91.5 %) were bro-1 and 4 (8.5 %) were bro-2 positive. Our results suggest that most M. nonliquefaciens clinical isolates show high-level macrolide resistance conferred by the A2058T mutation in the 23S rRNA gene. This study represents the first characterization of M. nonliquefaciens.

scholarly journals Comparison of Genospecies and Antimicrobial Resistance Profiles of Isolates in the Acinetobacter calcoaceticus-Acinetobacter baumannii Complex from Various Clinical Specimens

2012 ◽  
Vol 56 (12) ◽  
pp. 6267-6271 ◽  
Author(s):  
Ni Tien ◽  
Bang-Jau You ◽  
Hui-Lan Chang ◽  
Hsiu-Shen Lin ◽  
Chin-Yi Lee ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Acinetobacter Baumannii ◽  
Restriction Analysis ◽  
Acinetobacter Calcoaceticus ◽  
Its Region ◽  
Clinical Isolates ◽  
23S Rrna ◽  
Rrna Gene ◽  
Genotype 3 ◽  
Content Type

ABSTRACTThis study was conducted to compare the prevalences of antimicrobial resistance profiles of clinical isolates in theAcinetobacter calcoaceticus-Acinetobacter baumanniicomplex from sterile and nonsterile sites and to further study the relationship of antimicrobial resistance profiles and genospecies by amplified rRNA gene restriction analysis (ARDRA). A total of 1,381 isolates were tested with 12 different antibiotics to show their antimicrobial susceptibility profiles. A total of 205 clinical isolates were further analyzed by ARDRA of the intergenic spacer (ITS) region of the 16S-23S rRNA gene. It was found that the overall percentage of isolates from nonsterile sites (urine, sputum, pus, or catheter tip) that were resistant to the 12 antibiotics tested was significantly higher than that of isolates from sterile sites (cerebrospinal fluid [CSF], ascites fluid, and bloodstream) (46% versus 22%;P< 0.05). After ARDRA, it was found that 97% of the 62 isolates resistant to all antibiotics tested were theA. baumanniigenospecies, which was identified in only 31% of the isolates susceptible to all antibiotics tested. More genospecies diversity was identified in the isolates susceptible to all antibiotics tested, including genospecies of 13TU (34%), genotype 3 (29%), andA. calcoaceticus(5%). Furthermore, as 91% (10/11) of the isolates from CSF were susceptible to all antibiotics tested, theA. calcoaceticus-A. baumanniicomplex isolates with multidrug resistance could be less invasive than the more susceptible isolates. This study also indicated current emergence of carbapenem-, fluoroquinolone-, aminoglycoside-, and cephalosporin-resistantA. calcoaceticus-A. baumanniicomplex isolates in Taiwan.

scholarly journals Evidence for Multidrug Resistance in NonpathogenicMycoplasmaSpecies Isolated from South African Poultry

2018 ◽  
Vol 84 (21) ◽  
Author(s):  
Amanda Beylefeld ◽  
Pamela Wambulawaye ◽  
Dauda Garba Bwala ◽  
Johannes Jacobus Gouws ◽  
Obed Mooki Lukhele ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
South African ◽  
Macrolide Resistance ◽  
Quinolone Resistance ◽  
23S Rrna ◽  
Clear Correlation ◽  
Rrna Gene ◽  
Poultry Production ◽  
Content Type ◽  
23S Rrna Gene

ABSTRACTOne hundred seventy-eight mycoplasma strains isolated from South African poultry flocks between 2003 and 2015 were identified by full-genome sequencing and phylogenetic analysis of the 16S rRNA gene and were classified as follows:Mycoplasma gallisepticum(25%),M. gallinarum(25%),M. gallinaceum, (23%),M. pullorum(14%),M. synoviae(10%), andM. iners(3%), as well as oneAcheoplasma laidlawiistrain (1%). MIC testing was performed on the axenic samples, and numerous strains of each species were resistant to either chlortetracycline or tylosin or both, with variable sensitivity to enrofloxacin. The strains of all species tested remained sensitive to tiamulin, except for oneM. gallinaceumsample that demonstrated intermediate sensitivity. The mutation of A to G at position 2059 (A2059G) in the 23S rRNA gene, which is associated with macrolide resistance, was found in the South AfricanM. gallisepticumandM. synoviaestrains, as well as a clear correlation between macrolide resistance inM. gallinarumandM. gallinaceumand mutations G354A and G748A in the L4 ribosomal protein and 23S rRNA gene, respectively. No correlation between resistance and point mutations in the genes studied could be found forM. pullorum. Only a few strains were resistant to enrofloxacin, apart from oneM. synoviaestrain with point mutation D420N, which has been associated with quinolone resistance, and no other known markers for quinolone resistance were found in this study. Proportionally more antimicrobial-resistant strains were detected inM. gallinaceum,M. gallinarum, andM. pullorumthan inM. gallisepticumandM. synoviae. Of concern, threeM. gallinaceumstrains showed multidrug resistance to chlortetracycline, tylosin, and oxytetracycline.IMPORTANCENonpathogenic poultryMycoplasmaspecies are often overlooked due to their lesser impact on poultry health and production compared to the OIE-listed pathogenic strainsM. gallisepticumandM. synoviae. The use of antimicrobials as in-feed growth promoters and for the control of mycoplasmosis is common in poultry production across the world. Here, we provide evidence that certain nonpathogenicMycoplasmaspecies are acquiring multidrug resistance traits. This would have significant implications if these species, for which no vaccines are applied, are able to transfer their antibiotic resistance genes to other mycoplasmas and bacteria that may enter the human food chain.

scholarly journals In VitroActivity of the New Fluoroketolide Solithromycin (CEM-101) against Macrolide-Resistant and -Susceptible Mycoplasma genitalium Strains

2014 ◽  
Vol 58 (6) ◽  
pp. 3151-3156 ◽  
Author(s):  
Jørgen Skov Jensen ◽  
Prabhavathi Fernandes ◽  
Magnus Unemo
Keyword(s):  
Clinical Trials ◽  
Sexually Transmitted Infections ◽  
Antimicrobial Agents ◽  
Mycoplasma Genitalium ◽  
Macrolide Resistance ◽  
23S Rrna ◽  
Rrna Gene ◽  
Content Type ◽  
Sexually Transmitted

ABSTRACTMycoplasma genitaliumhas become well established as an etiological agent of sexually transmitted infections, but due to its fastidious growth requirements, only a fewM. genitaliumstrains are available to determine the MICs of currently used and new antimicrobial agents. Recent clinical trials have suggested that treatment with azithromycin has decreasing efficacy due to an increasing prevalence of macrolide resistance, and alternative treatment with moxifloxacin is similarly under pressure from emerging resistance. Thus, there is an urgent need for new antimicrobials. Thein vitroactivity of the newly developed fluoroketolide solithromycin (CEM-101) was evaluated against a collection of 40M. genitaliumstrains, including 15 with high-level macrolide resistance and 5 multidrug-resistant strains with resistance to both macrolides and quinolones. Furthermore, the MIC of solithromycin was correlated with mutations in the 23S rRNA gene and in the genes encoding ribosomal proteins L4 and L22. Thein vitroresults showed that solithromycin has activity againstM. genitaliumsuperior to that of other macrolides, doxycycline, and fluoroquinolones. Accordingly, this new fluoroketolide might be an effective option for treatment ofM. genitaliuminfections. However, the efficacy of solithromycin in clinical trials with follow-up for test of cure and detection of genotypic and phenotypic resistance needs to be evaluated prior to widespread use. In a phase 2 clinical trial, solithromycin was highly effective as a single oral dose againstC. trachomatisandNeisseria gonorrhoeae, suggesting that solithromycin could be a treatment option for several sexually transmitted infections, including in syndromic treatment of urethral and vaginal discharge.

scholarly journals A study of community-acquired Mycoplasma pneumoniae in Yantai, China

2018 ◽  
Vol 49 (2) ◽  
pp. 160-163
Author(s):  
Hong-Xia Yu ◽  
Mao-Mao Zhao ◽  
Zeng-Hui Pu ◽  
Yuan-Rong Ju ◽  
Yan Liu
Keyword(s):  
Mycoplasma Pneumoniae ◽  
Community Acquired Pneumonia ◽  
Macrolide Resistance ◽  
23S Rrna ◽  
Diagnostic Tools ◽  
Rrna Gene ◽  
Resistance Mutations ◽  
First Line ◽  
Tract Infections

Introduction: Community-acquired pneumonia (CAP) is a global disease responsible for a large number of deaths, with significant economic impact. As diagnostic tools have increased in sensitivity, understanding of the etiology of CAP has begun to change. Mycoplasma pneumoniae is one of the major pathogens causing CAP. Macrolides and related antibiotics are first-line treatments for M. pneumoniae. Macrolide resistance has been spreading for 15 years and now occurs in worldwide. We undertook the first study on macrolide resistance of M. pneumoniae in Yantai. This may be helpful to determine the appropriate therapy for CAP in this population. Objective: To investigate the rate and mechanism of macrolide resistance in Yantai. Methods: Pharyngeal swab samples were collected from adult CAP patients. Samples were assayed by polymerase chain reaction (PCR) and cultivated to test for M. pneumoniae. Nested PCR was used to specifically amplify M. pneumoniae 23S rRNA gene fragments containing mutations, and amplicons were analyzed by CE-SSCP for macrolide resistance mutations. Results were confirmed by sequencing. Twenty-seven strains of M. pneumoniae were isolated and the activities of nine antibiotics against M. pneumoniae were tested in vitro. Results: Out of 128 samples tested, 27 were positive for M. pneumoniae. Mycoplasma 100% macrolides resistance to Mycoplasma pneumoniae. The mechanism of macrolides resistance was A2063G point mutation in the sequence directly binding to macrolides in the 23S rRNA V domain in vitro. The mean pyretolytic time for the fluoroquinolone group was 4.7 ±2.9 d, which was significantly shorter than 8.2 ±4.1 d for the azithromycin group. Conclusions: Macrolides are not the first-line treatment for M. pneumoniae respiratory tract infections in Yantai.

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