Macrolide resistance genes and susceptibility to azithromycin in P. intermedia isolates obtained from patients with periodontal disease.

ABSTRACT Corynebacterium jeikeium is an opportunistic pathogen primarily of immunocompromised (neutropenic) patients. Broad-spectrum resistance to antimicrobial agents is a common feature of C. jeikeium clinical isolates. We studied the profiles of susceptibility of 20 clinical strains of C. jeikeium to a range of antimicrobial agents. The strains were separated into two groups depending on the susceptibility to erythromycin (ERY), with one group (17 strains) representing resistant organisms (MIC > 128 μg/ml) and the second group (3 strains) representing susceptible organisms (MIC ≤ 0.25 μg/ml). The ERY resistance crossed to other members of the macrolide-lincosamide-streptogramin B (MLSb) group. Furthermore, this resistance was inducible with MLSb agents but not non-MLSb agents. Expression of ERY resistance was linked to the presence of an allele of the class X erm genes,erm(X)cj, with >93% identity to other ermgenes of this class. Our evidence indicates that erm(X)cj is integrated within the chromosome, which contrasts with previous reports for the plasmid-associated erm(X) genes found inC. diphtheriae and C. xerosis. In 40% ofC. jeikeium strains, erm(X)cj is present within the transposon, Tn5432. However, in the remaining strains, the components of Tn5432 (i.e., the erm and transposase genes) have separated within the chromosome. The rearrangement of Tn5432 leads to the possibility that the other drug resistance genes have become included in a new composite transposon bound by the IS1249 elements.

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Macrolide-Resistance Genes in Clinical Isolates ofStreptococcus pyogenes

Microbial Drug Resistance ◽

10.1089/107662902760190671 ◽

2002 ◽

Vol 8 (2) ◽

pp. 129-132 ◽

Cited By ~ 15

Author(s):

Carmela Cascone ◽

Maria Santagati ◽

Silvana Noviello ◽

Francesco Iannelli ◽

Silvano Esposito ◽

...

Keyword(s):

Resistance Genes ◽

Macrolide Resistance ◽

Clinical Isolates

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Evaluation ofShigellaSpecies Azithromycin CLSI Epidemiological Cutoff Values and Macrolide Resistance Genes

Journal of Clinical Microbiology ◽

10.1128/jcm.01422-18 ◽

2019 ◽

Vol 57 (4) ◽

Cited By ~ 4

Author(s):

Muna Salah ◽

Issa Shtayeh ◽

Raed Ghneim ◽

Randa Al-Qass ◽

Ali Sabateen ◽

...

Keyword(s):

Resistance Genes ◽

Diffusion Zone ◽

Shigella Flexneri ◽

Macrolide Resistance ◽

Disk Diffusion ◽

Content Type ◽

Zone Diameter ◽

Cutoff Values ◽

Macrolide Resistance Gene ◽

Content Support

ABSTRACTAzithromycin (AZM) has been recommended by the American Academy of Pediatrics for the treatment of shigellosis in children. In this study, 502Shigellaspecies isolated between 2004 and 2014 were tested for AZM epidemiological cutoff values (ECV) by disk diffusion. AZM MICs and the presence of the macrolide resistance genes [erm(A),erm(B),erm(C),ere(A),ere(B),mph(A),mph(B),mph(D),mef(A), andmsr(A)] were determined for all 56 (11.1%) isolates with an AZM disk diffusion zone diameter of ≤15 mm. The distribution of AZM ECV MICs was also determined for 186Shigellaisolates with a disk zone diameter of ≥16 mm. Finally, pulsed-field gel electrophoresis (PFGE) was performed on 15Shigella flexneriisolates with an AZM disk zone diameter of <16 mm from different years and geographic locations. Serotyping the 502Shigellaspecies isolates revealed that 373 (74%) wereS. sonnei, 119 (24%) wereS. flexneri,and 10 (2%) wereS. boydii. Of the 119Shigella flexneriisolates, 48 (42%) isolates had an AZM disk diffusion zone diameter of ≤15 mm and a MIC of ≥16 µg/ml. With the exception of one isolate, all were positive for the macrolide resistance genemph(A).S. flexneriPFGE showed four distinct patterns, with patterns I and II presenting with 92.3% genetic similarity. On the other hand, 2 (0.5%) of the 373S. sonneiisolates had the AZM non-wild-type (NWT) ECV phenotype (those with acquired or mutational resistance), as the AZM MICs were ≥32 µg/ml and the isolates were positive for themph(A) gene. Overall, ourS. flexneriresults are in concordance with the CLSI AZM ECV, but isolates with an AZM disk diffusion zone diameter between 14 and 15 mm should be carefully evaluated, as theS. flexneriAZM MIC for NWT isolates may need adjustment to 32 µg/ml. Our data onS. sonneisupport that the AZM NWT ECV should be 11 mm for the disk diffusion zone diameter and ≥32 µg/ml for the MICs.

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Impact of Long-Term Erythromycin Therapy on the Oropharyngeal Microbiome and Resistance Gene Reservoir in Non-Cystic Fibrosis Bronchiectasis

mSphere ◽

10.1128/msphere.00103-18 ◽

2018 ◽

Vol 3 (2) ◽

pp. e00103-18 ◽

Cited By ~ 15

Author(s):

Jocelyn M. Choo ◽

Guy C. J. Abell ◽

Rachel Thomson ◽

Lucy Morgan ◽

Grant Waterer ◽

...

Keyword(s):

Resistance Gene ◽

Quantitative Pcr ◽

Resistance Genes ◽

Low Dose ◽

Controlled Trial ◽

Macrolide Resistance ◽

Microbiota Composition ◽

Content Type ◽

Commensal Microbiota

ABSTRACT Long-term macrolide therapy reduces rates of pulmonary exacerbation in bronchiectasis. However, little is known about the potential for macrolide therapy to alter the composition and function of the oropharyngeal commensal microbiota or to increase the carriage of transmissible antimicrobial resistance. We assessed the effect of long-term erythromycin on oropharyngeal microbiota composition and the carriage of transmissible macrolide resistance genes in 84 adults with bronchiectasis, enrolled in the Bronchiectasis and Low-dose Erythromycin Study (BLESS) 48-week placebo-controlled trial of twice-daily erythromycin ethylsuccinate (400 mg). Oropharyngeal microbiota composition and macrolide resistance gene carriage were determined by 16S rRNA gene amplicon sequencing and quantitative PCR, respectively. Long-term erythromycin treatment was associated with a significant increase in the relative abundance of oropharyngeal Haemophilus parainfluenzae (P = 0.041) and with significant decreases in the relative abundances of Streptococcus pseudopneumoniae (P = 0.024) and Actinomyces odontolyticus (P = 0.027). Validation of the sequencing results by quantitative PCR confirmed a significant decrease in the abundance of Actinomyces spp. (P = 0.046). Erythromycin treatment did not result in a significant increase in the number of subjects who carried erm(A), erm(B), erm(C), erm(F), mef(A/E), and msrA macrolide resistance genes. However, the abundance of erm(B) and mef(A/E) gene copies within carriers who had received erythromycin increased significantly (P < 0.05). Our findings indicate that changes in oropharyngeal microbiota composition resulting from long-term erythromycin treatment are modest and are limited to a discrete group of taxa. Associated increases in levels of transmissible antibiotic resistance genes within the oropharyngeal microbiota highlight the potential for this microbial system to act as a reservoir for resistance. IMPORTANCE Recent demonstrations that long-term macrolide therapy can prevent exacerbations in chronic airways diseases have led to a dramatic increase in their use. However, little is known about the wider, potentially adverse impacts of these treatments. Substantial disruption of the upper airway commensal microbiota might reduce its contribution to host defense and local immune regulation, while increases in macrolide resistance carriage would represent a serious public health concern. Using samples from a randomized controlled trial, we show that low-dose erythromycin given over 48 weeks influences the composition of the oropharyngeal commensal microbiota. We report that macrolide therapy is associated with significant changes in the relative abundances of members of the Actinomyces genus and with significant increases in the carriage of transmissible macrolide resistance. Determining the clinical significance of these changes, relative to treatment benefit, now represents a research priority.

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