Molecular characterization of macrolide resistance determinants [erm(B) and mef(A)] in Streptococcus pneumoniae and viridans group streptococci (VGS) isolated from adult patients with cystic fibrosis (CF)

Tazumi, Akihiro; Maeda, Yasunori; Goldsmith, Colin E.; Coulter, Wilson A.; Mason, Charlene; Millar, B.C.; McCalmont, Mark; Rendall, J.; Elborn, J. Stuart; Matsuda, Motoo; Moore, John E.

doi:10.1093/jac/dkp213

Cited by 28 publications

(27 citation statements)

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“…Staphylococcal resistance to macrolides went from 83% in the first year to 97% in the second year and, finally, to 100% in the third year after starting therapy (303). The long-term use of azithromycin in CF patients also leads to macrolide resistance in the commensal viridans group streptococci, as assessed by molecular characterization (299). Since the incidence of nontuberculous mycobacterial (NTM) pulmonary infections is also increasing among CF patients, it is feared that azithromycin therapy may induce selection or acquisition of macrolide resistance in NTM (167,215).…”

Section: Macrolide Resistancementioning

confidence: 99%

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Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications

2010

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SUMMARY Macrolides have diverse biological activities and an ability to modulate inflammation and immunity in eukaryotes without affecting homeostatic immunity. These properties have led to their long-term use in treating neutrophil-dominated inflammation in diffuse panbronchiolitis, bronchiectasis, rhinosinusitis, and cystic fibrosis. These immunomodulatory activities appear to be polymodal, but evidence suggests that many of these effects are due to inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and nuclear factor kappa B (NF-κB) activation. Macrolides accumulate within cells, suggesting that they may associate with receptors or carriers responsible for the regulation of cell cycle and immunity. A concern is that long-term use of macrolides increases the emergence of antimicrobial resistance. Nonantimicrobial macrolides are now in development as potential immunomodulatory therapies.

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Section: Macrolide Resistancementioning

confidence: 99%

“…There are three principal mechanisms responsible for acquired macrolide resistance (299,343). The first is due to ribosomal target modification, which is mediated by methylases encoded by the erm(B) gene.…”

Section: Macrolide Resistancementioning

confidence: 99%

Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications

2010

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“…Altogether, the CF patient is at very high risk for colonization with drug-resistant VGS. In one study where macrolide resistance was measured for VGS isolated from respiratory cultures of CF patients, 95% of VGS were macrolide nonsusceptible and 80% were fully resistant (52).…”

Section: Antimicrobial Susceptibilities Of Viridansmentioning

confidence: 99%

It's Not Easy Being Green: the Viridans Group Streptococci, with a Focus on Pediatric Clinical Manifestations

2010

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2The viridans group streptococci (VGS) are a heterogeneous group of organisms that can be human commensals, colonizing the gastrointestinal and genitourinary tracts in addition to the oral mucosa. VGS are generally considered to be of low pathogenic potential in immunocompetent individuals. However, in certain patient populations, VGS can cause invasive disease, such as endocarditis, intra-abdominal infection, and shock. Within the VGS, the rates and patterns of antimicrobial resistance vary greatly depending upon the species identification and the patient population. In general, Streptococcus mitis group organisms are resistant to more antimicrobial agents than the other VGS species. This review addresses current VGS taxonomy, in addition to the current methodologies being used in clinical microbiology laboratories for identification of VGS. Automated systems struggle overall with species level identification and susceptibility testing for VGS. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) identification is emerging as a potential alternative for organism identification. A review of recent pediatric-specific data regarding the clinical manifestations of VGS revealed that the Streptococcus anginosus group (SAG) organisms may be important pathogens in pediatric patients and that the VGS may contribute to disease in patients with cystic fibrosis. It also appears that rates of antimicrobial resistance in VGS in pediatric patients are surpassing those of the adult population. TAXONOMY AND MICROBIOLOGYThe viridans group streptococci (VGS) are a heterogeneous group of organisms that can be both commensal flora and pathogens in humans. They are the "grab bag" that remains when the beta-hemolytic streptococci, enterococci, and pneumococci are excluded from the streptococci. The purpose of this review is to summarize the currently accepted taxonomic classification of this group of organisms, examine the state of the art for identification of the VGS, and then focus on the pediatric clinical manifestations associated with the VGS.Perhaps the only consistency observed in discussions regarding the taxonomy of the VGS is a lack of consistency. The taxonomy is very controversial, and for many years, a standardized naming scheme or typing system for this group of organisms was lacking; therefore, discussions on this topic frequently include the phrase "poorly classified." There are now at least 30 recognized species of VGS (11,14).

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“…The only other association of the latter species with any illness comes from two reports of its isolation from the sputum of adults with cystic fibrosis (17,26). It is therefore interesting that an adult with cystic fibrosis was the source of our S. infantis isolate, VMC58 (see Table S2 in the supplemental material).…”

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confidence: 99%

Oral Streptococcal Bacteremia in Hospitalized Patients: Taxonomic Identification and Clinical Characterization

et al. 2012

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Oral streptococci have been associated with systemic diseases, including infective endocarditis and neutropenic bacteremia. We analyzed 58 recent oral streptococcal bloodstream isolates, and we obtained clinical and demographic data for source patients. The sodA gene was found to be a better target than the 16S-23S rRNA internal transcribed spacer for DNA sequence-based species identification. Together, Streptococcus mitis and Streptococcus oralis were significantly more likely than the 12 combined remaining species to be isolated from neutropenic patients. Streptococci are the most abundant inhabitants of the human mouth (6, 24), and they gain frequent access to the bloodstream through periodontal lesions or oral abrasions created by routine activities (32). This can lead to serious illnesses, including infective endocarditis (IE) (28) and neutropenic bacteremia (29). The taxonomy of the oral streptococci has long been a source of confusion (4,9,20,22,31). Sequencing of the 16S rRNA gene has clarified the situation immensely (13); however, this approach lacks the sensitivity required to distinguish certain closely related species, including Streptococcus mitis and Streptococcus oralis (12), or to allow for strain typing or phylogenetic analysis within species. Genes possessing greater variability have therefore been examined, including the 16S-23S rRNA intergenic transcribed spacer (ITS) (2), protein-coding housekeeping genes (1, 5, 7, 10, 12, 14, 15, 19, 23), or both (17, 18). Consensus concerning the gene(s) best suited for these purposes has yet to emerge. Further, although previous studies have identified oral streptococci from clinical blood cultures using definitive sequencing methods (12,23,30), none have reported detailed clinical information about underlying disease. We set out to do both.Bloodstream cultures performed at Virginia Commonwealth University Medical Center Hospital from May 2003 to May 2008 were presumptively identified as containing streptococci by the clinical microbiology laboratory. A computer script was used to exclude nonoral species. To avoid analysis of contaminants, isolation plates were requested only when two or more reports originated from separate cultures of the same patient. One colony from each available isolation plate was grown in broth culture and examined macroscopically and microscopically. If any differences were observed in separate cultures derived from the same patient, both cultures were retained. Otherwise, a single culture from each patient was cryopreserved, and aliquots were removed for PCR amplification.To determine the species identity and phylogenetic relatedness of each isolate, the 16S-23S ITS was amplified using the 6R and 13BF primers described previously (2). When products were not obtained from some isolates, we noted that the final three nucleotides of the 6R primer did not align with 23S rRNA sequences in GenBank from several species of interest. We therefore shortened and simplified the 6R primer, creating 6R-S, and shortened the 13BF primer to ma...

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Molecular characterization of macrolide resistance determinants [erm(B) and mef(A)] in Streptococcus pneumoniae and viridans group streptococci (VGS) isolated from adult patients with cystic fibrosis (CF)

Abstract: Long-term treatment with azithromycin in CF patients may reduce antibiotic susceptibility in commensal VGS, where these organisms may potentially act as a reservoir of macrolide resistance determinants for newly acquired and antibiotic-susceptible pathogens.

Cited by 28 publications

References 14 publications

Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications

Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications

It's Not Easy Being Green: the Viridans Group Streptococci, with a Focus on Pediatric Clinical Manifestations

Oral Streptococcal Bacteremia in Hospitalized Patients: Taxonomic Identification and Clinical Characterization

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