title: Antibiotic susceptibility and molecular mechanisms of macrolide resistance in streptococci isolated from adult cystic fibrosis patients.
abstract: The cystic fibrosis (CF) airways are colonized by polymicrobial communities with high bacterial load and are influenced by frequent antibiotic exposures. This community includes diverse streptococci, some of which have been directly or indirectly associated with pulmonary exacerbations. As many streptococci are naturally competent, horizontal transfer of antibiotic-resistant determinants coupled with frequent and/or chronic antibiotic exposure may contribute to high resistance rates. In this study, we assessed antibiotic resistance in 413 streptococcal isolates from adult CF patients against nine antibiotics relevant in CF treatment. We observed very low rates of cephalosporin resistance [cefepime and ceftriaxone ( < 2%)], and higher rates of resistance to tetracycline (∼34%) and sulfamethoxazole/trimethoprim (∼45%). The highest rate of antibiotic resistance was to the macrolides [azithromycin (56.4%) and erythromycin (51.6%)]. We also investigated the molecular mechanisms of macrolide resistance and found that only half of our macrolide-resistant streptococci isolates contained the mef (efflux pump) or erm (methylation of 23S ribosomal target site) genes. The majority of isolates were, however, found to have point mutations at position 2058 or 2059 of the 23S ribosomal subunit - a molecular mechanism of resistance not commonly reported in the non-pyogenic and non-pneumococcal streptococci, and unique in comparison with previous studies. The high rates of resistance observed here may result in poor outcomes where specific streptococci are contributing to CF airway disease and serve as a reservoir of resistance genes within the CF airway microbiome.
authors.affiliation: Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
authors.forename: Christina S
authors.initials: CS
authors.lastname: Thornton
authors.affiliation: Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
authors.forename: Margot E
authors.initials: ME
authors.lastname: Grinwis
authors.affiliation: Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Sibley
authors.affiliation: Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, Alberta T2N 4N1, Canada.|Department of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada.|Adult Cystic Fibrosis Clinic, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Parkins
authors.affiliation: Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, Alberta T2N 4N1, Canada.|Department of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada.|Adult Cystic Fibrosis Clinic, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
authors.forename: Harvey R
authors.initials: HR
authors.lastname: Rabin
authors.affiliation: Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario L8S 4L8, Canada.|Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Surette
mesh_terms: D000328:Adult; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000382:microbiology*; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D006801:Humans; D018942:Macrolides / Q000494:pharmacology*; D008297:Male; D008826:Microbial Sensitivity Tests; D013290:Streptococcal Infections / Q000188:drug therapy / Q000382:microbiology*; D013291:Streptococcus / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D055815:Young Adult
chemical_list: D001426:Bacterial Proteins; D018942:Macrolides