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)

• Published in: Journal of antimicrobial chemotherapy Vol. 64; no. 3; pp. 501 - 506
• Main Authors: Tazumi, Akihiro, Maeda, Yasunori, Goldsmith, Colin E., Coulter, Wilson A., Mason, Charlene, Millar, B. Cherie, McCalmont, Mark, Rendall, Jackie, Elborn, J. Stuart, Matsuda, Motoo, Moore, John E.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.09.2009; Oxford Publishing Limited (England)
• Subjects: Adult; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; antibiotic resistance; Antibiotics; Antibiotics. Antiinfectious agents. Antiparasitic agents; azithromycin; Azithromycin - therapeutic use; Bacterial Proteins - genetics; Biological and medical sciences; commensal; Cystic fibrosis; Cystic Fibrosis - complications; Cystic Fibrosis - drug therapy; DNA, Bacterial - chemistry; DNA, Bacterial - genetics; Drug resistance; Drug Resistance, Bacterial; Errors of metabolism; erythromycin; Erythromycin - pharmacology; Humans; Macrolides - pharmacology; Medical sciences; Membrane Proteins - genetics; Metabolic diseases; Methyltransferases - genetics; Microbial Sensitivity Tests; Miscellaneous hereditary metabolic disorders; Molecular biology; Molecular Sequence Data; Pharmacology. Drug treatments; Sequence Analysis, DNA; Streptococcal Infections - microbiology; Streptococcus - drug effects; Streptococcus - genetics; Streptococcus - isolation & purification; Streptococcus anginosus; Streptococcus australis; Streptococcus gordonii; Streptococcus infantis; Streptococcus infections; Streptococcus mitis; Streptococcus oralis; Streptococcus parasanguinis; Streptococcus pneumoniae; Streptococcus salivarius; Streptococcus sanguinis; azithromycin; commensal; antibiotic resistance; erythromycin; Human; Treatment resistance; Nucleotide sequence; Respiratory disease; Azithromycin; Metabolic diseases; Cystic fibrosis; Erythromycin; Macrolide; Genetic disease; Streptococcus pneumoniae; Streptococcaceae; Antibiotic; Bacteria; Micrococcales; Digestive diseases; Adult; Protein synthesis inhibitor; Antibacterial agent; Clinical isolate; Pancreatic disease
• DOI: 10.1093/jac/dkp213
• ISSN: 0305-7453

Objectives Although long-term use of azithromycin has shown a significant clinical improvement for patients with cystic fibrosis (CF), its long-term effect on the susceptibility of commensal flora within CF airways has not yet been examined. We therefore suggest that long-term use of azithromycin increases macrolide resistance in commensal streptococci. Methods Erythromycin susceptibility in naturally colonizing viridans group streptococci (VGS) was characterized, as well as macrolide resistance gene determinants through sequence analysis, in pneumococci (n = 15) and VGS [n = 84; i.e. Streptococcus salivarius (n = 30), Streptococcus mitis (n = 17), Streptococcus sanguinis (n = 11), Streptococcus oralis (n = 10), Streptococcus parasanguinis (n = 6), Streptococcus gordonii (n = 3), Streptococcus infantis (n = 3), Streptococcus cristatus (n = 2), Streptococcus anginosus (n = 1) and Streptococcus australis (n = 1)] isolated from sputum from 24 adult CF patients, who were on oral azithromycin therapy for at least the previous 7 months. Results Almost three-quarters of isolates (74; 74.7%) were resistant to erythromycin, whilst a further 15 (15.2%) had reduced susceptibility, leaving only 10 (10.1%) isolates susceptible to erythromycin. The majority (89.8%) were not susceptible to erythromycin, as demonstrated by possession of the erm(B) gene in 25/99 (25.3%), the mef(A) gene in 1/99 (1.0%), the mef(E) gene in 75/99 (75.8%) and both erm(B) and mef(E) genes simultaneously in 11/99 (11.1%). These results indicate that genotypic resistance for macrolides is common in VGS in adult CF patients, with efflux being over three times more frequent. Conclusions 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.