JAC Advance Access published online on July 7, 2009
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkp213
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Original research |
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)
1 Northern Ireland Public Health Laboratory, Department of Bacteriology, Belfast City Hospital, Lisburn Road, Belfast BT9 7AD, Northern Ireland, UK 2 Laboratory for Molecular Biology, School of Environmental Health Sciences, Azabu University, Sagamihara 229, Japan 3 School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK 4 School of Dentistry, Queen's University of Belfast, Royal Group of Hospitals, Belfast, Northern Ireland, UK 5 Northern Ireland Regional Adult Cystic Fibrosis Unit, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB, Northern Ireland, UK 6 Respiratory Medicine, Queen's University of Belfast, Department of Respiratory Medicine, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB, Northern Ireland, UK
Received 17 March 2009; returned 20 April 2009; revised 15 May 2009; accepted 27 May 2009
* Corresponding author. Northern Ireland Public Health Laboratory, Department of Bacteriology, Belfast City Hospital, Belfast BT9 7AD, Northern Ireland, UK. Tel: +44-28-9026-3554; Fax: +44-28-9026-3991; E-mail: jemoore{at}niphl.dnet.co.uk
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.
Key Words: antibiotic resistance , azithromycin , commensal , erythromycin
A. T. and Y. M. played an equal role in this study.