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).
OBJECTIVE
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.
Tazumi
Akihiro
A
Department of Bacteriology, Northern Ireland Public Health Laboratory, Belfast City Hospital, Lisburn Road, Belfast BT9 7AD, Northern Ireland, UK.
Maeda
Yasunori
Y
Goldsmith
Colin E
CE
Coulter
Wilson A
WA
Mason
Charlene
C
Millar
B Cherie
BC
McCalmont
Mark
M
Rendall
Jackie
J
Elborn
J Stuart
JS
Matsuda
Motoo
M
Moore
John E
JE
D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017963:Azithromycin / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000235:genetics*; D003550:Cystic Fibrosis / Q000150:complications / Q000188:drug therapy; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D024881:Drug Resistance, Bacterial; D004917:Erythromycin / Q000494:pharmacology; D006801:Humans; D018942:Macrolides / Q000494:pharmacology*; D008565:Membrane Proteins / Q000235:genetics*; D008780:Methyltransferases / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D013290:Streptococcal Infections / Q000382:microbiology*; D013291:Streptococcus / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D018942:Macrolides; C117866:MefA protein, Streptococcus; D008565:Membrane Proteins; D004917:Erythromycin; D017963:Azithromycin; C111078:ErmTR protein, bacteria; D008780:Methyltransferases