JAC Advance Access originally published online on August 31, 2005
Journal of Antimicrobial Chemotherapy 2005 56(4):633-642; doi:10.1093/jac/dki301
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In vitro selection of mutants of Streptococcus pneumoniae resistant to macrolides and linezolid: relationship with susceptibility to penicillin G or macrolides
1 Infectious Disease Department, Archet Hospital, Route Saint Antoine de Ginestière, Nice 06202, France; 2 Institut Pasteur, 25 Rue du Docteur Roux, 75724, Cedex 15 Paris, France
Received 1 March 2005; returned 27 April 2005; revised 21 June 2005; accepted 25 July 2005
* Corresponding author. Tel: +33-492035626; Fax: +33-493965454; E-mail: carsenti.h{at}chu-nice.fr
Objectives: To evaluate the rate of acquisition of resistance to linezolid and macrolides in Streptococcus pneumoniae isolates with different levels of susceptibility to penicillin and erythromycin.
Materials and methods: Thirty strains of S. pneumoniae were tested by serial passages in subinhibitory concentrations of each antibiotic by the spiral method. The four copies of the 23S rRNA rrl gene of parent strains and linezolid-resistant mutants were amplified and sequenced.
Results: The rate of acquisition of macrolide resistance did not differ when C-14 and C-16 macrolides were tested. Resistance to linezolid in strains susceptible to penicillin and erythromycin was difficult to produce. For mutants with low-level resistance to linezolid the cut-off value of the MIC was between 6 and 8 mg/L depending on the strain. All linezolid-resistant mutants displayed a mutation in 2–4 copies of the 23S rRNA rrl gene, mainly the G2576U mutation (27/30) with an additional C2610U mutation observed in certain mutants. Two new mutations were also noted, namely C2612A and C2571G. In three linezolid-resistant mutants no mutation was identified within the studied domain, suggesting another mechanism of resistance.
Conclusions: Linezolid resistance in pneumococcal strains susceptible to penicillin and macrolides was more difficult to obtain than with macrolides. Increased resistance to these agents may therefore influence the clinical use of linezolid.
Keywords: pneumococcus , oxazolidinones , resistance
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