In vitro selection of mutants of Streptococcus pneumoniae resistant to macrolides and linezolid: relationship with susceptibility to penicillin G or macrolides.
OBJECTIVE
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.


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.
Carsenti-Dellamonica
H
H
Infectious Disease Department, Archet Hospital, Route Saint Antoine de Ginestière, Nice 06202, France. carsenti.h@chu-nice.fr
Galimand
M
M
Vandenbos
F
F
Pradier
C
C
Roger
P M
PM
Dunais
B
B
Sabah
M
M
Mancini
G
G
Dellamonica
P
P
D000081:Acetamides / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004917:Erythromycin / Q000494:pharmacology*; D000069349:Linezolid; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics*; D023303:Oxazolidinones / Q000494:pharmacology*; D010400:Penicillin G / Q000494:pharmacology*; D012338:RNA, Ribosomal, 23S / Q000235:genetics; D012641:Selection, Genetic; D015572:Spiramycin / Q000494:pharmacology*; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000235:genetics*
D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D012338:RNA, Ribosomal, 23S; D004917:Erythromycin; D015572:Spiramycin; D000069349:Linezolid; D010400:Penicillin G