Activity of linezolid against Gram-positive cocci possessing genes conferring resistance to protein synthesis inhibitors

Abstract

Linezolid belongs to a new class of antimicrobials, the oxazolidinones, that act by inhibiting protein synthesis. To detect cross-resistance with other inhibitors of protein synthesis (chloramphenicol, macrolides, lincosamides, streptogramins, aminoglycosides and tetracyclines), the in vitro activity of linezolid was determined against isolates harbouring known genes conferring resistance to these antimicrobials. Neither the presence of modifying enzymes (LinA, LinA', LinB, Vgb, Vat, SatA, ANT(4') (4")-I, AAC(6')-APH(2"), APHA-3 and Cat), nor the presence of an efflux mechanism (MsrA, MefE, MefA, MreA, Vga, TetK and TeL), nor the modification or protection of antimicrobial target (because of ribosomal methylases or TetM and TetO) affected linezolid activity as demonstrated by similar in vitro activity against resistant isolates and sensitive control isolates.

Efficacy of Linezolid in Treatment of Experimental Endocarditis Caused by Methicillin-Resistant Staphylococcus aureus

“…This may offer an advantage over other antimicrobial compounds since many of the newer fluoroquinolones exhibit resistance after even shorter dosing periods (11). Cross-resistance to linezolid and to antimicrobial agents having similar modes of action (50S ribosomal protein inhibitors) from the macrolide, lincosamide, and streptogramin B group has not been reported to date (9). Cross-resistance was not evident in this study given that this strain of MRSA was resistant in vitro to erythromycin, clarithromycin, and clindamycin.…”

Linezolid versus Vancomycin in Treatment of Complicated Skin and Soft Tissue Infections

“…Until recently, therapy for MRSA strains with multidrug resistance has been limited to vancomycin. New drugs with activity against MRSA have been developed, and linezolid is one of these agents (10).…”

Resistance to Linezolid Caused by Modifications at Its Binding Site on the Ribosome

“…The development of new antibiotics is apparently not an attractive business despite the expanding problem of antibiotic resistance in pathogenic bacteria. At the introduction of linezolid, it was claimed that there would be no cross-resistance to linezolid and that resistance would be rare and difficult for the bacteria to develop (20,103), but resistance does appear (reviewed in references 61 and 85). This minireview will present in detail how several types of modifications at the linezolid binding site on the ribosome can cause resistance to linezolid and other oxazolidinones.…”