Abstract
BackgroundLinezolid is one of the most effective treatments against Gram-positive pathogens. However, linezolid-resistant/intermediate strains have recently emerged in worldwide. The purpose of this study was to analyse the prevalence and resistance mechanisms of linezolid-resistant/intermediate staphylococci and enterococci in Shanghai, China.ResultsThirty-two linezolid-resistant/intermediate strains, including 14 Staphylococcus capitis, three Staphylococcus aureus, 14 Enterococcus faecalis and one Enterococcus faecium clinical isolates, were collected in this study which displayed linezolid MICs of 8 to 512 μg/ml, 8–32 μg/ml, 4–8 μg/ml and 4 μg/ml, respectively. All linezolid-resistant S. capitis isolates had a novel C2131T mutation and a G2603T mutation in the 23S rRNA region, and some had a C316T (Arg106Cys) substitution in protein L4 and/or harboured cfr. Linezolid-resistant S. aureus isolates carried a C389G (Ala130Gly) substitution in protein L3, and/or harboured cfr. The cfr gene was flanked by two copies of the IS256-like element, with a downstream orf1 gene. Linezolid-resistant/intermediate enterococci lacked major resistance mechanisms. The semi-quantitative biofilm assay showed that 14 linezolid-resistant E. faecalis isolates produced a larger biofilm than linezolid-susceptible E. faecalis strains. Transmission electron microscopy showed the cell walls of linezolid-resistant/intermediate strains were thicker than linezolid-susceptible strains.ConclusionOur data indicated that major resistance mechanisms, such as mutations in 23S rRNA and ribosomal proteins L3 and L4, along with cfr acquisition, played an important role in linezolid resistance. Secondary resistance mechanisms, such as biofilm formation and cell wall thickness, should also be taken into account.
Highlights
Linezolid is one of the most effective treatments against Gram-positive pathogens
The fifteen enterococcal isolates demonstrated either linezolidintermediate (LI) or low-level linezolid resistance (MICs 4–8 μg/ml). These strains were resistant to erythromycin, chloramphenicol, ciprofloxacin and tetracycline, but susceptible to vancomycin (MICs, 0.5– 2 μg/ml), teicoplanin (MICs, 0.12–0.25 μg/ml), penicillin (MICs, 0.5–4 μg/ml) and ampicillin (MICs,
Surveillance data in our study suggested that all the LR S. capitis were recovered from bacteraemia patients, whereas LR S. aureus (LRSA) came from respiratory tract specimens
Summary
Linezolid is one of the most effective treatments against Gram-positive pathogens. Linezolidresistant/intermediate strains have recently emerged in worldwide. Gram-positive cocci pose a worldwide threat to human health. The emergence of antibiotic resistance in Grampositive cocci, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant staphylococci (VRS) and vancomycin-resistant enterococci (VRE), has created a clinical demand for effective novel therapeutic agents. Linezolid (LZD), the first member of the oxazolidinone class of antibiotics, was approved for clinical use in 2000 and has a broad spectrum of activity against a variety of Gram-positive pathogens. It acts by inhibiting protein synthesis via binding to the peptidyl transferase centre of the. The occurrence of LR strains has been reported worldwide [3,4,5]
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