Long-lasting successful dissemination of resistance to oxazolidinones in MDR Staphylococcus epidermidis clinical isolates in a tertiary care hospital in France

Abstract

ObjectivesPatient- and procedure-related changes in modern medicine have turned CoNS into one of the major nosocomial pathogens. Treatments of CoNS infections are challenging owing to the large proportion of MDR strains and oxazolidinones often remain the last active antimicrobial molecules. Here, we have investigated a long-lasting outbreak (2010–13) due to methicillin- and linezolid-resistant (LR) CoNS (n = 168), involving 72 carriers and 49 infected patients.MethodsAntimicrobial susceptibilities were tested by the disc diffusion method and MICs were determined by broth microdilution or Etest. The clonal relationship of LR Staphylococcus epidermidis (LRSE) was first determined using a semi-automated repetitive element palindromic PCR (rep-PCR) method. Then, WGS was performed on all cfr-positive LRSE (n = 30) and LRSE isolates representative of each rep-PCR-defined clone (n = 17). Self-transferability of cfr-carrying plasmids was analysed by filter-mating experiments.ResultsThis outbreak was caused by the dissemination of three clones (ST2, ST5 and ST22) of LRSE. In these clones, linezolid resistance was caused by (i) mutations in the chromosome-located genes encoding the 23S RNA and L3 and L4 ribosomal proteins, but also by (ii) the dissemination of two different self-conjugative plasmids carrying the cfr gene encoding a 23S RNA methylase. By monitoring linezolid prescriptions in two neighbouring hospitals, we highlighted that the spread of LR-CoNS was strongly associated with linezolid use.ConclusionsPhysicians should be aware that plasmid-encoded linezolid resistance has started to disseminate among CoNS and that rational use of oxazolidinones is critical to preserve these molecules as efficient treatment options for MDR Gram-positive pathogens.

The Right Time to Safely Re-Evaluate Empirical Antimicrobial Treatment of Hip or Knee Prosthetic Joint Infections

“…However, a short course does not seem to be associated with an increased risk of adverse renal outcomes [34]. A shorter probabilistic treatment may also be beneficial in the case of linezolid use, as it limits the development of drug resistance and reduces side-effects, which are associated with the treatment duration [7,8,[35][36][37][38].…”

Dissemination ofStaphylococcus epidermidisST22 With Stable, High-Level Resistance to Linezolid and Tedizolid in the Greek-Turkish Region (2008–2016)

“…1 The resistant phenotype has been related to the occurrence of mutations in genes coding for the V domain of 23SrRNA and ribosomal proteins L3/L4 or cfr acquisition. 1 The LRSE-ST22 isolates have been associated with infection and colonization cases in Spain, France, Germany, and, particularly, Greece, and most of these LRSE-ST22 arise after treatment with linezolid.…”

“…1 The resistant phenotype has been related to the occurrence of mutations in genes coding for the V domain of 23SrRNA and ribosomal proteins L3/L4 or cfr acquisition. 1 The LRSE-ST22 isolates have been associated with infection and colonization cases in Spain, France, Germany, and, particularly, Greece, and most of these LRSE-ST22 arise after treatment with linezolid. [1][2][3][4][5][6][7] In this study, we aimed to characterize the first methicillin-and linezolid-resistant S. epidermidis from a patient without previous linezolid exposure in Turkey and to assess its genetic similarity to the close geographical S. epidermidis from Greece.…”

Clinical Outcomes Associated With Linezolid Resistance in Leukemia Patients With Linezolid-Resistant Staphylococcus epidermidis Bacteremia

“…Furthermore, our group has recently identified that linezolid resistance in our institution is almost exclusively due to clonal spread of CC5 isolates harboring cfr and mutations in the L3 and L4 ribosomal proteins, with selection of linezolid resistance being largely attributable to prior linezolid exposure [ 12 ]. Other groups worldwide have also reported the emergence and clonal spread of CC5 isolates in settings where linezolid is commonly used [ 8 , 10 , 22 , 23 ]. In light of these data, both infection control and antimicrobial stewardship appear to play an important role in limiting the further spread of LRSE.…”