ZAAPS programme results for 2016: an activity and spectrum analysis of linezolid using clinical isolates from medical centres in 42 countries.

Objectives: To report the linezolid activity, resistance mechanisms and epidemiological typing of selected isolates observed during the 2016 Zyvox® Annual Appraisal of Potency and Spectrum (ZAAPS) programme.
Methods: A total of 8325 organisms were consecutively collected from 76 centres in 42 countries (excluding the USA). Broth microdilution susceptibility testing was performed and isolates displaying linezolid MICs of ≥4 mg/L were molecularly characterized.
Results: Linezolid inhibited 99.8% of all Gram-positive pathogens at the respective susceptible breakpoints and showed a modal MIC of 1 mg/L, except for CoNS, for which the modal MIC result was 0.5 mg/L. Among isolates displaying linezolid MICs of ≥4 mg/L, one Staphylococcus aureus (linezolid MIC of 4 mg/L) harboured cfr and belonged to ST72, while four CoNS (MICs of 16-32 mg/L; ST2) showed drug target alterations. Two Enterococcus faecium (ST117) from a single site in Rome were linezolid non-susceptible (MICs of 8 mg/L) and had G2576T mutations. Eight linezolid-non-susceptible Enterococcus faecalis (MICs of 4 mg/L; 4 sites in 4 countries; ST256, ST480, ST766 and ST775) carried optrA and isolates carrying optrA from the same medical centre were genetically related. One Streptococcus gallolyticus (MIC of 4 mg/L) and one Streptococcus mitis (MIC of 16 mg/L) carried optrA and G2576T mutations, respectively. Conclusions: These results document the continued long-term in vitro potency of linezolid. Alterations in the 23S rRNA and/or L3/L4 proteins remain the main oxazolidinone resistance mechanisms in E. faecium and CoNS, whereas optrA emerged as the sole mechanism in E. faecalis. Surveillance and infection control will be important strategies to detect optrA and prevent it from disseminating.