ZAAPS Program results for 2015: an activity and spectrum analysis of linezolid using clinical isolates from medical...

To report the linezolid in vitro activity obtained during the 2015 ZAAPS Program.

In total, 7587 organisms causing documented infections were consecutively collected in 65 centres in 32 ex-USA countries. Broth microdilution susceptibility testing was performed. Isolates displaying linezolid MIC results of ≥ 4 mg/L were molecularly characterized.

Linezolid inhibited >99.9% of Staphylococcus aureus at ≤ 2 mg/L, with MIC50 results of 1 mg/L, regardless of methicillin resistance. A similar linezolid MIC50 result (0.5 mg/L) was observed for CoNS, with the vast majority of isolates (99.7%) also inhibited at ≤ 2 mg/L. Three CoNS (linezolid MIC, 16-64 mg/L) from Italy were found to contain alterations in the 23S rRNA and/or L3/L4 ribosomal proteins. One isolate also harboured cfr. Linezolid exhibited consistent modal MIC and MIC50 results (1 mg/L) for enterococci regardless of species or vancomycin resistance. One Enterococcus faecalis (linezolid MIC, 8 mg/L) from Galway, Ireland, carried optrA. One Enterococcus faecium (linezolid MIC, 16 mg/L) from Italy contained a G2576T mutation in the 23S rRNA. All Streptococcus pneumoniae, viridans group streptococci and β-haemolytic streptococci were inhibited by linezolid at ≤ 2, ≤ 2 and ≤ 1 mg/L, respectively, with equivalent MIC90 results (1 mg/L for all groups).

These results document the continued long-term and stable in vitro potency of linezolid and a limited number of isolates with decreased susceptibility to linezolid (MIC, ≥4 mg/L). The latter isolates showed primarily mutations in the 23S rRNA gene and/or L3/L4 proteins, with plasmid-mediated resistance (cfr and optrA) also present, albeit at a low prevalence.