In vitro activity of recently introduced Gram-positive-specific antimicrobial agents against Australian methicillin-resistant Staphylococcus aureus isolates

Existing therapeutic options are limited for severe methicillin-resistant Staphylococcus aureus (MRSA) infections. Newer antimicrobials with anti-MRSA activity have been introduced, but evaluation of pre-existing resistance in the Australian setting is limited. Our objectives are to characterise the antimicrobial susceptibility profile of the common MRSA sequence types (STs) in Australia relating to newer antimicrobial agents to determine the association between non-susceptibility and ST, trends in minimum inhibitory concentration (MIC) for antimicrobial classes, and genomic associations with resistance phenotypes. One-hundred clinical MRSA isolates were selected, representing the ten most common ST clones determined by national surveillance data in Australia. MIC was determined for ceftaroline, ceftobiprole, tedizolid, dalbavancin, eravacycline, omadacycline, delafloxacin, lefamulin and vancomycin. The associations between non-susceptibility and common resistance mechanisms for the isolates were characterised by whole-genome sequencing. All isolates were susceptible to ceftaroline, ceftobiprole, dalbavancin, eravacycline, tedizolid, and vancomycin. Thirty-nine isolates, comprising all ST239, PVL-negative ST22 and ST45 isolates, eight of ten ST8 isolates and one of ten ST78 isolates, were resistant to delafloxacin (when community-acquired-pneumonia site-specific breakpoints were applied). One isolate of ST239 was resistant to lefamulin, and two isolates of ST1 had elevated omadacycline MIC. There was a correlation between delafloxacin non-susceptibility and known associated mutations. Newer Gram-positive antimicrobial agents, apart from delafloxacin, demonstrate good in vitro activity against Australian MRSA STs. Susceptibility testing prior to use of delafloxacin, lefamulin and omadacycline should be considered. When the use of these agents becomes commonplace, ongoing monitoring for resistance is recommended.