In vivo acquired resistance to daptomycin during methicillin-resistant Staphylococcus aureus bacteremia

Description of the phenotypic and genotypic evolution of MRSA strains that became resistant to DAP in two unrelated patients with bacteremia under Daptomycin treatment, in two hospitals in the South of France.Daptomycin MICs were determined using broth microdilution method on the two pairs of isogenic (DAP-S/DAP-R) S. aureus isolated from bloodstream were sequenced by illumina Miseq. The two cases revealed the DAP-R acquisition of MRSA strains in approximatively 3 weeks in patients treated by DAP. The isolates belonged to the widespread ST5 (patient A) and ST8 (patient B) lineages and were of spa-type t777 and t622, respectively. SNP analysis comparing each couple of DAP-S/DAP-R isolates from each patient confirmed that the isolates were isogenic. The detected mutations were identified in MprF protein: L826F (Patient A) and S295L (Patient B).This study highlights the non-systematic cross-resistance between DAP and glycopeptides and the importance to monitor DAP MIC in persistent MRSA bacteremia.