627. Molecular Epidemiology of Daptomycin-resistant Staphylococcus aureus Causing Bloodstream Infections

BACKGROUND: Daptomycin (Dap) has become increasingly important to combat infections caused by Staphylococcus aureus (SA). However, reports of daptomycin nonsusceptible (DNS) SA strains have emerged over the recent years, specifically with alteration of the MprF gene. Mutations in this gene lead to an increase in lysyl-phosphatidyl glycerol production resulting in a lower susceptibility to Dap and cationic antimicrobial peptides. Point mutations in the cls2 gene have also been associated with DNS SA through similar mechanisms of action. This study describes the gene mutations involved in our patients with SA bloodstream infections (BSIs) that developed Dap resistance. METHODS: This is a retrospective study in a tertiary healthcare system in southeast Michigan. SA blood isolates were sequenced through a gene-by-gene approach using Ridom SeqSphere. Charts were reviewed for clinical and laboratory data. Dap minimum inhibitory concentrations (MICs) were determined by E-test. DNS was defined as an MIC > 1.0 µg/mL. RESULTS: From December 3, 2015 to May 8, 2017, 7 patients were identified with DNS SA BSI. Mean age of the patients was 59 (SD = 13.7) and 86% were male. Mean bacteremia duration was 7 days (SD = 6.3), mean hospital length of stay was 13 days (SD = 9.8), 5 isolates were methicillin-resistant SA, and 2 were methicillin-sensitive SA. When comparing molecular sequencing of all seven patients with their Dap-sensitive strains vs. resistant strains, all patients, except for patient 3, had a point mutation at different allele loci in the MprF gene (Table 1). Additionally, two patients had point mutations in the cls2 gene. When comparing all 27 strains from the seven patients, each cluster was attributed to an individual patient with the exception of cluster one that included patients 5 and 6 suggesting transmission (Figure 1). CONCLUSION: DNS SA is infrequent; however, the present study shows that it can emerge both from methicillin-resistant and -susceptible SA most commonly when developing MprF and cls2 gene mutations as seen in our patients. Patient 3 was the exception in our analysis and likely developed DNS SA through another gene mutation. Further studies are necessary to know the frequency of each mutation with all genes associated with DNS SA, and epidemiological risk factors of transmission. [Image: see text] [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures