Comparison of linezolid step-down therapy to standard parenteral therapy in methicillin-resistant Staphylococcus aureus bloodstream infections

Int J Antimicrob Agents. 2021 Mar 27:106329. doi: 10.1016/j.ijantimicag.2021.106329. Online ahead of print.


OBJECTIVE: Data supporting oral step-down therapy in methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) are sparse; linezolid offers potential in this setting. The study objective was to determine the effectiveness and safety of oral step-down linezolid compared to standard parenteral therapy (SPT) in MRSA BSI.

METHODS: Retrospective cohort performed in adults who received step-down/outpatient linezolid or SPT (vancomycin or daptomycin) for MRSA BSI between 1/2011-12/2019. Primary outcome was 90-day infection-related readmission (IRR) from clinical worsening/relapse or infection recurrence.

RESULTS: 215 patients included: 54 linezolid, 161 SPT. Infection sources were: skin (34%), bone/joint (15%), endocarditis (13%), other (32%), multiple (6%). Patients that received SPT more commonly had complicated bacteremia (72% vs 41%, P<0.0001) and metastatic foci (45% vs 20%, P=0.001). 90-day IRR occurred in 17% and 26% of the linezolid and SPT groups, respectively (P=0.185). When accounting for disease severity, linezolid use was not independently associated with 90-day IRR (adjOR, 1.0; 95%CI, 0.24-4.3; P=0.99). There were no differences in all-cause 90-day mortality (4% vs 6%, P=0.49) or overall incidence of therapy-attributable adverse events (17% vs 16%, P=0.84) for linezolid or SPT groups. More patients in the SPT group developed an adverse effect requiring re-hospitalization (12% vs 1%, P=0.024), which were most commonly line-related infections.

CONCLUSIONS: Oral step-down linezolid had similar clinical and safety outcomes when compared to SPT for MRSA BSI, except linezolid was associated with fewer adverse events requiring re-hospitalization. Additional research is needed exploring step-down linezolid use in MRSA BSI, particularly in patients requiring shorter durations of outpatient therapy.

PMID:33785363 | DOI:10.1016/j.ijantimicag.2021.106329