(1619) Mono and Dual Anti-MRSA Regimens for Children With Sepsis: A Multicenter Probabilistic Linkage Study

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) sepsis is associated with high morbidity and mortality. Vancomycin (Vanc) is the accepted empiric therapy, despite difficulty reliably achieving therapeutic levels. We examine the practices and outcomes in children with MRSA sepsis who were treated with Vanc alone or dual anti-MRSA therapy.

Methods: This retrospective cohort study probabilistically links the Improving Pediatric Sepsis Outcomes (IPSO) database and the Pediatric Health Information Systems (PHIS) database. Children 1m-18y with sepsis who received Vanc and had suspected or confirmed MRSA based on diagnosis codes were included. Patients receiving Vanc alone or dual therapy (Vanc + another anti-MRSA drug) ± 1 day from the time of sepsis onset were compared. A multivariable regression model was constructed with an interaction term examining mono- vs dual therapy with and without critical sepsis. Data are presented as counts (%), median (interquartile range), or adjusted odds ratio (95% confidence interval). Significance is P< 0.05.

Results: Among the 1624 encounters, 1118 (68.8) received monotherapy. The median age was 8y (3,13) and 727 (44.8%) were female, with no significant difference between groups. The monotherapy group had a significantly lower prevalence of critical sepsis (399 [35.7] vs 220 [43.5], P< 0.01), more with chronic comorbidities (944 [84.4] vs 326 [64.4], P< 0.001), less acute kidney injury (248 (22.2) vs 150 (29.6), P=0.001), more immunocompromised (140 [12.5] vs 37 [7.3], P=0.002), more with indwelling catheters (189 [16.9] vs 51 [10.1], P< 0.001), less pressor use (246 [22] vs 160 [31.6], P< 0.001), and lower mortality (19 [1.7] vs 19 [3.8], P=0.01). Without critical sepsis, there was no difference in the adjusted odds of mortality between the monotherapy and dual therapy groups. Among patients with critical sepsis, the adjusted odds of mortality was lower among patients receiving dual therapy compared to monotherapy (Odds Ratio 0.20 [0.07, 0.56], P=0.002), though not all covariates could be included in the model given the low prevalence of mortality.

Conclusions: In a cohort of children with MRSA and sepsis, mortality was lower than previous reports. Clinicians prescribe dual anti-MRSA therapy at time of sepsis recognition to patients who are more acutely ill.