Abstract

BackgroundHospital-acquired and ventilator-associated pneumonia (HAP/VAP) cause significant morbidity and mortality. Guidelines recommend broad-spectrum empiric antibiotic therapy, including treatment for Pseudomonas aeruginosa (PSAR) and methicillin-resistant Staphylococcus aureus (MRSA), followed by de-escalation (DE). This study sought to assess the impact of DE on treatment failure.MethodsThis single-center retrospective cohort study screened all adult patients with a discharge diagnosis code for pneumonia from 2016–2019. Patients were enrolled if they met pre-defined criteria for HAP/VAP ≥48 hours after admission. Date of pneumonia diagnosis was defined as day 0. Spectrum scores were calculated, and DE was defined as a score reduction on day 3 versus day 1. Patients with DE were compared to patients with no de-escalation (NDE). Data were compared using chi-square, Mann-Whitney U, or T-tests. The primary outcome was composite treatment failure, defined as all-cause mortality or re-admission for pneumonia within 30 days of diagnosis, analyzed using a Cox proportional hazards analysis to control for confounding variables. Figure 1. Study Schematic Table 1. Spectrum Score Assignment ResultsOf 11860 admissions screened, 1812 unique patient-admissions were included (1102 HAP, 710 VAP). Fewer patients received DE (876 DE vs. 1026 NDE). Groups were well-matched at baseline, although more patients receiving DE had respiratory cultures ordered (56.6% vs. 50.6%, P=0.011). Patients receiving DE experienced a 65% and 44% reduction in anti-MRSA and anti-PSAR therapies by day 3, respectively. There was no difference in composite treatment failure (35.0% DE vs. 33.8% NDE, P=0.604). DE was not associated with treatment failure on Cox multivariate regression analysis (HR 1.13, 95% CI 0.97-1.33, P=0.149). Patients receiving DE had fewer antimicrobial days (median 9 vs. 11, P< 0.0001), episodes of Clostridioides difficile (2.2% vs. 3.8%, P=0.046), and days of hospitalization (median 20 vs. 22 days, P=0.006).Figure 2: Median Spectrum Scores (SS) Days 0 to 28 Table 2: Cox Regression Analysis ConclusionDE and NDE resulted in similar rates of composite treatment failure at 30 days; however, DE was associated with fewer antimicrobial days, episodes of C. difficile, and days of hospitalization. Spectrum scores can objectively identify DE, but further studies are needed to fully understand their utility in this context.Disclosures Tamara Krekel, PharmD, BCPS, BCIDP, Merck (Speaker’s Bureau) David J. Ritchie, PharmD, BCPS (AQ-ID), AbbVie (Speaker’s Bureau)Merck (Speaker’s Bureau)

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