Background: Pseudomonas aeruginosa is the most common gram-negative bacteria isolated from intensive care units (ICUs) across the United States. Nosocomial infections with P. aeruginosa have been strongly associated with mortality rates of 60%. Monte Carlo simulations have demonstrated that extended infusion (EI: 4-hour infusion) cefepime achieves a higher cumulative fraction of response against P. aeruginosa. The purpose of this study was to compare clinical outcomes between traditional infusion (TI: 30-minute infusion IV) and EI cefepime administration regimens of ICU patients for the management of P. aeruginosa bacteremia or pneumonia.
Methods: This retrospective, multi-center, cohort review compared EI to TI cefepime to determine if EI cefepime improved outcomes. The primary objective is to determine the 28-day mortality rate of EI compared to TI cefepime for ICU patients with a documented P. aeruginosa bacteremia or pneumonia. Secondary objectives included length of stay (LOS) in the ICU, days on mechanical ventilation, and overall cefepime treatment days between EI and TI regimens.
Results: EI cefepime was associated with a statistically significant decrease in 28-day all-cause mortality as compared to TI cefepime in ICU patients (10% vs 30%, p=0.0172, Figure 1). ICU LOS was significantly shorter in EI versus TI cefepime arms (16 days vs. 24 days, p=0.016). Other variables such as number of treatment days, days on mechanical ventilation, cefepime (grams) per person per treatment course were not statistically significant (Figure 2). In the multivariate analysis, SOFA score (OR, 1.333; 95% CI, 1.087-1.637) was independently associated with 28-day mortality. Conversely, minimum inhibitory concentration (MIC) ≤2 (OR, 0.26; 95% CI, 0.667-0.984) and EI cefepime (OR, 0.247; 95% CI, 0.723-0.841) were associated with decreased mortality.
Conclusion: An EI cefepime regimen in ICU patients for the treatment of P. aeruginosa bacteremia or pneumonia was associated with decreased 28-day all-cause mortality and LOS in the ICU. SOFA score was an independent predictor of 28-day mortality while an MIC ≤2 and administration of EI cefepime were independent predictors of decreased mortality per multivariate analysis. Additional, large prospective studies are needed to confirm our results.
D. Rose, None
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