The effect of delays in second-dose antibiotics on patients with severe sepsis and septic shock.

BACKGROUND

Early antibiotics are fundamental to sepsis management. Second-dose antibiotic delays were associated with increased mortality in a recent study. Study objectives include: 1) determine factors associated with delays in second-dose antibiotic administration; 2) evaluate if delays influence clinical outcomes.

METHODS

ED-treated adults (≥18 years; n = 1075) with severe sepsis or septic shock receiving ≥2 doses of intravenous antibiotics were assessed, retrospectively, for second-dose antibiotic delays (dose time > 25% of recommended interval). Predictors of delay and impact on outcomes were determined, controlling for MEDS score, 30 mL/kg fluids and antibiotics within three hours of sepsis onset, lactate, and renal failure, among others.

RESULTS

In total, 335 (31.2%) patients had delayed second-dose antibiotics. A total of 1864 second-dose antibiotics were included, with 354 (19.0%) delays identified by interval (delayed/total doses): 6-h (36/67) = 53.7%; 8-h (165/544) = 30.3%; 12-h (114/436) = 26.1%; 24-h (21/190) = 8.2%; 48-h (0/16) = 0%. In-hospital mortality in the timely group was 15.5% (shock-17.6%) and 13.7% in the delayed group (shock-16.9%). Increased odds of delay were observed for ED boarding (OR 2.54, 95% 1.81-3.55), shorter dosing intervals (6/8-h- OR 2.99, 95% CI 1.95-4.57; 12-h- OR 2.46, 95% CI 1.72-3.51), receiving 30 mL/kg fluids by three hours (OR 1.42, 95% CI 1.06-1.90), and renal failure (OR 2.57, 95% CI 1.50-4.39). Delays were not associated with increased mortality (OR 0.87, 95% CI 0.58-1.29) or other outcomes.

CONCLUSIONS

Factors associated with delayed second-dose antibiotics include ED boarding, antibiotics requiring more frequent dosing, receiving 30 mL/kg fluid, and renal failure. Delays in second-dose administration were not associated with mortality or other outcomes.