SAN FRANCISCO, CA—Critically ill patients who receive inappropriate antibiotics in the intensive care unit (ICU) for more than 24 hours have a progressively higher mortality rate that corresponds with duration of antibiotics; however, these same antibiotics do not appear to be a risk factor for mortality within the first 24 hours of administration, a study concluded at IDWeek 2013.

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Pending results of cultures, most patients with sepsis in the ICU are given broad-spectrum empirical antibiotics, including carbapenems, reported Dr. Rui Min Foo, of the division of infectious diseases, National University Health System, Singapore, and colleagues. “However, few have looked at the timing of appropriate antibiotics and its association with mortality,” Dr. Foo added.

In this prospective observational study, 230 patients with positive blood cultures from 2007–2011 admitted to medical and surgical ICUs in a 1000-bed hospital were identified. Based on in vitro culture and sensitivity results, appropriate antibiotic therapy was defined.

“Using pharmacy and clinical records, patients were grouped based on time to appropriate antibiotics from time of culture: <24 hours, 24–48 hours, 48–72 hours, >72 hours,” the investigators noted. Also analyzed were demographic, clinical, and outcomes data. The primary outcome was mortality.

Within 7 days of a positive culture, 38 patients (16.5%) had died. No difference was observed in 7-day mortality in those who received inappropriate antibiotics within the initial 24 hours compared with those with appropriate antibiotics (HR 1.63; 95% CI 0.84–3.15; P=0.15). In addition, inappropriate antibiotics use in the first 24 hours was not a risk factor for overall hospital mortality (HR 0.86 95% CI 0.48–1.54; P=0.63).

However, beyond the initial 24 hours, mortality was found to increase significantly with duration of inappropriate antibiotics as well as progressively: at 48 hours, HR 2.96 (95% CI 1.40–6.26; P<0.001); at 72 hours, HR 5.14 (95% CI 2.43–10.89; P<0.001); and ≥72 hours, HR 23.15 (95% CI 9.56–56.07; P<0.001).

In a multivariable COX proportional hazards survival analysis, inappropriate antibiotics at 72 hours (HR 6.79; 95% CI 3.15–14.62; P<0.001) and liver disease (HR 4.17; 95% CI 1.60–10.85; P=0.003) were associated with an increased 7-day mortality, while surgical ICU patients had a lower mortality (HR 0.28; 95% CI 0.11–0.67; P=0.004).

“Novel technologies which can shorten the time to appropriate antibiotics may improve outcomes without the risk of selecting for resistant pathogens,” Dr. Foo concluded.