Influence of antibiotic therapy on mortality of critical surgical illness caused or complicated by infection.

Background: Conceptually, appropriateness of antibiotic therapy includes choice of agent relative to susceptibility of pathogens as well as dosing, timing of onset, and duration of therapy, but is most commonly considered in terms of choice of antibiotic. It has been suggested that inappropriate antibiotic selection can result in increased mortality. This study was performed to elucidate the role of scheduled, rotating antibiotic therapy in defining mortality among febrile, infected surgical ICU patients.

Methods: Prospective inception-cohort study of 356 patients during their initial episode of fever (temperature > 38.2 degrees C), caused by infection diagnosed by positive cultures or direct inspection (some cases of peritonitis). Collected data included age, gender, admission APACHE III score, peak temperature, microbial isolates and susceptibility, source of infection, multiple organ dysfunction score, mortality, and several time intervals (time that cultures were collected, time from collection to antibiotic prescription, time from collection to antibiotic administration, duration of therapy).

Results: The mean age was 63 +/- 1 years, the mean APACHE III score was 74 +/- 2 points, the mean multiple organ dysfunction score was 8 +/- 1 points, and overall mortality was 31%. Neither the source of infection nor the specific isolate influenced mortality. Antibiotic therapy was appropriate (covered the isolates) in 94% of cases, and did not influence mortality. Duration of therapy was identical between groups (5.1 +/- 0.3 vs. 5.4 +/- 0.3 days, p = 0.61). By logistic regression (dependent variable = mortality), APACHE III score OR 1.025, 95% C.I. 1.021-1.04) and delayed antibiotic administration (30-min intervals, OR 1.021, 95% C.I. 1.003-1.038) were independent predictors of mortality.

Conclusions: The use of scheduled monthly antibiotic cycling in the surgical ICU is associated with a high rate of "appropriate" antibiotic therapy, and appears to maintain or improve resistance patterns. Because antibiotic therapy was mostly appropriate for isolates, initial inappropriate therapy could not be identified as a risk factor for mortality. However, in the setting of appropriate antibiotic choice, the prompt initial administration of antibiotics appears to be crucial for survival, but neither site of infection nor specific pathogen are influential.