Association of Excessive Duration of Antibiotic Therapy for Intra-Abdominal Infection with Subsequent Extra-Abdominal Infection and Death: A Study of 2,552 Consecutive Infections

Background: We hypothesized that a longer duration of antibiotic treatment for intra-abdominal infections (IAI) would be associated with an increased risk of extra-abdominal infections (EAI) and high mortality. Methods: We reviewed all IAI occurring in a single institution between 1997 and 2010. The IAI were divided into two groups consisting of those with a subsequent EAI and those without; the data for each group were analyzed. Patients with EAI following IAI were matched in a 1: 2 ratio with patients who did not develop EAI on the basis of their Acute Physiology and Chronic Health Evaluation (APACHE II) score +/- 1 point. Statistical analyses were done with the Student t-test, chi(2) analysis, Wilcoxon rank sum test, and multi-variable analysis. Results: We identified 2,552 IAI, of which 549 (21.5%) were followed by EAI. Those IAI that were followed by EAI were associated with a longer initial duration of antimicrobial therapy than were IAI without subsequent EAI (median 14 d [inter-quartile range (IQR) 10-22 d], vs. 10 d [IQR 6-15 d], respectively, p < 0.01), a higher APACHE II score (16.6 +/- 0.3 vs. 11.2 +/- 0.2 points, p < 0.01), and higher in-hospital mortality (17.1% vs. 5.4%, p < 0.01). The rate of EAI following IAI in patients treated initially with antibiotics for 0-7 d was 13.3%, vs. 25.1% in patients treated initially for > 7 d (p< 0.01). A successful match was made of 469 patients with subsequent EAI to 938 patients without subsequent EAI, resulting in a mean APACHE II score of 15.2 for each group. After matching, IAI followed by EAI were associated with a longer duration of initial antimicrobial therapy than were IAI without subsequent EAI (median 14 d [9-22 d], vs. 11 d [7-16 d], respectively, p < 0.01), and with a higher in-hospital mortality (14.9% vs. 9.0%, respectively, p < 0.01). Logistic regression showed that days of antimicrobial therapy for IAI was an independent predictor of subsequent EAI (p < 0.001). Conclusions: A longer duration of antibiotic therapy for IAI is associated with an increased risk of subsequent EAI and increased mortality.