OBJECTIVES: To examine the impact of antibiotic duration on the risk of superinfection (SI) development after adjusting for a cumulative antibiotic spectrum score (CASS).

METHODS: This was a retrospective cohort study using data (2010-2017) from a tertiary care hospital in the US. Adult patients with severe sepsis or septic shock who received at least one antibiotic were included. Based on the calculated spectrum scores for every antibiotic, a CASS was estimated for each day of antibiotic exposure. Duration of antibiotic exposures was classified into four groups (group 1: 1-3 days, group 2: 4-7 days, group 3: 8-10 days, group 4: 11-14 days). The outcome was the development of a superinfection (multi-drug resistant bacteria, Clostridioides difficile, or Candida species) > 3 days after cohort entry. Cox proportional hazard regressions were conducted to calculate the adjusted hazard ratio (HR) of SIs while controlling for numerous covariates including a CASS.

RESULTS: Of 10221 patients included in the analysis, 2107 (20.6%) developed a superinfection. The incidence rate of a superinfection was 0.495 per 100 person-days. Compared to those with no SI, the SI cohort was in more serious conditions (APACHE score: 17.0±5.8 vs. 16.2±5.7, p < 0.001) and had higher comorbidities (Charlson score: 6.2±3.1 vs. 6.0±3.3, p = 0.047). After cohort entry, patients with SI were found to have increased days of exposure to mechanical ventilation (mean difference [MD] 0.90 days, 95% CI: 0.35-1.44), urinary catheters (MD 0.72 days, 95% CI: 0.18-1.27), and vasopressors (MD 0.59 days, 95% CI: 0.17-1.01) than those with no SI. The adjusted HRs of SIs were 2.520 (95% CI: 1.533-4.141), 2.458 (95% CI: 1.191-5.074), and 1.792 (95% CI: 0.486-6.601) for group 2, 3, and 4, respectively, compared to group 1.

CONCLUSIONS: The risk of SIs increased as the duration of antibiotic exposures increased, which supports the utility of antibiotic de-escalation strategy.