Increased Risk of Sepsis During Hospital Readmission Following Exposure to Certain Antibiotics During Hospitalization

Abstract

Background. A recent study found an increased risk of sepsis following infection related hospitalizations, possibly mediated by antibiotic-associated microbiome disruption as demonstrated in animal models.We examined the risk of hospital readmission coded as sepsis within 90 days following the receipt of an antibiotic course in US hospitals. Methods. Using adult hospitalization and pharmacy data from the Truven Health MarketScan Hospital Drug Database, 2006-2010, we retrospectively identified a cohort of hospitalized patients and determined subsequent sepsis, based on ICD-9-CM codes, during a readmission within 90 days after discharge from the index visit. Our primary exposure was any antibiotic with a high risk for microbiome disruption administered during the index visit (3rd-/4th-generation cephalosporin, fluoroquinolone, lincosamide, beta-lactam/beta-lactamase inhibitor combination, oral vancomycin, or carbapenem). We compared the risk of sepsis in exposed patients to patients without any antibiotic exposure (the referent group) using multivariate logistic regression, controlling for potential confounding factors from the index discharge. Also, we compared the risk for patients exposed to any non-high risk antibiotic to the referent group and considered a dose-response exposure for antibiotic therapy days during the index visit. Results. Among 473 hospitals, we randomly selected 9,386,961 adult index visits without current or prior sepsis diagnosis; 0.6% had sepsis during readmission within 90 days of discharge. Exposure to a high risk antibiotic during the index visit was associated with a greater risk of sepsis during readmission compared to patients with no antibiotic exposure, OR = 1.50 95% CI = 1.47-1.53. We observed a significant dose-response for days of antibiotic therapy (figure). Conclusion. The observed increased risk for subsequent sepsis following receipt of antibiotics that significantly disrupt the microbiome, including a dose-response effect, supports the idea that microbiome disruption confers increased risk for subsequent severe infections. Better understanding the role of antibiotic-mediated microbiome disruption in sepsis will be important for future sepsis prevention.