Addition of aminoglycosides reduces recurrence of infections with multidrug-resistant Gram-negative bacilli in patients with sepsis and septic shock

Abstract

Aminoglycosides and beta-lactams have been a recommended regimen in the treatment of sepsis and septic shock despite lack of mortality benefit. Previous studies have examined emergence of resistance for the same bacterial isolate using old dosing regimens and during a narrow follow up window. We hypothesized that combination regimens employing aminoglycosides will decrease the cumulative incidence of infections due to multidrug resistant (MDR) Gram-negative bacilli (GNB) compared to beta-lactams alone. All adult patients admitted to Barnes Jewish Hospital in St. Louis, MO between 2010 and 2017 with the diagnosis of sepsis or septic shock were included in this retrospective cohort study. Patients were divided into 2 treatment groups: with and without aminoglycosides. We extracted patients' demographics, severity of presentation, administered antibiotics, follow up cultures with susceptibility results for a period of 4-60 days, and mortality. After propensity score matching, a Fine-Gray sub-distribution proportional hazards model summarized the estimated incidence of subsequent infections with MDR GNB in the presence of all-cause death as a competing risk. 10212 septic patients were included with 1996 (19.5%) treated with at least 2 antimicrobials including one aminoglycoside. After propensity score matching, the cumulative incidence of MDR GNB infections between 4-60 days was lower in the combination group with an incidence of 0.073 at 60 days (95% CI [0.062, 0.085]) vs 0.116 (95% CI [0.102, 0.130]) in patients not receiving aminoglycosides. Patients younger than 65 years and with hematologic malignancies had a larger treatment effect in subgroup analyses. Addition of aminoglycosides to beta-lactams may protect against subsequent infections due to MDR GNB in patients with sepsis and septic shock.