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

Objectives: Aminoglycosides and β-lactams have been recommended for treatment of sepsis/septic shock despite a lack of mortality benefit. Previous studies have examined resistance emergence for the same bacterial isolate using old dosing regimens and during a narrow follow-up window. We hypothesised that combination regimens employing aminoglycosides will decrease the cumulative incidence of infections due to multidrug-resistant (MDR) Gram-negative bacilli (GNB) compared with β-lactams alone. Methods: All adult patients admitted to Barnes Jewish Hospital between 2010 and 2017 with a diagnosis of sepsis/septic shock were included in this retrospective cohort study. Patients were divided into two treatment groups, with and without aminoglycosides. Patient demographics, severity of presentation, administered antibiotics, follow-up cultures with susceptibility results for a period of 4–60 days, and mortality were extracted. After propensity score matching, a Fine–Gray subdistribution proportional hazards model summarised the estimated incidence of subsequent infections with MDR-GNB in the presence of all-cause death as a competing risk. Results: A total of 10 212 septic patients were included, with 1996 (19.5%) treated with at least two 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 (incidence at 60 days 0.073, 95% CI 0.062–0.085) versus patients not receiving aminoglycosides (0.116, 95% CI 0.102–0.130). Patients aged ≤65 years and with haematological malignancies had a larger treatment effect in subgroup analyses. Conclusion: Addition of aminoglycosides to β-lactams may protect against subsequent infections due to MDR-GNB in patients with sepsis/septic shock.