Short-Course Adjunctive Gentamicin as Empirical Therapy in Patients With Severe Sepsis and Septic Shock: A Prospective Observational Cohort Study

Abstract

Background.: Metaanalyses failed to demonstrate clinical benefits of beta lactam plus aminoglycoside combination therapy compared to beta lactam monotherapy in patients with sepsis. However, few data exist on the effects of short-course adjunctive aminoglycoside therapy in sepsis patients with organ failure or shock.

Methods.: We prospectively enrolled consecutive patients with severe sepsis or septic shock in 2 intensive care units in the Netherlands from 2011 to 2015. Local antibiotic protocols recommended empirical gentamicin add-on therapy in only 1 of the units. We used logistic regression analyses to determine the association between gentamicin use and the number of days alive and free of renal failure, shock, and death, all on day 14.

Results.: Of 648 patients enrolled, 245 received gentamicin (222 of 309 [72%] in hospital A and 23 of 339 [7%] in hospital B) for a median duration of 2 days (interquartile range, 1-3). The adjusted odds ratios associated with gentamicin use were 1.39 (95% confidence interval [CI], 1.00-1.94) for renal failure, 1.34 (95% CI, 0.96-1.86) for shock duration, and 1.41 (95% CI, 0.94-2.12) for day-14 mortality. Based on in vitro susceptibilities, inappropriate (initial) gram-negative coverage was given in 9 of 245 (4%) and 18 of 403 (4%) patients treated and not treated with gentamicin, respectively (P = .62).

Conclusions.: Short-course empirical gentamicin use in patients with sepsis was associated with an increased incidence of renal failure but not with faster reversal of shock or improved survival in a setting with low prevalence of antimicrobial resistance.

Keywords: acute kidney injury; gentamicin; mortality.; renal failure; sepsis.