Short-course aminoglycosides as adjunctive empirical therapy in patients with Gram-negative bloodstream infection, a cohort study

J.W Timotëus Deelen,W.C Rottier,A.G.M Buiting,J.W Dorigo-Zetsma,J.A.J.W Kluytmans,P.D Van Der Linden,S.F.T Thijsen,B.J.M Vlaminckx,A.J.L Weersink,H.S.M Ammerlaan,M.J.M Bonten,C.H Van Werkhoven

doi:10.1016/j.cmi.2020.04.041

Abstract

ObjectiveShort-course aminoglycosides as adjunctive empirical therapy to β-lactams in patients with a clinical suspicion of sepsis are used to broaden antibiotic susceptibility coverage and to enhance bacterial killing. We quantified the impact of this approach on 30-day mortality in a subset of sepsis patients with a Gram-negative bloodstream infection. MethodsFrom a prospective cohort study conducted in seven hospitals in the Netherlands between June 2013 and November 2015, we selected all patients with Gram-negative bloodstream infection (GN-BSI). Short-course aminoglycoside therapy was defined as tobramycin, gentamicin or amikacin initiated within a 48-hour time window around blood-culture obtainment, and prescribed for a maximum of 2 days. The outcome of interest was 30-day all-cause mortality. Confounders were selected a priori for adjustment using a propensity score analysis with inverse probability weighting. ResultsA total of 626 individuals with GN-BSI who received β-lactams were included; 156 (24.9%) also received aminoglycosides for a median of 1 day. Patients receiving aminoglycosides more often had septic shock (31/156, 19.9% versus 34/470, 7.2%) and had an eight-fold lower risk of inappropriate treatment (3/156, 1.9% versus 69/470, 14.7%). Thirty-day mortality was 17.3% (27/156) and 13.6% (64/470) for patients receiving and not receiving aminoglycosides, respectively; yielding crude and adjusted odds ratios for 30-day mortality for patients treated with aminoglycosides of 1.33 (95% CI 0.80–2.15) and 1.57 (0.84–2.93), respectively. ConclusionsShort-course adjunctive aminoglycoside treatment as part of empirical therapy with β-lactam antibiotics in patients with GN-BSI did not result in improved outcomes, despite better antibiotic coverage of pathogens.

Highlights

IntroductionCombination therapy with aminoglycosides does not provide a benefit for patients with sepsis compared with b-lactam monotherapy [1]
Treatment restrictions were more prevalent among patients not receiving aminoglycosides (143/470 (30.4%) compared with 30/156 (19.2%) among those without aminoglycosides)
These results add to an increasing body of evidence regarding the absence of clinical benefits of short-term adjunctive aminoglycosides as part of empirical treatment strategies

Summary

Introduction

Combination therapy with aminoglycosides does not provide a benefit for patients with sepsis compared with b-lactam monotherapy [1]. This combination is recommended in the Surviving Sepsis guidelines and several national guidelines, including those of Sweden and France [2e4]. In the Netherlands, the sepsis guideline suggests the addition of a short course (one or two doses) of empirical aminoglycosides when the patient is at increased risk of infection with an extended-spectrum b-lactamase-producing pathogen. In locally adapted guidelines in Dutch hospitals, recommendations range from no aminoglycosides at all to a short 1- to 2-day course of aminoglycosides in every patient with sepsis This strategy is widely but inconsistently employed, and aside from differences in local guidelines, drivers for this heterogeneity are unknown

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Results

Conclusion