Short-course aminoglycosides as adjunctive empirical therapy in patients with Gram-negative bloodstream infection, a cohort study
Deelen, J W Timotëus; Rottier, Wouter C; Buiting, Anton G M; Dorigo-Zetsma, J Wendelien; Kluytmans, Jan A J W; van der Linden, Paul D; Thijsen, Steven F T; Vlaminckx, Bart J M; Weersink, Annemarie J L; Ammerlaan, Heidi S M; Bonten, Marc J M; van Werkhoven, Cornelis H
(2021) Clinical Microbiology and Infection, volume 27, issue 2, pp. 269 - 275
(Article)
Abstract
Objective: Short-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.
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Methods: From 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. Results: A 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. Conclusions: Short-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.
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Keywords: Aminoglycoside, Antibiotic resistance, Bacteraemia, Bloodstream infection, ESBL, Gentamicin, Inappropriate therapy, Mortality, Microbiology (medical), Infectious Diseases, Journal Article
ISSN: 1198-743X
Publisher: Elsevier Limited
Note: Funding Information: This work was supported by the Netherlands Organization for Healthcare Research and Development (ZonMW, project number 205200007 ) and R-GNOSIS (funding from the European Community's Seventh Framework Programme FP7/2007-2013 under Grant Agreement no. 282512). Funding Information: This work was supported by the Netherlands Organization for Healthcare Research and Development (ZonMW, project number 205200007) and R-GNOSIS (funding from the European Community's Seventh Framework Programme FP7/2007-2013 under Grant Agreement no. 282512). Publisher Copyright: © 2020 The Author(s)
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