TY - JOUR
T1 - Attributable mortality of antibiotic resistance in Gram-negative infections in the Netherlands
T2 - a parallel matched cohort study
AU - Rottier, Wouter C
AU - Deelen, J W Timotëus
AU - Caruana, Giorgia
AU - Buiting, Anton G M
AU - Dorigo-Zetsma, J Wendelien
AU - Kluytmans, Jan A J W
AU - van der Linden, Paul D
AU - Thijsen, Steven F T
AU - Vlaminckx, Bart J M
AU - Weersink, Annemarie J L
AU - Ammerlaan, Heidi S M
AU - Bonten, Marc J M
N1 - Funding Information:
The authors have no conflicts of interest to disclose. This work was supported by a research grant from the Netherlands Organisation for Health Research and Development (project number 205200007 ).
Publisher Copyright:
© 2020 The Authors
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/5
Y1 - 2021/5
N2 - Objectives: Antibiotic resistance in Gram-negative bacteria has been associated with increased mortality. This was demonstrated mostly for third-generation cephalosporin-resistant (3GC-R) Enterobacterales bacteraemia in international studies. Yet, the burden of resistance specifically in the Netherlands and created by all types of Gram-negative infection has not been quantified. We therefore investigated the attributable mortality of antibiotic resistance in Gram-negative infections in the Netherlands. Methods: In eight hospitals, a sample of Gram-negative infections was identified between 2013 and 2016, and separated into resistant and susceptible infection cohorts. Both cohorts were matched 1:1 to non-infected control patients on hospital, length of stay at infection onset, and age. In this parallel matched cohort set-up, 30-day mortality was compared between infected and non-infected patients. The impact of resistance was then assessed by dividing the two separate risk ratios (RRs) for mortality attributable to Gram-negative infection. Results: We identified 1954 Gram-negative infections, of which 1190 (61%) involved Escherichia coli, 210 (11%) Pseudomonas aeruginosa, and 758 (39%) bacteraemia. Resistant Gram-negatives caused 243 infections (12%; 189 (78%) 3GC-R Enterobacterales, nine (4%) multidrug-resistant P. aeruginosa, no carbapenemase-producing Enterobacterales). Subsequently, we matched 1941 non-infected controls. After adjustment, point estimates for RRs comparing mortality between infections and controls were similarly higher than 1 in case of resistant infections and susceptible infections (1.42 (95% confidence interval 0.66–3.09) and 1.32 (1.06–1.65), respectively). By dividing these, the RR reflecting attributable mortality of resistance was calculated as 1.08 (0.48–2.41). Conclusions: In the Netherlands, antibiotic resistance did not increase 30-day mortality in Gram-negative infections.
AB - Objectives: Antibiotic resistance in Gram-negative bacteria has been associated with increased mortality. This was demonstrated mostly for third-generation cephalosporin-resistant (3GC-R) Enterobacterales bacteraemia in international studies. Yet, the burden of resistance specifically in the Netherlands and created by all types of Gram-negative infection has not been quantified. We therefore investigated the attributable mortality of antibiotic resistance in Gram-negative infections in the Netherlands. Methods: In eight hospitals, a sample of Gram-negative infections was identified between 2013 and 2016, and separated into resistant and susceptible infection cohorts. Both cohorts were matched 1:1 to non-infected control patients on hospital, length of stay at infection onset, and age. In this parallel matched cohort set-up, 30-day mortality was compared between infected and non-infected patients. The impact of resistance was then assessed by dividing the two separate risk ratios (RRs) for mortality attributable to Gram-negative infection. Results: We identified 1954 Gram-negative infections, of which 1190 (61%) involved Escherichia coli, 210 (11%) Pseudomonas aeruginosa, and 758 (39%) bacteraemia. Resistant Gram-negatives caused 243 infections (12%; 189 (78%) 3GC-R Enterobacterales, nine (4%) multidrug-resistant P. aeruginosa, no carbapenemase-producing Enterobacterales). Subsequently, we matched 1941 non-infected controls. After adjustment, point estimates for RRs comparing mortality between infections and controls were similarly higher than 1 in case of resistant infections and susceptible infections (1.42 (95% confidence interval 0.66–3.09) and 1.32 (1.06–1.65), respectively). By dividing these, the RR reflecting attributable mortality of resistance was calculated as 1.08 (0.48–2.41). Conclusions: In the Netherlands, antibiotic resistance did not increase 30-day mortality in Gram-negative infections.
KW - Bacteraemia
KW - Burden of antimicrobial resistance
KW - Enterobacterales
KW - Extended-spectrum beta-lactamase
KW - Nonbacteraemic infection
UR - http://www.scopus.com/inward/record.url?scp=85090480373&partnerID=8YFLogxK
U2 - 10.1016/j.cmi.2020.07.014
DO - 10.1016/j.cmi.2020.07.014
M3 - Article
C2 - 32698043
SN - 1198-743X
VL - 27
SP - 742
EP - 749
JO - Clinical Microbiology and Infection
JF - Clinical Microbiology and Infection
IS - 5
ER -