Attributable mortality of antibiotic resistance in gram-negative infections in the Netherlands: a parallel matched cohort study

Wouter C. Rottier; J. W.Timotëus Deelen; Giorgia Caruana; Anton G.M. Buiting; J. Wendelien Dorigo-Zetsma; Jan A.J.W. Kluytmans; Paul D. van der Linden; Steven F.T. Thijsen; Bart J.M. Vlaminckx; Annemarie J.L. Weersink; Heidi S.M. Ammerlaan; Marc J.M. Bonten

doi:10.1016/j.cmi.2020.07.014

Attributable mortality of antibiotic resistance in gram-negative infections in the Netherlands: a parallel matched cohort study

Wouter C. Rottier^*
, J. W.Timotëus Deelen
, Giorgia Caruana
, Anton G.M. Buiting
, J. Wendelien Dorigo-Zetsma
, Jan A.J.W. Kluytmans
, Paul D. van der Linden
, Steven F.T. Thijsen
, Bart J.M. Vlaminckx
, Annemarie J.L. Weersink
, Heidi S.M. Ammerlaan
, Marc J.M. Bonten

^*Corresponding author for this work

Utrecht University
University of Sassari
ETZ Elisabeth
Tergooi Ziekenhuis
Amphia Hospital
Tergooi Ziekenhuis
Diakonessenhuis
St. Antonius Ziekenhuis
Meander Medical Center
Catharina Hospital

Research output: Contribution to journal › Article › Academic › peer-review

7 Citations (Scopus)

21 Downloads (Pure)

Abstract

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.

Original language	English
Pages (from-to)	742-749
Number of pages	8
Journal	Clinical Microbiology and Infection
Volume	27
Issue number	5
DOIs	https://doi.org/10.1016/j.cmi.2020.07.014
Publication status	Published - May 2021
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2020 The Authors

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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Cite this

Rottier, W. C., Deelen, J. W. T., Caruana, G., Buiting, A. G. M., Dorigo-Zetsma, J. W., Kluytmans, J. A. J. W., van der Linden, P. D., Thijsen, S. F. T., Vlaminckx, B. J. M., Weersink, A. J. L., Ammerlaan, H. S. M., & Bonten, M. J. M. (2021). Attributable mortality of antibiotic resistance in gram-negative infections in the Netherlands: a parallel matched cohort study. Clinical Microbiology and Infection, 27(5), 742-749. https://doi.org/10.1016/j.cmi.2020.07.014

@article{af21f66de857461888c388a073bf533c,

title = "Attributable mortality of antibiotic resistance in gram-negative infections in the Netherlands: a parallel matched cohort study",

abstract = "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.",

author = "Rottier, \{Wouter C.\} and Deelen, \{J. W.Timot{\"e}us\} and Giorgia Caruana and Buiting, \{Anton G.M.\} and Dorigo-Zetsma, \{J. Wendelien\} and Kluytmans, \{Jan A.J.W.\} and \{van der Linden\}, \{Paul D.\} and Thijsen, \{Steven F.T.\} and Vlaminckx, \{Bart J.M.\} and Weersink, \{Annemarie J.L.\} and Ammerlaan, \{Heidi S.M.\} and Bonten, \{Marc J.M.\}",

note = "Publisher Copyright: {\textcopyright} 2020 The Authors",

year = "2021",

month = may,

doi = "10.1016/j.cmi.2020.07.014",

language = "English",

volume = "27",

pages = "742--749",

journal = "Clinical Microbiology and Infection",

issn = "1198-743X",

publisher = "Elsevier",

number = "5",

}

Rottier, WC, Deelen, JWT, Caruana, G, Buiting, AGM, Dorigo-Zetsma, JW, Kluytmans, JAJW, van der Linden, PD, Thijsen, SFT, Vlaminckx, BJM, Weersink, AJL, Ammerlaan, HSM & Bonten, MJM 2021, 'Attributable mortality of antibiotic resistance in gram-negative infections in the Netherlands: a parallel matched cohort study', Clinical Microbiology and Infection, vol. 27, no. 5, pp. 742-749. https://doi.org/10.1016/j.cmi.2020.07.014

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.

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.

UR - https://www.scopus.com/pages/publications/85090480373

U2 - 10.1016/j.cmi.2020.07.014

DO - 10.1016/j.cmi.2020.07.014

M3 - Article

C2 - 32698043

AN - SCOPUS:85090480373

SN - 1198-743X

VL - 27

SP - 742

EP - 749

JO - Clinical Microbiology and Infection

JF - Clinical Microbiology and Infection

IS - 5

ER -

Attributable mortality of antibiotic resistance in gram-negative infections in the Netherlands: a parallel matched cohort study

Abstract

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