The Association Between Empirical Antibiotic Treatment and Mortality in Severe Infections Caused by Carbapenem-resistant Gram-negative Bacteria: A prospective study

AIDA Study Group

doi:10.1093/cid/ciy371

The Association Between Empirical Antibiotic Treatment and Mortality in Severe Infections Caused by Carbapenem-resistant Gram-negative Bacteria: A prospective study

AIDA Study Group

Bar-Ilan University - Azrieli Faculty of Medicine

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

36 Scopus citations

Abstract

Background. Empirical colistin should be avoided. We aimed to evaluate the association between covering empirical antibiotics (EAT) and mortality for infections caused by carbapenem-resistant gram-negative bacteria (CRGNB). Methods. This was a secondary analysis of a randomized controlled trial, including adults with bloodstream infections, pneumonia, or urosepsis caused by CRGNB. All patients received EAT followed by covering targeted therapy. The exposure variable was covering EAT in the first 48 hours. The outcome was 28-day mortality. We adjusted the analyses by multivariable regression analysis and propensity score matching. Results. The study included 406 inpatients with severe CRGNB infections, mostly Acinetobacter baumannii (312/406 [77%]). Covering EAT was given to 209 (51.5%) patients, mostly colistin (n = 200). Patients receiving noncovering EAT were older, more frequently unconscious and dependent, carrying catheters, and mechanically ventilated with pneumonia. Mortality was 84 of 197 (42.6%) with noncovering vs 96 of 209 (45.9%) with covering EAT (P = .504). Covering EAT was not associated with survival in the adjusted analysis; rather, there was a weak association with mortality (odds ratio [OR], 1.37; 95% confidence interval [CI], 1.02-1.84). Results were similar for colistin monotherapy and colistin-carbapenem combination EAT. In the propensity score-matched cohort (n = 338) covering antibiotics were not significantly associated with mortality (OR, 1.42; 95% CI, .91-2.22). Similar results were obtained in an analysis of 14-day mortality. Conclusions. Empirical use of colistin before pathogen identification, with or without a carbapenem, was not associated with survival following severe infections caused by CRGNBs, mainly A. baumannii.

Original language	English
Pages (from-to)	1815-1823
Number of pages	9
Journal	Clinical Infectious Diseases
Volume	67
Issue number	12
DOIs	https://doi.org/10.1093/cid/ciy371
State	Published - 2018

Bibliographical note

Publisher Copyright:
© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].

Funding

This work was funded by the AIDA project (Preserving old antibiotics for the future: assessment of clinical efficacy by a pharmacokinetic/pharmacodynamic approach to optimize effectiveness and reduce resistance for off-patent antibiotics) (grant number Health-F3-2011-278348) Financial support. This work was funded by the AIDA project (Preserving old antibiotics for the future: assessment of clinical efficacy by a pharmacokinetic/pharmacodynamic approach to optimize effectiveness and reduce resistance for off-patent antibiotics) (grant number Health-F3-2011–278348) Potential conflicts of interest. G. L. D. has received research funding from Pfizer, Achaogen, Rempex, MSD and Gilead. E. D. M. has received research funding from MSD, Pfizer, bioMérieux, AbbVie, Sanofi-Aventis, Medtronic, and DiaSorin. Y. C. has received research funding from MSD, AstraZeneca, Allecra Therapeutics, DaVoltera, Intercell AG, bioMérieux SA, Rempex Pharmaceuticals, Nariva, Achoagen, Roche, Pfizer, and Shionogi. All other authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Funders	Funder number
Allecra Therapeutics
Rempex Pharmaceuticals
bioMérieux SA
Pfizer
AstraZeneca
Roche
Sanofi
Medtronic
Gilead Sciences
AbbVie
Meso Scale Diagnostics
Infocomm Development Authority of Singapore	Health-F3-2011–278348
Shionogi

Keywords

Appropriate empirical antibiotics
Carbapenemase-producing
Colistin
Gram-negative bacteria
Multidrug-resistant bacteria

UN SDGs

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

Access to Document

10.1093/cid/ciy371

Cite this

@article{dfe6d5d1b10940b98b0b5897704ee0fb,

title = "The Association Between Empirical Antibiotic Treatment and Mortality in Severe Infections Caused by Carbapenem-resistant Gram-negative Bacteria: A prospective study",

abstract = "Background. Empirical colistin should be avoided. We aimed to evaluate the association between covering empirical antibiotics (EAT) and mortality for infections caused by carbapenem-resistant gram-negative bacteria (CRGNB). Methods. This was a secondary analysis of a randomized controlled trial, including adults with bloodstream infections, pneumonia, or urosepsis caused by CRGNB. All patients received EAT followed by covering targeted therapy. The exposure variable was covering EAT in the first 48 hours. The outcome was 28-day mortality. We adjusted the analyses by multivariable regression analysis and propensity score matching. Results. The study included 406 inpatients with severe CRGNB infections, mostly Acinetobacter baumannii (312/406 [77%]). Covering EAT was given to 209 (51.5%) patients, mostly colistin (n = 200). Patients receiving noncovering EAT were older, more frequently unconscious and dependent, carrying catheters, and mechanically ventilated with pneumonia. Mortality was 84 of 197 (42.6%) with noncovering vs 96 of 209 (45.9%) with covering EAT (P = .504). Covering EAT was not associated with survival in the adjusted analysis; rather, there was a weak association with mortality (odds ratio [OR], 1.37; 95% confidence interval [CI], 1.02-1.84). Results were similar for colistin monotherapy and colistin-carbapenem combination EAT. In the propensity score-matched cohort (n = 338) covering antibiotics were not significantly associated with mortality (OR, 1.42; 95% CI, .91-2.22). Similar results were obtained in an analysis of 14-day mortality. Conclusions. Empirical use of colistin before pathogen identification, with or without a carbapenem, was not associated with survival following severe infections caused by CRGNBs, mainly A. baumannii.",

keywords = "Appropriate empirical antibiotics, Carbapenemase-producing, Colistin, Gram-negative bacteria, Multidrug-resistant bacteria",

author = "{AIDA Study Group} and Yael Zak-Doron and Benattar, {Yael Dishon} and Iris Pfeffer and Daikos, {George L.} and Anna Skiada and Anastasia Antoniadou and Emanuele Durante-Mangoni and Roberto Andini and Giusi Cavezza and Leonard Leibovici and Dafna Yahav and Noa Eliakim-Raz and Yehuda Carmeli and Amir Nutman and Mical Paul and Yaakov Dickstein and Roni Bitterman and Hiba Zayyad and Fidi Koppel and Sergey Altunin and Nizar Andria and Ami Neuberger and Anat Stern and Neta Petersiel and Marina Raines and Amir Karban and Oren Zusman and Michal Elbaz and Heyam Atamna and Vered Daitch and Tanya Babich and Amos Adler and Inbar Levi and Daikos, {George L.} and Ioannis Pavleas and Antigoni Kotsaki and Domenico Iossa and Mariano Bernardo and Lorenzo Bertolino and Giuseppe Giuffr{\`e} and Roberto Giurazza and Susanna Cuccurullo and Maria Galdo and Patrizia Murino and Adriano Cristinziano and Antonio Corcione and Rosa Zampino and Pafundi, {Pia Clara} and Johan Mouton and Lena Friberg",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].",

year = "2018",

doi = "10.1093/cid/ciy371",

language = "אנגלית",

volume = "67",

pages = "1815--1823",

journal = "Clinical Infectious Diseases",

issn = "1058-4838",

publisher = "Oxford University Press",

number = "12",

}

TY - JOUR

T1 - The Association Between Empirical Antibiotic Treatment and Mortality in Severe Infections Caused by Carbapenem-resistant Gram-negative Bacteria

T2 - A prospective study

AU - AIDA Study Group

AU - Zak-Doron, Yael

AU - Benattar, Yael Dishon

AU - Pfeffer, Iris

AU - Daikos, George L.

AU - Skiada, Anna

AU - Antoniadou, Anastasia

AU - Durante-Mangoni, Emanuele

AU - Andini, Roberto

AU - Cavezza, Giusi

AU - Leibovici, Leonard

AU - Yahav, Dafna

AU - Eliakim-Raz, Noa

AU - Carmeli, Yehuda

AU - Nutman, Amir

AU - Paul, Mical

AU - Dickstein, Yaakov

AU - Bitterman, Roni

AU - Zayyad, Hiba

AU - Koppel, Fidi

AU - Altunin, Sergey

AU - Andria, Nizar

AU - Neuberger, Ami

AU - Stern, Anat

AU - Petersiel, Neta

AU - Raines, Marina

AU - Karban, Amir

AU - Zusman, Oren

AU - Elbaz, Michal

AU - Atamna, Heyam

AU - Daitch, Vered

AU - Babich, Tanya

AU - Adler, Amos

AU - Levi, Inbar

AU - Daikos, George L.

AU - Pavleas, Ioannis

AU - Kotsaki, Antigoni

AU - Iossa, Domenico

AU - Bernardo, Mariano

AU - Bertolino, Lorenzo

AU - Giuffrè, Giuseppe

AU - Giurazza, Roberto

AU - Cuccurullo, Susanna

AU - Galdo, Maria

AU - Murino, Patrizia

AU - Cristinziano, Adriano

AU - Corcione, Antonio

AU - Zampino, Rosa

AU - Pafundi, Pia Clara

AU - Mouton, Johan

AU - Friberg, Lena

PY - 2018

Y1 - 2018

N2 - Background. Empirical colistin should be avoided. We aimed to evaluate the association between covering empirical antibiotics (EAT) and mortality for infections caused by carbapenem-resistant gram-negative bacteria (CRGNB). Methods. This was a secondary analysis of a randomized controlled trial, including adults with bloodstream infections, pneumonia, or urosepsis caused by CRGNB. All patients received EAT followed by covering targeted therapy. The exposure variable was covering EAT in the first 48 hours. The outcome was 28-day mortality. We adjusted the analyses by multivariable regression analysis and propensity score matching. Results. The study included 406 inpatients with severe CRGNB infections, mostly Acinetobacter baumannii (312/406 [77%]). Covering EAT was given to 209 (51.5%) patients, mostly colistin (n = 200). Patients receiving noncovering EAT were older, more frequently unconscious and dependent, carrying catheters, and mechanically ventilated with pneumonia. Mortality was 84 of 197 (42.6%) with noncovering vs 96 of 209 (45.9%) with covering EAT (P = .504). Covering EAT was not associated with survival in the adjusted analysis; rather, there was a weak association with mortality (odds ratio [OR], 1.37; 95% confidence interval [CI], 1.02-1.84). Results were similar for colistin monotherapy and colistin-carbapenem combination EAT. In the propensity score-matched cohort (n = 338) covering antibiotics were not significantly associated with mortality (OR, 1.42; 95% CI, .91-2.22). Similar results were obtained in an analysis of 14-day mortality. Conclusions. Empirical use of colistin before pathogen identification, with or without a carbapenem, was not associated with survival following severe infections caused by CRGNBs, mainly A. baumannii.

AB - Background. Empirical colistin should be avoided. We aimed to evaluate the association between covering empirical antibiotics (EAT) and mortality for infections caused by carbapenem-resistant gram-negative bacteria (CRGNB). Methods. This was a secondary analysis of a randomized controlled trial, including adults with bloodstream infections, pneumonia, or urosepsis caused by CRGNB. All patients received EAT followed by covering targeted therapy. The exposure variable was covering EAT in the first 48 hours. The outcome was 28-day mortality. We adjusted the analyses by multivariable regression analysis and propensity score matching. Results. The study included 406 inpatients with severe CRGNB infections, mostly Acinetobacter baumannii (312/406 [77%]). Covering EAT was given to 209 (51.5%) patients, mostly colistin (n = 200). Patients receiving noncovering EAT were older, more frequently unconscious and dependent, carrying catheters, and mechanically ventilated with pneumonia. Mortality was 84 of 197 (42.6%) with noncovering vs 96 of 209 (45.9%) with covering EAT (P = .504). Covering EAT was not associated with survival in the adjusted analysis; rather, there was a weak association with mortality (odds ratio [OR], 1.37; 95% confidence interval [CI], 1.02-1.84). Results were similar for colistin monotherapy and colistin-carbapenem combination EAT. In the propensity score-matched cohort (n = 338) covering antibiotics were not significantly associated with mortality (OR, 1.42; 95% CI, .91-2.22). Similar results were obtained in an analysis of 14-day mortality. Conclusions. Empirical use of colistin before pathogen identification, with or without a carbapenem, was not associated with survival following severe infections caused by CRGNBs, mainly A. baumannii.

KW - Appropriate empirical antibiotics

KW - Carbapenemase-producing

KW - Colistin

KW - Gram-negative bacteria

KW - Multidrug-resistant bacteria

UR - http://www.scopus.com/inward/record.url?scp=85057530481&partnerID=8YFLogxK

U2 - 10.1093/cid/ciy371

DO - 10.1093/cid/ciy371

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 29718143

AN - SCOPUS:85057530481

SN - 1058-4838

VL - 67

SP - 1815

EP - 1823

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

IS - 12

ER -

The Association Between Empirical Antibiotic Treatment and Mortality in Severe Infections Caused by Carbapenem-resistant Gram-negative Bacteria: A prospective study

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this