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Invasive Candida Infections and the Harm From Antibacterial Drugs in Critically Ill Patients: Data From a Randomized, Controlled Trial to Determine the Role of Ciprofloxacin, Piperacillin-Tazobactam, Meropenem, and Cefuroxime

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@article{6ee8480406304d0cbcde759c1704adeb,
title = "Invasive Candida Infections and the Harm From Antibacterial Drugs in Critically Ill Patients: Data From a Randomized, Controlled Trial to Determine the Role of Ciprofloxacin, Piperacillin-Tazobactam, Meropenem, and Cefuroxime",
abstract = "OBJECTIVE:: Use of antibiotics in critically ill patients may increase the risk of invasive Candida infection. The objective of this study was to determine whether increased exposure to antibiotics is associated with increased prevalence of invasive Candida infection.DESIGN:: Substudy using data from a randomized controlled trial, the Procalcitonin And Survival Study 2006-2010.SETTING:: Nine multidisciplinary ICUs across Denmark.PATIENTS:: A total of 1,200 critically ill patients.INTERVENTION:: Patients were randomly allocated to either a {"}high exposure{"} antibiotic therapy (intervention arm, n = 604) or a {"}standard exposure{"} guided by current guidelines (n = 596).MEASUREMENTS AND MAIN RESULTS:: Seventy-four patients met the endpoint, {"}invasive Candida infection,{"} 40 in the high exposure arm and 34 in standard exposure arm (relative risk = 1.2; 95{\%} CI, 0.7-1.8; p = 0.52). Among medical patients in the high exposure arm, the use of ciprofloxacin and piperacillin/tazobactam was 51{\%} and 75{\%} higher than in the standard exposure arm; no difference in antibiotic exposure was observed between the randomized arms in surgical patients. Among medical intensive care patients, invasive Candida infection was more frequent in the high exposure arm (6.2{\%}; 27/437) than in standard exposure arm (3.3{\%}; 14/424) (hazard ratio = 1.9; 95{\%} CI, 1.0-3.6; p = 0.05). Ciprofloxacin used at study entry independently predicted invasive Candida infection (adjusted hazard ratio = 2.1 [1.1-4.1]); the risk gradually increased with duration of ciprofloxacin therapy: six of 384 in patients not exposed (1.6{\%}), eight of 212 (3.8{\%}) when used for 1-2 days (hazard ratio = 2.5; 95{\%} CI, 0.9-7.3), and 31 of 493 (6.3{\%}) when used for 3 days (hazard ratio = 3.8; 95{\%} CI, 1.6-9.3; p = 0.002). Patients with any ciprofloxacin-containing antibiotic regimen the first 3 days in the trial had a higher risk of invasive Candida infection than did patients on any antibiotic regimen not containing ciprofloxacin (unadjusted hazard ratio = 3.7; 95{\%} CI, 1.6-8.7; p = 0.003; adjusted hazard ratio, 3.4; 95{\%} CI, 1.4-8.0; p = 0.006).CONCLUSIONS:: High exposure to antibiotics is associated to increased risk of invasive Candida infection in medical intensive care patients. Patients with ciprofloxacin-containing regimens had higher risk of invasive Candida infection. Other antibiotics, such as meropenem, piperacillin/tazobactam, and cefuroxime, were not associated with such a risk.",
keywords = "APACHE, Age Factors, Aged, Anti-Bacterial Agents, Candidiasis, Invasive, Cefuroxime, Ciprofloxacin, Critical Illness, Denmark, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Humans, Intensive Care Units, Male, Middle Aged, Penicillanic Acid, Piperacillin, Single-Blind Method, Thienamycins",
author = "Jensen, {Jens Ulrik} and Lars Hein and Bettina Lundgren and Bestle, {Morten H} and Thomas Mohr and Andersen, {Mads H} and Jesper L{\o}ken and Hamid Tousi and Peter S{\o}e-Jensen and Lauritsen, {Anne O} and Strange, {Ditte Gry} and Petersen, {John A} and Katrin Thormar and Larsen, {Kim M} and Niels-Erik Drenck and Jannik Helweg-Larsen and Johansen, {Maria E} and Kristian Reinholdt and M{\o}ller, {Jens K} and Bente Olesen and Arendrup, {Maiken C} and Andersen, {Christian {\O}stergaard} and Alessandro Cozzi-Lepri and Jesper Grarup and Lundgren, {Jens D} and {for the Procalcitonin And Survival Study Group} and Arash Afshari",
year = "2015",
doi = "10.1097/CCM.0000000000000746",
language = "English",
volume = "43",
pages = "594--602",
journal = "Critical Care Medicine",
issn = "0090-3493",
publisher = "Lippincott Williams & Wilkins",
number = "3",

}

RIS

TY - JOUR

T1 - Invasive Candida Infections and the Harm From Antibacterial Drugs in Critically Ill Patients

T2 - Data From a Randomized, Controlled Trial to Determine the Role of Ciprofloxacin, Piperacillin-Tazobactam, Meropenem, and Cefuroxime

AU - Jensen, Jens Ulrik

AU - Hein, Lars

AU - Lundgren, Bettina

AU - Bestle, Morten H

AU - Mohr, Thomas

AU - Andersen, Mads H

AU - Løken, Jesper

AU - Tousi, Hamid

AU - Søe-Jensen, Peter

AU - Lauritsen, Anne O

AU - Strange, Ditte Gry

AU - Petersen, John A

AU - Thormar, Katrin

AU - Larsen, Kim M

AU - Drenck, Niels-Erik

AU - Helweg-Larsen, Jannik

AU - Johansen, Maria E

AU - Reinholdt, Kristian

AU - Møller, Jens K

AU - Olesen, Bente

AU - Arendrup, Maiken C

AU - Andersen, Christian Østergaard

AU - Cozzi-Lepri, Alessandro

AU - Grarup, Jesper

AU - Lundgren, Jens D

AU - for the Procalcitonin And Survival Study Group

AU - Afshari, Arash

PY - 2015

Y1 - 2015

N2 - OBJECTIVE:: Use of antibiotics in critically ill patients may increase the risk of invasive Candida infection. The objective of this study was to determine whether increased exposure to antibiotics is associated with increased prevalence of invasive Candida infection.DESIGN:: Substudy using data from a randomized controlled trial, the Procalcitonin And Survival Study 2006-2010.SETTING:: Nine multidisciplinary ICUs across Denmark.PATIENTS:: A total of 1,200 critically ill patients.INTERVENTION:: Patients were randomly allocated to either a "high exposure" antibiotic therapy (intervention arm, n = 604) or a "standard exposure" guided by current guidelines (n = 596).MEASUREMENTS AND MAIN RESULTS:: Seventy-four patients met the endpoint, "invasive Candida infection," 40 in the high exposure arm and 34 in standard exposure arm (relative risk = 1.2; 95% CI, 0.7-1.8; p = 0.52). Among medical patients in the high exposure arm, the use of ciprofloxacin and piperacillin/tazobactam was 51% and 75% higher than in the standard exposure arm; no difference in antibiotic exposure was observed between the randomized arms in surgical patients. Among medical intensive care patients, invasive Candida infection was more frequent in the high exposure arm (6.2%; 27/437) than in standard exposure arm (3.3%; 14/424) (hazard ratio = 1.9; 95% CI, 1.0-3.6; p = 0.05). Ciprofloxacin used at study entry independently predicted invasive Candida infection (adjusted hazard ratio = 2.1 [1.1-4.1]); the risk gradually increased with duration of ciprofloxacin therapy: six of 384 in patients not exposed (1.6%), eight of 212 (3.8%) when used for 1-2 days (hazard ratio = 2.5; 95% CI, 0.9-7.3), and 31 of 493 (6.3%) when used for 3 days (hazard ratio = 3.8; 95% CI, 1.6-9.3; p = 0.002). Patients with any ciprofloxacin-containing antibiotic regimen the first 3 days in the trial had a higher risk of invasive Candida infection than did patients on any antibiotic regimen not containing ciprofloxacin (unadjusted hazard ratio = 3.7; 95% CI, 1.6-8.7; p = 0.003; adjusted hazard ratio, 3.4; 95% CI, 1.4-8.0; p = 0.006).CONCLUSIONS:: High exposure to antibiotics is associated to increased risk of invasive Candida infection in medical intensive care patients. Patients with ciprofloxacin-containing regimens had higher risk of invasive Candida infection. Other antibiotics, such as meropenem, piperacillin/tazobactam, and cefuroxime, were not associated with such a risk.

AB - OBJECTIVE:: Use of antibiotics in critically ill patients may increase the risk of invasive Candida infection. The objective of this study was to determine whether increased exposure to antibiotics is associated with increased prevalence of invasive Candida infection.DESIGN:: Substudy using data from a randomized controlled trial, the Procalcitonin And Survival Study 2006-2010.SETTING:: Nine multidisciplinary ICUs across Denmark.PATIENTS:: A total of 1,200 critically ill patients.INTERVENTION:: Patients were randomly allocated to either a "high exposure" antibiotic therapy (intervention arm, n = 604) or a "standard exposure" guided by current guidelines (n = 596).MEASUREMENTS AND MAIN RESULTS:: Seventy-four patients met the endpoint, "invasive Candida infection," 40 in the high exposure arm and 34 in standard exposure arm (relative risk = 1.2; 95% CI, 0.7-1.8; p = 0.52). Among medical patients in the high exposure arm, the use of ciprofloxacin and piperacillin/tazobactam was 51% and 75% higher than in the standard exposure arm; no difference in antibiotic exposure was observed between the randomized arms in surgical patients. Among medical intensive care patients, invasive Candida infection was more frequent in the high exposure arm (6.2%; 27/437) than in standard exposure arm (3.3%; 14/424) (hazard ratio = 1.9; 95% CI, 1.0-3.6; p = 0.05). Ciprofloxacin used at study entry independently predicted invasive Candida infection (adjusted hazard ratio = 2.1 [1.1-4.1]); the risk gradually increased with duration of ciprofloxacin therapy: six of 384 in patients not exposed (1.6%), eight of 212 (3.8%) when used for 1-2 days (hazard ratio = 2.5; 95% CI, 0.9-7.3), and 31 of 493 (6.3%) when used for 3 days (hazard ratio = 3.8; 95% CI, 1.6-9.3; p = 0.002). Patients with any ciprofloxacin-containing antibiotic regimen the first 3 days in the trial had a higher risk of invasive Candida infection than did patients on any antibiotic regimen not containing ciprofloxacin (unadjusted hazard ratio = 3.7; 95% CI, 1.6-8.7; p = 0.003; adjusted hazard ratio, 3.4; 95% CI, 1.4-8.0; p = 0.006).CONCLUSIONS:: High exposure to antibiotics is associated to increased risk of invasive Candida infection in medical intensive care patients. Patients with ciprofloxacin-containing regimens had higher risk of invasive Candida infection. Other antibiotics, such as meropenem, piperacillin/tazobactam, and cefuroxime, were not associated with such a risk.

KW - APACHE

KW - Age Factors

KW - Aged

KW - Anti-Bacterial Agents

KW - Candidiasis, Invasive

KW - Cefuroxime

KW - Ciprofloxacin

KW - Critical Illness

KW - Denmark

KW - Dose-Response Relationship, Drug

KW - Drug Administration Schedule

KW - Female

KW - Humans

KW - Intensive Care Units

KW - Male

KW - Middle Aged

KW - Penicillanic Acid

KW - Piperacillin

KW - Single-Blind Method

KW - Thienamycins

U2 - 10.1097/CCM.0000000000000746

DO - 10.1097/CCM.0000000000000746

M3 - Journal article

VL - 43

SP - 594

EP - 602

JO - Critical Care Medicine

JF - Critical Care Medicine

SN - 0090-3493

IS - 3

ER -

ID: 44941784