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
C2 - 25493970
SN - 0090-3493
VL - 43
SP - 594
EP - 602
JO - Critical Care Medicine
JF - Critical Care Medicine
IS - 3
ER -