Invasive Candida Infections and the Harm From Antibacterial Drugs in Critically Ill Patients. Issue 3 (March 2015)

• Record Type: Journal Article
• Authors: Jensen, Jens-Ulrik S.; Hein, Lars; Lundgren, Bettina; Bestle, Morten H.; Mohr, Thomas; Andersen, Mads H.; Løken, Jesper; Tousi, Hamid; Søe-Jensen, Peter; Lauritsen, Anne Ø.; Strange, Ditte; Petersen, John A.; Thormar, Katrin; Larsen, Kim M.; Drenck, Niels-Erik; Helweg-Larsen, Jannik; Johansen, Maria E.; Reinholdt, Kristian; Møller, Jens K.; Olesen, Bente; Arendrup, Maiken C.; Østergaard, Christian; Cozzi-Lepri, Alessandro; Grarup, Jesper; Lundgren, Jens D.
• Is Part Of: Critical care medicine. Volume 43:Issue 3(2015)
• Publication Date: 2015-03
• Subjects: Critical care medicine -- Periodicals; Soins intensifs -- Périodiques; 616.028
• DOI: 10.1097/CCM.0000000000000746
• Languages: English
• ISSNs: 0090-3493

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Objective:</title> <p>Use of antibiotics in critically ill patients may increase the risk of invasive <italic>Candida</italic> infection. The objective of this study was to determine whether increased exposure to antibiotics is associated with increased prevalence of invasive <italic>Candida</italic> infection.</p> </sec> <sec> <title>Design:</title> <p>Substudy using data from a randomized controlled trial, the Procalcitonin And Survival Study 2006–2010.</p> </sec> <sec> <title>Setting:</title> <p>Nine multidisciplinary ICUs across Denmark.</p> </sec> <sec> <title>Patients:</title> <p>A total of 1, 200 critically ill patients.</p> </sec> <sec> <title>Intervention:</title> <p>Patients were randomly allocated to either a "high exposure" antibiotic therapy (intervention arm, <italic>n</italic> = 604) or a "standard exposure" guided by current guidelines (<italic>n</italic> = 596).</p> </sec> <sec> <title>Measurements and Main Results:</title> <p>Seventy-four patients met the endpoint, "invasive <italic>Candida</italic> infection, " 40 in the high exposure arm and 34 in standard exposure arm (relative risk = 1.2; 95% CI, 0.7–1.8; <italic>p</italic> = 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 <italic>Candida</italic> 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; <italic>p</italic> = 0.05). Ciprofloxacin used at study entry independently predicted invasive <italic>Candida</italic> 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; <italic>p</italic> = 0.002). Patients with any ciprofloxacin-containing antibiotic regimen the first 3 days in the trial had a higher risk of invasive <italic>Candida</italic> infection than did patients on any antibiotic regimen not containing ciprofloxacin (unadjusted hazard ratio = 3.7; 95% CI, 1.6–8.7; <italic>p</italic> = 0.003; adjusted hazard ratio, 3.4; 95% CI, 1.4–8.0; <italic>p</italic> = 0.006).</p> </sec> <sec> <title>Conclusions:</title> <p>High exposure to antibiotics is associated to increased risk of invasive <italic>Candida</italic> infection in medical intensive care patients. Patients with ciprofloxacin-containing regimens had higher risk of invasive <italic>Candida</italic> infection. Other antibiotics, such as meropenem, piperacillin/tazobactam, and cefuroxime, were not associated with such a risk.</p> </sec> </abstract>