INTRODUCTION: Intra-abdominal infections represent the second most frequently acquired infection in the intensive care unit (ICU), with mortality rates ranging from 20% to 50%. Candida spp. may be responsible for up to 10-30% of cases. This study assesses risk factors for development of intra-abdominal candidiasis (IAC) among patients admitted to ICU. METHODS: We performed a case-control study in 26 European ICUs during the period January 2015-December 2016. Patients at least 18 years old who developed an episode of microbiologically documented IAC during their stay in the ICU (at least 48 h after admission) served as the case cohort. The control group consisted of adult patients who did not develop episodes of IAC during ICU admission. Matching was performed at a ratio of 1:1 according to time at risk (i.e. controls had to have at least the same length of ICU stay as their matched cases prior to IAC onset), ICU ward and period of study. RESULTS: During the study period, 101 case patients with a diagnosis of IAC were included in the study. On univariate analysis, severe hepatic failure, prior receipt of antibiotics, prior receipt of parenteral nutrition, abdominal drain, prior bacterial infection, anastomotic leakage, recurrent gastrointestinal perforation, prior receipt of antifungal drugs and higher median number of abdominal surgical interventions were associated with IAC development. On multivariate analysis, recurrent gastrointestinal perforation (OR 13.90; 95% CI 2.65-72.82, p = 0.002), anastomotic leakage (OR 6.61; 95% CI 1.98-21.99, p = 0.002), abdominal drain (OR 6.58; 95% CI 1.73-25.06, p = 0.006), prior receipt of antifungal drugs (OR 4.26; 95% CI 1.04-17.46, p = 0.04) or antibiotics (OR 3.78; 95% CI 1.32-10.52, p = 0.01) were independently associated with IAC. CONCLUSIONS: Gastrointestinal perforation, anastomotic leakage, abdominal drain and prior receipt of antifungals or antibiotics may help to identify critically ill patients with higher probability of developing IAC. Prospective studies are needed to identify which patients will benefit from early antifungal treatment.

1st Division of Infectious Diseases Cotugno Hospital AORN dei Colli Naples Italy

A Li Sa Liguria Health Authority Genoa Italy

APHP; Medical and Infectious Diseases ICU Bichat Hospital 75018 Paris France

Attikon General University Hospital Athens Greece

C H Vila Nova de Gaia Espinho Vila Nova de Gaia Portugal

Centre Hospitalier de Versailles Versailles France

Centro de Investigación Biomedica En Red Enfermedades Respiratorias Instituto de Salud Carlos 3 Madrid Spain

Clinica Malattie Infettive Ospedale Policlinico San Martino IRCCS L go R Benzi 10 16132 Genoa Italy

Clinical Microbiology and ATB Centre Institute of Medical Biochemistry and Laboratory Diagnostics General University Hospital Prague Czech Republic

Département d'Anesthésie Réanimation CHU Bichat Claude Bernard HUPNVS APHP Paris France

Department of Anesthesia and Intensive Care University Hospital of Modena Modena Italy

Department of Anesthesia Intensive Care and Emergency Policlinico Paolo Giaccone Palermo Italy

Department of Anesthesiology and Intensive Care Medicine Heidelberg University Hospital Heidelberg Germany

Department of Critical Care University Hospital Attikon Attikon Medical School Νational and Kapodistrian University of Athens Athens Greece

Department of Diagnostics and Public Health Infectious Disease Unit University of Verona Verona Italy

Department of Emergency and Intensive Care Medicine Centro Hospitalar Universitário São João Faculdade de Medicina da Universidade Do Porto E Grupo de Infecção E Sépsis Porto Portugal

Department of General Internal Medicine Medical Intensive Care Unit University Hospitals Leuven Leuven UK

Department of Health Sciences University of Genoa Genoa Italy

Department of Infectious Diseases Manchester University NHS Foundation Trust Wythenshawe Hospital Manchester UK

Department of Intensive Care Anesthesiology and Emercency Medicine Fondazione Policlinico Universitario Agostino Gemelli IRCCS Rome Italy

Department of Intensive Care Medicine Multidisciplinary Intensive Care Research Organization St James's Hospital Dublin Ireland

Department of Intensive Care Medicine University Hospital Brussels 1090 Jette Belgium

Department of Intensive Care University Medical Center Groningen Groningen the Netherlands

Department of Laboratory Medicine and National Reference Centre for Mycosis University Hospitals of Leuven Leuven Belgium

Department of Medical Microbiology Medical Faculty of Palackeho University Olomouc Czech Republic

Department of Medical Sciences Infectious Diseases University of Turin Turin Italy

Department of Microbiology and Immunology and Transplantation KU Leuven Leuven Belgium

Department of Public Health and Infectious Diseases Sapienza University of Rome Rome Italy

Department of Surgical Oncological and Oral Science University of Palermo Palermo Italy

Faculty of Biology Medicine and Health Division of Evolution Infection and Genomics University of Manchester Manchester UK

Faculty of Medicine and Pharmacy Vrije Unversiteit Brussel 1090 Brussels Belgium

G Gennimatas General Hospital of Thessaloniki Thessaloniki Greece

German Centre for Infection Research Partner Site Bonn Cologne Cologne Germany

Healthcare Planning Unit Ospedale Policlinico San Martino IRCCS Genoa Italy

Infectious Diseases Clinic Santa Maria della Misericordia University Hospital of Udine ASUFC Udine Italy

Infectious Diseases Department Azienda Sanitaria Universitaria Integrata Di Trieste Trieste Italy

Infectious Diseases Unit Department of Medical and Surgical Science S Orsola Malpighi Hospital University of Bologna Bologna Italy

Institute for Biomedical Research and Innovation Palermo Italy

Institute of Infectious Diseases Fondazione Policlinico Universitario A Gemelli IRCCS Università Cattolica del Sacro Cuore Rome Italy

Istituto di Anestesiologia e Rianimazione Università Cattolica del Sacro Cuore Milan Italy

Medical Direction Santa Corona Hospital ASL 2 Regional Health System of Liguria Pietra Ligure Italy

Ospedale Civile SS Giovanni e Paolo Venice Italy

Pneumology Department Respiratory Institute Hospital Clinic of Barcelona Institut d'Investigacions Biomèdiques August Pi 1 Sunyer University of Barcelona Barcelona Spain

Pole Anesthésie Réanimation SAMU Rouen University Hospital Rouen France

Radboud Umc Center for Infectious Diseases Radboud University Medical Center Nijmegen The Netherlands

Service de Réanimation Et USC Médico Chirurgicale AP HP Hôpitaux Universitaires de L'Est Parisien Pôle TVAR Hôpital Tenon Paris France

Servicio de Cuidados Críticos y Urgencias Hospital San Juan de Dios del Aljarafe Bormujos Seville Spain

UMR 1137 IAME Team 5 DeSCID Decision Sciences in Infectious Diseases Control and Care Inserm Univ Paris Diderot Sorbonne Paris Cité Paris France

Universitair Ziekenhuis Brussel VUB University Brussels Belgium

Université de Paris INSERM UMR 1152 PHERE Paris France

Université Paris Diderot Hopital Bichat Réanimation Medicale et Des Maladies Infectieuses Paris France

University of Cologne Faculty of Medicine and University Hospital Cologne Chair Translational Research Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases Cologne Germany

University of Cologne Faculty of Medicine and University Hospital Cologne Clinical Trials Centre Cologne Cologne Germany

University of Cologne Faculty of Medicine and University Hospital Cologne Department 1 of Internal Medicine Excellence Center for Medical Mycology Cologne Germany

Zobrazit více v PubMed

De Waele J, Lipman J, Sakr Y, et al. Abdominal infections in the intensive care unit: characteristics, treatment and determinants of outcome. BMC Infect Dis. 2014;14:420. doi: 10.1186/1471-2334-14-420. PubMed DOI PMC

Vincent JL, Rello J, Marshall J, et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009;302(21):2323–2329. doi: 10.1001/jama.2009.1754. PubMed DOI

Finfer S, Bellomo R, Lipman J, French C, Dobb G, Myburgh J. Adult-population incidence of severe sepsis in Australian and New Zealand intensive care units. Intensive Care Med. 2004;30(4):589–596. doi: 10.1007/s00134-004-2157-0. PubMed DOI

Montravers P, Mira JP, Gangneux JP, Leroy O, Lortholary O, AmarCand Study Group A multicentre study of antifungal strategies and outcome of Candida spp. peritonitis in intensive-care units. Clin Microbiol Infect. 2011;17(7):1061–7. doi: 10.1111/j.1469-0691.2010.03360.x. PubMed DOI

Blot S, Antonelli M, Arvaniti K, et al. Epidemiology of intra-abdominal infection and sepsis in critically ill patients: "AbSeS", a multinational observational cohort study and ESICM Trials Group Project. Intensive Care Med. 2019;45(12):1703–1717. doi: 10.1007/s00134-019-05819-3. PubMed DOI PMC

Augustin P, Kermarrec N, Muller-Serieys C, et al. Risk factors for multidrug resistant bacteria and optimization of empirical antibiotic therapy in postoperative peritonitis. Crit Care. 2010;14(1):R20. doi: 10.1186/cc8877. PubMed DOI PMC

Bassetti M, Castaldo N, Cattelan A, et al. Ceftolozane/tazobactam for the treatment of serious Pseudomonas aeruginosa infections: a multicentre nationwide clinical experience. Int J Antimicrob Agents. 2019;53(4):408–415. doi: 10.1016/j.ijantimicag.2018.11.001. PubMed DOI

Sartelli M, Catena F, Ansaloni L, et al. Complicated intra-abdominal infections worldwide: the definitive data of the CIAOW Study. World J Emerg Surg. 2014;9:37. doi: 10.1186/1749-7922-9-37. PubMed DOI PMC

de Ruiter J, Weel J, Manusama E, Kingma WP, van der Voort PH. The epidemiology of intra-abdominal flora in critically ill patients with secondary and tertiary abdominal sepsis. Infection. 2009;37(6):522–527. doi: 10.1007/s15010-009-8249-6. PubMed DOI

Sandven P, Qvist H, Skovlund E, Giercksky KE, NORGAS Group, the Norwegian Yeast Study Group. Significance of Candida recovered from intraoperative specimens in patients with intra-abdominal perforations. Crit Care Med. 2002;30(3):541–7. 10.1097/00003246-200203000-00008. PubMed

Montravers P, Dupont H, Gauzit R, et al. Candida as a risk factor for mortality in peritonitis. Crit Care Med. 2006;34(3):646–652. doi: 10.1097/01.CCM.0000201889.39443.D2. PubMed DOI

Klingspor L, Tortorano AM, Peman J, et al. Invasive Candida infections in surgical patients in intensive care units: a prospective, multicentre survey initiated by the European Confederation of Medical Mycology (ECMM) (2006–2008). Clin Microbiol Infect. 2015;21(1):87e1–e10. 10.1016/j.cmi.2014.08.011. PubMed

Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the infectious diseases society of America. Clin Infect Dis. 2016;62(4):e1–50. doi: 10.1093/cid/civ933. PubMed DOI PMC

Chou EH, Mann S, Hsu TC, et al. Incidence, trends, and outcomes of infection sites among hospitalizations of sepsis: a nationwide study. PLoS ONE. 2020;15(1):e0227752. doi: 10.1371/journal.pone.0227752. PubMed DOI PMC

Dupont H, Bourichon A, Paugam-Burtz C, Mantz J, Desmonts JM. Can yeast isolation in peritoneal fluid be predicted in intensive care unit patients with peritonitis? Crit Care Med. 2003;31(3):752–757. doi: 10.1097/01.CCM.0000053525.49267.77. PubMed DOI

Dupont H, Guilbart M, Ntouba A, et al. Can yeast isolation be predicted in complicated secondary non-postoperative intra-abdominal infections? Crit Care. 2015;19:60. doi: 10.1186/s13054-015-0790-3. PubMed DOI PMC

Xia R, Wang D. Risk factors of invasive candidiasis in critical cancer patients after various gastrointestinal surgeries: a 4-year retrospective study. Medicine (Baltimore) 2019;98(44):e17704. doi: 10.1097/MD.0000000000017704. PubMed DOI PMC

Parkins MD, Sabuda DM, Elsayed S, Laupland KB. Adequacy of empirical antifungal therapy and effect on outcome among patients with invasive Candida species infections. J Antimicrob Chemother. 2007;60(3):613–618. doi: 10.1093/jac/dkm212. PubMed DOI

Valerio M, Rodriguez-Gonzalez CG, Munoz P, et al. Evaluation of antifungal use in a tertiary care institution: antifungal stewardship urgently needed. J Antimicrob Chemother. 2014;69(7):1993–1999. doi: 10.1093/jac/dku053. PubMed DOI

Bassetti M, Righi E, Ansaldi F, et al. A multicenter multinational study of abdominal candidiasis: epidemiology, outcomes and predictors of mortality. Intensive Care Med. 2015;41(9):1601–1610. doi: 10.1007/s00134-015-3866-2. PubMed DOI

Yan T, Li SL, Ou HL, Zhu SN, Huang L, Wang DX. Appropriate source control and antifungal therapy are associated with improved survival in critically ill surgical patients with intra-abdominal candidiasis. World J Surg. 2020 doi: 10.1007/s00268-020-05380-x. PubMed DOI

Bassetti M, Giacobbe DR, Vena A, et al. Incidence and outcome of invasive candidiasis in intensive care units (ICUs) in Europe: results of the EUCANDICU project. Crit Care. 2019;23(1):219. doi: 10.1186/s13054-019-2497-3. PubMed DOI PMC

Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol. 1994;47(11):1245–1251. doi: 10.1016/0895-4356(94)90129-5. PubMed DOI

Bassetti M, Marchetti M, Chakrabarti A, et al. A research agenda on the management of intra-abdominal candidiasis: results from a consensus of multinational experts. Intensive Care Med. 2013;39(12):2092–2106. doi: 10.1007/s00134-013-3109-3. PubMed DOI

Hosmer DW LS, Sturdivant RX. Applied logistic regression. 3rd ed. Hoboken: Wiley.

Sganga G, Wang M, Capparella MR, et al. Evaluation of anidulafungin in the treatment of intra-abdominal candidiasis: a pooled analysis of patient-level data from 5 prospective studies. Eur J Clin Microbiol Infect Dis. 2019;38(10):1849–1856. doi: 10.1007/s10096-019-03617-9. PubMed DOI PMC

Bassetti M, Peghin M, Carnelutti A, et al. Clinical characteristics and predictors of mortality in cirrhotic patients with candidemia and intra-abdominal candidiasis: a multicenter study. Intensive Care Med. 2017;43(4):509–518. doi: 10.1007/s00134-017-4717-0. PubMed DOI

Lagunes L, Rey-Perez A. What s new in intraabdominal candidiasis in critically ill patients, a review. Hosp Pract (1995). 2019;47(4):171–6. 10.1080/21548331.2019.1677032. PubMed

Peman J, Aguilar G, Valia JC, et al. Javea consensus guidelines for the treatment of Candida peritonitis and other intra-abdominal fungal infections in non-neutropenic critically ill adult patients. Rev Iberoam Micol. 2017;34(3):130–142. doi: 10.1016/j.riam.2016.12.001. PubMed DOI

Munoz P, Agnelli C, Guinea J, et al. Is biofilm production a prognostic marker in adults with candidaemia? Clin Microbiol Infect. 2018;24(9):1010–1015. doi: 10.1016/j.cmi.2018.01.022. PubMed DOI

Munoz P, Vena A, Valerio M, et al. Risk factors for late recurrent candidaemia. A retrospective matched case-control study. Clin Microbiol Infect. 2016;22(3):277e11–20. 10.1016/j.cmi.2015.10.023. PubMed

Jensen JU, Hein L, Lundgren B, et al. 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. Crit Care Med. 2015;43(3):594–602. doi: 10.1097/CCM.0000000000000746. PubMed DOI

Zaoutis TE, Prasad PA, Localio AR, et al. Risk factors and predictors for candidemia in pediatric intensive care unit patients: implications for prevention. Clin Infect Dis. 2010;51(5):e38–45. doi: 10.1086/655698. PubMed DOI PMC

Dudoignon E, Alanio A, Anstey J, et al. Outcome and potentially modifiable risk factors for candidemia in critically ill burns patients: a matched cohort study. Mycoses. 2019;62(3):237–246. doi: 10.1111/myc.12872. PubMed DOI

Rashid MU, Weintraub A, Nord CE. Effect of new antimicrobial agents on the ecological balance of human microflora. Anaerobe. 2012;18(2):249–253. doi: 10.1016/j.anaerobe.2011.11.005. PubMed DOI

Mayer FL, Wilson D, Hube B. Candida albicans pathogenicity mechanisms. Virulence. 2013;4(2):119–128. doi: 10.4161/viru.22913. PubMed DOI PMC

Cole GT, Halawa AA, Anaissie EJ. The role of the gastrointestinal tract in hematogenous candidiasis: from the laboratory to the bedside. Clin Infect Dis. 1996;22(Suppl 2):S73–88. doi: 10.1093/clinids/22.supplement_2.s73. PubMed DOI

Eggimann P, Francioli P, Bille J, et al. Fluconazole prophylaxis prevents intra-abdominal candidiasis in high-risk surgical patients. Crit Care Med. 1999;27(6):1066–1072. doi: 10.1097/00003246-199906000-00019. PubMed DOI

Senn L, Eggimann P, Ksontini R, et al. Caspofungin for prevention of intra-abdominal candidiasis in high-risk surgical patients. Intensive Care Med. 2009;35(5):903–908. doi: 10.1007/s00134-009-1405-8. PubMed DOI

Ostrosky-Zeichner L, Shoham S, Vazquez J, et al. MSG-01: A randomized, double-blind, placebo-controlled trial of caspofungin prophylaxis followed by preemptive therapy for invasive candidiasis in high-risk adults in the critical care setting. Clin Infect Dis. 2014;58(9):1219–1226. doi: 10.1093/cid/ciu074. PubMed DOI

Vena A, Bouza E, Valerio M, et al. Candidemia in non-ICU surgical wards: comparison with medical wards. PLoS ONE. 2017;12(10):e0185339. doi: 10.1371/journal.pone.0185339. PubMed DOI PMC

Molina J, Penalva G, Gil-Navarro MV, et al. Long-term impact of an educational antimicrobial stewardship program on hospital-acquired candidemia and multidrug-resistant bloodstream infections: a quasi-experimental study of interrupted time-series analysis. Clin Infect Dis. 2017;65(12):1992–1999. doi: 10.1093/cid/cix692. PubMed DOI

Martin-Gutierrez G, Penalva G, Ruiz-Perez de Pipaon M, et al. Efficacy and safety of a comprehensive educational antimicrobial stewardship program focused on antifungal use. J Infect. 2020. 10.1016/j.jinf.2020.01.002. PubMed

Dimopoulos G, Matthaiou DK, Righi E, Merelli M, Bassetti M. Elderly versus non-elderly patients with intra-abdominal candidiasis in the ICU. Minerva Anestesiol. 2017;83(11):1126–36. 10.23736/S0375-9393.17.11528-2. PubMed

Vena A, Bouza E, Corisco R, et al. Efficacy of a "checklist" intervention bundle on the clinical outcome of patients with candida bloodstream infections: a quasi-experimental pre-post study. Infect Dis Ther. 2020 doi: 10.1007/s40121-020-00281-x. PubMed DOI PMC

Cardozo C, Cuervo G, Salavert M, et al. An evidence-based bundle improves the quality of care and outcomes of patients with candidaemia. J Antimicrob Chemother. 2019 doi: 10.1093/jac/dkz491. PubMed DOI

Vergidis P, Clancy CJ, Shields RK, et al. Intra-abdominal candidiasis: the importance of early source control and antifungal treatment. PLoS One. 2016;11(4):e0153247. doi: 10.1371/journal.pone.0153247. PubMed DOI PMC

Intra-abdominal infections survival guide: a position statement by the Global Alliance For Infections In Surgery