Intensive Care Med (2014) 40:1429–1448 DOI 10.1007/s00134-014-3355-z MY PAPER 20 YEARS LATER Philippe Eggimann Candida colonization index and subsequent Didier Pittet infection in critically ill surgical patients: 20 years later Received: 20 March 2014 Abstract Introduction: For dec- Results: The recognition of specific Accepted: 23 May 2014 ades, clinicians dealing with characteristics among underlying Published online: 17 June 2014 immunocompromised and critically ill conditions, such as neutropenia, solid Ó The Author(s) 2014. This article is patients have perceived a link organ transplantation, and surgical published with open access at and nonsurgical critical illness, has Springerlink.com between Candida colonization and subsequent infection. However, the enabled the description of distinct pathophysiological progression from epidemiological patterns in the colonization to infection was clearly development of invasive candidiasis. established only through the formal Conclusions: Despite its limited description of the colonization index bedside practicality and before con- (CI) in critically ill patients. Unfortu- firmation of potentially more accurate nately, the literature reflects intense predictors, such as specific biomark- confusion about the pathophysiology ers, the CI remains an important way P. Eggimann of invasive candidiasis and specific to characterize the dynamics of colo- Adult Critical Care Medicine and Burn associated risk factors. Meth- nization, which increases early in Unit, Centre Hospitalier Universitaire patients who develop invasive Vaudois (CHUV), Lausanne, Switzerland ods: We review the contribution of e-mail: [email protected] the CI in the field of Candida infection candidiasis. and its development in the 20 years D. Pittet ()) following its original description in Keywords Candida albicans Á Faculty of Medicine, Infection Control 1994. The development of the CI Candidemia Á Invasive candidiasis Á Program and WHO Collaborating Center on enabled an improved understanding of Colonization Á Colonization index Á Patient Safety, University of Geneva the pathogenesis of invasive candidi- Empirical treatment Á Hospitals (HUG), Rue Gabrielle-Perret- Nosocomial infections Gentil 4, 1205 Geneva, Switzerland asis and the use of targeted empirical e-mail: [email protected] antifungal therapy in subgroups of Tel.: ?41 22 372 9844 patients at increased risk for infection. Introduction Early empirical treatment of severe candidiasis has improved survival, but is responsible for the overuse of Candida spp. colonization occurs in up to 80 % of critically antifungals [12–14]. This overuse not only contributes to ill patients after 1 week in intensive care [1–3]. This very high a huge financial burden, but has also promoted a shift to proportion contrasts strongly with the low rate of invasive Candida species with reduced susceptibility to antifungal candidiasis in less than 10 % of them [4, 5]. Despite recent agents [15, 16]. Unfortunately, recent guidelines resulting advances in microbiological techniques, early diagnosis of from expert consensus failed to provide high-level rec- invasive candidiasis remains problematic and microbiologi- ommendations about empirical antifungal treatment or to cal documentation often occurs late in the course of infection clarify the nature of such treatment strategies [8, 17, 18]. [6–8]. This explains its high crude and attributable mortality, Despite limited levels of evidence, empirical treatment i.e., in the range reported for septic shock [9–11]. currently relies on the positive predictive value of risk 1430 assessment strategies, such as the colonization index (CI), Solid organ transplant recipients Candida score, and predictive rules based on combina- tions of risk factors [19–21]. Anti-rejection therapy increases the risk for Aspergillus Improved knowledge of the pathophysiological spec- and other filamentous fungal infections in solid organ ificities of invasive candidiasis should promote better use transplant recipients, except among those receiving small of clinical tools in the evaluation of patients who could bowel and liver transplants, in whom additional specific truly benefit from early antifungal therapy [22]. In con- surgical factors further modify the epidemiology of dis- trast to most bacterial infections, invasive candidiasis is ease [34, 35]. Prolonged and intense impairment of characterized by a 7–10-day delay between exposure to cellular T cell-mediated immune response may contribute risk factors and infection development [23–25]. This time to the high proportion of cutaneous and mucosal candi- window provides a unique opportunity for the imple- diasis [36]. This factor has justified the use of systematic mentation of a structured approach to the rigorous antifungal prophylaxis in these patients in whom, as selection of patients likely to benefit from early empirical among neutropenic patients and bone marrow transplant antifungal treatment [19, 26]. recipients, breakthrough Candida spp. infection develops The CI is the most widely studied clinical tool for the with strains resistant to the agent used [18]. early risk assessment of invasive candidiasis among at- risk patients. The primary objective of this review is to highlight its role in this setting. The use of colonization Nonsurgical critically ill patients dynamics, as assessed by the CI, for the early detection of patients likely to benefit from early antifungal treatment is In nonsurgical critically ill patients, the continuous and also explored in comparison with other tools currently prolonged support of failing organs and the selective available in clinical practice. Finally, we also propose a pressure of broad-spectrum antibiotics constitute key risk research agenda for the next decade. factors for invasive candidiasis. Support of organ failure requires the use of numerous devices, such as intravas- cular catheters, endotracheal tubes, naso- and oro-gastric Pathophysiology of invasive candidiasis tubes, and Foley catheters, which are frequently colonized by Candida spp. as a result of the high affinity of their biofilm [1]. These specificities may explain progressive Nosocomial exogenous transmission of Candida has been colonization in a high proportion of patients after pro- well described [27]. Of note, both endogenous and longed stay in the intensive care unit (ICU) [6, 37, 38]. exogenous colonization can co-exist in the clinical setting They may also explain a higher proportion of catheter- [1]. However, carefully designed studies using genotyping related infections in the absence of severe immune of Candida strains confirmed that endogenous coloniza- impairment [39]. In this context, the role of exposure to tion is responsible for the large majority of severe steroids largely used to improve the speed of recovery candidiasis [28, 29]. from circulatory failure remains to be determined. The epidemiology of invasive candidiasis has some Limited data are available on the usefulness of pro- important differences in immunocompromised and criti- phylaxis and recent guidelines did not include cally ill patients (Fig. 1). recommendation for antifungal prophylaxis in nonsurgi- cal critically ill patients [17, 18, 40]. Neutropenic and bone marrow transplant recipients Neutrophils are essential in the defense against invasive Critically ill patients recovering from abdominal candidiasis [30]. Their prolonged absence in neutropenic surgery patients or those with functional impairment after bone marrow transplantation, combined with the selective Additional factors should be considered in patients after pressure of frequent and repetitive exposure to antibacte- abdominal surgery [41]. Any perforation or opening of the rial agents, plays a major role in the development of digestive tract results in contamination of the peritoneum invasive candidiasis in these patients. A high density of by bowel flora. In most cases, surgical cleaning of the Candida spp. on mucosal surfaces injured by chemother- abdominal cavity, eventually combined with antibiotics, is apy develops progressively and is responsible for fungal sufficient to allow full recovery [42]. Except for patients translocation with a high risk of candidemia. The use of presenting with nosocomial peritonitis and some of those systematic antifungal prophylaxis in the past three decades presenting with septic shock and multiple organ failure, explains the epidemiology of Candida infection, typi- the identification of Candida spp. has no clinical signifi- cally characterized by breakthrough invasive candidiasis cance under these conditions [22]. Recurrent peritonitis [31, 32]. Infection is almost always caused by a Candida following anastomotic leakage or persistent inflammation strain resistant to the antifungal agent used [15, 33]. may be required for the progression of Candida spp. 1431 Candidaspp. Gram positive Gram negative Red cell Macrophage Neutropenic patients Solid organ transplant recipients Candida spp. Gram positive Gram negative Red cell Macrophage Lymphocyte Neutrophil Critically ill surgical patients Critically ill non-surgical patients Fig. 1 Pathophysiology of invasive candidiasis in different patient populations. Detailed mechanisms are summarized in the corresponding sections of the text 1432 colonization to invasive candidiasis [43]. However, the 1970s of Candida infection in surgical patients, mani- development of invasive candidiasis requires concomitant festing as ‘‘disseminated candidiasis’’ and characterized exposure to additional