Elsevier

Clinics in Chest Medicine

Volume 38, Issue 3, September 2017, Pages 493-509
Clinics in Chest Medicine

Candidemia in the Intensive Care Unit

https://doi.org/10.1016/j.ccm.2017.04.010Get rights and content

Section snippets

Key points

  • Candida is the most common invasive mycosis in critically ill patients.

  • Candidemia in the intensive care unit extends the length of stay, increases health care costs, and carries a high crude mortality.

  • The contribution of non-albicans Candida species to this infection is on the rise.

  • The role of antifungal administration before culture confirmation of candidemia in critical care units remains debatable.

  • Echinocandins are the drug class of choice for the treatment of established intensive care unit

Background

Candida is the most common invasive fungus in critically ill patients, and the candidemia rate in ICUs is about 10 to 20 times that of non-ICU settings.1, 2 Among critical care areas, the highest incidence belongs to burn units.3 Candidemia can impose a significant operational and budgetary burden on an ICU: it was shown to prolong ICU stay by nearly 13 days in one study while adding an estimated $8570 (€7800) in attributable costs in another, driven primarily by sepsis treatment itself.4, 5

Mycology

Candida spp are detected in the laboratory by their macroscopic growth as cream- to yellow-colored colonies (Fig. 1) or by microscopic visualization of budding yeast cells (Fig. 2, inset). C albicans is a dimorphic fungus capable of existence in either the yeast or the mycelial form depending on environmental conditions such as temperature. C albicans is also noteworthy for the ability to form true hyphae or elongated buds called pseudohyphae (see Fig. 2, main panel). Its hyphae originate from

Clinical Factors

Like many ubiquitous fungi, Candida spp can inhabit normal human hosts as gut commensals and colonizers of mucocutaneous surfaces without causing disease. Superficial candidiasis occurs in the presence of defects in both the innate and the adaptive cell-mediated immune responses that are vital antifungal defenses. An example of the former is vulvovaginal candidiasis in uncontrolled diabetes mellitus promoted by impaired neutrophil chemotaxis present in diabetics.31 The latter is exemplified by

Catheter-Related Bloodstream Infection

The bloodstream is the third most common site of infection in ICUs worldwide, reported in 15% of an international critically ill population in a point-prevalence study.51 Nosocomial bloodstream infections (BSIs) are intimately related to the presence of a CVC; it is not surprising, therefore, that about 50% of BSIs occur in the ICU. Central line–associated bloodstream infections (CLABSIs) are associated with increased mortality and health care costs.52, 53 Along with Pseudomonas aeruginosa,

Culture

Growth in culture remains the gold standard for diagnosing candidal infections, but this method suffers from delayed results, the potential for inadequate sampling by clinicians, and possible suppression by antifungal therapy. Obtaining cultures from sterile nonblood sites is associated with procedural risks. In an attempt to address these shortcomings, the matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF) system has been developed for the rapid speciation

Untargeted Therapy

Untargeted antifungal therapy against Candida can be classified according to the trigger for its initiation.88 Prophylaxis refers to treatment based on clinical patient characteristics that confer increased vulnerability to IC (eg, Ostrosky-Zeichner rule). Preemptive therapy is administered for microbiological (eg, colonization) and/or serologic (eg, BG) evidence but not proof of infection. Therapy started in the face of persistent sepsis alone is considered empirical. Optimal untargeted

Outcomes

Candidemia remains a highly lethal condition linked to several clinical, microbiological, and host factors. Many, but not all, reports have found an association between greater time to administration of appropriate antifungal therapy and increased risk of death.65, 110, 111, 112, 113 The same association has been observed for source control, although at least in the case of CVCs, definitive statements are hampered by the absence of robust trial data. Although a correlation between Candida

Summary

The last decade has ushered in major changes in several aspects of ICU candidemia. It has been marked by increasing recognition of non-albicans species as prominent pathogens in this infection. Efforts to expedite diagnosis have led to advances in culture-based identification as well as in the development of molecular diagnostics. These nonculture methods generally have high NPV but low PPV. Echinocandins have supplanted azoles as first-line antifungal agents for the treatment of confirmed

First page preview

First page preview
Click to open first page preview

References (123)

  • A. Casadevall et al.

    Immunoglobulins in defense, pathogenesis, and therapy of fungal diseases

    Cell Host Microbe

    (2012)
  • H. Wisplinghoff et al.

    Inflammatory response and clinical course of adult patients with nosocomial bloodstream infections caused by Candida spp

    Clin Microbiol Infect

    (2006)
  • S. Ahmad et al.

    Invasive candidiasis: a review of nonculture-based laboratory diagnostic methods

    Indian J Med Microbiol

    (2012)
  • Y. Skrobik et al.

    Why Candida sepsis should matter to ICU physicians

    Crit Care Clin

    (2013)
  • M.G. Petri et al.

    Epidemiology of invasive mycosis in ICU patients: a prospective multicenter study in 435 non-neutropenic patients

    Intensive Care Med

    (1997)
  • M.E. Bougnoux et al.

    Candidemia and candiduria in critically ill patients admitted to intensive care units in France: incidence, molecular diversity, management, and outcome

    Intensive Care Med

    (2008)
  • P.M. Olaechea et al.

    Economic impact of Candida colonization and Candida infection in the critically ill patient

    Eur J Clin Microbiol Infect Dis

    (2004)
  • A.A. Cleveland et al.

    Declining incidence of candidemia and the shifting epidemiology of Candida resistance in two US metropolitan areas, 2008-2013: results from population-based surveillance

    PLoS One

    (2015)
  • O. Leroy et al.

    Epidemiology, management, and risk factors for death of invasive Candida infections in critical care: a multicenter, prospective, observational study in France (2005-2006)

    Crit Care Med

    (2009)
  • D.L. Horn et al.

    Epidemiology and outcomes of candidemia in 2019 patients: data from the prospective antifungal therapy alliance registry

    Clin Infect Dis

    (2009)
  • O. Lortholary et al.

    Worrisome trends in incidence and mortality of candidemia in intensive care units (Paris area, 2002-2010)

    Intensive Care Med

    (2014)
  • M. Bassetti et al.

    Epidemiological trends in nosocomial candidemia in intensive care

    BMC Infect Dis

    (2006)
  • D. Abi-Said et al.

    The epidemiology of hematogenous candidiasis caused by different Candida species

    Clin Infect Dis

    (1997)
  • A.L. Colombo et al.

    Prognostic factors and historical trends in the epidemiology of candidemia in critically ill patients: an analysis of five multicenter studies sequentially conducted over a 9-year period

    Intensive Care Med

    (2014)
  • G.H. Xie et al.

    Impact of invasive fungal infection on outcomes of severe sepsis: a multicenter matched cohort study in critically ill surgical patients

    Crit Care

    (2008)
  • F.J. González de Molina et al.

    Assessment of candidemia-attributable mortality in critically ill patients using propensity score matching analysis

    Crit Care

    (2012)
  • O. Gudlaugsson et al.

    Attributable mortality of nosocomial candidemia, revisited

    Clin Infect Dis

    (2003)
  • M.E. Falagas et al.

    Attributable mortality of candidemia: a systematic review of matched cohort and case-control studies

    Eur J Clin Microbiol Infect Dis

    (2006)
  • M.A. Pfaller et al.

    Epidemiology and outcomes of invasive candidiasis due to non-albicans species of Candida in 2,496 patients: data from the prospective antifungal therapy (PATH) registry 2004-2008

    PLoS One

    (2014)
  • A. Holley et al.

    Temporal trends, risk factors and outcomes in albicans and non-albicans candidaemia: an international epidemiological study in four multidisciplinary intensive care units

    Int J Antimicrob Agents

    (2009)
  • A.F. Shorr et al.

    Do clinical features allow for accurate prediction of fungal pathogenesis in bloodstream infections? Potential implications of the increasing prevalence of non-albicans candidemia

    Crit Care Med

    (2007)
  • G. Dimopoulos et al.

    Candida albicans versus non-albicans intensive care unit-acquired bloodstream infections: differences in risk factors and outcome

    Anesth Analg

    (2008)
  • J.K. Chow et al.

    Factors associated with candidemia caused by non-albicans Candida species versus Candida albicans in the intensive care unit

    Clin Infect Dis

    (2008)
  • E.G. Playford et al.

    Candidemia in nonneutropenic critically ill patients: risk factors for non-albicans Candida spp

    Crit Care Med

    (2008)
  • A. Malani et al.

    Candida glabrata fungemia: experience in a tertiary care center

    Clin Infect Dis

    (2005)
  • Y. Cohen et al.

    Early prediction of Candida glabrata fungemia in nonneutropenic critically ill patients

    Crit Care Med

    (2010)
  • L. Klingspor 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)
  • H.M. Blumberg et al.

    Risk factors for candidal bloodstream infections in surgical intensive care unit patients: the NEMIS prospective multicenter study

    Clin Infect Dis

    (2001)
  • P.E. Charles et al.

    Candidemia in critically ill patients: difference of outcome between medical and surgical patients

    Intensive Care Med

    (2003)
  • A.G. Mowat et al.

    Chemotaxis of polymorphonuclear leukocytes from patients with diabetes mellitus

    N Engl J Med

    (1971)
  • D.R. Reagan et al.

    Characterization of the sequence of colonization and nosocomial candidemia using DNA fingerprinting and a DNA probe

    J Clin Microbiol

    (1990)
  • M. Nucci et al.

    Revisiting the source of candidemia: skin or gut?

    Clin Infect Dis

    (2001)
  • A.Y. Koh et al.

    Mucosal damage and neutropenia are required for Candida albicans dissemination

    PLoS Pathog

    (2008)
  • J. Delaloye et al.

    Invasive candidiasis as a cause of sepsis in the critically ill patient

    Virulence

    (2014)
  • H. Muskett et al.

    Risk factors for invasive fungal disease in critically ill adult patients: a systematic review

    Crit Care

    (2011)
  • B.J. Kullberg et al.

    Invasive candidiasis

    N Engl J Med

    (2015)
  • D. Pittet et al.

    Candida colonization and subsequent infections in critically ill surgical patients

    Ann Surg

    (1994)
  • J.H. Shin et al.

    Biofilm production by isolates of Candida species recovered from nonneutropenic patients: comparison of bloodstream isolates with isolates from other sources

    J Clin Microbiol

    (2002)
  • F. Lanternier et al.

    Inherited CARD9 deficiency in otherwise healthy children and adults with Candida species-induced meningoencephalitis, colitis, or both

    J Allergy Clin Immunol

    (2015)
  • F. Lanternier et al.

    Deep dermatophytosis and inherited CARD9 deficiency

    N Engl J Med

    (2013)
  • Cited by (42)

    • Automatic classification of Candida species using Raman spectroscopy and machine learning

      2023, Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy
      Citation Excerpt :

      Indiscriminate or prolonged antibiotic therapy is a major factor in developing candidiasis [8], and growth in culture is still the gold standard for Candida spp. its identification and diagnosis. However, culture-based methods have several drawbacks, such as species growth ratio, risk of inadequate sampling, and possible suppression by antifungal therapy [9]. Alternative techniques not based on cultures and widely used nowadays are the polymerase chain reaction (PCR) or the enzyme-linked immunosorbent assay (ELISA) [10].

    • Clinical impact of Candida respiratory tract colonization and acute lung infections in critically ill patients with COVID-19 pneumonia

      2022, Microbial Pathogenesis
      Citation Excerpt :

      Bronchial colonization by Candida spp. is prevalent among patients who use automatic ventilation in the intensive care unit (ICU). Candida colonization has been found in approximately 30% of people who used mechanical ventilation (MV) for longer than 48 h and in 50% of those diagnosed with ventilator-associated pneumonia (VAP) [9,10]. Isolation of Candida spp. via the respiratory tract is linked to longer periods of MV, ICU admission, and hospital stay, with attendant poorer outcomes [11–13].

    View all citing articles on Scopus

    Disclosure Statement: The authors have nothing to disclose.

    View full text