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ESICM/ESCMID task force on practical management of invasive candidiasis in critically ill patients

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Abstract

Introduction

The term invasive candidiasis (IC) refers to both bloodstream and deep-seated invasive infections, such as peritonitis, caused by Candida species. Several guidelines on the management of candidemia and invasive infection due to Candida species have recently been published, but none of them focuses specifically on critically ill patients admitted to intensive care units (ICUs).

Material and Methods

In the absence of available scientific evidence, the resulting recommendations are based solely on epidemiological and clinical evidence in conjunction with expert opinion. The task force used the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach to evaluate the recommendations and assign levels of evidence. The recommendations and their strength were decided by consensus and, if necessary, by vote (modified Delphi process). Descriptive statistics were used to analyze the results of the Delphi process. Statements obtaining > 80% agreement were considered to have achieved consensus.

Conclusions

The heterogeneity of this patient population necessitated the creation of a mixed working group comprising experts in clinical microbiology, infectious diseases and intensive care medicine, all chosen on the basis of their expertise in the management of IC and/or research methodology. The working group’s main goal was to provide clinicians with clear and practical recommendations to optimize microbiological diagnosis and treatment of IC. The Systemic Inflammation and Sepsis and Infection sections of the European Society of Intensive Care Medicine (ESICM) and the Critically Ill Patients Study Group of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) therefore decided to develop a set of recommendations for application in non-immunocompromised critically ill patients.

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References

  1. O’Leary R-A, Einav S, Leone M et al (2018) Management of invasive candidiasis and candidaemia in critically ill adults: expert opinion of the European Society of Anaesthesia Intensive Care Scientific Subcommittee. J Hosp Infect 1:1. https://doi.org/10.1016/j.jhin.2017.11.020

    Article  Google Scholar 

  2. Baldesi O, Bailly S, Ruckly S et al (2017) ICU-acquired candidaemia in France: epidemiology and temporal trends, 2004-2013—a study from the REA-RAISIN network. J Infect 75:59–67. https://doi.org/10.1016/j.jinf.2017.03.011

    Article  PubMed  Google Scholar 

  3. Pfaller MA, Andes DR, Diekema DJ et al (2014) Epidemiology and outcomes of invasive candidiasis due to non-albicans species of Candida in 2496 patients: data from the Prospective Antifungal Therapy (PATH) registry 2004–2008. PLoS One 9:e101510. https://doi.org/10.1371/journal.pone.0101510

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Colombo AL, Guimarães T, Sukienik T et al (2014) 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 40:1489–1498. https://doi.org/10.1007/s00134-014-3400-y

    Article  PubMed  PubMed Central  Google Scholar 

  5. Pappas PG, Kauffman CA, Andes DR et al (2016) Clinical practice guideline for the management of candidiasis: 2016 update by the infectious diseases society of America. Clin Infect Dis 62:e1–e50. https://doi.org/10.1093/cid/civ933

    Article  PubMed  Google Scholar 

  6. Martin-Loeches I, Diaz E, Valles J et al (2014) Risks for multidrug-resistant pathogens in the ICU. Curr Opin Crit Care 20:516–524. https://doi.org/10.1097/MCC.0000000000000124

    Article  PubMed  Google Scholar 

  7. Delaloye J, Calandra T (2014) Invasive candidiasis as a cause of sepsis in the critically ill patient. Virulence 5:161–169. https://doi.org/10.4161/viru.26187

    Article  PubMed  Google Scholar 

  8. Calandra T, Roberts JA, Antonelli M et al (2016) Diagnosis and management of invasive candidiasis in the ICU: an updated approach to an old enemy. Crit Care 20:125. https://doi.org/10.1186/s13054-016-1313-6

    Article  PubMed  PubMed Central  Google Scholar 

  9. Vincent J-LJ-L, Martin-Loeches I, Annane D (2016) What patient data should be collected in this randomized controlled trial in sepsis? Intensive Care Med 42:2011–2013. https://doi.org/10.1007/s00134-016-4560-8

    Article  PubMed  Google Scholar 

  10. Garey KW, Rege M, Pai MP et al (2006) Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study. Clin Infect Dis 43:25–31. https://doi.org/10.1086/504810

    Article  CAS  PubMed  Google Scholar 

  11. Bassetti M, Ansaldi F, Diaz-Martin A et al (2014) A multicenter study of septic shock due to candidemia: outcomes and predictors of mortality. Intensive Care Med 40:839–845. https://doi.org/10.1007/s00134-014-3310-z

    Article  CAS  PubMed  Google Scholar 

  12. Paiva J-A, Charles P-E (2017) Biomarker-guided antifungal therapy in patients with suspected invasive candidiasis: ready for prime time? Intensive Care Med 43:1889–1891. https://doi.org/10.1007/s00134-017-4990-y

    Article  PubMed  Google Scholar 

  13. Cornely OA, Bassetti M, Calandra T et al (2012) ESCMID* guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect 18(Suppl 7):19–37. https://doi.org/10.1111/1469-0691.12039

    Article  CAS  PubMed  Google Scholar 

  14. Tagliaferri E, Menichetti F (2015) Treatment of invasive candidiasis: between guidelines and daily clinical practice. Expert Rev Anti Infect Ther 13:685–689. https://doi.org/10.1586/14787210.2015.1029916

    Article  CAS  PubMed  Google Scholar 

  15. Echeverria PM, Kett DH, Azoulay E (2011) Candida prophylaxis and therapy in the ICU. Semin Respir Crit Care Med 32:159–173. https://doi.org/10.1055/s-0031-1275528

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  17. Guyatt G, Gutterman D, Baumann MH et al (2006) Grading strength of recommendations and quality of evidence in clinical guidelines: report from an American college of chest physicians task force. Chest 129:174–181. https://doi.org/10.1378/chest.129.1.174

    Article  PubMed  Google Scholar 

  18. Helmer O (1967) Analysis of the future. The RAND corporation, Santa Monica, California. https://www.rand.org/pubs/papers/P3558.html. Accessed 26 Nov 2018.

  19. Hsu J, Brożek JL, Terracciano L et al (2011) Application of GRADE: making evidence-based recommendations about diagnostic tests in clinical practice guidelines. Implement Sci 6:62. https://doi.org/10.1186/1748-5908-6-62

    Article  PubMed  PubMed Central  Google Scholar 

  20. Schünemann HJ, Mustafa R, Brozek J et al (2016) GRADE Guidelines: 16. GRADE evidence to decision frameworks for tests in clinical practice and public health. J Clin Epidemiol 76:89–98. https://doi.org/10.1016/j.jclinepi.2016.01.032

    Article  PubMed  Google Scholar 

  21. Ullmann AJ, Cornely OA, Donnelly JP et al (2012) ESCMID* guideline for the diagnosis and management of Candida diseases 2012: developing European guidelines in clinical microbiology and infectious diseases. Clin Microbiol Infect 18(Suppl 7):1–8. https://doi.org/10.1111/1469-0691.12037

    Article  CAS  PubMed  Google Scholar 

  22. Shan Y-S, Sy ED, Wang S-T et al (2006) Early presumptive therapy with fluconazole for occult Candida infection after gastrointestinal surgery. World J Surg 30:119–126. https://doi.org/10.1007/s00268-005-7807-z

    Article  PubMed  Google Scholar 

  23. León C, Ostrosky-Zeichner L, Schuster M (2014) What’s new in the clinical and diagnostic management of invasive candidiasis in critically ill patients. Intensive Care Med 40:808–819. https://doi.org/10.1007/s00134-014-3281-0

    Article  CAS  PubMed  Google Scholar 

  24. Lopez-Cortes LE, Almirante B, Cuenca-Estrella M et al (2016) Empirical and targeted therapy of candidemia with fluconazole versus echinocandins: a propensity score-derived analysis of a population-based, multicentre prospective cohort. Clin Microbiol Infect 22:733.e1–733.e8. https://doi.org/10.1016/j.cmi.2016.05.008

    Article  CAS  Google Scholar 

  25. Rodriguez A, Martin-Loeches I, Yebenes JC (2016) New definition of sepsis and septic shock: what does it give us? Med Intensiva. https://doi.org/10.1016/j.medin.2016.03.008

    Article  PubMed  Google Scholar 

  26. Pittet D, Monod M, Suter PM et al (1994) Candida colonization and subsequent infections in critically ill surgical patients. Ann Surg 220:751–758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Ostrosky-Zeichner L, Sable C, Sobel J et al (2007) Multicenter retrospective development and validation of a clinical prediction rule for nosocomial invasive candidiasis in the intensive care setting. Eur J Clin Microbiol Infect Dis 26:271–276. https://doi.org/10.1007/s10096-007-0270-z

    Article  CAS  PubMed  Google Scholar 

  28. Leon C, Ruiz-Santana S, Saavedra P et al (2006) A bedside scoring system (“Candida score”) for early antifungal treatment in nonneutropenic critically ill patients with Candida colonization. Crit Care Med 34:730–737. https://doi.org/10.1097/01.CCM.0000202208.37364.7D

    Article  PubMed  Google Scholar 

  29. Paphitou NI, Ostrosky-Zeichner L, Rex JH (2005) Rules for identifying patients at increased risk for candidal infections in the surgical intensive care unit: approach to developing practical criteria for systematic use in antifungal prophylaxis trials. Med Mycol 43:235–243

    Article  PubMed  Google Scholar 

  30. Dupont H, Bourichon A, Paugam-Burtz C et al (2003) Can yeast isolation in peritoneal fluid be predicted in intensive care unit patients with peritonitis? Crit Care Med 31:752–757. https://doi.org/10.1097/01.CCM.0000053525.49267.77

    Article  PubMed  Google Scholar 

  31. Michalopoulos AS, Geroulanos S, Mentzelopoulos SD (2003) Determinants of candidemia and candidemia-related death in cardiothoracic ICU patients. Chest 124:2244–2255

    Article  PubMed  Google Scholar 

  32. Guillamet CV, Vazquez R, Micek ST et al (2015) Development and validation of a clinical prediction rule for candidemia in hospitalized patients with severe sepsis and septic shock. J Crit Care 30:715–720. https://doi.org/10.1016/j.jcrc.2015.03.010

    Article  PubMed  Google Scholar 

  33. Hermsen ED, Zapapas MK, Maiefski M et al (2011) Validation and comparison of clinical prediction rules for invasive candidiasis in intensive care unit patients: a matched case-control study. Crit Care 15:R198. https://doi.org/10.1186/cc10366

    Article  PubMed  PubMed Central  Google Scholar 

  34. Leroy G, Lambiotte F, Thévenin D et al (2011) Evaluation of “Candida score” in critically ill patients: a prospective, multicenter, observational, cohort study. Ann Intensive Care 1:50. https://doi.org/10.1186/2110-5820-1-50

    Article  PubMed  PubMed Central  Google Scholar 

  35. Montravers P, Perrigault PF, Timsit JF et al (2017) Antifungal therapy for patients with proven or suspected Candida peritonitis: Amarcand2, a prospective cohort study in French intensive care units. Clin Microbiol Infect 23:117.e1–117.e8. https://doi.org/10.1016/j.cmi.2016.10.001

    Article  CAS  Google Scholar 

  36. Clancy CJ, Nguyen MH (2013) Finding the “missing 50%” of invasive candidiasis: how nonculture diagnostics will improve understanding of disease spectrum and transform patient care. Clin Infect Dis 56:1284–1292. https://doi.org/10.1093/cid/cit006

    Article  PubMed  Google Scholar 

  37. Martin-Loeches I, Garnacho-Montero J, Nseir S (2017) Focus on infection and sepsis 2017. Intensive Care Med 43:867–869. https://doi.org/10.1007/s00134-017-4787-z

    Article  PubMed  Google Scholar 

  38. Martin-Loeches I, Perner A, Loeches IM, Perner A (2016) Focus on infection and sepsis in intensive care patients. Intensive Care Med 42:491–493. https://doi.org/10.1007/s00134-016-4234-6

    Article  PubMed  Google Scholar 

  39. Kirby JE, Delaney M, Qian Q, Gold HS (2009) Optimal use of Myco/F lytic and standard BACTEC blood culture bottles for detection of yeast and mycobacteria. Arch Pathol Lab Med 133:93–96. https://doi.org/10.1043/1543-2165-133.1.93

    Article  PubMed  Google Scholar 

  40. Jekarl DW, Lee S-Y, Lee S et al (2012) Comparison of the Bactec Fx Plus, Mycosis IC/F, Mycosis/F Lytic blood culture media and the BacT/Alert 3D FA media for detection of Candida species in seeded blood culture specimens containing therapeutic peak levels of fluconazole. J Clin Lab Anal 26:412–419. https://doi.org/10.1002/jcla.21535

    Article  PubMed  PubMed Central  Google Scholar 

  41. Köck R, Eiβing LC, Boschin MG et al (2013) Evaluation of bactec mycosis IC/F and plus aerobic/F blood culture bottles for detection of Candida in the presence of antifungal agents. J Clin Microbiol 51:3683–3687. https://doi.org/10.1128/JCM.02048-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Idelevich EA, Grunewald CM, Wüllenweber J, Becker K (2014) Rapid identification and susceptibility testing of Candida spp. from positive blood cultures by combination of direct MALDI-TOF mass spectrometry and direct inoculation of Vitek 2. PLoS One 9:e114834. https://doi.org/10.1371/journal.pone.0114834

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Stone NRH, Gorton RL, Barker K et al (2013) Evaluation of PNA-FISH yeast traffic light for rapid identification of yeast directly from positive blood cultures and assessment of clinical impact. J Clin Microbiol 51:1301–1302. https://doi.org/10.1128/JCM.00028-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Guinea J, Zaragoza Ó, Escribano P et al (2014) Molecular identification and antifungal susceptibility of yeast isolates causing fungemia collected in a population-based study in Spain in 2010 and 2011. Antimicrob Agents Chemother 58:1529–1537. https://doi.org/10.1128/AAC.02155-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Avni T, Leibovici L, Paul M (2011) PCR diagnosis of invasive candidiasis: systematic review and meta-analysis. J Clin Microbiol 49:665–670. https://doi.org/10.1128/JCM.01602-10

    Article  PubMed  PubMed Central  Google Scholar 

  46. Lamoth F, Jaton K, Prod’hom G et al (2010) Multiplex blood PCR in combination with blood cultures for improvement of microbiological documentation of infection in febrile neutropenia. J Clin Microbiol 48:3510–3516. https://doi.org/10.1128/JCM.00147-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Metzgar D, Frinder MW, Rothman RE et al (2016) The IRIDICA BAC BSI Assay: rapid, sensitive and culture-independent identification of bacteria and candida in blood. PLoS One 11:e0158186. https://doi.org/10.1371/journal.pone.0158186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. León C, Ruiz-Santana S, Saavedra P et al (2016) Contribution of Candida biomarkers and DNA detection for the diagnosis of invasive candidiasis in ICU patients with severe abdominal conditions. Crit Care 20:149. https://doi.org/10.1186/s13054-016-1324-3

    Article  PubMed  PubMed Central  Google Scholar 

  49. Ramos JT, Villar S, Bouza E et al (2017) Performance of a quantitative PCR-based assay and beta-d-glucan detection for diagnosis of invasive candidiasis in very-low-birth-weight preterm neonatal patients (CANDINEO Study). J Clin Microbiol 55:2752–2764. https://doi.org/10.1128/JCM.00496-17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Beyda ND, Alam MJ, Garey KW (2013) Comparison of the T2Dx instrument with T2Candida assay and automated blood culture in the detection of Candida species using seeded blood samples. Diagn Microbiol Infect Dis 77:324–326. https://doi.org/10.1016/j.diagmicrobio.2013.07.007

    Article  CAS  PubMed  Google Scholar 

  51. Mylonakis E, Clancy CJ, Ostrosky-Zeichner L et al (2015) T2 magnetic resonance assay for the rapid diagnosis of candidemia in whole blood: a clinical trial. Clin Infect Dis 60:892–899. https://doi.org/10.1093/cid/ciu959

    Article  CAS  PubMed  Google Scholar 

  52. Mikulska M, Calandra T, Sanguinetti M et al (2010) The use of mannan antigen and anti-mannan antibodies in the diagnosis of invasive candidiasis: recommendations from the Third European Conference on Infections in Leukemia. Crit Care 14:R222. https://doi.org/10.1186/cc9365

  53. Martínez-Jiménez MC, Muñoz P, Valerio M et al (2015) Candida biomarkers in patients with candidaemia and bacteraemia. J Antimicrob Chemother 70:2354–2361. https://doi.org/10.1093/jac/dkv090

    Article  CAS  PubMed  Google Scholar 

  54. Tissot F, Lamoth F, Hauser PM et al (2013) β-glucan antigenemia anticipates diagnosis of blood culture-negative intraabdominal candidiasis. Am J Respir Crit Care Med 188:1100–1109. https://doi.org/10.1164/rccm.201211-2069OC

    Article  PubMed  Google Scholar 

  55. De Pauw B, Walsh TJ, Donnelly JP et al (2008) Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) C. Clin Infect Dis 46:1813–1821. https://doi.org/10.1086/588660

    Article  PubMed  Google Scholar 

  56. Persat F, Ranque S, Derouin F et al (2008) Contribution of the (1---3)-beta-d-glucan assay for diagnosis of invasive fungal infections. J Clin Microbiol 46:1009–1013. https://doi.org/10.1128/JCM.02091-07

    Article  PubMed  Google Scholar 

  57. León C, Ruiz-Santana S, Saavedra P et al (2012) Value of β-d-glucan and Candida albicans germ tube antibody for discriminating between Candida colonization and invasive candidiasis in patients with severe abdominal conditions. Intensive Care Med 38:1315–1325. https://doi.org/10.1007/s00134-012-2616-y

    Article  CAS  PubMed  Google Scholar 

  58. Posteraro B, Tumbarello M, De Pascale G et al (2016) (1,3)-β-d-Glucan-based antifungal treatment in critically ill adults at high risk of candidaemia: an observational study. J Antimicrob Chemother 71:2262–2269. https://doi.org/10.1093/jac/dkw112

    Article  CAS  PubMed  Google Scholar 

  59. Lahmer T, Rasch S, Schnappauf C et al (2016) Comparison of serum galactomannan and 1,3-beta-d-glucan determination for early detection of invasive pulmonary aspergillosis in critically ill patients with hematological malignancies and septic shock. Mycopathologia 181:505–511. https://doi.org/10.1007/s11046-016-0011-x

    Article  CAS  PubMed  Google Scholar 

  60. Coopersmith CM, de Backer D, Deutschman CS et al (2018) Surviving sepsis campaign: research priorities for sepsis and septic shock. Intensive Care Med. https://doi.org/10.1007/s00134-018-5175-z

    Article  PubMed  PubMed Central  Google Scholar 

  61. Guilbart M, Zogheib E, Ntouba A et al (2016) Compliance with an empirical antimicrobial protocol improves the outcome of complicated intra-abdominal infections: a prospective observational study. Br J Anaesth 117:66–72. https://doi.org/10.1093/bja/aew117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Micek ST, Arnold H, Juang P et al (2014) Effects of empiric antifungal therapy for septic shock on time to appropriate therapy for Candida infection: a pilot study. Clin Ther 36:1226–1232. https://doi.org/10.1016/j.clinthera.2014.06.028

    Article  PubMed  Google Scholar 

  63. Garnacho-Montero J, Díaz-Martín A, García-Cabrera E et al (2013) Impact on hospital mortality of catheter removal and adequate antifungal therapy in Candida spp. bloodstream infections. J Antimicrob Chemother 68:206–213. https://doi.org/10.1093/jac/dks347

    Article  CAS  PubMed  Google Scholar 

  64. Pierce CG, Lopez-Ribot JL (2013) Candidiasis drug discovery and development: new approaches targeting virulence for discovering and identifying new drugs. Expert Opin Drug Discov 8:1117–1126. https://doi.org/10.1517/17460441.2013.807245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Playford EG, Webster AC, Sorrell TC, Craig JC (2006) Antifungal agents for preventing fungal infections in non-neutropenic critically ill and surgical patients: systematic review and meta-analysis of randomized clinical trials. J Antimicrob Chemother 57:628–638. https://doi.org/10.1093/jac/dki491

    Article  CAS  PubMed  Google Scholar 

  66. Shorr AF, Chung K, Jackson WL et al (2005) Fluconazole prophylaxis in critically ill surgical patients: a meta-analysis. Crit Care Med 33:1928–1935 (quiz 1936)

    Article  CAS  PubMed  Google Scholar 

  67. Vardakas KZ, Samonis G, Michalopoulos A et al (2006) Antifungal prophylaxis with azoles in high-risk, surgical intensive care unit patients: a meta-analysis of randomized, placebo-controlled trials. Crit Care Med 34:1216–1224. https://doi.org/10.1097/01.CCM.0000208357.05675.C3

    Article  CAS  PubMed  Google Scholar 

  68. Cruciani M, de Lalla F, Mengoli C (2005) Prophylaxis of Candida infections in adult trauma and surgical intensive care patients: a systematic review and meta-analysis. Intensive Care Med 31:1479–1487. https://doi.org/10.1007/s00134-005-2794-y

    Article  PubMed  Google Scholar 

  69. Playford EG, Webster AC, Sorrell TC, Craig JC (2006) Antifungal agents for preventing fungal infections in non-neutropenic critically ill patients. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.cd004920.pub2

    Article  PubMed  Google Scholar 

  70. Whaley SG, Berkow EL, Rybak JM et al (2016) Azole antifungal resistance in Candida albicans and emerging non-albicans Candida species. Front Microbiol 7:2173. https://doi.org/10.3389/fmicb.2016.02173

    Article  PubMed  Google Scholar 

  71. Pappas PG, Kauffman CA, Andes D et al (2009) Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 48:503–535. https://doi.org/10.1086/596757

    Article  CAS  PubMed  Google Scholar 

  72. Bow EJ, Evans G, Fuller J et al (2010) Canadian clinical practice guidelines for invasive candidiasis in adults. Can J Infect Dis Med Microbiol 21:e122–e150

    Article  PubMed  PubMed Central  Google Scholar 

  73. Pang Y-K, Ip M, You JHS (2017) Potential clinical and economic outcomes of active beta-d-glucan surveillance with preemptive therapy for invasive candidiasis at intensive care units: a decision model analysis. Eur J Clin Microbiol Infect Dis 36:187–194. https://doi.org/10.1007/s10096-016-2796-4

    Article  CAS  PubMed  Google Scholar 

  74. Azoulay E, Dupont HH, Tabah A et al (2012) Systemic antifungal therapy in critically ill patients without invasive fungal infection*. Crit Care Med 40:813–822. https://doi.org/10.1097/CCM.0b013e318236f297

    Article  CAS  PubMed  Google Scholar 

  75. Wissing H, Ballus J, Bingold TM et al (2013) Intensive care unit-related fluconazole use in Spain and Germany: patient characteristics and outcomes of a prospective multicenter longitudinal observational study. Infect Drug Resist 6:15–25. https://doi.org/10.2147/IDR.S38945

    Article  PubMed  PubMed Central  Google Scholar 

  76. Piarroux R, Grenouillet F, Balvay P et al (2004) Assessment of preemptive treatment to prevent severe candidiasis in critically ill surgical patients. Crit Care Med 32:2443–2449

    Article  PubMed  Google Scholar 

  77. Bailly S, Bouadma L, Azoulay E et al (2015) Failure of empirical systemic antifungal therapy in mechanically ventilated critically ill patients. Am J Respir Crit Care Med 191:1139–1146. https://doi.org/10.1164/rccm.201409-1701OC

    Article  CAS  PubMed  Google Scholar 

  78. Leroy O, Bailly S, Gangneux J-P et al (2016) Systemic antifungal therapy for proven or suspected invasive candidiasis: the AmarCAND 2 study. Ann Intensive Care 6:2. https://doi.org/10.1186/s13613-015-0103-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Golan Y, Wolf MP, Pauker SG et al (2005) Empirical anti-Candida therapy among selected patients in the intensive care unit: a cost-effectiveness analysis. Ann Intern Med 143:857–869

    Article  PubMed  Google Scholar 

  80. Schuster MG, Edwards JE, Sobel JD et al (2008) Empirical fluconazole versus placebo for intensive care unit patients: a randomized trial. Ann Intern Med 149:83–90

    Article  PubMed  Google Scholar 

  81. Timsit J-F, Azoulay E, Schwebel C et al (2016) Empirical micafungin treatment and survival without invasive fungal infection in adults with ICU-acquired sepsis, Candida colonization, and multiple organ failure: the EMPIRICUS randomized clinical trial. JAMA. https://doi.org/10.1001/jama.2016.14655

    Article  PubMed  Google Scholar 

  82. Sinnollareddy MG, Roberts MS, Lipman J et al (2016) In vivo microdialysis to determine subcutaneous interstitial fluid penetration and pharmacokinetics of fluconazole in intensive care unit patients with sepsis. Antimicrob Agents Chemother 60:827–832. https://doi.org/10.1128/AAC.02461-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Sinnollareddy MG, Roberts JA, Lipman J et al (2015) Pharmacokinetic variability and exposures of fluconazole, anidulafungin, and caspofungin in intensive care unit patients: data from multinational Defining Antibiotic Levels in Intensive care unit (DALI) patients Study. Crit Care 19:33. https://doi.org/10.1186/s13054-015-0758-3

    Article  PubMed  PubMed Central  Google Scholar 

  84. Perlin DS (2015) Echinocandin resistance in Candida. Clin Infect Dis 61(Suppl 6):S612–S617. https://doi.org/10.1093/cid/civ791

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Pfaller MA, Diekema DJ, Ostrosky-Zeichner L et al (2008) Correlation of MIC with outcome for Candida species tested against caspofungin, anidulafungin, and micafungin: analysis and proposal for interpretive MIC breakpoints. J Clin Microbiol 46:2620–2629. https://doi.org/10.1128/JCM.00566-08

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Puig-Asensio M, Pemán J, Zaragoza R et al (2014) Impact of therapeutic strategies on the prognosis of candidemia in the ICU. Crit Care Med 42:1423–1432. https://doi.org/10.1097/CCM.0000000000000221

    Article  CAS  PubMed  Google Scholar 

  87. Muilwijk EW, Schouten JA, van Leeuwen HJ et al (2014) Pharmacokinetics of caspofungin in ICU patients. J Antimicrob Chemother 69:3294–3299. https://doi.org/10.1093/jac/dku313

    Article  CAS  PubMed  Google Scholar 

  88. Lempers VJ, Schouten JA, Hunfeld NG et al (2015) Altered micafungin pharmacokinetics in intensive care unit patients. Antimicrob Agents Chemother 59:4403–4409. https://doi.org/10.1128/AAC.00623-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Grau S, Luque S, Campillo N et al (2015) Plasma and peritoneal fluid population pharmacokinetics of micafungin in post-surgical patients with severe peritonitis. J Antimicrob Chemother 70:2854–2861. https://doi.org/10.1093/jac/dkv173

    Article  CAS  PubMed  Google Scholar 

  90. Dupont H, Massias L, Jung B et al (2017) Pharmacokinetic study of anidulafungin in ICU patients with intra-abdominal candidiasis. J Antimicrob Chemother 72:1429–1432. https://doi.org/10.1093/jac/dkw568

    Article  CAS  PubMed  Google Scholar 

  91. Ashley ESD, Lewis R, Lewis JS et al (2006) Pharmacology of systemic antifungal agents. Clin Infect Dis 43:S28–S39. https://doi.org/10.1086/504492

    Article  Google Scholar 

  92. Mora-Duarte J, Betts R, Rotstein C et al (2002) Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med 347:2020–2029. https://doi.org/10.1056/NEJMoa021585

    Article  CAS  PubMed  Google Scholar 

  93. Kuse E-R, Chetchotisakd P, da Cunha CA et al (2007) Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial. Lancet 369:1519–1527. https://doi.org/10.1016/S0140-6736(07)60605-9

    Article  CAS  PubMed  Google Scholar 

  94. Scudeller L, Viscoli C, Menichetti F et al (2014) An Italian consensus for invasive candidiasis management (ITALIC). Infection 42:263–279. https://doi.org/10.1007/s15010-013-0558-0

    Article  CAS  PubMed  Google Scholar 

  95. Kett DH, Shorr AF, Reboli AC et al (2011) Anidulafungin compared with fluconazole in severely ill patients with candidemia and other forms of invasive candidiasis: support for the 2009 IDSA treatment guidelines for candidiasis. Crit Care 15:R253. https://doi.org/10.1186/cc10514

    Article  PubMed  PubMed Central  Google Scholar 

  96. Gonçalves-Pereira J, Póvoa P (2011) Echinocandins—first line in invasive candidiasis: how strong is this “strong” evidence? Crit Care 15:461. https://doi.org/10.1186/cc10580 (author reply 461)

    Article  PubMed  PubMed Central  Google Scholar 

  97. Andes DR, Safdar N, Baddley JW et al (2012) Impact of treatment strategy on outcomes in patients with candidemia and other forms of invasive candidiasis: a patient-level quantitative review of randomized trials. Clin Infect Dis 54:1110–1122. https://doi.org/10.1093/cid/cis021

    Article  CAS  PubMed  Google Scholar 

  98. Murri R, Scoppettuolo G, Ventura G et al (2016) Initial antifungal strategy does not correlate with mortality in patients with candidemia. Eur J Clin Microbiol Infect Dis 35:187–193. https://doi.org/10.1007/s10096-015-2527-2

    Article  CAS  PubMed  Google Scholar 

  99. Chen Q, Lin M-H, Chen M-L et al (2012) Efficacy and safety of micafungin for invasive candida infections: a meta-analysis of randomized controlled trials. Chin Med J (Engl) 125:345–351

    CAS  Google Scholar 

  100. Wang J-F, Xue Y, Zhu X-B, Fan H (2015) Efficacy and safety of echinocandins versus triazoles for the prophylaxis and treatment of fungal infections: a meta-analysis of RCTs. Eur J Clin Microbiol Infect Dis 34:651–659. https://doi.org/10.1007/s10096-014-2287-4

    Article  CAS  PubMed  Google Scholar 

  101. Garnacho-Montero J, Díaz-Martín A, Cantón-Bulnes L et al (2018) Initial antifungal strategy reduces mortality in critically ill patients with candidemia: a propensity score-adjusted analysis of a multicenter study. Crit Care Med 46:384–393. https://doi.org/10.1097/CCM.0000000000002867

    Article  PubMed  Google Scholar 

  102. Garey KW, Pai MP, Suda KJ et al (2007) Inadequacy of fluconazole dosing in patients with candidemia based on Infectious Diseases Society of America (IDSA) guidelines. Pharmacoepidemiol Drug Saf 16:919–927. https://doi.org/10.1002/pds.1365

    Article  CAS  PubMed  Google Scholar 

  103. Yang Q, Wang T, Xie J et al (2016) Pharmacokinetic/pharmacodynamic adequacy of echinocandins against Candida spp. in intensive care unit patients and general patient populations. Int J Antimicrob Agents 47:397–402. https://doi.org/10.1016/j.ijantimicag.2016.02.004

    Article  CAS  PubMed  Google Scholar 

  104. Gustot T, Ter Heine R, Brauns E et al (2018) Caspofungin dosage adjustments are not required for patients with Child-Pugh B or C cirrhosis. J Antimicrob Chemother 73:2493–2496. https://doi.org/10.1093/jac/dky189

    Article  CAS  PubMed  Google Scholar 

  105. Di Bonaventura G, Spedicato I, Picciani C et al (2004) In vitro pharmacodynamic characteristics of amphotericin B, caspofungin, fluconazole, and voriconazole against bloodstream isolates of infrequent Candida species from patients with hematologic malignancies. Antimicrob Agents Chemother 48:4453–4456. https://doi.org/10.1128/AAC.48.11.4453-4456.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Lewis RE (2011) Current concepts in antifungal pharmacology. Mayo Clin Proc 86:805–817. https://doi.org/10.4065/mcp.2011.0247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Johansen HK, Gotzsche PC (2000) Amphotericin B lipid soluble formulations vs amphotericin B in cancer patients with neutropenia. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.cd000969

    Article  PubMed  Google Scholar 

  108. Keane S, Geoghegan P, Povoa P et al (2018) Systematic review on the first line treatment of amphotericin B in critically ill adults with candidemia or invasive candidiasis. Expert Rev Anti Infect Ther. https://doi.org/10.1080/14787210.2018.1528872

    Article  PubMed  Google Scholar 

  109. Silva S, Rodrigues C, Araújo D et al (2017) Candida species biofilms’ antifungal resistance. J Fungi 3:8. https://doi.org/10.3390/jof3010008

    Article  CAS  Google Scholar 

  110. Muakkassa FK, Ghannoum M (2016) Updates on therapeutic strategies against Candida (and Aspergillus) biofilm related infections. Springer, Cham, pp 95–103

    Google Scholar 

  111. Chaves F, Garnacho-Montero J, Del Pozo JL et al (2018) Diagnosis and treatment of catheter-related bloodstream infection: clinical guidelines of the Spanish society of infectious diseases and clinical microbiology and (SEIMC) and the Spanish society of Spanish society of intensive and critical care medicine A. Med Intens 42:5–36. https://doi.org/10.1016/j.medin.2017.09.012

    Article  CAS  Google Scholar 

  112. Vazquez J, Reboli AC, Pappas PG et al (2014) Evaluation of an early step-down strategy from intravenous anidulafungin to oral azole therapy for the treatment of candidemia and other forms of invasive candidiasis: results from an open-label trial. BMC Infect Dis 14:97. https://doi.org/10.1186/1471-2334-14-97

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Bailly S, Leroy O, Montravers P et al (2015) Antifungal de-escalation was not associated with adverse outcome in critically ill patients treated for invasive candidiasis: post hoc analyses of the AmarCAND2 study data. Intensive Care Med 41:1931–1940. https://doi.org/10.1007/s00134-015-4053-1

    Article  CAS  PubMed  Google Scholar 

  114. Guarascio AJ, Slain D, McKnight R et al (2013) A matched-control evaluation of an antifungal bundle in the intensive care unit at a university teaching hospital. Int J Clin Pharm 35:145–148. https://doi.org/10.1007/s11096-012-9712-5

    Article  PubMed  Google Scholar 

  115. Martínez-Jiménez MC, Muñoz P, Valerio M et al (2015) Combination of Candida biomarkers in patients receiving empirical antifungal therapy in a Spanish tertiary hospital: a potential role in reducing the duration of treatment. J Antimicrob Chemother 70:3107–3115. https://doi.org/10.1093/jac/dkv241

    Article  CAS  PubMed  Google Scholar 

  116. Rouzé A, Loridant S, Poissy J et al (2017) Biomarker-based strategy for early discontinuation of empirical antifungal treatment in critically ill patients: a randomized controlled trial. Intensive Care Med 43:1668–1677. https://doi.org/10.1007/s00134-017-4932-8

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  118. Kauffman CA (2015) Complications of candidemia in ICU patients: endophthalmitis, osteomyelitis, endocarditis. Semin Respir Crit Care Med 36:641–649. https://doi.org/10.1055/s-0035-1562891

    Article  PubMed  Google Scholar 

  119. Fernández-Cruz A, Cruz Menárguez M, Muñoz P et al (2015) The search for endocarditis in patients with candidemia: a systematic recommendation for echocardiography? A prospective cohort. Eur J Clin Microbiol Infect Dis 34:1543–1549. https://doi.org/10.1007/s10096-015-2384-z

    Article  PubMed  Google Scholar 

  120. Rodríguez-Adrián LJ, King RT, Tamayo-Derat LG et al (2003) Retinal lesions as clues to disseminated bacterial and candidal infections: frequency, natural history, and etiology. Med (Baltim) 82:187–202. https://doi.org/10.1097/01.md.0000076008.64510.f1

    Article  Google Scholar 

  121. De Waele JJ, Vogelaers D, Blot S, Colardyn F (2003) Fungal infections in patients with severe acute pancreatitis and the use of prophylactic therapy. Clin Infect Dis 37:208–213. https://doi.org/10.1086/375603

    Article  PubMed  Google Scholar 

  122. Tsuruta R, Mizuno H, Kaneko T et al (2007) Preemptive therapy in nonneutropenic patients with Candida infection using the Japanese guidelines. Ann Pharmacother 41:1137–1143. https://doi.org/10.1345/aph.1K010

    Article  CAS  PubMed  Google Scholar 

  123. Hanson KE, Pfeiffer CD, Lease ED et al (2012) β-d-glucan surveillance with preemptive anidulafungin for invasive candidiasis in intensive care unit patients: a randomized pilot study. PLoS One 7:e42282. https://doi.org/10.1371/journal.pone.0042282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Ostrosky-Zeichner L, Shoham S, Vazquez J et al (2014) 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 58:1219–1226. https://doi.org/10.1093/cid/ciu074

    Article  CAS  PubMed  Google Scholar 

  125. Prattes J, Hoenigl M, Rabensteiner J et al (2014) Serum 1,3-beta-d-glucan for antifungal treatment stratification at the intensive care unit and the influence of surgery. Mycoses 57:679–686. https://doi.org/10.1111/myc.12221

    Article  CAS  PubMed  Google Scholar 

  126. Knitsch W, Vincent J-L, Utzolino S et al (2015) A randomized, placebo-controlled trial of preemptive antifungal therapy for the prevention of invasive candidiasis following gastrointestinal surgery for intra-abdominal infections. Clin Infect Dis 61:1671–1678. https://doi.org/10.1093/cid/civ707

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Kollef M, Micek S, Hampton N et al (2012) Septic shock attributed to Candida infection: importance of empiric therapy and source control. Clin Infect Dis 54:1739–1746. https://doi.org/10.1093/cid/cis305

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Ignacio Martin-Loeches.

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COIs declared by the authors: IML: Lectures: Thermofisher, Polyphor, J&J, Virogates, MSD. Advisory board: Fresenius Kabi, MaaT Pharma, Bayer, Gilead, Clinigen, Biotest, Accelerate. JGM has received speaker honoraria from Astellas and MSD. MB has participated in the past five years in advisory boards and/or received speaker honoraria from Achaogen, Angelini, Astellas, AstraZeneca, Bayer, Basilea, Cidara, Gilead, Menarini, MSD, Nabriva, Paratek, Pfizer, Roche, The Medicine Company, Shionogi, Tetraphase, VenatoRx, and Vifor. SSK has received honoraria for participating in advisory boards or as a speaker for Merck, Pfizer, Hikma, Pasteur Aventis, Gilead. JDW has consulted for Accelerate, AtoxBio, Bayer Healthcare, Cubist, MSD, Pfizer (honoraria were paid to his institution). PM: Personal fees and non-financial support from Astellas, Astrazeneca, Basilea, Bayer, Cubist, Menarini, MSD, Parexel, Pfizer, Tetraphase, and The Medicines Company unrelated to the submitted work. GD: Advisory boards and/or received speaker honoraria from Astellas, Bayer, Cidara, Gilead, MSD, Nabriva, Paratek, Pfizer, Tetraphase, Cipla India, Glenmark India, Infectopharm Germany. MCE has received grant support from Astellas Pharma, bioMerieux, Gilead Sciences, Merck Sharp & Dohme, Pfizer, Schering Plough, CIDARA, Amplyx, F2G, Scynexis, Soria Melguizo SA, and Ferrer International. He is a founding Partner of the start-up Micología Molecular SL.

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Martin-Loeches, I., Antonelli, M., Cuenca-Estrella, M. et al. ESICM/ESCMID task force on practical management of invasive candidiasis in critically ill patients. Intensive Care Med 45, 789–805 (2019). https://doi.org/10.1007/s00134-019-05599-w

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