Invasive Candida Infection

Abstract

The frequency of fungal infections, which are associated with high mortality and morbidity, is increasing. The most common agents in fungal infections are Candida species. The most important risk factor in Candida infections is colonization of the skin and mucous membranes with Candida species. Invasive interventions such as vascular and urinary catheterization increase the risk of colonization and infection. Immunosuppressive therapy, neutrophil and lymphocyte defects, phagocyte abnormalities, hospitalization in an intensive care unit, use of broad-spectrum antibiotics, mechanical ventilation, parenteral nutrition and abdominal surgery are also risk factors. The absence of distinguishing symptoms or signs from other infections causes candida infections to be overlooked and diagnosed late. For this reason, candida colonization index, Ostrosky clinical prediction rule and candida scoring systems, which are easy to apply for clinical diagnosis, have been developed. For definitive diagnosis, yeast or hyphae forms must be demonstrated in blood or tissue cultures. In these infections, which have a high risk of mortality, early intervention reduces the mortality rate. Treatment methods are divided into four groups as prophylactic, empirical, pre-emptive and targeted therapy. In patients with high risk for fungal infection, the preventive treatment method applied to prevent infection is prophylactic treatment. Empirical treatment is the treatment method applied in patients with unexplained fever and candida growth in non-sterile areas. For highly probable invasive candidiasis, preemptive treatment is applied in patients in shock, while targeted therapy is given in cases of candida invasion in sterile environments.

Keywords

• candidemia
• candidiasis
• candida infection

İnvazif Kandida Enfeksiyonu

Abstract

Yüksek mortalite ve morbidite ile ilişkili olan fungal enfeksiyonların sıklığı giderek artmaktadır. Fungal enfeksiyonlarda en fazla saptanan etkenler kandida türleridir. Kandida enfeksiyonlarında en önemli risk faktörü, deri ve mukozaların kandida türleriyle kolonize olmasıdır. Vasküler ve üriner kateter uygulanması gibi invazif girişimler kolonizasyon ve enfeksiyon riskini arttırmaktadır. İmmunsupresif tedavi alımı, nötrofil ve lenfosit defektleri, fagosit anormallikleri, yoğun bakım ünitesinde yatışı olması, geniş spektrumlu antibiyotik kullanımı, mekanik ventilasyon, parenteral beslenme ve abdominal cerrahi de risk faktörlerindendir. Diğer enfeksiyonlardan ayırt edici semptom veya bulgusunun olmaması, kandida enfeksiyonlarının gözden kaçmasına ve geç tanı konulmasına sebep olmaktadır. Bu nedenle klinik tanı için uygulanabilirliği kolay olan kandidanın kolonize olma indeksi, Ostrosky klinik tahmin kuralı ve kandida skorlaması sistemleri geliştirilmiştir. Kesin tanı için maya veya hif formlarının, kan veya doku kültürlerinde gösterilmesi gerekmektedir. Mortalite riski yüksek olan bu enfeksiyonlarda, erken müdahale ölüm oranını azaltmaktadır. Tedavi yöntemleri profilaktik, ampirik, preempitif ve hedefe yönelik tedavi olmak üzere dört gruba ayrılmaktadır. Fungal enfeksiyon açısından yüksek riskli hastalarda, enfeksiyonun gelişmemesi için uygulanan koruyucu tedavi yöntemi profilaktik tedavidir. Ampirik tedavi, nedeni açıklanamayan ateşi olan ve steril olmayan alanlarda kandida üremesi saptanan hastalarda uygulanan tedavi yöntemidir. Yüksek olası invazif kandidiyazis için şokta olan hastalarda preempitif tedavi uygulanırken, steril ortamlarda kandida invazyonu gösterilen durumlarda hedefe yönelik tedavi verilmektedir.

Keywords

• kandidiyazis
• kandidemi
• kandida enfeksiyonu

References

1. Leon C, Alvarez-Lerma F, Ruiz-Santana S, Leon MA, Nolla-Salas J, Jorda R E, et al. Fungal colonization and/or infection in non-neutropenic critically ill patients: result of the EPCAN observtional study. Eur J Clin Microbiol Infect Dis. 2009; 28: 233-42.
2. Arman D. Yoğun bakım unitesinde gelişen fungal infesiyonlar. Ulusoy S, Arman D, Uzun O, editorler. Fungal Enfeksiyonlar Ankara. Bilimsel Tıp Yayınevi. 2008.
3. Bouza E, Munoz P. Epidemiology of candidemia in intensive care units. Int J Antimicrob Agents 2008; 32: 87-9.
4. Peres-Bota D, Rodriguez-Villalobos H, Dimopoulus G, Melot C, Vincent J-L. Potential risk factors for infection with Candida spp. in critically ill patients. Clin Microbiol Infect 2004; 10: 550-5.
5. Vincent J-L, Rello J, Marshall J, Silva E, Anzueto A, Martin CD et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009; 302(21): 2323-9.
6. Esen Ş. Yoğun bakımda fungal enfeksiyonlar. Arman D, Odabaşı Z, editorler. Fungal İnfeksiyonlar ve Tedavisi Ankara: Bilimsel Tıp Yayınevi 2009: 125-35.
7. Savcı Ü, Yılmaz N. Çeşitli örneklerden izole edilen Candidaların tür dağılımı ve antifungal direnç oranları. Turk J Clin Lab. 2017; 8(3): 85-90.
8. Matthaiou DK, Christodoulopoulou T, Dimopoulos G. How to treat fungal infections in ICU patients. BMC Infect Dis. 2015; 15: 205.

9. Topçu Willke A, Çerikcioğlu N,Söyletir G, Doğanay M, editörler. Enfeksiyon Hastalıkları ve Mikrobiyolojisi Etkenlere Göre Enfeksiyonlar Cilt 2. İstanbul: Nobel Tıp Kitabevleri; 2002:1797-809.
10. Bilgehan H. Candida’ların tarihçesi, ekolojisi ve dağılımı. Tümbay E, editör. Candida ve İnfeksiyonları. Türk Mikrobiyoloji Cemiyeti Yayınları No:6. İzmir: Bilgehan Basımevi; 1986:1-8.
11. Pittet D, Monad M, Suter PM, Frenk E, Auckenthler R. Candida colonization and subsequent infections in critically ill surgical patients. Ann Surg. 1994; 220: 751-8.
12. Akalın H. Nozokomiyal fungal infeksiyonlar. Willke TA, Soyletir G, Doğanay M, editorler. Enfeksiyon Hastalıkları ve Mikrobiyoloji 3. Baskı İstanbul: Nobel Tıp Kitabevi 2008: 616-24.
13. Wenzel RP. Nosocomial candidiasis: risk factors and attributable mortality. Clin Infect Dis. 1995; 20: 1531-4.
14. Ghannoum MA, Abu Elteen KH. Pathogenicity determinants of Candida. Mycoses. 1990; 33: 265-82.
15. Wingard JR: Infections duo to resistant Candida species in a patients with cancer who receiving chemotherapy. Clin Infect Dis. 1994; 19: 49-53.
16. Hong Nguyen M, James EP, Arthur JM, David CT: The changing face of candidemia: Emergence of non-candida albicans species and antifungal resistance. Am J Med. 1996; 100: 617-23.
17. Seneviratne CJ, Jin L, Samaranayake LP. Biofilm lifestyle of Kandida: a mini review. Oral Dis. 2008; 14(7): 582-90.
18. Yucesoy M. Hastane infeksiyonları ve funguslar. Yuce A, Cakır N, editorler. Hastane İnfeksiyonları 2. Baskı İzmir: İzmir Guven Kitabevi 2009: 228-37.
19. Hedderwick SA, Lyons MJ, Liu M, Vazquez JA. Kauffman CA. Epidemiology of yeast colonization in the intensive care unit. Eur J Clin Microbiol Infect Dis. 2000; 19: 663-70.
20. Almirnate B, Rodriguez D, Park BJ, Cuenca-Estrella M, Planes AM, Almela M, Epidemiology and predictors of mortality in cases of Candida bloodstream. J Clin Microbiol. 2005; 43(4): 1829-35.
21. Ponikowski P, Van Veldhuisen DJ, Comin-Colet J, Ertl G, Komajda M, Mareev V, et al. Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency. Eur Heart J. 2015; 36(11): 657-68.
22. Bassetti M, Righi E, Costa A, Fasce R, Molinari MP, Rosso R. Epidemiological trends in nosocomial candidemia in intensive care. BMC Infect Dis. 2006; 6: 21.
23. Pappas PG. Invasive candidiasis. Infect Dis Clin North Am. 2006; 20: 485-506.
24. Picazzo JJ, Gonzalez-Romo F, Candel JF. Candidemia in the critically ill patient. Int J Antimicrob Agent. 2008; 32(2): 83-5.
25. Holley A, Dulhunty J, Blot S, Lipman J, Lobo S, Dancer C. Temporal trends, risk factors and outcomes in albicans and non-albicans candidemia: an international epidemiological study in four multidisciplinary intensive care units. Int J Antimicrob. 2009; 33(6): 554.e1-7. https://doi.org/10.1016/j.ijantimicag.2008.10.035
26. Paiva JA, Pereira JM, Tabah A, Mikstacki A, de Carvalho FB, Koulenti D. Characteristics and risk factors for 28-day mortality of hospital acquired fungemias in ICUs: data from the EUROBACT study.Crit Care. 2016; 20: 53.
27. Calandra T, Roberts JA, Antonelli M, Bassetti M, Vincent JL. Diagnosis and management of invasive candidiasis in the ICU: an updated approach to an old enemy. Crit Care. 2016; 20(1): 125.
28. Eggimann P, Garbino J, Pittet D. Epidemiology of Candida species infections in critically ill non-immunosuppresessed patients. Lancet Infect Dis. 2003; 3: 685-702.
29. Bougnoux ME, Kac G, Aegerter P, d’Enfert C, Fagon JY, Group CS. Candidemia and candiduria in critically ill patients admitted to intensive care units in France: incidence, molecular diversity, management and outcome. Intensive Care Med. 2008; 34: 292-9.
30. Walsh TJ, Merz WG. Pathologic features in the human alimentary tract associated with invasiveness of Candida tropicalis. Am J Clin Pathol 1986; 85: 803-8.
31. Kayabaş U. Yoğun bakım unitelerinde fungal, viral, paraziter enfeksiyonlar ve yaklaşım. Turkiye Klinikleri. 2006; 2: 50-6.
32. Yalcın AN. Fungemiler. Ulusoy S, Arman D, Uzun O, editorler. Fungal Enfeksiyonlar Ankara. Bilimsel Tıp Yayınevi. 2006: 117-30.
33. Edwards JE. Candida Species. In: Mandell, Bennett, Dolin, editorler: Principles and Practice of Infectious Diseases, 6th ed., Churchill Livingstone, 2005: 2938-57.
34. Leleu G, Aegerter P, Guidet B. Systemic candidiasis in intensive care units: a multicenter, matched-cohort study. J Crit Care. 2002; 17: 168-75.
35. Agvald-Ohman C, Klıngspor L, Hjelmqvıst, Edlund C. Invasive candidiasis in long term patients at a multidisciplinary intensive care unit: Candida colonization index, risk factors, treatment and outcome. Scand J Infect Dis. 2008; 40: 145-53.
36. Ahmed A, Azim A, Baronia AK, Marak KR, Gurjar M. Risk prediction for invasive candidiasis. Indian journal of critical care medicine: peer-reviewed, official publication Indian J Crit Care Med. 2014; 18(10): 682-8.
37. Leon C, Ruiz-Santana S, Saavedra P, Almirante B, Nolla-Salas J, Alvarez-Lerma F,et al. A bedside scoring system ("Candida score") for early antifungal treatment in nonneutropenic critically ill patients with Candida colonization. Crit Care Med. 2006; 34(3): 730-7.
38. Ibanez-Nolla J, Torres-Rodriguez JM, Nolla M, Leon MA, Mendez R, Soria G, et al. The utility of serology in diagnosing candidosis in non-neutropenic critically ill patients. Mycoses. 2001; 44: 47-53.
39. Yalcın AN. Fungemiler. Ulusoy S, Arman D, Uzun O (editorler). Fungal Enfeksiyonlar Ankara. Bilimsel Tıp Yayınevi 2006: 117-30.
40. Van Veen SQ, Claas EC, Kuijper EJ. Highthroughput identification of bacteria and yeast by matrix-assisted laser desorption ionization-time of flight mass spectrometry in conventional medical microbiology J Clin Microbiol.2010; 48(3): 900-7.
41. Meersseman W, Lagrou K, Maertens J, Wilmer A, Hermans G, Vanderschueren S, et al. Galactomannan in bronchoalveolar lavage fluid. Am J Respir Crit Care Med. 2008; 177: 27-34.
42. Azap OK, Arslan H. Tanı yontemleri. Arman D, editor. Yoğun Bakım Unitesinde Fungal Enfeksiyonlar Ankara: Bilimsel Tıp Yayınevi 2008; 19-26.
43. Cruciani M, Lalla F, Mengoli C. Prophylaxis of Candida infections in adult trauma and surgical intensive care patients: a systematic review and metaanalysis. Intensive Care Med. 2005; 31: 1479-87.
44. Yeo SF, Wong B. Current status of nonculture methods for dignosis of invasive fungal infections. Clin Microbiol Rev. 2002; 15: 465-84.
45. Singh N, Paterson DL. Aspergillus infections in transplant recipients. Clin Microbiol Rev. 2005; 18: 44-69.
46. Digby J, Kalbfleisch J, Glenn A, Larsen A, Browder W, Williams D. Serum glucan levels are not specific for presence of fungal infections in intensive care unit patients. Clin Diagn Lab Immunol. 2003; 10: 882-5.
47. Avni T, Leibovici L, Paul M. PCR diagnosis of invasive candidiasis: systematic review and meta-analysis. J Clin Microbiol. 2011; 49(2): 665-70.
48. Croxatto A, Prod’hom G, Greub G. Applications of MALDITOF mass spectrometry in clinica ldiagnostic microbiology. FEMS Microbiol Rev. 2012; 36: 380-407.
49. Yılmaz S, Duyan S, Artuk C, Diktaş H. Mikrobiyolojik tanımlamada MALDI-TOF MS uygulamaları TAF preventive. Medicine Bulletin. 2014; 13: 421-6.
50. Paramythiotou E, Frantzeskaki F, Flevari A, Armaganidis A, Dimopoulos G. Invasive fungal infections in the ICU: how to approach, how to treat. Molecules. 2014; 19(1): 1085-119.
51. Pasqualini L, Mencacci A, Leli C, Montagna P, Cardaccia A, Cenci E. Diagnostic performance of a multiple real-time PCR assay in patients with 60 suspected sepsis hospitalized in an internal medicine ward. J Clin Microbiol. 2012; 50(4): 1285-8.
52. Vazquez J, Reboli AC, Pappas PG, Patterson TF, Reinhardt J, Chin-Hong P. 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. BMC Infect Dis. 2014; 14: 97.
53. Kollef M, Micek S, Hampton N, Doherty JA, Kumar A. Septic shock attributed to Candida infection: importance of empiric therapy and source control. Clin Infec Dis. 2012; 54(12): 1739-46.
54. Strollo S, Lionakis MS, Adjemian J, Steiner CA, Prevots DR. Epidemiology of hospitalizations associated with invasive candidiasis, United States, 2002–2012. Emerg Infect Dis. 2017; 23(1): 7.
55. Cornely OA, Bassetti M, Calandra T, et al. ESCMID guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect. 2012; 18 (Suppl. 7): 19-37.
56. ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients Haematologica; 2017; 102(3): 433-44.