NON-ALBICANS SPECIES: MAIN ACTORS OF CANDIDEMIA? SEVEN-YEAR EXPERIENCE FROM A SINGLE CENTRE

Öz

Objective: Candidemia is a major cause of mortality among healthcare-associated infections. Considering the increase in non-albicans species in recent years, it is important to define the treatment approach by identifying Candida at the species level. The aim of this study was to evaluate the epidemiological characteristics, risk factors and mortality of patients with candidemia in our hospital. Material and Method: Forty-four patients with Candida species isolated from at least one bottle of blood culture taken during hospitalization between January 2013 and October 2019 were included in the study. Patients’ demographic information, comorbidities, duration of hospitalization and ward, neutropenia, total parenteral nutrition (TPN), steroid administration and invasive device use, antimicrobial treatments used in the last month, source of candidemia, acute phase indicators, Candida species and antifungal resistance, antifungal treatment, clinical response and mortality were evaluated retrospectively. Candida species and antifungal susceptibilities were identified using the automated system VITEK®2 (bioMérieux, Marcy l’Etoile, France). Results: A total of 44 patients with candidemia participated; the median age was 57, and 27 (61.3%) were male. The median length of stay was 33.5 days. Forty-two (95.4%) of the cases were accompanied by multiple comorbidities, and the most common aetiology was malignancy (59%). Most (97.7%) of the patients had received broad-spectrum antibiotic treatment in the last month. Central venous catheters (CVCs) were used in 35 (79.5%) of the cases and 50% of them were treated with TPN. Candida albicans (54.6%) was the most common species, followed by Candida tropicalis (18.2%). Non-albicans species were observed to increase over time. Thirty-day mortality was 36.3%.Conclusion: Non-albicans candidemia was found to have increased over the years in our study. The main risk factors for candidemia were determined as the presence of comorbidities, especially malignancy, prior broad-spectrum antibiotherapy use, TPN treatment and the presence of CVC. The mortality rate in this study was also consistent with the literature.

Anahtar Kelimeler

• Candidemia
• epidemiology
• risk factors

KANDİDEMİLERİN BAŞ AKTÖRÜ ALBİCANS DIŞI TÜRLER MİDİR? YEDİ YILLIK TEK MERKEZ DENEYİMİ

Öz

Amaç: Kandidemiler sağlık bakımı ile ilişkili infeksiyonlar arasında mortalitesi yüksek olan bir grubu oluşturmaktadır. Albicans dışı türlerin sebep olduğu kandidemilerin indidansındaki artış, tür düzeyinde tanımlamanın ve bu sayede etkin antifungal tedaviyi uygulamanın önemini ortaya koymuştur. Çalışmamızda; hastanemizdeki kandidemi olgularının epidemiyolojik özellikleri, risk faktörleri ve mortaliteleri açısından değerlendirilmesi amaçlanmıştır. Gereç ve Yöntem: Ocak 2013-Ekim 2019 tarihleri arasında yatışı sırasında alınan en az bir şişe kan kültüründe Candida türlerinin izole edildiği 44 hasta çalışmaya dahil edildi. Hastaların demografik bilgileri, komorbiditeleri, yatış süresi-yattığı ünite, son bir ayda yapılan cerrahi girişimler, nötropeni, total parenteral beslenme (TPN), steroid uygulaması ve invazif araç kullanımı, son bir ayda ve ayrıca kandidemi sırasında kullandığı antimikrobiyal tedaviler, kandideminin kaynağı, akut faz göstergeleri, Candida türü ve antifungal direnci, antifungal tedavi türü ve süresi, tedaviye klinik yanıt ve gelişen mortaliteler retrospektif olarak değerlendirildi. Candida türleri ve antifungal duyarlılıkları VITEK®2 (bioMérieux, Marcy l’Etoile, Fransa) otomatize sistemi ile tanımlandı. Bulgular: Toplam 44 kandidemili hastanın; ortanca yaşı 57 (0- 87), 27 (%61,3)’si erkek, 17 (%38,6)’si kadındı. Ortanca yatış süresi 33,5 gündü. Olguların 42 (%95,4)’sine çeşitli komorbiditeler eşlik etmekte olup, en sık etyoloji malignite (%59) olarak saptandı. Hastaların 43 (%97,7)’ü son bir ayda geniş spektrumlu antibiyotik tedavisi almıştı. Olguların 35 (%79,5)’inde SVK vardı ve yarısına TPN tedavisi uygulanıyordu. Tür dağılımında en sık Candida albicans (%54,6) görülürken, ikinci sırayı Candida tropicalis (%18,2) izliyordu ve zamanla albicans dışı türlerin arttığı gözlendi. Otuz günlük mortalite %36,3 olarak saptandı. Sonuç: Çalışmamızda tek merkezin kandidemi sonuçları irdelenmiş; yıllar içinde albicans dışı kandidemilerin artış gösterdiği saptanmıştır. Kandidemi için başlıca risk faktörlerinin malignite başta olmak üzere komorbiditelerin varlığı, öncesinde geniş spektrumlu antibiyoterapi uygulanması, TPN tedavisi ve SVK varlığı olarak belirlenmiştir. Mortalite oranı da literatürle uyumludur.

Anahtar Kelimeler

• Kandidemi
• epidemiyoloji
• risk faktörleri

Kaynakça

1. 1. Horn DL, Neofytos D, Anaissie EJ, Fishman JA, Steinbach WJ, Olyaei AJ, et al. Epidemiology and outcomes of candidemia in 2019 patients: data from the prospective antifungal therapy alliance registry. Clin Infect Dis 2009;48(12):1695-703.
2. 2. Willke A. Kandidemi: nasıl değerlendirilmeli ne yapılmalı. İnfeksiyon Dergisi 2007;21:117-22.
3. 3. Tortorano AM, Peman J, Bernhardt H, Klingspor L, Kibbler CC, Faure O, et al. Epidemiology of candidaemia in Europe: results of 28-month European Confederation of Medical Mycology (ECMM) hospital-based surveillance study. Eur J Clin Microbiol Infect Dis 2004;23(4):317-22.
4. 4. Eggimann P, Garbino J, Pittet D. Epidemiology of Candida species infections in critically ill non-immunosuppressed patients. Lancet Infect Dis 2003;3(11):685-702.
5. 5. Pilmis B. Yang ZT, Lontenier F, Lortholary O. Systemic Candidiasis. In: Cohen j, Powerly W, Opal S, editors. Infectious Diseases (Fourth Edition), Elsevier limited; 2017. p.439-45.
6. 6. Mylonakis E, Clancy CJ, Ostrosky-Zeichner L, Garey KW, Alangaden GJ, Vazquez JA, et al. T2 magnetic resonance assay for the rapid diagnosis of candidemia in whole blood: a clinical trial. Clin Infect Dis 2015;60(6):892-9.
7. 7. Pfaller MA, Diekema DJ, Turnidge JD, Castanheira M, Jones RN. Twenty years of the SENTRY antifungal surveillance program: results for Candida species from 1997-2016. Open Forum Infect Dis 2019;6(Suppl 1):S79-94.
8. 8. O’Grady NP, Alexander M, Burns LA, Dellinger EP, Garland J, Heard SO. Guidelines for the prevention of intravascular catheter-related infections. Clin Infect Dis 2011;52(9):e162- 93.

9. 9. Bassetti M, Merelli M, Righi E, Diaz-Martin A, Rosello EM, Luzzati R, et al. Epidemiology, species distribution, antifungal susceptibility, and outcome of candidemia across five sites in Italy and Spain. J Clin Microbiol 2013;51(12):4167-72.
10. 10. Guinea J. Global trends in the distribution of Candida species causing candidemia. Clin Microbiol Infect 2014;20(S6):5-10.
11. 11. Tragiannidis A, Fegeler W, Rellensmann G, Debus V, Müller V, Hoernig-Franz I, et al. Candidaemia in a european paediatric university hospital: a 10-year observational study. Clin Microbiol Infect 2012;18(2):E27-30.
12. 12. Almirante B, Rodríguez D, Park BJ, Cuenca-Estrella M, Planes AM, Almela M, et al. ors of mortality in cases of Candida bloodstream infection: results from populationbased surveillance, Barcelona, Spain, from 2002 to 2003. J Clin Microbiol 2005;43(4):1829-35.
13. 13. Bassetti M, Giacobbe DR, Vena A, Trucchi C, Ansaldi F, Antonelli M, 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.
14. 14. Tukenmez Tigen E, Bilgin H, Perk Gurun H, Dogru A, Ozben B, Cerikcioglu N, et al. Risk factors, characteristics, and outcomes of candidemia in an adult intensive care unit in Turkey. Am J Infect Control 2017;45(6):e61-e63.
15. 15. Yapar N, Pullukcu H, Avkan-Oguz V, Sayin-Kutlu S, Ertugrul B, Sacar S, et al. Evaluation of species distribution and risk factors of candidemia: a multicenter case-control study. Med Mycol 2011;49(1):26-31.
16. 16. Ulu Kilic A, Alp E, Cevahir F, Ture Z, Yozgat N. Epidemiology and cost implications of candidemia, a 6-year analysis from a developing country. Mycoses 2017;60(3):198-203.
17. 17. Yeşilkaya A, Azap Ö, Aydın M, Akçil Ok M. Epidemiology, species distribution, clinical characteristics and mortality of candidaemia in a tertiary care university hospital in Turkey, 2007-2014. Mycoses 2017;60(7):433-9.
18. 18. Greenberg RG, Benjamin DK Jr. Neonatal candidiasis: diagnosis, prevention, and treatment. J Infect 2014;69(1):S19-22.
19. 19. Wang H, Liu N, Yin M, Han H, Yue J, Zhang F, et al. The epidemiology, antifungal use and risk factors of death in elderly patients with candidemia: a multicentre retrospective study. BMC Infect Dis 2014;14:609.
20. 20. Luzzati R, Allegranzi B, Antozzi L, Masala L, Pegoraro E, Azzini A et al. Secular trends in nosocomial candidaemia in non-neutropenic patients in an Italian tertiary hospital. Clin Microbiol Infect 2005;11(11):908-13.
21. 21. Quindós G. Epidemiology of candidaemia and invasive candidiasis. A changing face. Rev Iberoam Micol 2014;31(1):42-8.
22. 22. Kotthoff-Burrell E. Candidemia (Blood Infection) and Other Candida Infections. Am J Respir Crit Care Med 2019;200(5):9-10.
23. 23. Bouza E, Muñoz P. Epidemiology of candidemia in intensive care units. Int J Antimicrob Agents 2008;32(2):S87-91.
24. 24. Yapar N, Akan M, Avkan-Oguz V, Ergon CM, Hancer M, Doluca M. Risk factors, incidence and outcome of candidemia in a Turkish intensive care unit: a five-year retrospective cohort study. APIC 2014;18(3):265-71.
25. 25. Yapar N. Epidemiology and risk factors for invasive candidiasis. Ther Clin Risk Manag 2014;10:95-105.
26. 26. Chen PY, Chuang YC, Wu UI, Sun HY, Wang JT, Sheng WH, et al. Clonality of fluconazole-nonsusceptable Candida tropicalis in bloodstream infections, Taiwan, 2011-2017. Emerg Infect Dis 2019;25(9):1660-7.
27. 27. Flevari A, Theodorakopoulou M, Velegraki A, Armaganidis A, Dimopoulos G. Treatment of invasive candidiasis in the elderly: a review. Clin Interv Aging 2013;8:1199-208.
28. 28. Wisplinghoff H, Ebbers J, Geurtz L, Stefanik D, Major Y, Edmond MB, et al. Nosocomial bloodstream infections due to Candida spp. in the USA: species distribution, clinical features and antifungal susceptibilities. Int J Antimicrob Agents 2014;43(1):78-81.
29. 29. Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, et al. Clinical practice guideline for the management of Candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 2016;62:e1-50.
30. 30. Falcone M, Giusy T, Gutiérrez-Gutiérrez B, Giammarco R, Paolo C, Chiara R, et al. Impact of initial antifungal therapy on the outcome of patients with candidemia and septic shock admitted to medical wards: A propensity score– adjusted analysis. Open Forum Infect Dis 2019;6(7):ofz251.