The Evaluatıon of Antıfungal Consumption: Multi Central Point-Prevalence Survey of Western Turkey

Öz

Objective: Antifungal consumption has increased in recent years due to new agents on the market. This increase leads to concern about drug resistance. Data about antifungal prescription in our country is limited. The aim of this study is to evaluate antifungal consumption in seven university hospital. Materials and Methods: A form was designed to record patients’ data. The antifungal consumption at the west side of Turkey in seven University Hospital were evaluated by point prevalence. Hospitalized patients with antifungal treatment were determined and the designed forms were filled at the scheduled day. SPSS was used to determine significance of data. Results: There were 4969 hospitalized patients totally and 112 (2.2%) of them were treated with antifungal agents at the day of point-prevalance. Out of 112 patients 56 (50%) were in hematology-oncology, 20 (17.8%) in ICU (intensive care unit), 23 (20.5%) in internal medicine and 13 (11.6%) in surgery clinics. Fluconazole [44 (39.3%)] was the most used antifungal agent, 34% of them had been using oral fluconazole for prophylaxis. All of the treatments, 38% were defined as targeted, 26.8% as empirical and 18.8% as pre-emptive. When the treatment indications were evaluated according to the clinic, the most pre-emptive antifungal usage was in the hemato-oncology clinic, 71.4% (15/21), while the empirical treatment was mostly used as 50% in the intensive care units. Conclusion: In this study antifungal consumption rate was 2.2%. Antifungal agents were mostly used in hematology and internal medicine clinics. The reason of starting an antifungal treatment was ‘proven fungal infection’ mostly. Although the most frequent isolated pathogens were Candida species, the choice of antifungal agent depended on the clinic where the patient was hospitalized. There was no significantly difference between the university hospitals according to antifungal consumption. This may be explained by the antifungal prescription policy in our country. Depending on this results the hospitals should monitor their own fungal pathogens. And according to isolated fungal pathogens antifungal treatment policy should be improved

Anahtar Kelimeler

• Antifungal consumption
• point prevalence
• invasive fungal infections

Antifungal Kullanımının Değerlendirilmesi: Türkiyenin Batısına Ait Çok Merkezli Nokta Prevelans Çalışması

Öz

Giriş ve Amaç: Son yıllarda yeni ajanların da kullanıma girmesiyle birlikte antifungal tüketimi giderek artmıştır. Bu durum, direnç gelişimi konusunda endişelere neden olmaktadır. Ülkemizde antifungal tüketimine ait veriler oldukça sınırlıdır. Bu çalışmada, Türkiye’nin batısındaki yedi üniversite hastanesinde yatan hastalarda antifungal kullanımının değerlendirilmesi amaçlanmıştır. Gereç ve Yöntemler: Çalışma ekibi tarafından hazırlanan antifungal kullanım formu, tüm merkezler tarafından, aynı gün içinde, antifungal kullanan tüm hastalar için, nokta prevalans yöntemi ile dolduruldu, elde edilen veriler SPSS programı ile değerlendirildi. Bulgular: Toplam hasta sayısı 4969 idi. Hastaların 112(%2.2) ’si antifungal tedavi almaktaydı. Bu 112 hastanın verileri değerlendirildiğinde; antifungal kullanan hastaların 56 (%50)’sı hematoloji-onkoloji, 20 (%17,8)’si yoğun bakım (YB), 23 (%20,5)’ü dahili bilimler ve 13 (%11,6)’ü cerrahi bilimlerde izlenmekteydi. En sık kullanılan antifungal flukonazol [44(%39,3)] olup %34.1’i profilaksi amacı ile kullanılmaktaydı. Tedavilerin %38’i hedefe yönelik, %26.8’i ampirik ve %18,8’i preemptif olarak tanımlanmıştı. Yattığı kliniğe göre tedavi endikasyonları değerlendirildiğinde en çok pre-emptif antifungal kullanımı hemato-onkoloji kliniğinde %71.4 (15/21) görülürken ampirik tedavi en çok yoğun bakımlarda %50 olmuştur. Sonuç: Çalışmamızda antifungal tüketim oranı %2.2 olup, antifungal ajanlar daha çok hematoloji ve dahili birimlerde kullanılmıştır. Antifungal tedaviye başlama nedeni en fazla 'kanıtlanmış mantar infeksiyonu' olarak gözlenmiştir. En sık izole edilen patojenler Candida türleri olmasına rağmen, antifungal ajan seçimi hastanın yattığı kliniğe bağlıdır. Antifungal tüketim açısından yedi merkez arasında anlamlı fark gözlenmemiştir. Bu durum ülkemizdeki antifungal kullanımı politikası ile açıklanabilir. Bu sonuçlara bağlı olarak her hastane kendi verilerini izlemelidir ve izole edilen fungal patojenlere göre antifungal tedavi politikası geliştirilmelidir.

Anahtar Kelimeler

• Antifungal kullanımı
• nokta prevalans
• invaziv fungal infeksiyonlar

Kaynakça

1. Referans 1. Kohler JR, Casadevall A, Perfect J. The spectrum of fungi that infects humans. Cold Spring Harbor Perspect Med. 2015;5:a019273.
2. Referans 2. Enoch DA, Yang H, Aliyu SH, Micallef C.The Changing Epidemiology of Invasive Fungal Infections. Methods Mol Biol. 2017;1508:17-65
3. Referans 3. Hilmioğlu-Polat S, Seyedmousavi S, Ilkit M, Hedayati MT, Inci R, Tumbay E, Denning DW. Estimated burden of serious human fungal diseases in Turkey. Mycoses. 2019 Jan;62(1):22-31. doi: 10.1111/myc.12842.
4. Referans 4. Hazar V, Tezcan Karasu G, Uygun V, et al. Risks and outcomes of invasive fungal infections in pediatric allogeneic hematopoietic stem cell transplant recipients receiving fluconazole prophylaxis: a multicenter cohort study by the Turkish Pediatric Bone Marrow Transplantation Study Group. Med Mycol. 2018. https://doi. org/10.1093/mmy/myy015
5. Referans 5. Vallabhaneni S, Baggs J, Tsay S, Srinivasan AR, Jernigan JA, Jackson BR.Trends in antifungal use in US hospitals, 2006-12. J Antimicrob Chemother. 2018 Oct 1;73(10):2867-2875.
6. Referans 6. Çağlar İ, Devrim İ, Özdemir H, Şahbudak Z, Sönmez G, Buyukcam A et. al. Antifungal consumption, indications and selection of antifungal drugs in paediatric tertiary hospitals in Turkey: Results from the first national point prevalence survey. J Glob Antimicrob Resist. 2018 (15):232-238.
7. Referans 7.Hamdy RF, Zaoutis TE, Seo SK. Antifungal stewardship considerations for adults and pediatrics. Virulence. 2017 Referans 8. Senol S, Eren-Kutsoylu O, Turhan O, Alp-Cavus S, Tasbakan M, et al. The evaluation of antifungal consumption: a point-prevalence survey Sep 2017 | Mycoses 60, pp.143-144
8. Referans 9. De Pauw B, Walsh TJ, Donnelly JP, et al; 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) Consensus Group. Clin Infect Dis 2008; 46:1813–21.

9. Referans 10. Açıkel A, Tezcan-Keleş G. Yoğun Bakım Ünitesi Enfeksiyonlarında Antibiyotik Kullanımı. Celal Bayar Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi 2017; 4(1): 571-573
10. Referans 11. 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 Jul;60(7):433-439
11. Referans 12. Meyer E, Schwab F, Gastmeier P, Ruden H, Heininger A. Antifungal use in intensive care units. J Antimicrob Chemother 2007; 60:619-24 Referans 13. Gross BN, Steib-Bauert M, Kern WV, Knoth H, Borde JP, Krebs S, et al. Hospital use of systemic antifungal drugs: a multi-center surveillance update from Germany. Infection 2015; 43:423-9.
12. Referans 14. Fung M, Kim J, Marty FM, Schwarzinger M, Koo S. Meta-Analysis and Cost Comparison of Empirical versus Pre-Emptive Antifungal Strategies in Hematologic Malignancy Patients with High-Risk Febrile Neutropenia. PLoS One 2015 Nov 10;10(11):e0140930.
13. Referans 15. Cordonnier C, Pautas C, Maury S, Vekhoff A, Farhat H, Suarez F et al. Empirical versus preemptive antifungal therapy for high-risk, febrile, neutropenic patients: a randomized, controlled trial. Clin Infect Dis. 2009 Apr 15;48(8):1042-51.
14. Referans 16. Maertens J, Theunissen K, Verhoef G, Verschakelen J, Lagrou K, Verbeken E, Wilmer A, et al. Galactomannan and computed tomography-based preemptive antifungal therapy in neutropenic patients at high risk for invasive fungal infection: a prospective feasibility study. Clin Infect Dis. 2005 Nov 1;41(9):1242-50.
15. Referans 17. Giacobbe DR, Maraolo AE, Simeon V, Magnè F, Pace MC, Gentile I et al. Changes in the relative prevalence of candidaemia due to non-albicans Candida species in adult in-patients: A systematic review, meta-analysis and meta-regression. Mycoses. 2020 Apr;63(4):334-342.
16. Referans 18. Ethier MC, Science M, Beyene J, Briel M, Lehrnbecher T, Sung L. Mould-active compared with fluconazole prophylaxis to prevent invasive fungal diseases in cancer patients receiving chemotherapy or haematopoietic stem-cell transplantation: a systematic review and meta-analysis of randomised controlled trials. Br J Cancer. 2012 May 8;106(10):1626-37.
17. Referans 19. Tissot F, Agrawal S, Pagano L, Petrikkos G, Groll AH, Skiada A, et al. ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica. 2017 Mar;102(3):433-444. doi: 10.3324/haematol.2016.152900.
18. Referans20. Dirican N. Kaviter akciğer lezyonu ile başvuran Hodkgin lenfoma olgusu. CBU-SBED; 2016: 3(2), 178-180
19. Referans 21. Özatik FY, Tunga Babaoğlu Ü, Erol K, Arslantaş D, Kaygısız B. The Assessment of Knowledge and Attitudes of Personnels working in a Training and Research Hospital located in Central Anatolia on Rational Drug Use. CBU-SBED: 2018, 5(1):10-16