Yıl: 2015 Cilt: 45 Sayı: 1 Sayfa Aralığı: 1 - 11 Metin Dili: Türkçe İndeks Tarihi: 29-07-2022

Candida ve Kandidoz: Epidemiyoloji, Tanı, Tedavi,Antifungal İlaç Direnci ve Konağın Genetik Yatkınlığında Güncel Durum

Öz:
Candida türleri, ökaryot fırsatçı patojenler olup hastane enfeksiyonu etkenleri arasında dünyada ön sıralarda yer almaktadır. Amerika'da hastanelerde gelişen nozokomiyal kan dolaşımı enfeksiyonlarının dördüncü sıklıktaki etkeni Candida türleridir. Avrupa'da kandidemi oranı ise her 100.000 kişide 1.2 ile 11 arasında değişmektedir. Candida'ların 200'den fazla türü bulunur, bunlar arasında dissemine kandidoz ile invazif olmayan deri ve mukoza kandidozlarının en sık nedeni Candida albicans'tır. Bununla birlikte, C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, C. lusitaniae, C. dubliniensis ve C. guilliermondii gibi albicans-dışı Candida türlerine bağlı kandidoz insidansı artmaktadır. Candida enfeksiyonunun hangi klinik şekilde sonlanacağı primer olarak konak savunması tarafından belirlenir. Klinik tablolar, deri ve mukoza kandidozları ile derin yerleşimli enfeksiyonlar olmak üzere iki gruba ayrılır. Deri ve mukoza enfeksiyonları içerisinde pamukçuk, Candida özefajiti, özefagus-dışı gastrointestinal kandidoz, Candida vaginiti ve deri kandidozu yer alır. Derin yerleşimli enfeksiyonlar; kronik dissemine kandidoz (hepatosplenik kandidoz), kandidemi ve çeşitli organların kandidozunu içerir. Mantar, invazif enfeksiyon oluşturmasına yardımcı olabilecek olan, proteinaz ve lipaz gibi enzimleri salgılama yeteneğindedir. Ancak, bu enzimlerin klinik açıdan önemi henüz aydınlatılamamıştır. Amerikan Enfeksiyon Hastalıkları Derneğinin Mikoz Çalışma Grubu (IDSA) ve Avrupa Klinik Mikrobiyoloji ve Enfeksiyon Hastalıkları Derneğinin Mantar Çalışma Grubu (ESCMID), farklı hasta gruplarında invazif kandidozun tedavisi için pratik kılavuzlar yayınlamışlardır. Vurgulanması gerekli bir diğer hususda, tedavi için önemli ölçütlerden birisinin de antifungal ilaç direnci olduğudur. Candida türleri, ilaçların hücre içerisine birikimini azaltan dışa atım pompalarının salınımı ile, antifungal hedef proteinlerinin yoğunluğunu ve yapısını değiştirerek veya hücre zarındaki sterol bileşimini değiştirerek antifungal ilaçlara karşı direnç geliştirebilirler. Ayrıca, kandidozların gelişmesinde genel risk faktörlerinin (örnek: bağışıklık sisteminin baskılanması) rolü önemli olmasına rağmen, bu durum tüm Candida enfeksiyonlarının gelişimini açıklamak için yeterli değildir. Birçok araştırmada; genetik farklılıklar ile kandidoz riski artışı arasında bir ilişkinin olduğu, mukoza kandidozu ve sistemik kandidozu ayırt ettirici farklı genetik yapıların bulunduğu bildirilmiştir. Bu makalede, Candida cinsi maya mantarlarının neden olduğu enfeksiyonların epidemiyolojisi, tanısı, tedavisi, antifungal ilaç direnci ve konak genetik yatkınlıklarına ilişkin güncel bilgiler özetlenmektedir
Anahtar Kelime:

Konular: Mantar Bilimi Mikrobiyoloji Biyoteknoloji ve Uygulamalı Mikrobiyoloji Enfeksiyon Hastalıkları

Candida and Candidosis: Updates on Epidemiology, Diagnosis, Treatment Antifungal Drug Resistance, and Host Genetic Susceptibility

Öz:
Candida and Candidosis: Updates on Epidemiology, Diagnosis, Treatment, Antifungal Drug Resistance, and Host Genetic SusceptibilityCandida species are eukaryotic fungal pathogens known to be aetiological agents of opportunistic and nosocomial infections in humans worldwide. Candida spp. are the fourth most common cause of nosocomial bloodstream infections acquired in hospitals in the United States. In Europe, candidemia rates vary between 1.2 and 11 per 100.000 population. There are over 200 species of Candida yeasts; among them, Candida albicans is the most common cause of disseminated and non-invasive mucocutaneous diseases. However, the incidence of candidosis due to non-albicans Candida spp. is increasing, including: C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, C. lusitaniae, C. dubliniensis and C. guilliermondii. The clinical outcome of Candida infections is primarily determined by the host's defense status and can be divided into mucocutaneous infections and deep-seated infections. Mucocutaneous infections include thrush, Candida esophagitis, nonesophageal gastrointestinal candidosis, Candida vaginitis, and cutaneous candidosis syndromes. Deep-seated infections include chronic disseminated candidosis (hepatosplenic candidosis), candidemia, and candidosis of various organ systems. The fungus is capable of secreting proteinases and lipases that can assist invasion, although the clinical importance of these enzymes is not clearBoth the Mycoses Study Group of the Infectious Diseases Society of America (IDSA) and the Infectious Diseases Group of the European Organisation for Research and Treatment of Cancer (EORTC) have published practice guidelines for the treatment of invasive candidosis in various patient populations. Of note, antifungal drug resistance was an important factor that needed to be considered for treatment. Candida spp. became resistant to antifungal agents due to the expression of efflux pumps that reduces drug accumulation, alteration of the structure or concentration of antifungal target proteins, and alteration of membrane sterol composition. Moreover, despite the important role played by general risk factors, i.e., an immunocompromised immune system, they did not explain all cases of infection. Several studies reported a link between genetic variation and an increased risk for Candida infections, with a different genetic pattern being discerned between mucosal and systemic candidosis. This article summarizes up-to-date information on the epidemiology, diagnosis, and treatment of infections caused by the genus Candida, as well as antifungal drug resistance and host genetic susceptibility in affected patients.
Anahtar Kelime:

Konular: Mantar Bilimi Mikrobiyoloji Biyoteknoloji ve Uygulamalı Mikrobiyoloji Enfeksiyon Hastalıkları
Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1. Pfaller MA, Andes DR, Diekema DJ, 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; 9:e101510. http://dx.doi.org/10.1371/journal.pone.0101510
  • 2. Pfaller MA, Diekema DJ, Jones RN, et al. International surveillance of bloodstream infections due to Candida species: frequency of occurrence and in vitro susceptibilities to fluconazole, ravuconazole, and voriconazole of isolates collected from 1997 through 1999 in the SENTRY antimicrobial surveillance program. J Clin Microbiol 2001; 39:3254-9. http://dx.doi.org/10.1128/JCM.39.9.3254-3259.2001
  • 3. Arendrup MC. Epidemiology of invasive candidiasis. Curr Opin Crit Care 2010; 16:445-52. http://dx.doi.org/10.1097/MCC.0b013e32833e84d2
  • 4. Jarvis WR. Epidemiology of nosocomial fungal infections, with emphasis on Candida species. Clin Infect Dis 1995; 20:1526-30. http://dx.doi.org/10.1093/clinids/20.6.1526
  • 5. Bitar D, Lortholary O, Le Strat Y, et al. Populationbased analysis of invasive fungal infections, France, 2001-2010. Emerg Infect Dis 2014; 20:1149-55. http://dx.doi.org/10.3201/eid2007.140087
  • 6. Marr KA, Seidel K, Slavin MA, et al. Prolonged fluconazole prophylaxis is associated with persistent protection against candidiasis-related death in allogeneic marrow transplant recipients: long-term follow-up of a randomized, placebo-controlled trial. Blood 2000; 96:2055-61.
  • 7. Kanda Y, Yamamoto R, Chizuka A, et al. Prophylactic action of oral fluconazole against fungal infection in neutropenic patients. A meta-analysis of 16 randomized, controlled trials. Cancer 2000; 89:1611-25. http://dx.doi.org/10.1002/1097-0142(20001001)89:7_____1 611::AID-CNCR27>3.0.CO;2-B
  • 8. Neofytos D, Horn D, Anaissie E, et al. Epidemiology and outcome of invasive fungal infection in adult hematopoietic stem cell transplant recipients: analysis of Multicenter Prospective Antifungal Therapy (PATH) Alliance registry. Clin Infect Dis 2009; 48:265-73. http://dx.doi.org/10.1086/595846
  • 9. Das I, Nightingale P, Patel M, Jumaa P. Epidemiology, clinical characteristics, and outcome of candidemia: experience in a tertiary referral center in the UK. Int J Infect Dis 2011; 15:e759-63. http://dx.doi.org/10.1016/j.ijid.2011.06.006
  • 10. Fan YC, Li WG, Zheng MH, Gao W, Zhang YY, Song LJ. Invasive fungal infection in patients with systemic lupus erythematosus: experience from a single institute of Northern China. Gene 2012; 506:184-7. http://dx.doi.org/10.1016/j.gene.2012.06.059
  • 11. Grabar S, Lanoy E, Allavena C, et al. Causes of the first AIDS-defining illness and subsequent survival before and after the advent of combined antiretroviral therapy. HIV Med 2008; 9:246-56. http://dx.doi.org/10.1111/j.1468-1293.2008.00554.x
  • 12. Viscoli C, Girmenia C, Marinus A, et al. Candidemia in cancer patients: A prospective, multicenter surveillance study by the Invasive Fungal Infection Group (IFIG) of the European Organization for Research and Treatment of Cancer (EORTC). Clin Infect Dis 1999; 28:1071-9. http://dx.doi.org/10.1086/514731
  • 13. Matthews RC. Pathogenicity determinants of Candida albicans: potential targets for immunotherapy? Microbiology 1994; 140(Pt7):1505-11. http://dx.doi.org/10.1099/13500872-140-7-1505
  • 14. Glockner A. Recurrent candidaemia and pacemaker wire infection with Candida albicans. Mycoses 2011; 54(Suppl 4):S20-3. http://dx.doi.org/10.1111/j.1439-0507.2011.02139.x
  • 15. Donlan RM, Costerton JW. Biofilms: survival mechanisms of clinically relevant microorganisms. Clin Microbiol Rev 2002; 15:167-93. http://dx.doi.org/10.1128/CMR.15.2.167-193.2002
  • 16. De Cremer K, Delattin N, De Brucker K, et al. Oral administration of the broad-spectrum antibiofilm compound toremifene inhibits Candida albicans and Staphylococcus aureus biofilm formation in vivo. Antimicrob Agents Chemother 2014; 58:7606-10. http://dx.doi.org/10.1128/AAC.03869-14
  • 17. Chambô Filho A, Souza Filho JB, Pignaton CC, Zon I, Fernandes AS, Cardoso LQ. Chronic mucocutaneous candidiasis: a case with exuberant cutaneous horns in nipples. An Bras Dermatol 2014; 89:641-4. http://dx.doi.org/10.1590/abd1806-4841.20143020
  • 18. Mastrolorenzo A, Giomi B, Cipollini EM, et al. Mycetomatoid infection of the penis by Candida albicans. Int J Dermatol 2012; 51:1082-5. http://dx.doi.org/10.1111/j.1365-4632.2011.05386.x
  • 19. Jalalat S, Hunter L, Yamazaki M, Head E, Kelly B. An outbreak of Candida albicans folliculitis masquerading as Malassezia folliculitis in a prison population. J Correct Health Care 2014; 20:154-62. http://dx.doi.org/10.1177/1078345813518636
  • 20. Bahunuthula RK, Thappa DM, Kumari R, Singh R, Munisamy M, Parija SC. Evaluation of role of Candida in patients with chronic paronychia. Indian J Dermatol Venereol Leprol 2015; 81:485-90. http://dx.doi.org/10.4103/0378-6323.158635
  • 21. Plantinga TS, Johnson MD, Scott WK, et al. Human genetic susceptibility to Candida infections. Med Mycol 2012; 50:785-94. http://dx.doi.org/10.3109/13693786.2012.690902
  • 22. Smeekens SP, van de Veerdonk FL, Kullberg BJ, Netea MG. Genetic susceptibility to Candida infections. EMBO Mol Med 2013; 5:805-13. http://dx.doi.org/10.1002/emmm.201201678
  • 23. Ferwerda B, Ferwerda G, Plantinga TS, et al. Human dectin-1 deficiency and mucocutaneous fungal infections. N Engl J Med 2009; 361:1760-7. http://dx.doi.org/10.1056/NEJMoa0901053
  • 24. Plantinga TS, van der Velden WJ, Ferwerda B, et al. Early stop polymorphism in human DECTIN-1 is associated with increased candida colonization in hematopoietic stem cell transplant recipients. Clin Infect Dis 2009; 49:724-32. http://dx.doi.org/10.1086/604714
  • 25. Plantinga TS, Johnson MD, Scott WK, et al. Toll-like receptor 1 polymorphisms increase susceptibility to candidemia. J Infect Dis 2012; 205:934-43. http://dx.doi.org/10.1093/infdis/jir867
  • 26. Nahum A, Dadi H, Bates A, Roifman CM. The L412F variant of Toll-like receptor 3 (TLR3) is associated with cutaneous candidiasis, increased susceptibility to cytomegalovirus, and autoimmunity. J Allergy Clin Immunol 2011; 127:528-31. http://dx.doi.org/10.1016/j.jaci.2010.09.031
  • 27. Babula O, Lazdane G, Kroica J, Ledger WJ, Witkin SS. Relation between recurrent vulvovaginal candidiasis, vaginal concentrations of mannose-binding lectin, and a mannose-binding lectin gene polymorphism in Latvian women. Clin Infect Dis 2003; 37:733-7. http://dx.doi.org/10.1086/377234
  • 28. Lev-Sagie A, Prus D, Linhares IM, Lavy Y, Ledger WJ, Witkin SS. Polymorphism in a gene coding for the inflammasome component NALP3 and recurrent vulvovaginal candidiasis in women with vulvar vestibulitis syndrome. Am J Obstet Gynecol 2009; 200:303.e1-6. http://dx.doi.org/10.1016/j.ajog.2008.10.039
  • 29. Choi EH, Foster CB, Taylor JG, et al. Association between chronic disseminated candidiasis in adult acute leukemia and common IL4 promoter haplotypes. J Infect Dis 2003; 187:1153-6. http://dx.doi.org/10.1086/368345
  • 30. Jurevic RJ, Bai M, Chadwick RB, White TC, Dale BA. Single-nucleotide polymorphisms (SNPs) in human beta-defensin 1: high-throughput SNP assays and association with Candida carriage in type I diabetics and nondiabetic controls. J Clin Microbiol 2003; 41:90-6. http://dx.doi.org/10.1128/JCM.41.1.90-96.2003
  • 31. Glocker EO, Hennigs A, Nabavi M, et al. A homozygous CARD9 mutation in a family with susceptibility to fungal infections. N Engl J Med 2009; 361:1727-35. http://dx.doi.org/10.1056/NEJMoa0810719
  • 32. van de Veerdonk FL, Plantinga TS, Hoischen A, et al. STAT1 mutations in autosomal dominant chronic mucocutaneous candidiasis. N Engl J Med 2011; 365:54-61. http://dx.doi.org/10.1056/NEJMoa1100102
  • 33. Lilic D. New perspectives on the immunology of chronic mucocutaneous candidiasis. Curr Opin Infect Dis 2002; 15:143-7. http://dx.doi.org/10.1097/00001432-200204000-00007
  • 34. Björses P, Aaltonen J, Horelli-Kuitunen N, Yaspo ML, Peltonen L. Gene defect behind APECED: a new clue to autoimmunity. Hum Mol Genet 1998; 7:1547- 53. http://dx.doi.org/10.1093/hmg/7.10.1547
  • 35. Puel A, Döffinger R, Natividad A, et al. Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I. J Exp Med 2010; 207:291-7. http://dx.doi.org/10.1084/jem.20091983
  • 36. Sun RT, Tian WJ, Xing XW, Gao SH, Wang SB. Association of cytokine gene polymorphisms with susceptibility to invasive candidiasis. Genet Mol Res 2015; 14:6859-64. http://dx.doi.org/10.4238/2015.June.18.29
  • 37. Arendrup MC, Sulim S, Holm A, et al. Diagnostic issues, clinical characteristics, and outcomes for patients with fungemia. J Clin Microbiol 2011; 49:3300-8. http://dx.doi.org/10.1128/JCM.00179-11
  • 38. Meyer MH, Letscher-Bru V, Jaulhac B, Waller J, Candolfi E. Comparison of Mycosis IC/F and plus Aerobic/F media for diagnosis of fungemia by the bactec 9240 system. J Clin Microbiol 2004; 42:773-7. http://dx.doi.org/10.1128/JCM.42.2.773-777.2004
  • 39. Cuenca-Estrella M, Verweij PE, Arendrup MC, et al. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: diagnostic procedures. Clin Microbiol Infect 2012; 18(Suppl 7): S9-18. http://dx.doi.org/10.1111/1469-0691.12038
  • 40. Dhiman N, Hall L, Wohlfiel SL, Buckwalter SP, Wengenack NL. Performance and cost analysis of matrix-assisted laser desorption ionization-time of flight mass spectrometry for routine identification of yeast. J Clin Microbiol 2011; 49:1614-6. http://dx.doi.org/10.1128/JCM.02381-10
  • 41. Spanu T, Posteraro B, Fiori B, et al. Direct maldi-tof mass spectrometry assay of blood culture broths for rapid identification of Candida species causing bloodstream infections: an observational study in two large microbiology laboratories. J Clin Microbiol 2012; 50:176-9. http://dx.doi.org/10.1128/JCM.05742-11
  • 42. Lamoth F, Jaton K, Prod'hom G, et al. Multiplex blood PCR in combination with blood cultures for improvement of microbiological documentation of infection in febrile neutropenia. J Clin Microbiol 2010; 48:3510-6. http://dx.doi.org/10.1128/JCM.00147-10
  • 43. Lucignano B, Ranno S, Liesenfeld O, et al. Multiplex PCR allows rapid and accurate diagnosis of bloodstream infections in newborns and children with suspected sepsis. J Clin Microbiol 2011; 49:2252-8. http://dx.doi.org/10.1128/JCM.02460-10
  • 44. Wallet F, Nseir S, Baumann L, et al. Preliminary clinical study using a multiplex real-time PCR test for the detection of bacterial and fungal DNA directly in blood. Clin Microbiol Infect 2010; 16:774-9. http://dx.doi.org/10.1111/j.1469-0691.2009.02940.x
  • 45. Lau A, Chen S, Sorrell T, et al. Development and clinical application of a panfungal PCR assay to detect and identify fungal DNA in tissue specimens. J Clin Microbiol 2007; 45:380-5. http://dx.doi.org/10.1128/JCM.01862-06
  • 46. Lau A, Halliday C, Chen SC, Playford EG, Stanley K, Sorrell TC. Comparison of whole blood, serum, and plasma for early detection of candidemia by multiplex-tandem PCR. J Clin Microbiol 2010; 48:811-6. http://dx.doi.org/10.1128/JCM.01650-09
  • 47. McMullan R, Metwally L, Coyle PV, et al. A prospective clinical trial of a real-time polymerase chain reaction assay for the diagnosis of candidemia in nonneutropenic, critically ill adults. Clin Infect Dis 2008; 46:890-6. http://dx.doi.org/10.1086/528690
  • 48. Wellinghausen N, Siegel D, Winter J, Gebert S. Rapid diagnosis of candidaemia by real-time PCR detection of Candida DNA in blood samples. J Med Microbiol 2009; 58(Pt 8):1106-11. http://dx.doi.org/10.1099/jmm.0.007906-0
  • 49. Avni T, Leibovici L, Paul M. PCR diagnosis of invasive candidiasis: systematic review and meta-analysis. J Clin Microbiol 2011; 49:665-70. http://dx.doi.org/10.1128/JCM.01602-10
  • 50. Subcommittee on Antifungal Susceptibility Testing of the ESCMID European Committee for Antimicrobial Susceptibility Testing (EUCAST). EUCAST definitive document EDef 7.1: method for the determination of broth dilution MICs of antifungal agents for fermentative yeasts. Clin Microbiol Infect 2008; 14:398-405. http://dx.doi.org/10.1111/j.1469-0691.2007.01935.
  • 51. Clinical and Laboratory Standards Institute. Reference method for broth dilution antifungal susceptibility testing of yeasts. Approved standard. 3rd ed. CLSI Document M27-A3, CLSI, Wayne, PA, 2008.
  • 52. Pfaller MA. Antifungal drug resistance: mechanisms, epidemiology, and consequences for treatment. Am J Med 2012; 125(1 Suppl):S3-13. http://dx.doi.org/10.1016/j.amjmed.2011.11.001
  • 53. Antifungal Susceptibility Testing Subcommittee of the European Committee on Antimicrobial Susceptibility Testing. EUCAST definitions of clinical breakpoints and epidemiological cut-off values. European Committee on Antimicrobial Susceptibility Testing, AFST-EUCAST, 2013.
  • 54. Arendrup MC, Cuenca-Estrella M, Lass-Flörl C, et al. EUCAST technical note on Candida and micafungin, anidulafungin and fluconazole. Mycoses 2014; 57: 377-9.
  • 55. The European Committee on Antimicrobial Susceptibility Testing - Subcommittee on Antifungal Susceptibility Testing (EUCAST-AFST). EUCAST Technical Note on fluconazole. Clin Microbiol Infect 2008; 14:193-5. http://dx.doi.org/10.1111/j.1469-0691.2007.01899.x
  • 56. The European Committee on Antimicrobial Susceptibility Testing - Subcommittee on Antifungal Susceptibility Testing (EUCAST-AFST). EUCAST Technical Note on voriconazole. Clin Microbiol Infect 2008; 14: 985-7. http://dx.doi.org/10.1111/j.1469-0691.2008.02087.x
  • 57. Pfaller MA, Diekema DJ, Sheehan DJ. Interpretive breakpoints for fluconazole and Candida revisited: a blueprint for the future of antifungal susceptibility testing. Clin Microbiol Rev 2006; 19:435-47. http://dx.doi.org/10.1128/CMR.19.2.435-447.2006
  • 58. Rodríguez-Tudela JL, Almirante B, RodríguezPardo D, et al. Correlation of the MIC and dose/MIC ratio of fluconazole to the therapeutic response of patients with mucosal candidiasis and candidemia. Antimicrob Agents Chemother 2007; 51:3599-604. http://dx.doi.org/10.1128/AAC.00296-07
  • 59. Arendrup MC, Cuenca-Estrella M, Lass-Flörl C, Hope WW. Breakpoints for antifungal agents: an update from EUCAST focussing on echinocandins against Candida spp. and triazoles against Aspergillus spp. Drug Resist Updat 2013; 16:81-95. http://dx.doi.org/10.1016/j.drup.2014.01.001
  • 60. Cowen LE, Sanglard D, Howard SJ, Rogers PD, Perlin DS. Mechanisms of antifungal drug resistance. Cold Spring Harb Perspect Med 2014; 5:a019752. http://dx.doi.org/10.1101/cshperspect.a019752
  • 61. Perlin DS, Shor E, Zhao Y. Update on antifungal drug resistance. Curr Clin Microbiol Rep 2015; 2:84-95. http://dx.doi.org/10.1007/s40588-015-0015-1
  • 62. Sanglard D, Odds FC. Resistance of Candida species to antifungal agents: molecular mechanisms and clinical consequences. Lancet Infect Dis 2002; 2:73-85. http://dx.doi.org/10.1016/S1473-3099(02)00181-0
  • 63. Cuenca-Estrella M. Antifungal drug resistance mechanisms in pathogenic fungi: from bench to bedside. Clin Microbiol Infect 2014; 20 (Suppl 6):S54-9. http://dx.doi.org/10.1111/1469-0691.12495
  • 64. Kanafani ZA, Perfect JR. Antimicrobial resistance: resistance to antifungal agents: mechanisms and clinical impact. Clin Infect Dis 2008; 46:120-8. http://dx.doi.org/10.1086/524071
  • 65. Perlin DS. Mechanisms of echinocandin antifungal drug resistance. Ann N Y Acad Sci 2015; 1354:1-11. http://dx.doi.org/10.1111/nyas.12831
  • 66. Perlin DS. Resistance to echinocandin-class antifungal drugs. Drug Resist Updat 2007; 10:121-30. http://dx.doi.org/10.1016/j.drup.2007.04.002
  • 67. Wang E, Farmakiotis D, Yang D, et al. The ever-evolving landscape of candidaemia in patients with acute leukaemia: non-susceptibility to caspofungin and multidrug resistance are associated with increased mortality. J Antimicrob Chemother 2015; 70:2362-8. http://dx.doi.org/10.1093/jac/dkv087
  • 68. Farmakiotis D, Tarrand JJ, Kontoyiannis DP. Drug-resistant Candida glabrata infection in cancer patients. Emerg Infect Dis 2014; 20:1833-40. http://dx.doi.org/10.3201/eid2011.140685
  • 69. Alexander BD, Johnson MD, Pfeiffer CD, et al. Increasing echinocandin resistance in Candida glabrata: clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations. Clin Infect Dis 2013; 56:1724-32. http://dx.doi.org/10.1093/cid/cit136
  • 70. 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):S19-37. http://dx.doi.org/10.1111/1469-0691.12039
  • 71. Hope WW, Castagnola E, Groll AH, et al. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: prevention and management of invasive infections in neonates and children caused by Candida spp. Clin Microbiol Infect 2012; 18(Suppl 7):S38-52. http://dx.doi.org/10.1111/1469-0691.12040
  • 72. Lortholary O, Petrikkos G, Akova M, et al. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: patients with HIV infection or AIDS. Clin Microbiol Infect 2012; 18(Suppl 7):S68-77. http://dx.doi.org/10.1111/1469-0691.12042
  • 73. Ullmann AJ, Akova M, Herbrecht R, et al. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: adults with haematological malignancies and after haematopoietic stem cell transplantation (HCT). Clin Microbiol Infect 2012; 18(Suppl 7):S53-67. http://dx.doi.org/10.1111/1469-0691.12041
  • 74. Ullmann AJ, Cornely OA, Donnelly JP, et al. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: developing European guidelines in clinical microbiology and infectious diseases. Clin Microbiol Infect 2012; 18(Suppl 7):S1-8. http://dx.doi.org/10.1111/1469-0691.12037
  • 75. Pappas PG, Kauffman CA, Andes D, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 2009; 48:503-35. http://dx.doi.org/10.1086/596757
  • 76. Fernández-Ruiz M, Aguado JM, Almirante B, et al. Initial use of echinocandins does not negatively influence outcome in Candida parapsilosis bloodstream infection: a propensity score analysis. Clin Infect Dis 2014; 58:1413-21. http://dx.doi.org/10.1093/cid/ciu158
  • 77. Chariyalertsak S, Sirisanthana T, Supparatpinyo K, Praparattanapan J, Nelson KE. Case-control study of risk factors for Penicillium marneffei infection in human immunodeficiency virus-infected patients in northern Thailand. Clin Infect Dis 1997; 24:1080-6. http://dx.doi.org/10.1086/513649
  • 78. Sugar AM, Liu XP. Combination antifungal therapy in treatment of murine pulmonary mucormycosis: roles of quinolones and azoles. Antimicrob Agents Chemother 2000; 44:2004-6. http://dx.doi.org/10.1128/AAC.44.7.2004-2006.2000
  • 79. Naouri M, Mazer JM. Finger onychomycosis due to Candida tropicalis: short-pulsed Nd:YAG laser therapy. Ann Dermatol Venereol 2013; 140:610-3. http://dx.doi.org/10.1016/j.annder.2013.04.079
  • 80. Lastauskiene E, Zinkeviciene A, Girkontaite I, Kaunietis A, Kvedariene V. Formic acid and acetic acid induced a programmed cell death in pathogenic Candida species. Curr Microbiol 2014; 69:303-10. http://dx.doi.org/10.1007/s00284-014-0585-9
APA SEYEDMOUSAVI S, İLKİT M, Durdu M, ERGİN Ç, HAMİTOĞLU POLAT S, MELCHERS W, VERWEIJ P (2015). Candida ve Kandidoz: Epidemiyoloji, Tanı, Tedavi,Antifungal İlaç Direnci ve Konağın Genetik Yatkınlığında Güncel Durum. , 1 - 11.
Chicago SEYEDMOUSAVI Seyedmojtaba,İLKİT MEHMET MACİT,Durdu Murat,ERGİN Çağrı,HAMİTOĞLU POLAT Süleyha,MELCHERS Willem,VERWEIJ Paul Candida ve Kandidoz: Epidemiyoloji, Tanı, Tedavi,Antifungal İlaç Direnci ve Konağın Genetik Yatkınlığında Güncel Durum. (2015): 1 - 11.
MLA SEYEDMOUSAVI Seyedmojtaba,İLKİT MEHMET MACİT,Durdu Murat,ERGİN Çağrı,HAMİTOĞLU POLAT Süleyha,MELCHERS Willem,VERWEIJ Paul Candida ve Kandidoz: Epidemiyoloji, Tanı, Tedavi,Antifungal İlaç Direnci ve Konağın Genetik Yatkınlığında Güncel Durum. , 2015, ss.1 - 11.
AMA SEYEDMOUSAVI S,İLKİT M,Durdu M,ERGİN Ç,HAMİTOĞLU POLAT S,MELCHERS W,VERWEIJ P Candida ve Kandidoz: Epidemiyoloji, Tanı, Tedavi,Antifungal İlaç Direnci ve Konağın Genetik Yatkınlığında Güncel Durum. . 2015; 1 - 11.
Vancouver SEYEDMOUSAVI S,İLKİT M,Durdu M,ERGİN Ç,HAMİTOĞLU POLAT S,MELCHERS W,VERWEIJ P Candida ve Kandidoz: Epidemiyoloji, Tanı, Tedavi,Antifungal İlaç Direnci ve Konağın Genetik Yatkınlığında Güncel Durum. . 2015; 1 - 11.
IEEE SEYEDMOUSAVI S,İLKİT M,Durdu M,ERGİN Ç,HAMİTOĞLU POLAT S,MELCHERS W,VERWEIJ P "Candida ve Kandidoz: Epidemiyoloji, Tanı, Tedavi,Antifungal İlaç Direnci ve Konağın Genetik Yatkınlığında Güncel Durum." , ss.1 - 11, 2015.
ISNAD SEYEDMOUSAVI, Seyedmojtaba vd. "Candida ve Kandidoz: Epidemiyoloji, Tanı, Tedavi,Antifungal İlaç Direnci ve Konağın Genetik Yatkınlığında Güncel Durum". (2015), 1-11.
APA SEYEDMOUSAVI S, İLKİT M, Durdu M, ERGİN Ç, HAMİTOĞLU POLAT S, MELCHERS W, VERWEIJ P (2015). Candida ve Kandidoz: Epidemiyoloji, Tanı, Tedavi,Antifungal İlaç Direnci ve Konağın Genetik Yatkınlığında Güncel Durum. Türk Mikrobiyoloji Cemiyeti Dergisi, 45(1), 1 - 11.
Chicago SEYEDMOUSAVI Seyedmojtaba,İLKİT MEHMET MACİT,Durdu Murat,ERGİN Çağrı,HAMİTOĞLU POLAT Süleyha,MELCHERS Willem,VERWEIJ Paul Candida ve Kandidoz: Epidemiyoloji, Tanı, Tedavi,Antifungal İlaç Direnci ve Konağın Genetik Yatkınlığında Güncel Durum. Türk Mikrobiyoloji Cemiyeti Dergisi 45, no.1 (2015): 1 - 11.
MLA SEYEDMOUSAVI Seyedmojtaba,İLKİT MEHMET MACİT,Durdu Murat,ERGİN Çağrı,HAMİTOĞLU POLAT Süleyha,MELCHERS Willem,VERWEIJ Paul Candida ve Kandidoz: Epidemiyoloji, Tanı, Tedavi,Antifungal İlaç Direnci ve Konağın Genetik Yatkınlığında Güncel Durum. Türk Mikrobiyoloji Cemiyeti Dergisi, vol.45, no.1, 2015, ss.1 - 11.
AMA SEYEDMOUSAVI S,İLKİT M,Durdu M,ERGİN Ç,HAMİTOĞLU POLAT S,MELCHERS W,VERWEIJ P Candida ve Kandidoz: Epidemiyoloji, Tanı, Tedavi,Antifungal İlaç Direnci ve Konağın Genetik Yatkınlığında Güncel Durum. Türk Mikrobiyoloji Cemiyeti Dergisi. 2015; 45(1): 1 - 11.
Vancouver SEYEDMOUSAVI S,İLKİT M,Durdu M,ERGİN Ç,HAMİTOĞLU POLAT S,MELCHERS W,VERWEIJ P Candida ve Kandidoz: Epidemiyoloji, Tanı, Tedavi,Antifungal İlaç Direnci ve Konağın Genetik Yatkınlığında Güncel Durum. Türk Mikrobiyoloji Cemiyeti Dergisi. 2015; 45(1): 1 - 11.
IEEE SEYEDMOUSAVI S,İLKİT M,Durdu M,ERGİN Ç,HAMİTOĞLU POLAT S,MELCHERS W,VERWEIJ P "Candida ve Kandidoz: Epidemiyoloji, Tanı, Tedavi,Antifungal İlaç Direnci ve Konağın Genetik Yatkınlığında Güncel Durum." Türk Mikrobiyoloji Cemiyeti Dergisi, 45, ss.1 - 11, 2015.
ISNAD SEYEDMOUSAVI, Seyedmojtaba vd. "Candida ve Kandidoz: Epidemiyoloji, Tanı, Tedavi,Antifungal İlaç Direnci ve Konağın Genetik Yatkınlığında Güncel Durum". Türk Mikrobiyoloji Cemiyeti Dergisi 45/1 (2015), 1-11.