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The Correlation of Biofilm Formation, Hemolytic and Coagulase Activites and Antifungal Susceptibility among Candida parapsilosis Isolates Recovered from Clinical Speciemens

Year 2020, Volume: 6 Issue: 3, 203 - 208, 02.10.2020
https://doi.org/10.30934/kusbed.777921

Abstract

Objective: The aim of this study was to investigate the virulence factors such as in vitro biofilm production, hemolytic and coagulase activity of Candida parapsilosis isolates and to compare these factors with antifungal susceptibilities.
Methods: Twenty six isolates from Kocaeli University and 14 isolates from Mersin University were included into this study. Haemolytic activity was tested by sheep blood agar with 3% glucose. Coagulase activity was tested by tube test method. Biofilm production was determined by modified Christensen macrotube method and scored as weak, intermediate or strong positive. The MIC values of the strains against fluconazole, caspofungin, micafungin, voriconazole and amphotericin B were measured with the automated system VITEK-2.
Results: Study isolates were from peripheral blood 23, blood catheter 7, urine 3, periton 3, nail samples 2, pleura and sputum samples each one. Of 40 isolates, biofilm production was detected in 32 (80%) and scored as 13 (32.5%) weak, 12 (30%) intermediate and 7 (17.5%) strong positive. In 50% of isolates alpha hemolysis and in 32.5% beta hemolysis was detected and 17.5% were nonhemolytic. Coagulase activity was negative in all isolates. All isolates were susceptible to voriconazole and amphotericin B. Fluconazole resistance was determined in two isolates having weak biofilm production. Caspofungin resistance was determined in 10 of isolates and 4 of them were also resistant to micafungin; 7 of them had haemolytic activity and 7 of them produced biofilm as well. Of these resistant 10 isolates 7 were from peripheral blood, 2 were from periton and one was from urine.
Conclusion: Biofilm production and haemolytic activity were the main virulence factors of C. parapsilosis and due to these factors it causes candidemia and intravenous catheter related infections. The treatment protocols of these infections may alter in parallel with changing epidemiology or antifungal susceptibility profiles. Studies included more isolates are needed.

References

  • Pfaller MA, Diekema DJ. Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev. 2007;20(1):133–163.
  • Trofa D, Ga´cser A, Nosanchuk JD. Candida parapsilosis, an emerging fungal pathogen. Clin Microbiol Rev. 2008;21(4):606–625.
  • Horasan ES, Ersöz G, Göksu M, ve ark. Increase in Candida parapsilosis fungemia in critical care units: a 6-years study. Mycopathologia. 2010;170(4):263-268.
  • Sav H, Baris A, Turan D, Altinbas R, Sen S. The frequency, antifungal susceptibility and enzymatic profiles of Candida species in cases of onychomycosis infection. Microb Pathog. 2018;116:257-262.
  • da Silva RL, Montelli AC, Sugizaki Mde F, ve ark. Outbreak of fungemia caused by Candida parapsilosis in a neonatal intensive care unit: molecular investigation through microsatellite analysis. Rev Iberoam Micol. 2013;30(2):112–115.
  • Magobo RE, Naicker SD, Wadula J, ve ark. Detection of neonatal unit clusters of Candida parapsilosis fungemia by microsatellite genotyping: results from laboratory based sentinel surveillance, South Africa, 2009-2010. Mycoses. 2017;60(5):320–327.
  • Treviño-Rangel Rde J, González JG, González GM. Aspartyl proteinase, phospholipase, esterase and hemolysin activities of clinical isolates of the Candida parapsilosis species complex. Med Mycol. 2013;51(3):331-335.
  • van Asbeck EC, Clemons KV, Stevens DA. Candida parapsilosis: a review of its epidemiology, pathogenesis, clinical aspects, typing and antimicrobial susceptibility. Crit Rev Microbiol. 2009;35(4):283–309.
  • da Silva BV, Silva LB, de Oliveira DB, ve ark. Species distribution, virulence factors, and antifungal susceptibility among Candida parapsilosis complex isolates recovered from clinical specimens. Mycopathologia 2015;180(5-6):333–343.
  • Abi-Chacra ÉA, Souza LO, Cruz LP, ve ark. Phenotypical properties associated with virulence from Clinical isolates belonging to the Candida parapsilosis complex. FEMS Yeast Res. 2013;13(8):831–848.
  • Brilhante RSN, Sales JA, da Silva MLQ, ve ark. Antifungal susceptibility and virulence of Candida parapsilosis species complex: an overview of their pathogenic potential. J Med Microbiol. 2018;67(7):903-914.
  • Luo G, Samaranayake LP, Yau JY. Candida species exhibit differential in vitro hemolytic activities. J Clin Microbiol. 2001;39(8):2971-2974.
  • Rodrigues AG, Pina-Vaz C, Costa-de-Oliveira S, Tavares C. Expression of plasma coagulase among pathogenic Candida species. J Clin Microbiol. 2003;41(12):5792-5793.
  • Christensen GD, Simpson, WA, Bisno AL, Beachey EH. Adherence of slime-producing strains of Staphylococcus epidermidis to smooth surfaces. Infect. Immun. 1982;37(1):318–326.
  • Clinical and Laboratory Standards Institute. Reference method for broth dilution antifungal susceptibility testing of yeasts; third edition, M27-A3. Wayne, PA, USA: CLSI; 2008.
  • Yapar N. Epidemiology and risk factors for invasive candidiasis. Ther Clin Risk Manag. 2014;10:95-105.
  • Ece G, Samlioglu P, Akkoclu G, Atalay S, Kose S. The evaluation of the distribution of yeast like fungi 'Candida Species' at a tertiary care center in western Turkey. Int J Med Sci. 2012;9(7):617-620.
  • Calgin MK, Cetinkol Y. Distribution and antifungal susceptibility patterns of Candida species at a university hospital in Northern Turkey. J Infect Dev Ctries. 2018 Feb 28;12(2):97-101.
  • Oktay E, Gülbudak H, Özgür D, Otağ F. Yoğun Bakım Ünitesi Hastaları Kan Kültürlerinden İzole Edilen Candida parapsilosis Suşlarının Mini Epidemiler Bakımından Araştırılması. Türk Mikrobiyol Cem Derg. 2015;45(1):41-47.
  • Pakshir K, Ravandeh M, Khodadadi H, Motamedifar M, Zomorodian K, Alipour S. Evaluation of exoenzyme activities, biofilm formation, and co-hemolytic effect in clinical isolates of Candida parapsilosis species complex. J Global Infect Dis. 2018;10:163-165.
  • Neji S, Hadrich I, Trabelsi H, ve ark. Virulence factors, antifungal susceptibility and molecular mechanisms of azole resistance among Candida parapsilosis complex isolates recovered from clinical specimens. J Biomed Sci. 2017;24(1):67.
  • Furlaneto MC, Góes HP, Perini HF, Dos Santos RC, Furlaneto-Maia L. How much do we know about hemolytic capability of pathogenic Candida species?. Folia Microbiol (Praha). 2018;63(4):405-412.
  • Tumbarello M, Posteraro B, Trecarichi EM, ve ark. Biofilm production by Candida species and inadequate antifungal therapy as predictors of mortality for patients with candidemia. J Clin Microbiol. 2007;45(6):1843–1850.
  • Silva S, Henriques M, Martins A, Oliveira R, Williams D, Azeredo J. Biofilms of non-albicans Candida species: quantification, structure and matrix composition. Med Mycol. 2009;47(7):681–689.
  • Song JW, Shin JH, Shint DH, ve ark. Differences in biofilm production by three genotypes of Candida parapsilosis from clinical sources. Med Mycol. 2005;43(7):657–661.
  • Tosun I, Akyuz Z, Guler NC, ve ark. Distribution, virulence attributes and antifungal susceptibility patterns of Candida parapsilosis Complex strains isolated from clinical samples. Med Mycol. 2013;51(5):483–492.
  • Melo AS, Bizerra FC, Freymüller E, Arthington-Skaggs BA, Colombo AL. Biofilm production and evaluation of antifungal susceptibility amongst clinical Candida spp. isolates, including strains of the Candida parapsilosis Complex. Med Mycol. 2011;49(3):253–262.
  • Yigit N, Aktas AE, Ayyildiz A. Detection of coagulase activity in pathogenic Candida species. Int Med Res. 2008;36(6):1378-1382.
  • Pfaller MA, Diekema DJ. Progress in antifungal susceptibility testing of Candida spp. by use of Clinical and Laboratory Standards Institute broth microdilution methods, 2010 to 2012. J Clin Microbiol. 2012; 50(9): 2846-2856.
  • Chassot F, Venturini TP, Piasentin FB, ve ark. Exploring the In Vitro Resistance of Candida parapsilosis to Echinocandins. Mycopathologia. 2016;181(9-10):663–670.
  • Canto´n E, Pema´n J, Quindo´s G, ve ark. Prospective multicenter study of the epidemiology, molecular identification, and antifungal susceptibility of Candida parapsilosis, Candida orthopsilosis, and Candida metapsilosis isolated from patients with candidemia. Antimicrob Agents Chemother. 2011;55(12): 5590–5596.
  • Chen YC, Linc YH, Chenc KW, Liic J, Tengc HJ, Lic SY. Molecular epidemiology and antifungal susceptibility of Candida parapsilosis sensu stricto, Candida orthopsilosis, and Candida metapsilosis in Taiwan. Diagn Microbiol Infect Dis. 2010;68(3):284–292.
  • Castanheira M, Deshpande LM, Davis AP, Rhomberg PR, Pfaller MA. Monitoring Antifungal Resistance in a Global Collection of Invasive Yeasts and Molds: Application of CLSI Epidemiological Cutoff Values and Whole-Genome Sequencing Analysis for Detection of Azole Resistance in Candida albicans. Antimicrob Agents Chemother. 2017;61(10):e00906-17.

Klinik Örneklerden İzole Edilmiş Candi̇da parapsi̇losi̇s Suşlarının Bi̇yofi̇lm Oluşturma, Hemoli̇ti̇k ve Koagülaz Akti̇vi̇teleri̇ ile Anti̇fungal Duyarlılıklarının Karşılaştırılması

Year 2020, Volume: 6 Issue: 3, 203 - 208, 02.10.2020
https://doi.org/10.30934/kusbed.777921

Abstract

Amaç: Candida parapsilosis suşlarının in vitro biyofilm oluşturma, hemoliz ve koagülaz aktiviteleri gibi virülans faktörlerinin araştırılması ve antifungal duyarlılıklarıyla karşılaştırılması amaçlanmıştır.
Yöntem: Kocaeli Üniversitesi’nden 26, Mersin Üniversitesi’nden 14 suş çalışmaya alınmıştır. Hemolitik aktivite %3 glikozlu koyun kanlı agarda 37oC’de 48 saatlik, koagülaz aktivite tüp test metodu ile 37oC’de 4 saatlik, biyofilm oluşumu ise modifiye Christensen makro tüp metodu ile %8 glikozlu Sabouraud Dekstroz sıvı besiyerinde 37oC’de 48-72 saatlik inkübasyon sonrasında değerlendirilerek belirlenmiştir. Flukonazol, kaspofungin, mikafungin, vorikonazol ve amfoterisin B’ye karşı MIK değerleri VİTEK-2 otomatize sistem ile belirlenmiştir.
Bulgular: Suşların 23’ü periferik kandan, 7’si damar içi kateterden, 3’er adet periton ve idrardan, 2 adet tırnak örneğinden, 1’er adet plevra ve balgam örneklerinden izole edilmiştir. Biyofilm aktivitesi tüm suşların 32’sinde (%80) saptamış olup, 13’ü (%32,5) zayıf, 12’si (%30) orta, 7’si (%17,5) ise güçlü pozitif olarak skorlanmıştır. Suşların yarısı alfa hemoliz, 13’ü (%32,5) beta hemoliz gösterirken, 7’sinde (%17,5) hemoliz saptanmamıştır. Koagülaz aktivitesi tüm suşlarda negatif bulunmuştur. Tüm suşlar vorikonazol ve amfoterisin B’ye duyarlı saptanmıştır. Biyofilm aktivitesi zayıf olan iki suşta flukonazol direncine rastlanmıştır. Periferik kandan izole edilmiş 7 suş ile 2’si periton ve biri idrar suşu olmak üzere toplam 10 suşta (%25) kaspofungin direnci saptanmıştır. Bu suşların 4’ünde aynı zamanda mikafungin direnci, 7’sinde hemolitik aktivite ve biyofilm oluşumu gözlenmiştir. Antifungal direnci ile virülans faktörleri arasında istatistiksel olarak anlamlı bir ilişki bulunamamıştır.
Sonuç: Biyofilm oluşturma ve hemolitik aktivite C. parapsilosis’in başlıca virülans faktörleridir ve sıklıkla bu faktörlere bağlı olarak kandidemi ve kateter enfeksiyonları oluşabilmektedir. Bu enfeksiyonların tedavi protokolleri epidemiyolojik ve antifungal duyarlılık paterni verilerine göre değişim gösterebilir. Daha fazla C. parapsilosis suşu kullanarak ileri çalışmalar yapılması önerilmektedir.

References

  • Pfaller MA, Diekema DJ. Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev. 2007;20(1):133–163.
  • Trofa D, Ga´cser A, Nosanchuk JD. Candida parapsilosis, an emerging fungal pathogen. Clin Microbiol Rev. 2008;21(4):606–625.
  • Horasan ES, Ersöz G, Göksu M, ve ark. Increase in Candida parapsilosis fungemia in critical care units: a 6-years study. Mycopathologia. 2010;170(4):263-268.
  • Sav H, Baris A, Turan D, Altinbas R, Sen S. The frequency, antifungal susceptibility and enzymatic profiles of Candida species in cases of onychomycosis infection. Microb Pathog. 2018;116:257-262.
  • da Silva RL, Montelli AC, Sugizaki Mde F, ve ark. Outbreak of fungemia caused by Candida parapsilosis in a neonatal intensive care unit: molecular investigation through microsatellite analysis. Rev Iberoam Micol. 2013;30(2):112–115.
  • Magobo RE, Naicker SD, Wadula J, ve ark. Detection of neonatal unit clusters of Candida parapsilosis fungemia by microsatellite genotyping: results from laboratory based sentinel surveillance, South Africa, 2009-2010. Mycoses. 2017;60(5):320–327.
  • Treviño-Rangel Rde J, González JG, González GM. Aspartyl proteinase, phospholipase, esterase and hemolysin activities of clinical isolates of the Candida parapsilosis species complex. Med Mycol. 2013;51(3):331-335.
  • van Asbeck EC, Clemons KV, Stevens DA. Candida parapsilosis: a review of its epidemiology, pathogenesis, clinical aspects, typing and antimicrobial susceptibility. Crit Rev Microbiol. 2009;35(4):283–309.
  • da Silva BV, Silva LB, de Oliveira DB, ve ark. Species distribution, virulence factors, and antifungal susceptibility among Candida parapsilosis complex isolates recovered from clinical specimens. Mycopathologia 2015;180(5-6):333–343.
  • Abi-Chacra ÉA, Souza LO, Cruz LP, ve ark. Phenotypical properties associated with virulence from Clinical isolates belonging to the Candida parapsilosis complex. FEMS Yeast Res. 2013;13(8):831–848.
  • Brilhante RSN, Sales JA, da Silva MLQ, ve ark. Antifungal susceptibility and virulence of Candida parapsilosis species complex: an overview of their pathogenic potential. J Med Microbiol. 2018;67(7):903-914.
  • Luo G, Samaranayake LP, Yau JY. Candida species exhibit differential in vitro hemolytic activities. J Clin Microbiol. 2001;39(8):2971-2974.
  • Rodrigues AG, Pina-Vaz C, Costa-de-Oliveira S, Tavares C. Expression of plasma coagulase among pathogenic Candida species. J Clin Microbiol. 2003;41(12):5792-5793.
  • Christensen GD, Simpson, WA, Bisno AL, Beachey EH. Adherence of slime-producing strains of Staphylococcus epidermidis to smooth surfaces. Infect. Immun. 1982;37(1):318–326.
  • Clinical and Laboratory Standards Institute. Reference method for broth dilution antifungal susceptibility testing of yeasts; third edition, M27-A3. Wayne, PA, USA: CLSI; 2008.
  • Yapar N. Epidemiology and risk factors for invasive candidiasis. Ther Clin Risk Manag. 2014;10:95-105.
  • Ece G, Samlioglu P, Akkoclu G, Atalay S, Kose S. The evaluation of the distribution of yeast like fungi 'Candida Species' at a tertiary care center in western Turkey. Int J Med Sci. 2012;9(7):617-620.
  • Calgin MK, Cetinkol Y. Distribution and antifungal susceptibility patterns of Candida species at a university hospital in Northern Turkey. J Infect Dev Ctries. 2018 Feb 28;12(2):97-101.
  • Oktay E, Gülbudak H, Özgür D, Otağ F. Yoğun Bakım Ünitesi Hastaları Kan Kültürlerinden İzole Edilen Candida parapsilosis Suşlarının Mini Epidemiler Bakımından Araştırılması. Türk Mikrobiyol Cem Derg. 2015;45(1):41-47.
  • Pakshir K, Ravandeh M, Khodadadi H, Motamedifar M, Zomorodian K, Alipour S. Evaluation of exoenzyme activities, biofilm formation, and co-hemolytic effect in clinical isolates of Candida parapsilosis species complex. J Global Infect Dis. 2018;10:163-165.
  • Neji S, Hadrich I, Trabelsi H, ve ark. Virulence factors, antifungal susceptibility and molecular mechanisms of azole resistance among Candida parapsilosis complex isolates recovered from clinical specimens. J Biomed Sci. 2017;24(1):67.
  • Furlaneto MC, Góes HP, Perini HF, Dos Santos RC, Furlaneto-Maia L. How much do we know about hemolytic capability of pathogenic Candida species?. Folia Microbiol (Praha). 2018;63(4):405-412.
  • Tumbarello M, Posteraro B, Trecarichi EM, ve ark. Biofilm production by Candida species and inadequate antifungal therapy as predictors of mortality for patients with candidemia. J Clin Microbiol. 2007;45(6):1843–1850.
  • Silva S, Henriques M, Martins A, Oliveira R, Williams D, Azeredo J. Biofilms of non-albicans Candida species: quantification, structure and matrix composition. Med Mycol. 2009;47(7):681–689.
  • Song JW, Shin JH, Shint DH, ve ark. Differences in biofilm production by three genotypes of Candida parapsilosis from clinical sources. Med Mycol. 2005;43(7):657–661.
  • Tosun I, Akyuz Z, Guler NC, ve ark. Distribution, virulence attributes and antifungal susceptibility patterns of Candida parapsilosis Complex strains isolated from clinical samples. Med Mycol. 2013;51(5):483–492.
  • Melo AS, Bizerra FC, Freymüller E, Arthington-Skaggs BA, Colombo AL. Biofilm production and evaluation of antifungal susceptibility amongst clinical Candida spp. isolates, including strains of the Candida parapsilosis Complex. Med Mycol. 2011;49(3):253–262.
  • Yigit N, Aktas AE, Ayyildiz A. Detection of coagulase activity in pathogenic Candida species. Int Med Res. 2008;36(6):1378-1382.
  • Pfaller MA, Diekema DJ. Progress in antifungal susceptibility testing of Candida spp. by use of Clinical and Laboratory Standards Institute broth microdilution methods, 2010 to 2012. J Clin Microbiol. 2012; 50(9): 2846-2856.
  • Chassot F, Venturini TP, Piasentin FB, ve ark. Exploring the In Vitro Resistance of Candida parapsilosis to Echinocandins. Mycopathologia. 2016;181(9-10):663–670.
  • Canto´n E, Pema´n J, Quindo´s G, ve ark. Prospective multicenter study of the epidemiology, molecular identification, and antifungal susceptibility of Candida parapsilosis, Candida orthopsilosis, and Candida metapsilosis isolated from patients with candidemia. Antimicrob Agents Chemother. 2011;55(12): 5590–5596.
  • Chen YC, Linc YH, Chenc KW, Liic J, Tengc HJ, Lic SY. Molecular epidemiology and antifungal susceptibility of Candida parapsilosis sensu stricto, Candida orthopsilosis, and Candida metapsilosis in Taiwan. Diagn Microbiol Infect Dis. 2010;68(3):284–292.
  • Castanheira M, Deshpande LM, Davis AP, Rhomberg PR, Pfaller MA. Monitoring Antifungal Resistance in a Global Collection of Invasive Yeasts and Molds: Application of CLSI Epidemiological Cutoff Values and Whole-Genome Sequencing Analysis for Detection of Azole Resistance in Candida albicans. Antimicrob Agents Chemother. 2017;61(10):e00906-17.
There are 33 citations in total.

Details

Primary Language Turkish
Subjects Medical Microbiology
Journal Section Original Article / Medical Sciences
Authors

Sema Aşkın Keçeli 0000-0002-2014-6395

Melike Kurt 0000-0001-6592-3701

Didem Özgür 0000-0002-8320-9453

Zehra Feza Otağ 0000-0002-8627-7937

Publication Date October 2, 2020
Submission Date August 8, 2020
Acceptance Date September 22, 2020
Published in Issue Year 2020 Volume: 6 Issue: 3

Cite

APA Keçeli, S. A., Kurt, M., Özgür, D., Otağ, Z. F. (2020). Klinik Örneklerden İzole Edilmiş Candi̇da parapsi̇losi̇s Suşlarının Bi̇yofi̇lm Oluşturma, Hemoli̇ti̇k ve Koagülaz Akti̇vi̇teleri̇ ile Anti̇fungal Duyarlılıklarının Karşılaştırılması. Kocaeli Üniversitesi Sağlık Bilimleri Dergisi, 6(3), 203-208. https://doi.org/10.30934/kusbed.777921
AMA Keçeli SA, Kurt M, Özgür D, Otağ ZF. Klinik Örneklerden İzole Edilmiş Candi̇da parapsi̇losi̇s Suşlarının Bi̇yofi̇lm Oluşturma, Hemoli̇ti̇k ve Koagülaz Akti̇vi̇teleri̇ ile Anti̇fungal Duyarlılıklarının Karşılaştırılması. KOU Sag Bil Derg. October 2020;6(3):203-208. doi:10.30934/kusbed.777921
Chicago Keçeli, Sema Aşkın, Melike Kurt, Didem Özgür, and Zehra Feza Otağ. “Klinik Örneklerden İzole Edilmiş Candi̇da parapsi̇losi̇s Suşlarının Bi̇yofi̇lm Oluşturma, Hemoli̇ti̇k Ve Koagülaz Akti̇vi̇teleri̇ Ile Anti̇fungal Duyarlılıklarının Karşılaştırılması”. Kocaeli Üniversitesi Sağlık Bilimleri Dergisi 6, no. 3 (October 2020): 203-8. https://doi.org/10.30934/kusbed.777921.
EndNote Keçeli SA, Kurt M, Özgür D, Otağ ZF (October 1, 2020) Klinik Örneklerden İzole Edilmiş Candi̇da parapsi̇losi̇s Suşlarının Bi̇yofi̇lm Oluşturma, Hemoli̇ti̇k ve Koagülaz Akti̇vi̇teleri̇ ile Anti̇fungal Duyarlılıklarının Karşılaştırılması. Kocaeli Üniversitesi Sağlık Bilimleri Dergisi 6 3 203–208.
IEEE S. A. Keçeli, M. Kurt, D. Özgür, and Z. F. Otağ, “Klinik Örneklerden İzole Edilmiş Candi̇da parapsi̇losi̇s Suşlarının Bi̇yofi̇lm Oluşturma, Hemoli̇ti̇k ve Koagülaz Akti̇vi̇teleri̇ ile Anti̇fungal Duyarlılıklarının Karşılaştırılması”, KOU Sag Bil Derg, vol. 6, no. 3, pp. 203–208, 2020, doi: 10.30934/kusbed.777921.
ISNAD Keçeli, Sema Aşkın et al. “Klinik Örneklerden İzole Edilmiş Candi̇da parapsi̇losi̇s Suşlarının Bi̇yofi̇lm Oluşturma, Hemoli̇ti̇k Ve Koagülaz Akti̇vi̇teleri̇ Ile Anti̇fungal Duyarlılıklarının Karşılaştırılması”. Kocaeli Üniversitesi Sağlık Bilimleri Dergisi 6/3 (October 2020), 203-208. https://doi.org/10.30934/kusbed.777921.
JAMA Keçeli SA, Kurt M, Özgür D, Otağ ZF. Klinik Örneklerden İzole Edilmiş Candi̇da parapsi̇losi̇s Suşlarının Bi̇yofi̇lm Oluşturma, Hemoli̇ti̇k ve Koagülaz Akti̇vi̇teleri̇ ile Anti̇fungal Duyarlılıklarının Karşılaştırılması. KOU Sag Bil Derg. 2020;6:203–208.
MLA Keçeli, Sema Aşkın et al. “Klinik Örneklerden İzole Edilmiş Candi̇da parapsi̇losi̇s Suşlarının Bi̇yofi̇lm Oluşturma, Hemoli̇ti̇k Ve Koagülaz Akti̇vi̇teleri̇ Ile Anti̇fungal Duyarlılıklarının Karşılaştırılması”. Kocaeli Üniversitesi Sağlık Bilimleri Dergisi, vol. 6, no. 3, 2020, pp. 203-8, doi:10.30934/kusbed.777921.
Vancouver Keçeli SA, Kurt M, Özgür D, Otağ ZF. Klinik Örneklerden İzole Edilmiş Candi̇da parapsi̇losi̇s Suşlarının Bi̇yofi̇lm Oluşturma, Hemoli̇ti̇k ve Koagülaz Akti̇vi̇teleri̇ ile Anti̇fungal Duyarlılıklarının Karşılaştırılması. KOU Sag Bil Derg. 2020;6(3):203-8.