KATYONİK STEROİD ANTİBİYOTİKLERDEN OLAN CSA-8, CSA-13, CSA-44, CSA-131 VE CSA-138'İN, KAN KÜLTÜRLERİNDEN İZOLE EDİLEN CANDIDA ALBICANS SUŞLARINA KARŞI ANTİFUNGAL ETKİLERİNİN ARAŞTIRILMASI

Cerageninler, antimikrobiyal peptitlere benzer aktivite gösteren, yeni bir grup katyonik steroid antimikrobiyal molekül- lerdir. Bu çalışmada kan kültürlerinden izole edilmiş Candida albicans suşlarına karşı katyonik steroid antibiyotiklerden olan CSA-8, CSA-13, CSA-44, CSA-131 ve CSA-138in in vitro antif ungal duyarlılıklarının belirlenmesi amaçlanmıştır. MİK ve MBK değerleri CLSI kurallarına uygun olarak mikrodilüsyon yöntemi ile belirlenmiştir. Duyarlılık test sonuçlarına göre MİK değerleri 0.125-128 µg/ml arasında değişmektedir. CSA-8, CSA-13, CSA-44, CSA-131 ve CSA-138 için MİK50 değerleri sırasıyla 0.5 µg/ml, 1 µg/ml, 1 µg/ml, 2 µg/ml ve 8 µg/mldir. MFK değerleri ise MİK değerlerine eşit yada iki katıdır. Çalışmamızın sonuçlarına göre, CSA-131 ve CSA-138 C.albicans inf eksiyonlarının tedavisinde kullanılabilecek iyi birer aday moleküldür. İleriki çalışmalarda bu moleküllerin güvenilirlik, etkinlik ve f armakokinetik parametrelerinin belirlen- mesi gerekmektedir.

Investigation of the Antifungal Activities of the Cationic Steroid Antibiotic CSA-8, CSA-13, CSA-44, CSA-131 and CSA-138 Against Candida albicans Isolated from Blood Cultures

The ceragenins, designed to mimic the activities of antimicrobial peptides, are a new class of antimicrobial agent. In this study, in vitro antif ungal activities of the novel cationic steroid molecules CSA-8, CSA-13, CSA-44, CSA-131 and CSA-138, were assessed against Candida albicans strains isolated f rom blood cultures. MICs and MBCs were determined by microdilu- tion technique according to CLSI guidelines. Susceptibility testing demonstrated that the MICs were ranging 0.125-128 µg/ ml. The MIC50 values of CSA-8, CSA-13, CSA-44, CSA-131 and CSA-138 were 0.5 µg/ml, 1 µg/ml, 1 µg/ml, 2 µg/ml and 8 µg/ml, respectively. The MFCs were equal to or two-f old greater than those of the MICs. According to our results, cationic steroid antibiotics especially, CSA-131 and CSA-138 appear to be good candidates in the treatment of C.albicans inf ections. Future studies should be perf ormed to correlate its saf ety, eff icacy and pharmacoki- netic parameters of these molecules.

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  • 1. Akalın H. Kandidemilerde risk faktörlerive risk değerlendirmesi, ANKEM Derg 2008;22(2):270-4. 2. Anaissie E. Opportunistic mycoses in the immuno compromised host: experience at a cancer center and review, Clin Inf ect Dis 1992;14(Suppl 1):45-53. http://dx.doi.org/10.1093/clinids/14.Supple- ment_1.S43 3. Bakır M, Çerikçioğlu N, Barton R, Yağcı A. Epidemiology of candidemia in a Turkish tertiary care hospital, APMIS 2006;114(9):601-10. http://dx.doi.org/10.1111/j .1600-0463.2006. apm_359.x 4. Bozkurt-Guzel C, Savage PB, Gerceker AA. In vitro activities of the novel ceragenin, CSA-13, alone or in combination with colistin, tobramycin and ciprofloxacin against Pseudomonas aerugino- sa strains isolated from cystic fibrosis patients, Chemotherapy 2011;57(6):505-10. http://dx.doi.org/10.1159/000335588 5. Chin JN, Jones RN, Sader HS, Savage PB, Rybak MJ. Potential synergy activity of the novel cerage- nin, CSA-13, against clinical isolates of Pseudomonas aeruginosa, including multidrug- resistant P.aeruginosa, J Antimicrob Chemother 2008;61(2):365-70. http://dx.doi.org/10.1093/jac/dkm457 6. Chin JN, Rybak MJ, Cheung CM, Savage PB. Antimicrobial activities of ceragenins against cli- nical isolates of resistant Staphylococcus aureus, Antimicrob Agents Chemother 2007;51(4):1268-73. http://dx.doi.org/10.1128/AAC.01325-06 7. Clinical and Laboratory Standards Institute (CLSI). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts; Approved Standard-Third Edition. M27- A3, Wayne, PA, USA, (2008). 8. Epand RF, Pollard JE, Wright JO, Savage PB, Epand RM. Depolarization, bacterial membrane composition, and the antimicrobial action of cera- genins, Antimicrob Agents Chemother 2010;54(9): 3708-13. http://dx.doi.org/10.1128/AAC.00380-10 9. Giacometti A, Cirioni O, Barchiesi F et al. In vitro susceptibility tests for cationic peptides: compari- son of broth microdilution methods for bacteria that grow aerobically, Antimicrob Agents Chemother 2000;44(6):1694-6. http://dx.doi.org/10.1128/AAC.44.6.1694-1696.2000 10. Guan Q, Li C, Schmidt EJ. Preparation and charac- terization of cholic acid-derived antimicrobial agents with controlled stabilities, Org Lett 2000; 2(18):2837-40. http://dx.doi.org/10.1021/ol0062704 11. Gültekin B, Eyigör M, Telli M, Aksoy M, Aydın N. Yedi yıllık dönemde kan kültürlerinden izole edi- len Candida türlerinin retrospektif olarak incelen- mesi, ANKEM Derg 2010;24(4):202-8. 12. Hancock RE. Cationic peptides: effectors in innate immunity and novel antimicrobials, Lancet Inf ect Dis 2001;1(3):156-64. http://dx.doi.org/10.1016/S1473-3099(01)00092-5 13. Howell MD, Streib JE, Kim BE et al. Ceragenins: a class of antiviral compounds to treat orthopox infections, J Invest Dermatol 2009;129(11):2668-75. http://dx.doi.org/10.1038/jid.2009.120 14. Isogai E, Isogai H, Takahashi K, Okumura K, Savage PB. Ceragenin CSA-13 exhibits antimicro- bial activity against cariogenic and periodonto- pathic bacteria, Oral Microbiol Immunol 2009;24(2): 170-2. http://dx.doi.org/10.1111/j.1399-302X.2008.00464.x 15. John E, Edwards JR. Candida species, “Mandell GL, Bennett JE, Dolin R (eds). Principles and Practise of Infectious Diseases, 4.baskı” kitabında s.2289, Churchill Livingstone, New York (1995). 16. Kamysz W, Okroj M, Lukasiak J. Novel properties of antimicrobial peptides, Acta Biochim Pol 2003;50(2):461-9. 17. Lai XZ, Feng Y, Pollard J et al. Ceragenins: cholic acid-based mimics of antimicrobial peptides, Acc Chem Res 2008;41(10):1233-40. http://dx.doi.org/10.1021/ar700270t 18. Lara D, Feng Y, Bader J, Savage P, Maldonado R. Anti-try panosomatid activity of ceragenins, J Parasitol 2010;96(3):638-42. http://dx.doi.org/10.1645/GE-2329.1 19. Leszczynska K, Namiot A, Fein DE et al. Bactericidal activities of the cationic steroid CSA- 13 and the cathelicidin peptide LL-37 against Helicobacter pylori in simulated gastric juice, BMC Microbiol 2009;9:187. http://dx.doi.org/10.1186/1471-2180-9-187 20. Levitz SM. Overview of host defenses in fungal infections, Clin Inf ect Dis 1992;14(Suppl 1):37-42. http://dx.doi.org/10.1093/clinids/14.Supple- ment_1.S37 21. Li C, Lewis MR, Gilbert AB, Noel MD, Scoville DH, Allman GW, Savage P. Antimicrobial activiti- es of amine- and guanidine-functionalized cholic acid derivatives, Antimicrob Agents Chemother 1999;43(6):1347-9. 22. National Committee for Clinical Laboratory Standards (NCCLS). Methods for Determining Bactericidal Activity of Antimicrobial Agents- Approved Guideline M26-A, Wayne, PA, USA, (1999). 23. Pfaller MA, Diekema DJ. Epidemiology of invasi- ve candidiasis: a persistent public health problem, Clin Microbiol Rev 2007;20(1):133-63. http://dx.doi.org/10.1128/CMR.00029-06 24. Saha S, Savage PB, Bal M. Enhancement of the efficacy of erythromycin in multiple antibiotic- resistant gram-negative bacterial pathogens, J Appl Microbiol 2008;105(3):822-8. http://dx.doi.org/10.1111/j.1365-2672.2008. 03820.x 25. Som A, Vemparala S, Ivanov I, Tew GN. Synthetic mimics of antimicrobial peptides, Biopolymers 2008;90(2):83-93. http://dx.doi.org/10.1002/bip.20970 26. Van’t Hof W, Veerman EC, Helmerhorst EJ, Amerongen AV. Antimicrobial peptides: properties and applicability, Biol Chem 2001;382(4):597-619.