EFFECT OF PH & TEMPERATURE ON THE PROTEINASE ACTIVITY OF CANDIDA ALBICANS IN VITRO IN RELATION TO THE ANTIFUNGAL AGENTS VIZ. CLOTRIMAZOLE AND NYSTATIN

Main Article Content

*Mohammed Sarosh Khan1, Muhammad Musthafa Poyil2, Adel Rasheed Khan3

Keywords

pH, Antifungal, Antifungal Agents, Clotrimazole, Nystatin, Proteinase Activity

Abstract

The candidiasis known as vulvovaginal candidiasis (VVC), which is welcomed on by the yeast Candida glabrata, is challenging to fix because of the predetermined number of restorative choices that are presently accessible. Antifungal medications containing azoles, whether they be foundational or skin, have been displayed to have a poor clinical viability because of reasons that poor person been made sense of. Notwithstanding the way that azole antifungal prescriptions are defenseless against the advancement of parasites in vitro, this is the situation. We analyzed the impact that pH has on the in vitro movement of eleven antifungal medications against forty C. glabrata disconnects and contrasted this movement with that of fifteen fluconazole-delicate and ten diminished fluconazole-defenselessness C. albicans strains. Our discoveries recommend that pH fundamentally affects the in vitro movement of antifungal medications. We researched the impact that pH has on the in vitro movement of 11 distinct antifungal prescriptions given that patients with VVC have a vaginal pH that is reliably somewhere in the range of 4 and 4.5. This was finished considering the way that patients with VVC have a vaginal pH that is reliably somewhere in the range of 4 and 4.5. Involving the CLSI technique for yeast defenselessness testing, in vitro vulnerability to flucytosine, fluconazole, voriconazole, posaconazole, itraconazole, ketoconazole, clotrimazole, miconazole, ciclopirox olamine, amphotericin B, and not entirely set in stone. Furthermore, amphotericin B and caspofungin in vitro not entirely set in stone. To decide if yeast is impervious to antifungal medicines, the CLSI procedure is utilized. Furthermore, in vitro defenselessness to fluconazole and voriconazole, as well as pos supports, were utilized to get the test material to pH upsides of 7, 6, 5, and 4. Notwithstanding the low pH conditions in which they were developed, C. glabrata disconnects kept up with their aversion to caspofungin and flucytosine. Then again, the MIC90 values for amphotericin B and each and every azole prescription that was inspected saw a significant increment. C. albicans strains that were less delicate to fluconazole were in like manner less delicate to amphotericin B and all azoles at pH 4, separately. When tried at a pH of 7, these C. albicans disconnects showed protection from fluconazole notwithstanding the way that they were receptive to other azole prescriptions. Then again, C. albicans disconnects that were delicate to fluconazole stayed delicate to azoles in any event, when the pH was low. This was on the grounds that fluconazole is an imidazole. This happened because of the way that fluconazole is an azole. The discoveries of clinical preliminaries upheld this end, which was predictable with its discoveries. While picking prescriptions for the treatment of intermittent C. glabrata vaginitis, clinical professionals should know about the restrictions of in vitro defenselessness testing prior to settling on treatment choices. With regards to evaluating defenselessness in vitro, a pH of 7.0 is for the most part respected to be the norm.

Downloads

References


[1]. American College of Obstetricians and Gynecologists. 2006. Vaginitis. ACOG Pract. Bull. No. 72 Obstet. Gynecol. 107:1195. [2]. American College of Obstetricians and Gynecologists. 2009. Vulvar disorders. ACOG Clinical Updates in Women’s Health Care vol. 8, no. 2, p 36. American College of Obstetricians and Gynecologists, Washington, DC. [3]. Anderson MR, Klink K, Cohrssen A. 2004. Evaluation of vaginal complaints. JAMA 291:1368 –1379. [4]. CLSI. 2008. Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard, third edition. CLSI document M27– A3. CLSI, Wayne, PA. [5]. Coppi G, Silingardi S, Girardello R, De Aloysio D, Manzardo S. 1993. Pharmacokinetics of ciclopirox olamine after vaginal application to rabbits and patients. J. Chemother. 5:302–306. [6]. Diekema DJ, et al. 2009. In vitro activity of seven systemically active antifungal agents against a large global collection of rare Candida species as determined by CLSI broth microdilution methods. J. Clin. Microbiol. 47:3170 –3177. [7]. Fidel PL, Jr, Vazquez JA, Sobel JD. 1999. Candida glabrata: review of epidemiology, pathogenesis, and clinical disease with comparison to C. albicans. Clin. Microbiol. Rev. 12:80 –96. [8]. Guaschino S, et al. 2001. Efficacy of maintenance therapy with topical boric acid in comparison with oral itraconazole in the treatment of recurrent vulvovaginal candidiasis. Am. J. Obstet. Gynecol. 184:598 –602. [9]. Gupta AK, Plott T. 2004. Ciclopirox: a broad-spectrum antifungal with antibacterial and anti-inflammatory properties. Int. J. Dermatol. 43[Suppl. 1]:3–8. [10]. Harada I, Mitsui K, Uchida K, Yamaguchi H. 1999. The in vitro properties of a new hydroxypyridone antimycotic rilopirox, with special reference to its anti-Candida activity. Jpn. J. Antibiot. 52:146 –152. [11]. Khan ZU, et al. 2008. Emergence of resistance to amphotericin B and triazoles in Candida glabrata vaginal isolates in a case of recurrent vaginitis. J. Chemother. 20:488 –491. [12]. Lee I, et al. 2010. Risk factors for fluconazole resistance in patients with Candida glabrata bloodstream infection: potential impact of control group selection on characterizing the association between previous fluconazole use and fluconazole resistance. Am. J. Infect. Control 38:456–460. [13]. Linhares IM, Summers PR, Larsen B, Giraldo PC, Witkin SS. 2011 Contemporary perspectives on vaginal pH and lactobacilli. Am. J. Obstet. Gynecol. 204:120.e1-5. [14]. Lyon GM, Karatela S, Sunay S, Adiri Y, Candida Surveillance Study Investigators. Antifungal susceptibility testing of Candida isolates from the Candida surveillance study. J. Clin. Microbiol. 48:1270 –1275. [15]. Manzardo S, Pinzetta A, Coppi G. 1993. Local tolerance of a new ciclopirox olamine vaginal preparation in rats and rabbits. J. Chemother. 5:307– 312. [16]. Marr KA, Rustad TR, Rex JH, White TC. 1999. The trailing end point phenotype in antifungal susceptibility testing is pH dependent. Antimicrob. Agents Chemother. 43:1383–1386. [17]. Niewerth M, et al. 2003. Ciclopirox olamine treatment affects the expression pattern of Candida albicans genes encoding virulence factors, iron metabolism proteins, and drug resistance factors. Antimicrob. Agents Chemother. 47:1805–1817. [18]. Phillips AJ. 2005. Treatment of non-albicans Candida vaginitis with amphotericin B vaginal suppositories. Am. J. Obstet. Gynecol. 192:2009 – 2012. [19]. Rex JH, Pfaller MA, Barry AL, Nelson PW, Webb CD. 1995. Antifungal susceptibility testing of isolates from a randomized, multicenter trial of fluconazole versus amphotericin B as treatment of nonneutropenic patients with candidemia. NIAID Mycoses Study Group and the Candidemia Study Group. Antimicrob. Agents Chemother. 39:40 –44. [20]. Richter SS, et al. 2005. Antifungal susceptibilities of Candida species causing vulvovaginitis and epidemiology of recurrent cases. J. Clin. Microbiol. 43:2155–2162. [21]. Rubin AI, Bagheri B, Scher RK. 2002. Six novel antimycotics. Am. J. Clin. Dermatol. 3:71–81. [22]. Sabatelli F, et al. 2006. In vitro activities of posaconazole, fluconazole, itraconazole, voriconazole, and amphotericin B against a large collection of clinically important molds and yeasts. Antimicrob. Agents Chemother. 50:2009 –2015. [23]. Sobel JD, Chaim W. 1997. Treatment of Torulopsis glabrata vaginitis: retrospective review of boric acid therapy. Clin. Infect. Dis. 24:649 –652. [24]. Sobel JD. 2003. Management of patients with recurrent vulvovaginal candidiasis. Drugs 63:1059 –1066. 25. Sobel JD. 2007. Vulvovaginal candidosis. Lancet 369:1961–1971. [25]. Sobel JD, Chaim W, Nagappan V, Leaman D. 2003. Treatment of vaginitis caused by Candida glabrata: use of topical boric acid and flucytosine. Am. J. Obstet. Gynecol. 189:1297. [26]. Sood G, Nyirjesy P, Weitz MV, Chatwani A. 2000. Terconazole cream for non-Candida albicans fungal vaginitis: results of a retrospective analysis. Infect. Dis. Obstet. Gynecol. 8:240 –243. [27]. Santana IL, Goncalves LM, de Vasconcellos AA, da Silva WJ, Cury JA, Del Bel Cury A (2013) Dietary carbohydrates modulate Candida albicans biofilm development on the denture surface. PLoS One 8: e64645. doi: 10.1371/journal.pone.0064645 PMID: 23737992 [28]. Alnuaimi AD, O'Brien-Simpson NM, Reynolds EC, McCullough MJ (2013) Clinical isolates and laboratory reference Candida species and strains have varying abilities to form biofilms. FEMS Yeast Res 13: 689–699. doi: 10.1111/1567-1364.12068 PMID: 23927631 [29]. Sumathy V, Zakaria Z, Jothy SL, Gothai S, Vijayarathna S, Yoga Latha L, et al. (2014) In vitro and in vivo antifungal activity of Cassia surattensis flower against Aspergillus Niger. MicrobPathog 77: 7–12. doi: 10.1016/j.micpath.2014.10.004 PMID: 25457794 [30]. Pande M, Dubey VK, Yadav SC, Jagannadham MV (2006) A novel serine protease cryptolepain from Cryptolepis buchanani: purification and biochemical characterization. J Agric Food Chem 54: 10141– 10150. PMID: 17177552 [31]. Goncalves LM, Del Bel Cury AA, Sartoratto A, Garcia Rehder VL, Silva WJ (2012) Effects of undecylenic acid released from denture liner on Candida biofilms. J Dent Res 91: 985–989. PMID: 22904206 [32]. Taniguchi L, de Fatima Faria B, Rosa RT, de Paula ECA, Gursky LC, Elifio Esposito SL, et al. (2009) Proposal of a low-cost protocol for colorimetric semi-quantification of secretory phospholipase by Candida albicans grown in planktonic and biofilm phases. J Microbiol Methods 78: 171–174. doi: 10.1016/j. mimet.2009.05.012 PMID: 19464327 [33]. Wong SS, Kao RY, Yuen KY, Wang Y, Yang D, Samaranayake LP, et al. (2014) In vitro and in vivo activity of a novel antifungal small molecule against Candida infections. PLoS One 9: e85836. doi: 10. 1371/journal.pone.0085836 PMID: 24465737 [34]. Yano J, Kolls JK, Happel KI, Wormley F, Wozniak KL, Fidel PL (2012) The acute neutrophil response mediated by S100 alarmins during vaginal Candida infections is independent of the Th17-pathway. PLoS One 7: e46311. doi: 10.1371/journal.pone.0046311 PMID: 23050010 [35]. O'Brien J, Wilson I, Orton T, Pognan F (2000) Investigation of the Alamar Blue (resazurin) fluorescent dye for the assessment of mammalian cell cytotoxicity. Eur J Biochem 267: 5421–5426. PMID: 10951200 [36]. Solis NV, Filler SG (2012) Mouse model of oropharyngeal candidiasis. Nat Protoc 7: 637–642. doi: 10. 1038/nprot.2012.011 PMID: 22402633 [37]. Ryder NS (1999) Antifungal agents. IDrugs 2: 1253–1255. PMID: 16113946 [38]. Neidrauer M, Ercan UK, Bhattacharyya A, Samuels J, Sedlak J, Trikha R, et al. (2014) Antimicrobial efficacy and wound-healing property of a topical ointment containing nitric-oxide-loaded zeolites. J Med Microbiol 63: 203–209. doi: 10.1099/jmm.0.067322-0 PMID: 24196133 [39]. Ohta K, Nishi H, Fukui A, Shigeishi H, Takechi M, Kamata N (2010) CX3CL1 expression induced by Candida albicans in oral fibroblasts. FEMS Immunol Med Microbiol 60: 179–185. doi: 10.1111/j.1574- 695X.2010.00734.x PMID: 20880200 [40]. Shahzad M, Sherry L, Rajendran R, Edwards CA, Combet E, Ramage G, et al. (2014) Utilising polyphenols for the clinical management of Candida albicans biofilms. Int J Antimicrob Agents 44: 269–273. doi: 10.1016/j.ijantimicag.2014.05.017 PMID: 25104135 [41]. Messier C, Grenier D (2011) Effect of licorice compounds licochalcone A, glabridin and glycyrrhizic acid on growth and virulence properties of Candida albicans. Mycoses 54: e801–806. doi: 10.1111/j. 1439-0507.2011.02028.x PMID: 21615543 [42]. Gresnigt MS, Joosten LA, Verschueren I, van der Meer JW, Netea MG, Dinarello CA, et al. (2012) Neutrophil-mediated inhibition of proinflammatory cytokine responses. J Immunol 189: 4806–4815. doi: 10. 4049/jimmunol.1103551 PMID: 23053514 [43]. Lermann U, Morschhauser J (2008) Secreted aspartic proteases are not required for invasion of reconstituted human epithelia by Candida albicans. Microbiology 154: 3281–3295. doi: 10.1099/mic.0.2008/ 022525-0 PMID: 18957582 [44]. Samaranayake YH, Dassanayake RS, Cheung BP, Jayatilake JA, Yeung KW, Yau JY, et al. (2006) Differential phospholipase gene expression by Candida albicans in artificial media and cultured human oral epithelium. Apmis 114: 857–866. PMID: 17207086 [45]. Linhares IM, Summers PR, Larsen B, Giraldo PC, Witkin SS. 2011 Contemporary perspectives on vaginal pH and lactobacilli. Am. J. Obstet. Gynecol. 204:120.e1-5.