ACTIVITY ANTI-C. TROPICALIS AND EFFECTS OF THE COMBINATION OF (S)-(-)-CITRONELLAL WITH FOUR ANTIFUNGAL APPLIED IN VULVOVAGINAL CANDIDIASIS
Keywords:
Enantiomer, Antifungal agents, Combination studies, Vulvovaginal candidiasisAbstract
Objective: Assess the antifungal potential of the enantiomer (S)-(-)-citronellal [(S)-(-)-CT] isolated and associated to amphotericin B, fluconazole, itraconazole and miconazole against C. tropicalis from vulvovaginal secretions.
Methods: The enantiomer was solubilized in Tween 80 and DMSO. Posteriorly diluted in sterile distilled water up to the concentration of 2048 µg/ml. The MIC of the product was determined by microdilution in RPMI-1640 obtaining dilutions of 1024-4 µg/ml. The MFC was determined by the SDA depletion technique from aliquots of 1 µl of the MIC, MIC × 2 and MIC × 4.
Results: The antifungal susceptibility testing and the interfering effects of the association of the enantiomer with the standard drugs were determined by disk-diffusion in SDA. The MIC of (S)-(-)-CT was 64 µg/ml and the MFC 128 µg/ml. A high resistance of the strands C. tropicalis to amphotericin B, itraconazole and miconazole were observed. The combination test of the enantiomer with the amphotericin B, as well as with the itraconazole resulted in synergism 2 (66.6%) of the yeasts and in association with the fluconazole 1 (33.3%) and miconazole 3 (100%) of synergic effect.
Conclusion: The (S)-(-)-CT alone is fungicide for the 3 fungal strains and in association with the four antifungals increased the inhibition zones, increasing the sensitivity.
Downloads
References
Achkar JM, Fries BC. Candida infections of the genitourinary tract. Clin Microbiol Rev 2010;23:253-73.
Parolin C, Marangoni A, Laghi L, Foschi C, Palomino RAN, Calonghi N, et al. Isolation of vaginal Lactobacilli and characterization of anti-Candida activity. PLoS One 2015;10:1-17.
Freydière AM, Guinet R, Boiron P. Yeast identification in the clinical microbiology laboratory: phenotypical methods. Med Mycol 2001;39:9-33.
Gandhi TN, Patel MG, Jain PMR. Antifungal susceptibility of Candida against six antifungal drugs by disk diffusion method Isolated from vulvovaginal Candidiasis. Int J Cur Res Rev 2015;7:20-5.
Foxman B, Muraglia R, Dietz JP, Sobel JD, Wagner J. Prevalence of recurrent vulvovaginal Candidiasis in 5 European countries and the United States: results from in internet panel survey. J Low Genit Tract Dis 2013;17:340-5.
Jack D, Sobel MD. Recurrent vulvovaginal Candidiasis. Am J Obstet Gynecol 2016;214:15-21.
Hong E, Dixit S, Fidel PL, Bradford J, Fischer G. Vulvovaginal Candidiasis as a chronic disease: diagnostic criteria and definition. J Low Genit Tract Dis 2014;18:31-8.
Behzadi P, Behzadi E, Ranjbar R. Urinary tract infections and Candida albicans. Cent Eur J Urol 2015;68:96-101.
Akortha EE, Nwaugo VO, Chikwe NO. Antifungal resistance among Candida species from patients with genitourinary tract infection isolated in benin city, edo state. Afr J Microbiol Res 2009;3:694-9.
Sobel JD, Chaim W. Treatment of Torulopsis glabrata vaginitis: retrospective review of boric acid therapy. Clin Infect Dis 1997;24:649-52.
Ahmad S, Khan AU. Prevalence of Candida species and potential risk factors for vulvovaginal candidiasis in Aligarh, India. Eur J Obstet Gynecol Reprod Biol 2009;144:68-71.
Kelen FDD, Alessandra RF, Marcia ELC, Terezinha IESA. Challenge for clinical laboratories: detection of antifungal resistance in Candida species causing vulvovaginal candidiasis. J Lab Med 2011;42:87-93.
Lata RP, Jayshri DP, Palak B, Sanjay DR, Parul DS. Prevalence of candida infection and its antifungal susceptibility pattern in tertiary care hospital, Ahmedabad. Nat J Med Res 2012;2:439-41.
Mishra RP, Iqbal. In vitro activity of medicinal plants against some bacterial and fungal isolates. Asian J Pharm Clin Res 2015;18:225-30.
Espinel-Ingroff A. Mechanisms of resistance to antifungal agents: yeasts and filamentous fungi. Revista Iberoamericana MicologÃa 2008;25:101-6.
Anusha N, Rohith V, Isabella T. Prescription errors in the department of obstetrics and gynaecology: a cross-sectional, observational study. Asian J Pharm Clin Res 2016;9;233-5.
Avoseh O, Oyedeji O, Rungqu P, Nkeh-Chungag B, Oyedeji A. Cymbopogon Species; ethonopharmacology, phytochemistry and the pharmacological importance. Molecules 2015;20:7438-53.
Batubara I, Suparto IH, Sa’diah S, Matsuoka R, Mitsunaga T. Effects of inhaled citronella oil and related compounds on rat body weight and brown adipose tissue sympathetic nerve. Nutrients 2015;7:1859-70.
Rosato A, Vitali C, Gallo D, Millillo MA, Mallamaci R. The inhibition of Candida species by selected oils and their synergism with amphotericin B. Phytomedicine 2008;15:635-8.
Wagner H, Ulrich-Merzenich G. Synergy research: approaching a new generation of phytopharmaceuticals. Phytomedicine 2009;16:97-110.
Nascimento PFC, Nascimento AC, Rodrigues CS, Antoniolli AR, Santos PO, Barbosa Júnior AM, et al. Atividade antimicrobiana dos óleos essenciais: uma abordagem multifatorial dos métodos. Rev Bras Farmacogn 2007;17:108-13.
Pereira FO, Mendes JM, Lima IO, Mota KSL, Oliveira WA, Lima EO. Antifungal activity of geraniol and citronellol, two monoterpenes alcohols, against Trichophyton rubrum involves inhibition of ergosterol biosynthesis. Pharm Biol 2014a;53:1-7.
Koneman EW, Allen SD, Janda WM, Schreckenberger PC, Win WCJ. Diagnóstico microbiológico. 6 ed. São Paulo: Médica e CientÃfica Ltda; 2008. p. 1565.
Ostrosky EA, Mizumoto MK, Lima MEL, Kaneko TM, Nishikawa SO, Freitas BR. Métodos para avaliação da atividade antimicrobiana de determinação de concentração mÃnima inibitória (CMI) de plantas medicinais. Rev Bras Farmacog 2008;18:301-7.
Cleeland R, Squires E. Evaluation of new antimicrobials in vitro and in experimental animal infections. Antibiot Lab Med 1991;3:739-87.
Hadacek F, Greger H. Testing of antifungal natural products: methodologies, comparability of results and assay coices. Phytochem Analysis 2000;11:137-47.
Nattinal committee for clinical laboratory standards (NCCLS). Reference method for broth dilution antifungal susceptibility testing of yeasts. Villanova 2002;17:M27-A2.
Morales G, Paredes A, Sierra P, Loyola LA. Antimicrobial activity of three Baccharis species used in the traditional medicine of Northern Chile. Molecules 2008;13:790-4.
Ernst ME, Klepser ME, Wolfe EJ, Pfaller MA. Antifungal dynamics of LY 303366, an investigational echinocandin B analog, against Candida ssp. Diagn Microbiol Infect Dis 1996;26:125-31.
Espinel-Ingroff A, Chaturvedi V, Fothergill A, Rinaldi MG. Optimal testing conditions for determining MICs and minimum fungicidal concentrations of new and established antifungal agents for uncommon molds: NCCLS collaborative study. J Clin Microbiol 2002;40:3776-81.
Bauer AW, Kirby WM, Sherris JC, Turck M. Antibiotic susceptibility testing by a standardized single disk method. Am J Clin Pathol 1966;45:493-6.
Clinical and Laboratory Standards Institute. Method for Antifungal Disk Diffusion Susceptibility Testing of Yeasts; Approved Guideline. 2nd. ed. CLSI document M44-A2. Wayne, PA: Clinical and Laboratory Standards Institute; 2009.
Oliveira RAG, Lima EO, Viera WL, Freire KRL, Trajano VN, Lima IO, et al. Estudo da interferência de óleos essenciais sobre a atividade de alguns antibióticos usados na clÃnica. Rev Bras Farmacogn 2006;16:77-82.
Cuenca-Estrella M. Combinations of antifungal agents in therapy-what value are they? J Antimicrob Chemother 2004;54:854-69.
Lima IO, Nóbrega FM, Oliveira WA, Lima EO, Menezes EA, Afrânio Cunha F, et al. Anti-Candida albicans effectiveness of citral and investigation of mode of action. Pharm Biol 2012;50:1536-41.
Zore GB, Thakre AD, Jadhav S, Karuppayil SM. Terpenoids inhibit Candida albicans growth affecting membrane integrity and arresto of cell cycle. Phytomedicine 2011b;18:1181-90.
Pereira CJN, Albuquerque RS, Figueiredo LN, Targino MAJ, Vieira De Brito DI, Rolón M, et al. Avaliação da atividade tripanocida, leishmanicida e citotóxica do geraniol e citronelal. Cad Cult Ciênc 2015;13:29-36.
Hafidh RR, Abdulamir AS, Vern LS, Abu Bakar F, Jahanshiri F, Sekawi Z. Inhibition of growth of highly resistant bacterial and fungal pathogens by a natural product. Open Microbiol J 2011;5:96-106.
MÃmica LMJ, Ueda SMY, Martino MDV, Navarini A, Martini IJ. Diagnóstico de infecção por Candida: avaliação de testes de identificação de espécies e caracterização do perfil de suscetibilidade. J Bras Patol Med Lab 2009;45:17-23.
Favalessa OC, Martins MA, Hahn RC. Aspectos micológicos e suscetibilidade in vitro de leveduras do gênero Candida em pacientes HIV-positivos provenientes do estado de mato grosso. Revista Sociedade Brasileira Med Trop 2010;43:673-7.
Nunes EB, Monteiro JCMS, Nunes NB, Vaz Paes L. Antifungal sensitivity profile for the Candida genus in a reference hospital in Northern Brazil. Revista Pan-Amazônica Saúde 2011;2:23-30.
Dalazen D, Zanrosso D, Wanderley L, Silva NL, Fuentefria AM. Comparação do perfil de suscetibilidade entre isolados clÃnicos de Candida spp. orais e vulvovaginais no Sul do Brasil. J Bras Patol Med Lab 2011;47:33-8.
Abaci O, Haliki-uztan A. Investigation of the susceptibility of Candida species isolated from denture wearers to different antifungal antibiotics. Afr J Microbiol Res 2011;5:1398-403.
Spampinato C, Leonardi D. Candinda infections, causes, targets, and resistance mechanisms: traditional and alternativa antifungal agents. Biomed Res Int 2013;2013:1-13.
Ahmad A, Khan A, Khan LA, Manzoor N. In vitro synergy of eugenol and methyleugenol with fluconazole against clinical Candida isolates. J Med Microbiol 2010;59:1178-84.
Roling EE, Klepser ME, Wasson A, Lewis RE, Ernst EJ, Pfaller MA. Antifungal activities of fluconazole, caspofungin (MK0991), and anidulafuingin (LY 303366) alon and in combination against Candida spp. And Cryptococcus neoformans via time-kill methods. Diagn Microbiol Infect Dis 2002;43:13-7.
Ribeiro DS, Velozo ES, Guimarães AG. Interaction between the rosemary essential oil (Rosmarinus officinalis L.) and antimicrobial drugs in the control of bacteria isolated from foods. J Biotechn Biod 2013;4:10-9.
Brehm-Stecher BF, Johnson EA. Sensitization of Staphylococcus aureus and Escherichia coli to antibiotics by the sequiterpenoids, nerolidol, farnesol, bisabolol and apritone. Antimicrob Agents Chemother 2003;47:3357-60.
Trombetta D, Castelli F, Sarpietro MG, Venuti V, Cristani M, Daniele C, et al. Mechanisms of antibacterial action of three monoterpenes. Antimicrob Agents Chemother 2005;49:2474-8.
Zore GB, Thakre AD, Rathod V, Karuppayil SM. Evaluation of anti-Candida potential of geranium oil constituents against clinical isolates of Candida albicans differentially sensitive to fluconazole: inhibition of growth, dimorphism and sensitization. Mycoses 2011a;54:e99-e109.
Sanchez ME, Turina A, Garcia DA, Veronica-Nolan M, Perillo MA. Surface activity of thymol: implications for an eventual pharmacological activity. Colloids Surf B 2004;34:77-86.
Braga PC, Alfieri M, Culici M, Dal Sasso M. Inhibitory activity of thymol against the formation and viability of Candida albicans hyphae. Mycoses 2007;50:502-6.