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Madurella mycetomatis Is Highly Susceptible to Ravuconazole

DOI: 10.1371/journal.pntd.0002942

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Abstract:

The current treatment of eumycetoma utilizing ketoconazole is unsatisfactory because of high recurrence rates, which often leads to complications and unnecessary amputations, and its comparatively high cost in endemic areas. Hence, an effective and affordable drug is required to improve therapeutic outcome. E1224 is a potent orally available, broad-spectrum triazole currently being developed for the treatment of Chagas disease. E1224 is a prodrug that is rapidly converted to ravuconazole. Plasma levels of E1224 are low and transient, and its therapeutically active moiety, ravuconazole is therapeutically active. In the present study, the in vitro activity of ravuconazole against Madurella mycetomatis, the most common etiologic agent of eumycetoma, was evaluated and compared to that of ketoconazole and itraconazole. Ravuconazole showed excellent activity with MICs ranging between ≤0.002 and 0.031 μg/ml, which were significantly lower than the MICs reported for ketoconazole and itraconazole. On the basis of our findings, E1224 with its resultant active moiety, ravuconazole, could be an effective and affordable therapeutic option for the treatment of eumycetoma.

References

[1]  Fahal AH, Elkhawad AO (2013) Managing mycetoma: guidelines for best practice. Expert Rev Dermatol 8: 301–7. doi: 10.1586/edm.13.31
[2]  Fahal AH (2011) Review: Mycetoma. Khartoum Med J 04: 514–523.
[3]  Ahmed AO, van Leeuwen W, Fahal A, van de Sande W, Verbrugh H, et al. (2004) Mycetoma caused by Madurella mycetomatis: a neglected infectious burden. Lancet Infect Dis 4: 566–74. doi: 10.1016/s1473-3099(04)01131-4
[4]  Kloezen W, Meis JF, Curfs-Breuker I, Fahal AH, van de Sande WW (2012) In vitro antifungal activity of isavuconazole against Madurella mycetomatis. Antimicrob Agents Chemother 56: 6054–6. doi: 10.1128/aac.01170-12
[5]  van Belkum A, Fahal AH, van de Sande WW (2011) In vitro susceptibility of Madurella mycetomatis to posaconazole and terbinafine. Antimicrob. Agents Chemother 55: 1771–3. doi: 10.1128/aac.01045-10
[6]  van de Sande WW, Luijendijk A, Ahmed AO, Bakker-Woudenberg IA, van Belkum A (2005) Testing of the in vitro susceptibilities of Madurella mycetomatis to six antifungal agents by using the Sensititre system in comparison with a viability-based 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)?-5-[(phenylamino)carbonyl]-2H-tetrazoliu?mhydroxide (XTT) assay and a modified NCCLS method. Antimicrob Agents Chemother 49: 1364–8. doi: 10.1128/aac.49.4.1364-1368.2005
[7]  Zein HA, Fahal AH, Mahgoub ES, El Hassan TA, Abdel-Rahman ME (2012) Predictors of cure, amputation and follow-up dropout among patients with mycetoma seen at the Mycetoma Research Centre, University of Khartoum, Sudan. Trans R Soc Trop Med Hyg 106: 639–44. doi: 10.1016/j.trstmh.2012.07.003
[8]  European Medicines Agency (2013). European Medicines Agency recommends suspension of marketing authorisations for oral ketoconazole. Benefit of oral ketoconazole does not outweigh risk of liver injury in fungal infections. Available: http://www.ema.europa.eu/docs/en_GB/docu?ment_library/Referrals_document/Ketocona?zole-containing_medicines/WC500146616.pd?f Accessed 23 May 2014.
[9]  Bartroli J, Turmo E, Algueró M, Boncompte E, Vericat ML, et al. (1998) New azole antifungals. 3. Synthesis and antifungal activity of 3-substituted-4(3H)-quinazolinones. J Med Chem 41: 1869–82. doi: 10.1021/jm9707277
[10]  Fung-Tomc JC, Huczko E, Minassian B, Bonner DP (1998) In vitro activity of a new oral triazole, BMS-207147 (ER-30346). Antimicrob Agents Chemother 42: 313–8.
[11]  Diekema DJ, Pfaller MA, Messer SA, Houston A, Hollis RJ, et al. (1999) In vitro activities of BMS-207147 against over 600 contemporary clinical bloodstream isolates of Candida species from the SENTRY Antimicrobial Surveillance Program in North America and Latin America. Antimicrob Agents Chemother 43: 2236–9.
[12]  Urbina JA, Payares G, Sanoja C, Lira R, Romanha AJ (2003) In vitro and in vivo activities of ravuconazole on Trypanosoma cruzi, the causative agent of Chagas disease. Int J Antimicrob Agents 21: 27–38. doi: 10.1016/s0924-8579(02)00273-x
[13]  Buckner FS, Urbina JA (2012) Recent Developments in Sterol 14-demethylase Inhibitors for Chagas Disease. Int J Parasitol Drugs Drug Resist 2: 236–42. doi: 10.1016/j.ijpddr.2011.12.002
[14]  de Hoog GS, Ahmed SA, Najafzadeh MJ, Sutton DA, Keisari MS, et al. (2013) Phylogenetic findings suggest possible new habitat and routes of infection of human eumycetoma. PLoS Negl Trop Dis 7(5): e2229. doi: 10.1371/journal.pntd.0002229
[15]  Ahmed AO, van de Sande WW, van Vianen W, van Belkum A, Fahal AH, et al. (2004) In vitro susceptibilities of Madurella mycetomatis to itraconazole and amphotericin B assessed by a modified NCCLS method and a viability-based 2,3-Bis(2-methoxy-4-nitro-5-sulfophenyl)?-5-[(phenylamino)carbonyl]-2H-tetrazoliu?mhydroxide (XTT) assay. Antimicrob Agents Chemother 48: 2742–6. doi: 10.1128/aac.48.7.2742-2746.2004
[16]  Cuenca-Estrella M, Gomez-Lopez A, Mellado E, Garcia-Effron G, Monzon A, et al. (2005) In vitro activity of ravuconazole against 923 clinical isolates of nondermatophyte filamentous fungi. Antimicrob Agents Chemother 49: 5136–8. doi: 10.1128/aac.49.12.5136-5138.2005
[17]  Minassian B, Huczko E, Washo T, Bonner D, Fung-Tomc J (2003) In vitro activity of ravuconazole against Zygomycetes, Scedosporium and Fusarium isolates. Clin Microbiol Infect 9: 1250–2. doi: 10.1111/j.1469-0691.2003.00755.x
[18]  Serena C, Ortoneda M, Capilla J, Pastor FJ, Sutton DA, et al. (2003) In vitro activities of new antifungal agents against Chaetomium spp. and inoculum standardization. Antimicrob Agents Chemother 47: 3161–4. doi: 10.1128/aac.47.10.3161-3164.2003
[19]  Yamazumi T, Pfaller MA, Messer SA, Houston A, Hollis RJ, et al. (2000) In vitro activities of ravuconazole (BMS-207147) against 541 clinical isolates of Cryptococcus neoformans. Antimicrob Agents Chemother 44: 2883–6. doi: 10.1128/aac.44.10.2883-2886.2000
[20]  Pfaller MA, Messer SA, Hollis RJ, Jones RN, Diekema DJ (2002) In vitro activities of ravuconazole and voriconazole compared with those of four approved systemic antifungal agents against 6,970 clinical isolates of Candida spp. Antimicrob Agents Chemother 46: 1723–7. doi: 10.1128/aac.46.6.1723-1727.2002
[21]  Andes D, Marchillo K, Stamstad T, Conklin R (2003) In vivo pharmacodynamics of a new triazole, ravuconazole, in a murine candidiasis model. Antimicrob Agents Chemother 47: 1193–9. doi: 10.1128/aac.47.4.1193-1199.2003
[22]  Clemons KV, Stevens DA (2001) Efficacy of ravuconazole in treatment of mucosal candidosis in SCID mice. Antimicrob Agents Chemother 45: 3433–6. doi: 10.1128/aac.45.12.3433-3436.2001
[23]  Hata K, Kimura J, Miki H, Toyosawa T, Moriyama M, et al. (1996) Efficacy of ER-30346, a novel oral triazole antifungal agent, in experimental models of aspergillosis, candidiasis, and cryptococcosis. Antimicrob Agents Chemother 40: 2243–7.
[24]  Pasqualotto AC, Denning DW (2008) New and emerging treatments for fungal infections. J Antimicrob Chemother. 61 Suppl 1i19–30. doi: 10.1093/jac/dkm428
[25]  E1224 Fifth Edition Global Investigator Brochure March 29, 2013.
[26]  Groll AH, Mickiene D, Petraitis V, Petraitiene R, Kelaher A, et al. (2005) Compartmental pharmacokinetics and tissue distribution of the antifungal triazole ravuconazole following intravenous administration of its di-lysine phosphoester prodrug (BMS-379224) in rabbits. J Antimicrob Chemother 56: 899–907. doi: 10.1093/jac/dki287
[27]  Mikamo H, Yin XH, Hayasaki Y, Shimamura Y, Uesugi K, et al. (2002) Penetration of ravuconazole, a new triazole antifungal, into rat tissues. Chemotherapy 48: 7–9. doi: 10.1159/000048580
[28]  Clemons KV1, Martinez M, Calderon L, Stevens DA (2002) Efficacy of ravuconazole in treatment of systemic murine histoplasmosis. Antimicrob Agents Chemother 46: 922–4. doi: 10.1128/aac.46.3.922-924.2002
[29]  Kirkpatrick WR1, Perea S, Coco BJ, Patterson TF (2002) Efficacy of ravuconazole (BMS-207147) in a guinea pig model of disseminated aspergillosis. J Antimicrob Chemother 49: 353–7. doi: 10.1093/jac/49.2.353

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