Abstract
Invasive fungal infections can cause significant morbidity and mortality in humans and different animal species, worldwide. Antifungal therapy remains a central component of protecting human and vertebrate animals against fungal infections. Depending on the strategy chosen, topical and/or systemic drugs can be used based on the clinical picture of the host and mycological identification of the etiologic agent. For effective treatment, it is important to correctly identify the causative agents at the species level, which will enable administration of suitable therapeutics and initiation of appropriate therapeutic modalities. In addition, the management of fungal infections in animals usually includes systemic or topical treatment of the animal and environmental decontamination if necessary. Only a few products are licensed for animals, and, as a consequence, off-label use of the drugs approved for use in humans is quite common.
This chapter focuses on the topical and systemic antifungal agents currently in use in veterinary practice. The therapeutic uses that have proved successfully in various animal species are summarized. This chapter also summarizes the currently available evidence for the emergence of resistance against these agents.
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References
Alastruey-Izquierdo A, Cuenca-Estrella M, Monzon A, Mellado E, Rodriguez-Tudela JL (2008) Antifungal susceptibility profile of clinical Fusarium spp. isolates identified by molecular methods. J Antimicrob Chemother 61(4):805–809
Alcazar-Fuoli L, Mellado E, Alastruey-Izquierdo A, Cuenca-Estrella M, Rodriguez-Tudela JL (2009) Species identification and antifungal susceptibility patterns of species belonging to Aspergillus section Nigri. Antimicrob Agents Chemother 53(10):4514–4517
Al-Yasiri MH, Normand AC, L’Ollivier C, Lachaud L, Bourgeois N, Rebaudet S, Piarroux R, Mauffrey JF, Ranque S (2016) Opportunistic fungal pathogen Candida glabrata circulates between humans and yellow-legged gulls. Sci Rep 6:36157
Andrews AH, Edwardson J (1981) Treatment of ringworm in calves using griseofulvin. Vet Rec 108:4980500
Arceneaux KA, Taboada J, Hosgood G (1998) Blastomycosis in dogs: 115 cases (1980–1995). J Am Vet Med Assoc 213(5):658–664
Arikan S (2002) Lipid-based antifungal agents: a concise overview. Cell Mol Biol Lett 7(3):919–922
Bachmann SP, Patterson TF, Lopez-Ribot JL (2002a) In vitro activity of caspofungin (MK-0991) against Candida albicans clinical isolates displaying different mechanisms of azole resistance. J Clin Microbiol 40(6):2228–2230
Bachmann SP, VandeWalle K, Ramage G, Patterson TF, Wickes BL, Graybill JR, Lopez-Ribot JL (2002b) In vitro activity of caspofungin against Candida albicans biofilms. Antimicrob Agents Chemother 46(11):3591–3596
Barchiesi F, Colombo AL, McGough DA, Rinaldi MG (1994) Comparative study of broth macrodilution and microdilution techniques for in vitro antifungal susceptibility testing of yeasts by using the National Committee for Clinical Laboratory Standards’ proposed standard. J Clin Microbiol 32(10):2494–2500
Barrs VR, van Doorn TM, Houbraken J, Kidd SE, Martin P, Pinheiro PD, Richardson M, Varga J, Samson RA (2013) Aspergillus felis sp. nov., an emerging agent of invasive aspergillosis in humans, cats, and dogs. PLoS One 8(6):e64871
Bechert U, Christensen JM, Poppenga R, Fahmy SA, Redig P (2010) Pharmacokinetics of terbinafine after single oral dose administration in red-tailed hawks (Buteo jamaicensis). J Avian Med Surg 24(2):122–130
Beernaert LA, Baert K, Marin P, Chiers K, De Backer P, Pasmans F, Martel A (2009a) Designing voriconazole treatment for racing pigeons: balancing between hepatic enzyme auto induction and toxicity. Med Mycol 47(3):276–285
Beernaert LA, Pasmans F, Van Waeyenberghe L, Dorrestein GM, Verstappen F, Vercammen F, Haesebrouck F, Martel A (2009b) Avian Aspergillus fumigatus strains resistant to both itraconazole and voriconazole. Antimicrob Agents Chemother 53(5):2199–2201
Beltaire KA, Cheong SH, Coutinho da Silva MA (2012) Retrospective study on equine uterine fungal isolates and antifungal susceptibility patterns (1999–2011). Equine Vet J Suppl 43:84–87
Benitah N (2006) Canine nasal aspergillosis. Clin Tech Small Anim Pract 21(2):82–88
Bensignor E, Grandemange E (2006) Comparison of an antifungal agent with a mixture of antifungal, antibiotic and corticosteroid agents for the treatment of Malassezia species otitis in dogs. Vet Rec 158(6):193–195
Benson JM, Nahata MC (1988) Clinical use of systemic antifungal agents. Clin Pharm 7(6):424–438
Bergan T, Vangdal M (1983) In vitro activity of antifungal agents against yeast species. Chemotherapy 29(2):104–110
Bolard J (1986) How do the polyene macrolide antibiotics affect the cellular membrane properties? Biochim Biophys Acta 864(3–4):257–304
Boothe DM, Herring I, Calvin J, Way N, Dvorak J (1997) Itraconazole disposition after single oral and intravenous and multiple oral dosing in healthy cats. Am J Vet Res 58(8):872–877
Bowman JC, Abruzzo GK, Flattery AM, Gill CJ, Hickey EJ, Hsu MJ, Kahn JN, Liberator PA, Misura AS, Pelak BA, Wang TC, Douglas CM (2006) Efficacy of caspofungin against Aspergillus flavus, Aspergillus terreus, and Aspergillus nidulans. Antimicrob Agents Chemother 50(12):4202–4205
Brammer KW, Farrow PR, Faulkner JK (1990) Pharmacokinetics and tissue penetration of fluconazole in humans. Rev Infect Dis 12(Suppl 3):S318–S326
Brilhante RS, Castelo Branco DS, Duarte GP, Paiva MA, Teixeira CE, Zeferino JP, Monteiro AJ, Cordeiro RA, Sidrim JJ, Rocha MF (2012) Yeast microbiota of raptors: a possible tool for environmental monitoring. Environ Microbiol Rep 4(2):189–193
Brilhante RS, de Alencar LP, Cordeiro Rde A, Castelo-Branco Dde S, Teixeira CE, Macedo Rde B, Lima DT, Paiva Mde A, Monteiro AJ, Alves ND, Franco de Oliveira M, Sidrim JJ, Rocha MF, Bandeira Tde J, Rodrigues Tde J (2013) Detection of Candida species resistant to azoles in the microbiota of rheas (Rhea americana): possible implications for human and animal health. J Med Microbiol 62(Pt 6):889–895
Brilhante RS, Bittencourt PV, Castelo-Branco Dde S, de Oliveira JS, Alencar LP, Cordeiro Rde A, Pinheiro M, Nogueira-Filho EF, Pereira-Neto Wde A, Sidrim JJ, Rocha MF (2016) Trends in antifungal susceptibility and virulence of Candida spp. from the nasolacrimal duct of horses. Med Mycol 54(2):147–154
Bromley MJ, van Muijlwijk G, Fraczek MG, Robson G, Verweij PE, Denning DW, Bowyer P (2014) Occurrence of azole-resistant species of Aspergillus in the UK environment. J Glob Antimicrob Resist 2(4):276–279
Brook D (1982) Diagnosis of equine endometrial candidiasis by direct smear and successful treatment with amphotericin B and oxytetracycline. J S Afr Vet Assoc 53(4):261–263
Brun S, Berges T, Poupard P, Vauzelle-Moreau C, Renier G, Chabasse D, Bouchara JP (2004) Mechanisms of azole resistance in petite mutants of Candida glabrata. Antimicrob Agents Chemother 48(5):1788–1796
Bunskoek PE, Seyedmousavi S, Gans SJ, van Vierzen PB, Melchers WJ, van Elk CE, Mouton JW, Verweij PE (2017) Successful treatment of azole-resistant invasive aspergillosis in a bottlenose dolphin with high-dose posaconazole. Med Mycol Case Rep 16:16–19
Bunting EM, Abou-Madi N, Cox S, Martin-Jimenez T, Fox H, Kollias GV (2009) Evaluation of oral itraconazole administration in captive Humboldt penguins (Spheniscus humboldti). J Zoo Wildl Med 40(3):508–518
Cafarchia C, Iatta R, Immediato D, Puttilli MR, Otranto D (2015) Azole susceptibility of Malassezia pachydermatis and Malassezia furfur and tentative epidemiological cut-off values. Med Mycol 53(7):743–748
Cartwright ME, Petruska J, Arezzo J, Frank D, Litwak M, Morrissey RE, MacDonald J, Davis TE (2009) Phospholipidosis in neurons caused by posaconazole, without evidence for functional neurologic effects. Toxicol Pathol 37(7):902–910
Chapman SW, Pappas P, Kauffmann C, Smith EB, Dietze R, Tiraboschi-Foss N, Restrepo A, Bustamante AB, Opper C, Emady-Azar S, Bakshi R (2004) Comparative evaluation of the efficacy and safety of two doses of terbinafine (500 and 1000 mg day(−1)) in the treatment of cutaneous or lymphocutaneous sporotrichosis. Mycoses 47(1–2):62–68
Chen BK, Friedlander SF (2001) Tinea capitis update: a continuing conflict with an old adversary. Curr Opin Pediatr 13(4):331–335
Clinkenbeard KD, Cowell RL, Tyler RD (1988) Disseminated histoplasmosis in dogs: 12 cases (1981–1986). J Am Vet Med Assoc 193(11):1443–1447
CLSI (2008) Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; approved standard-second edition. CLSI document. M38-A2. Clinical and Laboratory Standards Institute, Wayne
Coelho D, Silva S, Vale-Silva L, Gomes H, Pinto E, Sarmento A, Pinheiro MD (2011) Aspergillus viridinutans: an agent of adult chronic invasive aspergillosis. Med Mycol 49(7):755–759
Collins MS, Pappagianis D (1977) Uniform susceptibility of various strains of Coccidioides immitis to amphotericin B. Antimicrob Agents Chemother 11(6):1049–1055
Conte L, Ramis J, Mis R, Vilageliu J, Basi N, Forn J (1992) Pharmacokinetic study of [C-14] flutrimazole after oral and intravenous administration in dogs – comparison with clotrimazole. Arzneimittelforschung 42-1(6):854–858
Cordeiro Rde A, de Oliveira JS, Castelo-Branco Dde S, Teixeira CE, Marques FJ, Bittencourt PV, Carvalho VL, Bandeira Tde J, Brilhante RS, Moreira JL, Pereira-Neto Wde A, Sidrim JJ, Rocha MF (2015) Candida tropicalis isolates obtained from veterinary sources show resistance to azoles and produce virulence factors. Med Mycol 53(2):145–152
Cordoba S, Rodero L, Vivot W, Abrantes R, Davel G, Vitale RG (2008) In vitro interactions of antifungal agents against clinical isolates of Fusarium spp. Int J Antimicrob Agents 31(2):171–174
Cornelissen F, Van den Bossche H (1983) Synergism of the antimicrobial agents miconazole, bacitracin and polymyxin B. Chemotherapy 29(6):419–427
Cornely OA, Maertens J, Winston DJ, Perfect J, Ullmann AJ, Walsh TJ, Helfgott D, Holowiecki J, Stockelberg D, Goh YT, Petrini M, Hardalo C, Suresh R, Angulo-Gonzalez D (2007) Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med 356(4):348–359
Corrigan VK, Legendre AM, Wheat LJ, Mullis R, Johnson B, Bemis DA, Cepero L (2016) Treatment of disseminated aspergillosis with posaconazole in 10 dogs. J Vet Intern Med 30(1):167–173
Court MH (2013) Feline drug metabolism and disposition: pharmacokinetic evidence for species differences and molecular mechanisms. Vet Clin North Am Small Anim Pract 43(5):1039–1054
Cuenca-Estrella M, Gomez-Lopez A, Buitrago MJ, Mellado E, Garcia-Effron G, Rodriguez-Tudela JL (2006) In vitro activities of 10 combinations of antifungal agents against the multiresistant pathogen Scopulariopsis brevicaulis. Antimicrob Agents Chemother 50(6):2248–2250
Cutler RE, Blair AD, Kelly MR (1978) Flucytosine kinetics in subjects with normal and impaired renal function. Clin Pharmacol Ther 24(3):333–342
Day JN, Chau TT, Lalloo DG (2013) Combination antifungal therapy for cryptococcal meningitis. N Engl J Med 368(26):2522–2523
De Carli L, Larizza L (1988) Griseofulvin. Mutat Res 195(2):91–126
De Keyser H, Van den Brande M (1983) Ketoconazole in the treatment of dermatomycosis in cats and dogs. Vet Q 5(3):142–144
de Kruijff B, Gerritsen WJ, Oerlemans A, Demel RA, van Deenen LL (1974) Polyene antibiotic-sterol interactions in membranes of Acholeplasma laidlawii cells and lecithin liposomes. I. Specificity of the membrane permeability changes induced by the polyene antibiotics. Biochim Biophys Acta 339(1):30–43
de la Torre P, Reboli AC (2014) Micafungin: an evidence-based review of its place in therapy. Core Evid 9:27–39
Dekeyser H (1981) Activity of repeated administration of enilconazole (R-23979) against Trichophyton verrucosum in cattle – a clinical-trial. Tijdschr Diergeneeskd 106(16):799–805
Deng S, Hu H, Abliz P, Wan Z, Wang A, Cheng W, Li R (2011) A random comparative study of terbinafine versus griseofulvin in patients with tinea capitis in Western China. Mycopathologia 172(5):365–372
Denning DW (2002) Echinocandins: a new class of antifungal. J Antimicrob Chemother 49(6):889–891
Denning DW, Lee JY, Hostetler JS, Pappas P, Kauffman CA, Dewsnup DH, Galgiani JN, Graybill JR, Sugar AM, Catanzaro A et al (1994) NIAID mycoses study group multicenter trial of oral itraconazole therapy for invasive aspergillosis. Am J Med 97(2):135–144
Denning DW, Ribaud P, Milpied N, Caillot D, Herbrecht R, Thiel E, Haas A, Ruhnke M, Lode H (2002) Efficacy and safety of voriconazole in the treatment of acute invasive aspergillosis. Clin Infect Dis 34(5):563–571
Di Somma A, Bailey T, Silvanose C, Garcia-Martinez C (2007) The use of voriconazole for the treatment of aspergillosis in falcons (Falco species). J Avian Med Surg 21(4):307–316
Diaz M, Negroni R, Montero-Gei F, Castro LG, Sampaio SA, Borelli D, Restrepo A, Franco L, Bran JL, Arathoon EG, Pan-American Study Group et al (1992) A Pan-American 5-year study of fluconazole therapy for deep mycoses in the immunocompetent host. Clin Infect Dis 14(Suppl 1):S68–S76
Diflucan (2013) Product information: DIFLUCAN oral tablets, IV injection, oral suspension, fluconazole oral tablets, IV injection, oral suspension. Pfizer Inc., New York
Dodds Ashley ES, Lewis R, Lewis JS, Martin C, Andes D (2006) Pharmacology of systemic antifungal agents. Clin Infect Dis 43:S28–S39
Dolton MJ, Perera V, Pont LG, McLachlan AJ (2014) Terbinafine in combination with other antifungal agents for treatment of resistant or refractory mycoses: investigating optimal dosing regimens using a physiologically based pharmacokinetic model. Antimicrob Agents Chemother 58(1):48–54
Durdu M, Ilkit M, Tamadon Y, Tolooe A, Rafati H, Seyedmousavi S (2017) Topical and systemic antifungals in dermatology practice. Expert Rev Clin Pharmacol 10(2):225–237
Dutcher JD (1968) The discovery and development of amphotericin B. Dis Chest 54(Suppl 1):296–298
ECDC Technical Report (Kleinkauf N, Verweij PE, Arendrup MC, Donnelly PJ, Cuenca-Estrella M, Fraaije B, Melchers WJG, Adriaenssens N, Kema GHJ, Ullmann A, Bowyer P, Denning DW) (2013) Risk assessment on the impact of environmental usage of triazoles on the development and spread of resistance to medical triazoles in Aspergillus species. www.ecdc.europa.eu
Elewski BE (1999) Treatment of tinea capitis: beyond griseofulvin. J Am Acad Dermatol 40(6 Pt 2):S27–S30
EMA (1998) Parconazole. EMEA/MRL, 351/98-Final. The European agency for evalution of meicinal products. Veterinary medicines evluation. Unit. http://www.ema.europa.eu/docs/en_GB/document_library/Maximum_Residue_Limits_-_Report/2009/11/WC500015522.pdf
EMA (2012a) European public assessment report (EPAR) for Diflucan. European Medicines Agency
EMA (2012b) European public assessment report (EPAR) for Noxafil. European Medicines Agency
EMA (2012c) European public assessment report (EPAR) for Vfend. European Medicines Agency
Eng RH, Person A, Mangura C, Chmel H, Corrado M (1981) Susceptibility of zygomycetes to amphotericin B, miconazole, and ketoconazole. Antimicrob Agents Chemother 20(5):688–690
Eschenauer G, Depestel DD, Carver PL (2007) Comparison of echinocandin antifungals. Ther Clin Risk Manag 3(1):71–97
Espinel-Ingroff A, Chowdhary A, Gonzalez GM, Lass-Florl C, Martin-Mazuelos E, Meis J, Pelaez T, Pfaller MA, Turnidge J (2013) Multicenter study of isavuconazole MIC distributions and epidemiological cutoff values for Aspergillus spp. for the CLSI M38-A2 broth microdilution method. Antimicrob Agents Chemother 57(8):3823–3828
Estes KE, Penzak SR, Calis KA, Walsh TJ (2009) Pharmacology and antifungal properties of anidulafungin, a new echinocandin. Pharmacotherapy 29(1):17–30
Faergemann J, Zehender H, Denouel J, Millerioux L (1993) Levels of terbinafine in plasma, stratum corneum, dermis-epidermis (without stratum corneum), sebum, hair and nails during and after 250 mg terbinafine orally once per day for four weeks. Acta Derm Venereol 73(4):305–309
Faergemann J, Zehender H, Millerioux L (1994) Levels of terbinafine in plasma, stratum corneum, dermis-epidermis (without stratum corneum), sebum, hair and nails during and after 250 mg terbinafine orally once daily for 7 and 14 days. Clin Exp Dermatol 19(2):121–126
Favre B, Ryder NS (1996) Characterization of squalene epoxidase activity from the dermatophyte Trichophyton rubrum and its inhibition by terbinafine and other antimycotic agents. Antimicrob Agents Chemother 40(2):443–447
Fishburn F, Kelley DC (1967) Sporotrichosis in a horse. J Am Vet Med Assoc 151(1):45–46
Fisher MC, Henk DA, Briggs CJ, Brownstein JS, Madoff LC, McCraw SL, Gurr SJ (2012) Emerging fungal threats to animal, plant and ecosystem health. Nature 484(7393):186–194
Flammer K, Nettifee Osborne JA, Webb DJ, Foster LE, Dillard SL, Davis JL (2008) Pharmacokinetics of voriconazole after oral administration of single and multiple doses in African grey parrots (Psittacus erithacus timneh). Am J Vet Res 69(1):114–121
Fling ME, Kopf J, Tamarkin A, Gorman JA, Smith HA, Koltin Y (1991) Analysis of a Candida albicans gene that encodes a novel mechanism for resistance to benomyl and methotrexate. Mol Gen Genet 227(2):318–329
Foley JP, Legendre AM (1992) Treatment of coccidioidomycosis osteomyelitis with itraconazole in a horse. A brief report. J Vet Intern Med 6(6):333–334
Foy DS, Trepanier LA (2010) Antifungal treatment of small animal veterinary patients. Vet Clin North Am Small Anim Pract 40(6):1171–1188
Franz R, Kelly SL, Lamb DC, Kelly DE, Ruhnke M, Morschhauser J (1998) Multiple molecular mechanisms contribute to a stepwise development of fluconazole resistance in clinical Candida albicans strains. Antimicrob Agents Chemother 42(12):3065–3072
Frymus T, Gruffydd-Jones T, Pennisi MG, Addie D, Belak S, Boucraut-Baralon C, Egberink H, Hartmann K, Hosie MJ, Lloret A, Lutz H, Marsilio F, Mostl K, Radford AD, Thiry E, Truyen U, Horzinek MC (2013) Dermatophytosis in cats: ABCD guidelines on prevention and management. J Feline Med Surg 15(7):598–604
Furrow E, Groman RP (2009) Intranasal infusion of clotrimazole for the treatment of nasal aspergillosis in two cats. J Am Vet Med Assoc 235(10):1188–1193
Gabal MA (1986) Study on the evaluation of the use of thiabendazole in the treatment and control of bovine dermatophytosis. Mycopathologia 93(3):163–168
Gallis HA, Drew RH, Pickard WW (1990) Amphotericin B: 30 years of clinical experience. Rev Infect Dis 12(2):308–329
Gentry J, Montgerard C, Crandall E, Cruz-Espindola C, Boothe D, Bellah J (2014) Voriconazole disposition after single and multiple, oral doses in healthy, adult red-tailed hawks (Buteo jamaicensis). J Avian Med Surg 28(3):201–208
Glasmacher A, Molitor E, Hahn C, Bomba K, Ewig S, Leutner C, Wardelmann E, Schmidt-Wolf IG, Mezger J, Marklein G, Sauerbruch T (1998) Antifungal prophylaxis with itraconazole in neutropenic patients with acute leukaemia. Leukemia 12(9):1338–1343
Godfrey DR (1998) A case of feline paraneoplastic alopecia with secondary Malassezia-associated dermatitis. J Small Anim Pract 39(8):394–396
Gomez-Lopez A, Cuenca-Estrella M, Mellado E, Rodriguez-Tudela JL (2003a) In vitro evaluation of combination of terbinafine with itraconazole or amphotericin B against Zygomycota. Diagn Microbiol Infect Dis 45(3):199–202
Gomez-Lopez A, Garcia-Effron G, Mellado E, Monzon A, Rodriguez-Tudela JL, Cuenca-Estrella M (2003b) In vitro activities of three licensed antifungal agents against spanish clinical isolates of Aspergillus spp. Antimicrob Agents Chemother 47(10):3085–3088
Goncalves SS, Souza AC, Chowdhary A, Meis JF, Colombo AL (2016) Epidemiology and molecular mechanisms of antifungal resistance in Candida and Aspergillus. Mycoses 59(4):198–219
Graupmann-Kuzma A, Valentine BA, Shubitz LF, Dial SM, Watrous B, Tornquist SJ (2008) Coccidioidomycosis in dogs and cats: a review. J Am Anim Hosp Assoc 44(5):226–235
Gray KC, Palacios DS, Dailey I, Endo MM, Uno BE, Wilcock BC, Burke MD (2012) Amphotericin primarily kills yeast by simply binding ergosterol. Proc Natl Acad Sci U S A 109(7):2234–2239
Gregson L, Goodwin J, Johnson A, McEntee L, Moore CB, Richardson M, Hope WW, Howard SJ (2013) In vitro susceptibility of Aspergillus fumigatus to isavuconazole: correlation with itraconazole, voriconazole, and posaconazole. Antimicrob Agents Chemother 57(11):5778–5780
Greydanus-van der Putten SW, Klein WR, Blankenstein B, de Hoog GS, Koeman J (1994) Sporotrichosis in a horse. Tijdschr Diergeneeskd 119(17):500–502
Groll AH, Piscitelli SC, Walsh TJ (1998) Clinical pharmacology of systemic antifungal agents: a comprehensive review of agents in clinical use, current investigational compounds, and putative targets for antifungal drug development. Adv Pharmacol 44:343–500
Groll AH, Gea-Banacloche JC, Glasmacher A, Just-Nuebling G, Maschmeyer G, Walsh TJ (2003) Clinical pharmacology of antifungal compounds. Infect Dis Clin North Am 17(1):159–191, ix
Grover C, Arora P, Manchanda V (2012) Comparative evaluation of griseofulvin, terbinafine and fluconazole in the treatment of tinea capitis. Int J Dermatol 51(4):455–458
Guillot J, Bensignor E, Jankowski F, Seewald W, Chermette R, Steffan J (2003) Comparative efficacies of oral ketoconazole and terbinafine for reducing Malassezia population sizes on the skin of Basset Hounds. Vet Dermatol 14(3):153–157
Guinea J, Pelaez T, Recio S, Torres-Narbona M, Bouza E (2008) In vitro antifungal activities of isavuconazole (BAL4815), voriconazole, and fluconazole against 1,007 isolates of zygomycete, Candida, Aspergillus, Fusarium, and Scedosporium species. Antimicrob Agents Chemother 52(4):1396–1400
Gupta AK, Cooper EA (2008) Update in antifungal therapy of dermatophytosis. Mycopathologia 166(5–6):353–367
Gupta AK, Lyons DC (2015) The rise and fall of oral ketoconazole. J Cutan Med Surg 19(4):352–357
Hadfield TL, Smith MB, Winn RE, Rinaldi MG, Guerra C (1987) Mycoses caused by Candida lusitaniae. Rev Infect Dis 9(5):1006–1012
Hall M, Monka C, Krupp P, O’Sullivan D (1997) Safety of oral terbinafine: results of a postmarketing surveillance study in 25,884 patients. Arch Dermatol 133(10):1213–1219
Hamill RJ (2013) Amphotericin B formulations: a comparative review of efficacy and toxicity. Drugs 73(9):919–934
Hazen EL, Brown R (1951) Fungicidin, an antibiotic produced by a soil actinomycete. Proc Soc Exp Biol Med 76(1):93–97
Heidelberger C, Chaudhuri NK, Danneberg P, Mooren D, Griesbach L, Duschinsky R, Schnitzer RJ, Pleven E, Scheiner J (1957) Fluorinated pyrimidines, a new class of tumour-inhibitory compounds. Nature 179(4561):663–666
Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, Kern WV, Marr KA, Ribaud P, Lortholary O, Sylvester R, Rubin RH, Wingard JR, Stark P, Durand C, Caillot D, Thiel E, Chandrasekar PH, Hodges MR, Schlamm HT, Troke PF, de Pauw B, Invasive Fungal Infections Group of the European Organisation for Research and Treatment of Cancer and the Global Aspergillus Study Group (2002) Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 347(6):408–415
Hinsch B (1988) Ketoconazole treatment of disseminated coccidioidomycosis in a dog. Mod Vet Pract 69:161–162
Hnilica K, Medleau L, Cornelius L (2000) Evaluation of the toxicity of topical enilconazole in cats. In: 4th World Congress of Veterinary Dermatology, San Francisco, CA, USA
Hodges RD, Legendre AM, Adams LG, Willard MD, Pitts RP, Monce K, Needels CC, Ward H (1994) Itraconazole for the treatment of histoplasmosis in cats. J Vet Intern Med 8(6):409–413
Hofbauer B, Leitner I, Ryder NS (2002) In vitro susceptibility of Microsporum canis and other dermatophyte isolates from veterinary infections during therapy with terbinafine or griseofulvin. Med Mycol 40(2):179–183
Hofstra W, de Vries-Hospers HG, van der Waaij D (1979) Concentrations of nystatin in faeces after oral administration of various doses of nystatin. Infection 7(4):166–170
Hope WW, Castagnola E, Groll AH, Roilides E, Akova M, Arendrup MC, Arikan-Akdagli S, Bassetti M, Bille J, Cornely OA, Cuenca-Estrella M, Donnelly JP, Garbino J, Herbrecht R, Jensen HE, Kullberg BJ, Lass-Florl C, Lortholary O, Meersseman W, Petrikkos G, Richardson MD, Verweij PE, Viscoli C, Ullmann AJ, ESCMID Fungal Infection Study Group (2012) ESCMID* guideline for the diagnosis and management of Candida diseases 2012: prevention and management of invasive infections in neonates and children caused by Candida spp. Clin Microbiol Infect 18(Suppl 7):38–52
Hospenthal DR, Bennett JE (1998) Flucytosine monotherapy for cryptococcosis. Clin Infect Dis 27(2):260–264
Howard SJ, Cerar D, Anderson MJ, Albarrag A, Fisher MC, Pasqualotto AC, Laverdiere M, Arendrup MC, Perlin DS, Denning DW (2009) Frequency and evolution of azole resistance in Aspergillus fumigatus associated with treatment failure. Emerg Infect Dis 15(7):1068–1076
Humphrey MJ, Jevons S, Tarbit MH (1985) Pharmacokinetic evaluation of UK-49,858, a metabolically stable triazole antifungal drug, in animals and humans. Antimicrob Agents Chemother 28(5):648–653
Hussain Qadri SM, Flournoy DJ, Qadri SG, Ramirez EG (1986) Susceptibility of clinical isolates of yeasts to anti-fungal agents. Mycopathologia 95(3):183–187
Hyatt MW, Georoff TA, Nollens HH, Wells RL, Clauss TM, Ialeggio DM, Harms CA, Wack AN (2015) Voriconazole toxicity in multiple penguin species. J Zoo Wildl Med 46(4):880–888
Imhof A, Schaer DJ, Schanz U, Schwarz U (2006) Neurological adverse events to voriconazole: evidence for therapeutic drug monitoring. Swiss Med Wkly 136(45–46):739–742
Jacobs GJ, Medleau L, Calvert C, Brown J (1997) Cryptococcal infection in cats: factors influencing treatment outcome, and results of sequential serum antigen titers in 35 cats. J Vet Intern Med 11(1):1–4
Jaiswal A, Sharma RP, Garg AP (2007) An open randomized comparative study to test the efficacy and safety of oral terbinafine pulse as a monotherapy and in combination with topical ciclopirox olamine 8% or topical amorolfine hydrochloride 5% in the treatment of onychomycosis. Indian J Dermatol Venereol Leprol 73(6):393–396
Jensen JC (1989) Clinical pharmacokinetics of terbinafine (Lamisil). Clin Exp Dermatol 14(2):110–113
Kageyama S, Masuya M, Tanaka I, Oka K, Morita K, Tamaki S, Tsuji K, Katayama N, Sugimoto H, Kagawa Y, Kojima M, Shiku H (1999) Plasma concentration of itraconazole and its antifungal prophylactic efficacy in patients with neutropenia after chemotherapy for acute leukemia. J Infect Chemother 5(4):213–216
Kano R, Okubo M, Yanai T, Hasegawa A, Kamata H (2015) First isolation of azole-resistant Cryptococcus neoformans from feline cryptococcosis. Mycopathologia 180(5–6):427–433
Kathiravan MK, Salake AB, Chothe AS, Dudhe PB, Watode RP, Mukta MS, Gadhwe S (2012) The biology and chemistry of antifungal agents: a review. Bioorg Med Chem 20(19):5678–5698
Katiyar SK, Edlind TD (2001) Identification and expression of multidrug resistance-related ABC transporter genes in Candida krusei. Med Mycol 39(1):109–116
Kersemaekers WM, Dogterom P, Xu J, Marcantonio EE, de Greef R, Waskin H, van Iersel ML (2015) Effect of a high-fat meal on the pharmacokinetics of 300-milligram posaconazole in a solid oral tablet formulation. Antimicrob Agents Chemother 59(6):3385–3389
Kohler S, Wheat LJ, Connolly P, Schnizlein-Bick C, Durkin M, Smedema M, Goldberg J, Brizendine E (2000) Comparison of the echinocandin caspofungin with amphotericin B for treatment of histoplasmosis following pulmonary challenge in a murine model. Antimicrob Agents Chemother 44(7):1850–1854
Kohler LM, Monteiro PC, Hahn RC, Hamdan JS (2004) In vitro susceptibilities of isolates of Sporothrix schenckii to itraconazole and terbinafine. J Clin Microbiol 42(9):4319–4320
Kohler JR, Casadevall A, Perfect J (2015) The spectrum of fungi that infects humans. Cold Spring Harb Perspect Med 5(1):a019273
Kontoyiannis DP, Lewis RE, May GS, Osherov N, Rinaldi MG (2001) Aspergillus nidulans is frequently resistant to amphotericin B. Mycoses 45:406–407
Korenek NL, Legendre AM, Andrews FM, Blackford PYW, Breider MA, Rinaldi MG (1994) Treatment of mycotic rhinitis with itraconazole in three horses. J Vet Intern Med 8:224–227
Kotnik T (2002) Drug efficacy of terbinafine hydrochloride (Lamisil (R)) during oral treatment of cats, experimentally infected with Microsporum canis. J Vet Med B Infect Dis Vet Public Health 49(3):120–122
Kotnik T, Erzen NK, Kuzner J, Drobnic-Kosorok M (2001) Terbinafine hydrochloride treatment of Microsporum canis experimentally-induced ringworm in cats. Vet Microbiol 83(2):161–168
Krawiec DR, McKiernan BC, Twardock AR, Swenson CE, Itkin RJ, Johnson LR, Kurowsky LK, Marks CA (1996) Use of an amphotericin B lipid complex for treatment of blastomycosis in dogs. J Am Vet Med Assoc 209(12):2073–2075
Krishna G, Moton A, Ma L, Medlock MM, McLeod J (2009) Pharmacokinetics and absorption of posaconazole oral suspension under various gastric conditions in healthy volunteers. Antimicrob Agents Chemother 53(3):958–966
Krishna G, Ma L, Martinho M, O’Mara E (2012) Single-dose phase I study to evaluate the pharmacokinetics of posaconazole in new tablet and capsule formulations relative to oral suspension. Antimicrob Agents Chemother 56(8):4196–4201
Krishnan-Natesan S (2009) Terbinafine: a pharmacological and clinical review. Expert Opin Pharmacother 10(16):2723–2733
Kurtz MB, Douglas CM (1997) Lipopeptide inhibitors of fungal glucan synthase. J Med Vet Mycol 35(2):79–86
Labelle AL, Hamor RE, Barger AM, Maddox CW, Breaux CB (2009) Aspergillus flavus keratomycosis in a cat treated with topical 1% voriconazole solution. Vet Ophthalmol 12(1):48–52
Lackner M, de Hoog GS, Verweij PE, Najafzadeh MJ, Curfs-Breuker I, Klaassen CH, Meis JF (2012) Species-specific antifungal susceptibility patterns of Scedosporium and Pseudallescheria species. Antimicrob Agents Chemother 56(5):2635–2642
Lackner M, de Hoog GS, Yang L, Moreno LF, Ahmed SA, Andreas F, Kaltseis J, Nagl M, Lass-Florl C (2014) Proposed nomenclature for Pseudallescheria, Scedosporium and related genera. Fungal Divers 67(1):1–10
Lamb DC, Kelly DE, Schunck WH, Shyadehi AZ, Akhtar M, Lowe DJ, Baldwin BC, Kelly SL (1997) The mutation T315A in Candida albicans sterol 14alpha-demethylase causes reduced enzyme activity and fluconazole resistance through reduced affinity. J Biol Chem 272(9):5682–5688
Lamb DC, Kelly DE, White TC, Kelly SL (2000) The R467K amino acid substitution in Candida albicans sterol 14 alpha-demethylase causes drug resistance through reduced affinity. Antimicrob Agents Chemother 44(1):63–67
Lass-Florl C (2011) Triazole antifungal agents in invasive fungal infections: a comparative review. Drugs 71(18):2405–2419
Lass-Florl C, Alastruey-Izquierdo A, Cuenca-Estrella M, Perkhofer S, Rodriguez-Tudela JL (2009) In vitro activities of various antifungal drugs against Aspergillus terreus: global assessment using the methodology of the European committee on antimicrobial susceptibility testing. Antimicrob Agents Chemother 53(2):794–795
Latimer FG, Colitz CM, Campbell NB, Papich MG (2001) Pharmacokinetics of fluconazole following intravenous and oral administration and body fluid concentrations of fluconazole following repeated oral dosing in horses. Am J Vet Res 62(10):1606–1611
Lazarus HM, Blumer JL, Yanovich S, Schlamm H, Romero A (2002) Safety and pharmacokinetics of oral voriconazole in patients at risk of fungal infection: a dose escalation study. J Clin Pharmacol 42(4):395–402
Legendre AM, Rohrbach BW, Toal RL, Rinaldi MG, Grace LL, Jones JB (1996) Treatment of blastomycosis with itraconazole in 112 dogs. J Vet Intern Med 10(6):365–371
Lewis RE (2011) Current concepts in antifungal pharmacology. Mayo Clin Proc 86(8):805–817
Lewis RE, Liao G, Wang W, Prince RA, Kontoyiannis DP (2011) Voriconazole pre-exposure selects for breakthrough mucormycosis in a mixed model of Aspergillus fumigatus-Rhizopus oryzae pulmonary infection. Virulence 2(4):348–355
Loffler J, Kelly SL, Hebart H, Schumacher U, Lass-Florl C, Einsele H (1997) Molecular analysis of cyp51 from fluconazole-resistant Candida albicans strains. FEMS Microbiol Lett 151(2):263–268
Lopez-Ribot JL, McAtee RK, Perea S, Kirkpatrick WR, Rinaldi MG, Patterson TF (1999) Multiple resistant phenotypes of Candida albicans coexist during episodes of oropharyngeal candidiasis in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother 43(7):1621–1630
Lord AT, Mohandas K, Somanath S, Ambu S (2010) Multidrug resistant yeasts in synanthropic wild birds. Ann Clin Microbiol Antimicrob 9:11
Maertens JA (2004) History of the development of azole derivatives. Clin Microbiol Infect 10(Suppl 1):1–10
Maertens JA, Raad II, Marr KA, Patterson TF, Kontoyiannis DP, Cornely OA, Bow EJ, Rahav G, Neofytos D, Aoun M, Baddley JW, Giladi M, Heinz WJ, Herbrecht R, Hope W, Karthaus M, Lee DG, Lortholary O, Morrison VA, Oren I, Selleslag D, Shoham S, Thompson GR, Lee M, Maher RM, Schmitt-Hoffmann AH, Zeiher B, Ullmann AJ (2016) Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial. Lancet 387(10020):760–769
Malani AN, Kerr L, Obear J, Singal B, Kauffman CA (2014) Alopecia and nail changes associated with voriconazole therapy. Clin Infect Dis 59(3):e61–e65
Malik R, Wigney DI, Muir DB, Gregory DJ, Love DN (1992) Cryptococcosis in cats – clinical and mycological assessment of 29 cases and evaluation of treatment using orally-administered fluconazole. J Med Vet Mycol 30(2):133–144
Malik R, Craig AJ, Wigney DI, Martin P, Love DN (1996) Combination chemotherapy of canine and feline cryptococcosis using subcutaneously administered amphotericin B. Aust Vet J 73(4):124–128
Manavathu EK, Cutright JL, Loebenberg D, Chandrasekar PH (2000) A comparative study of the in vitro susceptibilities of clinical and laboratory-selected resistant isolates of Aspergillus spp. to amphotericin B, itraconazole, voriconazole and posaconazole (SCH 56592). J Antimicrob Chemother 46(2):229–234
Manire CA, Rhinehart HL, Pennick GJ, Sutton DA, Hunter RP, Rinaldi MG (2003) Steady-state plasma concentrations of itraconazole after oral administration in Kemp’s ridley sea turtles, Lepidochelys kempi. J Zoo Wildl Med 34(2):171–178
Marr KA, Lyons CN, Rustad TR, Bowden RA, White TC (1998) Rapid, transient fluconazole resistance in Candida albicans is associated with increased mRNA levels of CDR. Antimicrob Agents Chemother 42(10):2584–2589
Martin de la Escalera C, Aller AI, Lopez-Oviedo E, Romero A, Martos AI, Canton E, Peman J, Garcia Martos P, Martin-Mazuelos E (2008) Activity of BAL 4815 against filamentous fungi. J Antimicrob Chemother 61(5):1083–1086
Martino J, Fisher BT, Bosse KR, Bagatell R (2015) Suspected posaconazole toxicity in a pediatric oncology patient. Pediatr Blood Cancer 62(9):1682
Marty FM, Ostrosky-Zeichner L, Cornely OA, Mullane KM, Perfect JR, Thompson GR, Alangaden GJ, Brown JM, Fredricks DN, Heinz WJ, Herbrecht R, Klimko N, Klyasova G, Maertens JA, Melinkeri SR, Oren I, Pappas PG, Racil Z, Rahav G, Santos R, Schwartz S, Vehreschild JJ, Young JA, Chetchotisakd P, Jaruratanasirikul S, Kanj SS, Engelhardt M, Kaufhold A, Ito M, Lee M, Sasse C, Maher RM, Zeiher B, Vehreschild MJ, VITAL and FungiScope Mucormycosis Investigators (2016) Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis. Lancet Infect Dis 16(7):828–837
Maschmeyer G, Glasmacher A (2005) Pharmacological properties and clinical efficacy of a recently licensed systemic antifungal, caspofungin. Mycoses 48(4):227–234
Matsumoto K, Ikawa K, Abematsu K, Fukunaga N, Nishida K, Fukamizu T, Shimodozono Y, Morikawa N, Takeda Y, Yamada K (2009) Correlation between voriconazole trough plasma concentration and hepatotoxicity in patients with different CYP2C19 genotypes. Int J Antimicrob Agents 34(1):91–94
Mawby DI, Whittemore JC, Fowler LE, Papich MG (2016) Posaconazole pharmacokinetics in healthy cats after oral and intravenous administration. J Vet Intern Med 30(5):1703–1707
Mayer H (1983) Beitrag zur Therapie der Dermatomykosen beim Pferd. Berliner und Müncherner Tierärztliche Wochenschrift 96:458–459
McCurdy HD, Hepler DI, Larson KA (1981) Effectiveness of a topical antifungal agent (clotrimazole) in dogs. J Am Vet Med Assoc 179(2):163–165
McLellan GJ, Aquino SM, Mason DR, Kinyon JM, Myers RK (2006) Use of posaconazole in the management of invasive orbital aspergillosis in a cat. J Am Anim Hosp Assoc 42(4):302–307
Medleau L, Whiteweithers NE (1992) Treating and preventing the various forms of dermatophytosis. Vet Med 87(11):1096–1100
Mellado E, Garcia-Effron G, Alcazar-Fuoli L, Melchers WJ, Verweij PE, Cuenca-Estrella M, Rodriguez-Tudela JL (2007) A new Aspergillus fumigatus resistance mechanism conferring in vitro cross-resistance to azole antifungals involves a combination of cyp51A alterations. Antimicrob Agents Chemother 51(6):1897–1904
Miller WG, Padhye AA, van Bonn W, Jensen E, Brandt ME, Ridgway SH (2002) Cryptococcosis in a bottlenose dolphin (Tursiops truncatus) caused by Cryptococcus neoformans var. gattii. J Clin Microbiol 40(2):721–724
Miyazaki H, Miyazaki Y, Geber A, Parkinson T, Hitchcock C, Falconer DJ, Ward DJ, Marsden K, Bennett JE (1998) Fluconazole resistance associated with drug efflux and increased transcription of a drug transporter gene, PDH1, in Candida glabrata. Antimicrob Agents Chemother 42:1695–1701
Mohr J, Johnson M, Cooper T, Lewis JS, Ostrosky-Zeichner L (2008) Current options in antifungal pharmacotherapy. Pharmacotherapy 28(5):614–645
Moon WJ, Scheller EL, Suneja A, Livermore JA, Malani AN, Moudgal V, Kerr LE, Ferguson E, Vandenberg DM (2014) Plasma fluoride level as a predictor of voriconazole-induced periostitis in patients with skeletal pain. Clin Infect Dis 59(9):1237–1245
Moriello KA, Deboer DJ (1995) Efficacy of griseofulvin and itraconazole in the treatment of experimentally-induced dermatophytosis in cats. J Am Vet Med Assoc 207(4):439–444
Mukherjee PK, Sheehan D, Puzniak L, Schlamm H, Ghannoum MA (2011) Echinocandins: are they all the same? J Chemother 23(6):319–325
Nakamura Y, Saato H (1995) Sporothrix schenkii isolated from a cat in Japan. Mycoses 39:125–128
Negre A, Bensignor E, Guillot J (2009) Evidence-based veterinary dermatology: a systematic review of interventions for Malassezia dermatitis in dogs. Vet Dermatol 20(1):1–12
Nesbitt G, Fox P (1981) Clinical evaluation of Panolog Cream used to treat canine and feline dermatoses. Vet Med Small Anim Clin 76:535–538
Nyfeler R, Keller-Schierlein W (1974) Metabolites of microorganisms. 143. Echinocandin B, a novel polypeptide-antibiotic from Aspergillus nidulans var. echinulatus: isolation and structural components. Helv Chim Acta 57(8):2459–2477
O’Brien CR, Krockenberger MB, Martin P, Wigney DI, Malik R (2006) Long-term outcome of therapy for 59 cats and 11 dogs with cryptococcosis. Aust Vet J 84(11):384–392
Oakley KL, Moore CB, Denning DW (1999) Comparison of in vitro activity of liposomal nystatin against Aspergillus species with those of nystatin, amphotericin B (AB) deoxycholate, AB colloidal dispersion, liposomal AB, AB lipid complex, and itraconazole. Antimicrob Agents Chemother 43(5):1264–1266
Odds FC (2006) Drug evaluation: BAL-8557--a novel broad-spectrum triazole antifungal. Curr Opin Investig Drugs 7(8):766–772
Odds FC, Bossche HV (2000) Antifungal activity of itraconazole compared with hydroxy-itraconazole in vitro. J Antimicrob Chemother 45(3):371–373
Odds FC, Cheesman SL, Abbott AB (1986) Antifungal effects of fluconazole (UK 49858), a new triazole antifungal, in vitro. J Antimicrob Chemother 18(4):473–478
Ohwada J, Tsukazaki M, Hayase T, Oikawa N, Isshiki Y, Fukuda H, Mizuguchi E, Sakaitani M, Shiratori Y, Yamazaki T, Ichihara S, Umeda I, Shimma N (2003) Design, synthesis and antifungal activity of a novel water soluble prodrug of antifungal triazole. Bioorg Med Chem Lett 13(2):191–196
Oldenkamp EP (1979a) Natamycin treatment of ringworm in cattle in the United Kingdom. Vet Rec 105(24):5554–5556
Oldenkamp EP (1979b) Treatment of ringworm in horses with natamycin. Equine Vet J 11:36–38
Oldenkamp EP, Spanoghe L (1977) Natamycin-S treatment of ringworm in cattle. Epidemiological aspects. Tijdschr Diergeneeskd 102(2):124–125
Orosz S, Frazier DL (1995) Antifungal agents: a review of their pharmacology and therapeutic indications. J Avian Med Surg 9:8–18
Ostrosky-Zeichner L, Marr KA, Rex JH, Cohen SH (2003a) Amphotericin B: time for a new “gold standard”. Clin Infect Dis 37(3):415–425
Ostrosky-Zeichner L, Rex JH, Pappas PG, Hamill RJ, Larsen RA, Horowitz HW, Powderly WG, Hyslop N, Kauffman CA, Cleary J, Mangino JE, Lee J (2003b) Antifungal susceptibility survey of 2,000 bloodstream Candida isolates in the United States. Antimicrob Agents Chemother 47(10):3149–3154
Pappas PG, Bradsher RW, Chapman SW, Kauffman CA, Dine A, Cloud GA, Dismukes WE (1995) Treatment of blastomycosis with fluconazole: a pilot study. The National Institute of Allergy and Infectious Diseases Mycoses Study Group. Clin Infect Dis 20(2):267–271
Pappas PG, Rex JH, Sobel JD, Filler SG, Dismukes WE, Walsh TJ, Edwards JE, Infectious Diseases Society of America (2004) Guidelines for treatment of candidiasis. Clin Infect Dis 38(2):161–189
Pappas PG, Kauffman CA, Andes D, Benjamin DK Jr, Calandra TF, Edwards JE Jr, Filler SG, Fisher JF, Kullberg BJ, Ostrosky-Zeichner L, Reboli AC, Rex JH, Walsh TJ, Sobel JD, Infectious Diseases Society of America (2009) Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 48(5):503–535
Parkes LO, Cheng MP, Sheppard DC (2016) Visual hallucinations associated with high posaconazole concentrations in serum. Antimicrob Agents Chemother 60(2):1170–1171
Parkinson T, Falconer DJ, Hitchcock CA (1995) Fluconazole resistance due to energy-dependent drug efflux in Candida glabrata. Antimicrob Agents Chemother 39:1696–1699
Pascual A, Calandra T, Bolay S, Buclin T, Bille J, Marchetti O (2008) Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes. Clin Infect Dis 46(2):201–211
Pascual A, Csajka C, Buclin T, Bolay S, Bille J, Calandra T, Marchetti O (2012) Challenging recommended oral and intravenous voriconazole doses for improved efficacy and safety: population pharmacokinetics-based analysis of adult patients with invasive fungal infections. Clin Infect Dis 55(3):381–390
Patterson TF, Thompson GR, Denning DW, Fishman JA, Hadley S, Herbrecht R, Kontoyiannis DP, Marr KA, Morrison VA, Nguyen MH, Segal BH, Steinbach WJ, Stevens DA, Walsh TJ, Wingard JR, Young JA, Bennett JE (2016) Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 63(4):e1–e60
Peeters D, Clercx C (2007) Update on canine sinonasal aspergillosis. Vet Clin North Am Small Anim Pract 37(5):901–916, vi
Pelaez T, Alvarez-Perez S, Mellado E, Serrano D, Valerio M, Blanco JL, Garcia ME, Munoz P, Cuenca-Estrella M, Bouza E (2013) Invasive aspergillosis caused by cryptic Aspergillus species: a report of two consecutive episodes in a patient with leukaemia. J Med Microbiol 62(Pt 3):474–478
Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ, Harrison TS, Larsen RA, Lortholary O, Nguyen MH, Pappas PG, Powderly WG, Singh N, Sobel JD, Sorrell TC (2010) Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of America. Clin Infect Dis 50(3):291–322
Perkhofer S, Lechner V, Lass-Florl C (2009) In vitro activity of isavuconazole against aspergillus species and zygomycetes according to the methodology of the European Committee on Antimicrobial Susceptibility Testing. Antimicrob Agents Chemother 53(4):1645–1647
Petranyi G, Meingassner JG, Mieth H (1987) Antifungal activity of the allylamine derivative terbinafine in vitro. Antimicrob Agents Chemother 31(9):1365–1368
Pfaller MA, Diekema DJ (2004) Rare and emerging opportunistic fungal pathogens: concern for resistance beyond Candida albicans and Aspergillus fumigatus. J Clin Microbiol 42(10):4419–4431
Pfaller MA, Messer SA, Boyken L, Huynh H, Hollis RJ, Diekema DJ (2002) In vitro activities of 5-fluorocytosine against 8,803 clinical isolates of Candida spp.: global assessment of primary resistance using National Committee for Clinical Laboratory Standards susceptibility testing methods. Antimicrob Agents Chemother 46(11):3518–3521
Pfaller MA, Diekema DJ, Messer SA, Boyken L, Hollis RJ, Jones RN (2004) In vitro susceptibilities of rare Candida bloodstream isolates to ravuconazole and three comparative antifungal agents. Diagn Microbiol Infect Dis 48(2):101–105
Pfaller MA, Messer SA, Boyken L, Rice C, Tendolkar S, Hollis RJ, Doern GV, Diekema DJ (2005) Global trends in the antifungal susceptibility of Cryptococcus neoformans (1990 to 2004). J Clin Microbiol 43(5):2163–2167
Pfaller MA, Messer SA, Woosley LN, Jones RN, Castanheira M (2013) Echinocandin and triazole antifungal susceptibility profiles for clinical opportunistic yeast and mold isolates collected from 2010 to 2011: application of new CLSI clinical breakpoints and epidemiological cutoff values for characterization of geographic and temporal trends of antifungal resistance. J Clin Microbiol 51(8):2571–2581
Pinchbeck LR, Hillier A, Kowalski JJ, Kwochka KW (2002) Comparison of pulse administration versus once daily administration of itraconazole for the treatment of Malassezia pachydermatis dermatitis and otitis in dogs. J Am Vet Med Assoc 220(12):1807–1812
Plumb DC (1999) Veterinary drug handbook. PharmaVet Publishing, White Bear Lake
Polak A (1977) 5-Fluorocytosine--current status with special references to mode of action and drug resistance. Contrib Microbiol Immunol 4:158–167
Polak A, Scholer HJ (1975) Mode of action of 5-fluorocytosine and mechanisms of resistance. Chemotherapy 21(3–4):113–130
Power SB, Malone A (1987) An outbreak of ringworm in sheep in Ireland caused by Trichophyton verrucosum. Vet Rec 121:218–220
Pucket JD, Allbaugh RA, Rankin AJ (2012) Treatment of dematiaceous fungal keratitis in a dog. J Am Vet Med Assoc 240(9):1104–1108
Pursley TJ, Blomquist IK, Abraham J, Andersen HF, Bartley JA (1996) Fluconazole-induced congenital anomalies in three infants. Clin Infect Dis 22(2):336–340
Reidarson TH, Harrell JH, Rinaldi MG, McBain J (1998) Bronchoscopic and serologic diagnosis of Aspergillus fumigatus pulmonary infection in a bottlenose dolphin (Tursiops truncatus). J Zoo Wildl Med 29(4):451–455
Rezabek GH, Friedman AD (1992) Superficial fungal infections of the skin. Diagnosis and current treatment recommendations. Drugs 43(5):674–682
Rocha MF, Bandeira SP, de Alencar LP, Melo LM, Sales JA, Paiva MA, Teixeira CE, Castelo-Branco DS, Pereira-Neto WA, Cordeiro RA, Sidrim JJ, Brilhante RS (2017) Azole resistance in Candida albicans from animals: highlights on efflux pump activity and gene overexpression. Mycoses 60(7):462–468
Rochette F, Engelen M, Vanden Bossche H (2003) Antifungal agents of use in animal health – practical applications. J Vet Pharmacol Ther 26(1):31–53
Roffey SJ, Cole S, Comby P, Gibson D, Jezequel SG, Nedderman AN, Smith DA, Walker DK, Wood N (2003) The disposition of voriconazole in mouse, rat, rabbit, guinea pig, dog, and human. Drug Metab Dispos 31(6):731–741
Rosales MS, Marsella R, Kunkle G, Harris BL, Nicklin CF, Lopez J (2005) Comparison of the clinical efficacy of oral terbinafine and ketoconazole combined with cephalexin in the treatment of Malassezia dermatitis in dogs--a pilot study. Vet Dermatol 16(3):171–176
Rudramurthy SM, Chakrabarti A, Geertsen E, Mouton JW, Meis JF (2011) In vitro activity of isavuconazole against 208 Aspergillus flavus isolates in comparison with 7 other antifungal agents: assessment according to the methodology of the European Committee on Antimicrobial Susceptibility Testing. Diagn Microbiol Infect Dis 71(4):370–377
Ryder NS (1992) Terbinafine: mode of action and properties of the squalene epoxidase inhibition. Br J Dermatol 126(Suppl 39):2–7
Sanglard D, Ischer F, Calabrese D, Majcherczyk PA, Bille J (1999) The ATP binding cassette transporter gene CgCDR1 from Candida glabrata is involved in the resistance of clinical isolates to azole antifungal agents. Antimicrob Agents Chemother 43(11):2753–2765
Sanguinetti M, Posteraro B, Fiori B, Ranno S, Torelli R, Fadda G (2005) Mechanisms of azole resistance in clinical isolates of Candida glabrata collected during a hospital survey of antifungal resistance. Antimicrob Agents Chemother 49(2):668–679
Schauder S (2002) Itraconazole in the treatment of tinea capitis in children. Case reports with long-term follow-up evaluation. Review of the literature. Mycoses 45(1–2):1–9
Schmitt-Hoffmann A, Roos B, Heep M, Schleimer M, Weidekamm E, Brown T, Roehrle M, Beglinger C (2006a) Single-ascending-dose pharmacokinetics and safety of the novel broad-spectrum antifungal triazole BAL4815 after intravenous infusions (50, 100, and 200 milligrams) and oral administrations (100, 200, and 400 milligrams) of its prodrug, BAL8557, in healthy volunteers. Antimicrob Agents Chemother 50(1):279–285
Schmitt-Hoffmann A, Roos B, Maares J, Heep M, Spickerman J, Weidekamm E, Brown T, Roehrle M (2006b) Multiple-dose pharmacokinetics and safety of the new antifungal triazole BAL4815 after intravenous infusion and oral administration of its prodrug, BAL8557, in healthy volunteers. Antimicrob Agents Chemother 50(1):286–293
Schultz RM, Johnson EG, Wisner ER, Brown NA, Byrne BA, Sykes JE (2008) Clinicopathologic and diagnostic imaging characteristics of systemic aspergillosis in 30 dogs. J Vet Intern Med 22(4):851–859
Semis R, Nili SS, Munitz A, Zaslavsky Z, Polacheck I, Segal E (2012) Pharmacokinetics, tissue distribution and immunomodulatory effect of intralipid formulation of nystatin in mice. J Antimicrob Chemother 67(7):1716–1721
Seyedmousavi S, Guillot J, de Hoog GS (2013a) Phaeohyphomycoses, emerging opportunistic diseases in animals. Clin Microbiol Rev 26(1):19–35
Seyedmousavi S, Rijs AJ, Melchers WJ, Mouton JW, Verweij PE (2013b) In vitro activity of isavuconazole compared with itraconazole, voriconazole, and posaconazole in azole-resistant Aspergillus fumigatus. Proceeding of the 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), Denver, CO
Seyedmousavi S, Mouton JW, Melchers WJ, Bruggemann RJ, Verweij PE (2014a) The role of azoles in the management of azole-resistant aspergillosis: from the bench to the bedside. Drug Resist Updat 17(3):37–50
Seyedmousavi S, Samerpitak K, Rijs AJ, Melchers WJ, Mouton JW, Verweij PE, de Hoog GS (2014b) Antifungal susceptibility patterns of opportunistic fungi in the genera Verruconis and Ochroconis. Antimicrob Agents Chemother 58(6):3285–3292
Seyedmousavi S, Guillot J, Arne P, de Hoog GS, Mouton JW, Melchers WJ, Verweij PE (2015a) Aspergillus and aspergilloses in wild and domestic animals: a global health concern with parallels to human disease. Med Mycol 53(8):765–797
Seyedmousavi S, Verweij PE, Mouton JW (2015b) Isavuconazole, a broad-spectrum triazole for the treatment of systemic fungal diseases. Expert Rev Anti-Infect Ther 13(1):9–27
Seyedmousavi S, Rafati H, Ilkit M, Tolooe A, Hedayati MT, Verweij P (2017) Systemic antifungal agents: current status and projected future developments. Methods Mol Biol 1508:107–139
Shadomy S (1969) In vitro studies with 5-fluorocytosine. Appl Microbiol 17(6):871–877
Sharp NJH, Harvey CE, Obrien JA (1991) Treatment of canine nasal aspergillosis penicilliosis with fluconazole (UK-49,858). J Small Anim Pract 32(10):513–516
Shear NH, Villars VV, Marsolais C (1991) Terbinafine: an oral and topical antifungal agent. Clin Dermatol 9(4):487–495
Shemer A, Plotnik IB, Davidovici B, Grunwald MH, Magun R, Amichai B (2013) Treatment of tinea capitis – griseofulvin versus fluconazole – a comparative study. J Dtsch Dermatol Ges 11(8):737–741. 737–742
Shivaprakash MR, Geertsen E, Chakrabarti A, Mouton JW, Meis JF (2011) In vitro susceptibility of 188 clinical and environmental isolates of Aspergillus flavus for the new triazole isavuconazole and seven other antifungal drugs. Mycoses 54(5):e583–e589
Sidrim JJ, Maia DC, Brilhante RS, Soares GD, Cordeiro RA, Monteiro AJ, Rocha MF (2010) Candida species isolated from the gastrointestinal tract of cockatiels (Nymphicus hollandicus): in vitro antifungal susceptibility profile and phospholipase activity. Vet Microbiol 145(3–4):324–328
Singer LM, Meyer W, Firacative C, Thompson GR, Samitz E, Sykes JE (2014) Antifungal drug susceptibility and phylogenetic diversity among Cryptococcus isolates from dogs and cats in North America. J Clin Microbiol 52(6):2061–2070
Smith J, Safdar N, Knasinski V, Simmons W, Bhavnani SM, Ambrose PG, Andes D (2006) Voriconazole therapeutic drug monitoring. Antimicrob Agents Chemother 50(4):1570–1572
Smith JA, Papich MG, Russell G, Mitchell MA (2010) Effects of compounding on pharmacokinetics of itraconazole in black-footed penguins (Spheniscus demersus). J Zoo Wildl Med 41(3):487–495
Smith KM, Pucket JD, Gilmour MA (2014) Treatment of six cases of equine corneal stromal abscessation with intracorneal injection of 5% voriconazole solution. Vet Ophthalmol 17(Suppl 1):179–185
Sporanox (2017) Product information: SPORANOX oral capsules. Janssen Pharmaceuticals Inc., Titusville
Stewart J, Bianco D (2017) Treatment of refractory sino-nasal aspergillosis with posaconazole and terbinafine in 10 dogs. J Small Anim Pract 58(9):504–509
Sugiura K, Sugimoto N, Hosaka S, Katafuchi-Nagashima M, Arakawa Y, Tatsumi Y, Jo Siu W, Pillai R (2014) The low keratin affinity of efinaconazole contributes to its nail penetration and fungicidal activity in topical onychomycosis treatment. Antimicrob Agents Chemother 58(7):3837–3842
Sun HY, Singh N (2011) Mucormycosis: its contemporary face and management strategies. Lancet Infect Dis 11(4):301–311
Sutton DA, Sanche SE, Revankar SG, Fothergill AW, Rinaldi MG (1999) In vitro amphotericin B resistance in clinical isolates of Aspergillus terreus, with a head-to-head comparison to voriconazole. J Clin Microbiol 37(7):2343–2345
Sykes JE, Torres SM, Armstrong PJ, Lindeman CJ (2001) Itraconazole for treatment of sporotrichosis in a dog residing on a Christmas tree farm. J Am Vet Med Assoc 218(9):1440
Talbot JJ, Kidd SE, Martin P, Beatty JA, Barrs VR (2015) Azole resistance in canine and feline isolates of Aspergillus fumigatus. Comp Immunol Microbiol Infect Dis 42:37–41
Tan K, Brayshaw N, Tomaszewski K, Troke P, Wood N (2006) Investigation of the potential relationships between plasma voriconazole concentrations and visual adverse events or liver function test abnormalities. J Clin Pharmacol 46(2):235–243
Tassel D, Madoff MA (1968) Treatment of Candida sepsis and Cryptococcus meningitis with 5-fluorocytosine. A new antifungal agent. JAMA 206(4):830–832
Taylor A, Talbot J, Bennett P, Martin P, Makara M, Barrs VR (2014) Disseminated Scedosporium prolificans infection in a Labrador retriever with immune mediated haemolytic anaemia. Med Mycol Case Rep 6:66–69
Tell LA, Clemons KV, Kline Y, Woods L, Kass PH, Martinez M, Stevens DA (2010) Efficacy of voriconazole in Japanese quail (Coturnix japonica) experimentally infected with Aspergillus fumigatus. Med Mycol 48(2):234–244
Tortorano AM, Prigitano A, Dho G, Piccinini R, Dapra V, Viviani MA (2008) In vitro activity of conventional antifungal drugs and natural essences against the yeast-like alga Prototheca. J Antimicrob Chemother 61(6):1312–1314
Troke PF, Hockey HP, Hope WW (2011) Observational study of the clinical efficacy of voriconazole and its relationship to plasma concentrations in patients. Antimicrob Agents Chemother 55(10):4782–4788
Trommer H, Neubert RH (2006) Overcoming the stratum corneum: the modulation of skin penetration. A review. Skin Pharmacol Physiol 19(2):106–121
Ullmann AJ, Lipton JH, Vesole DH, Chandrasekar P, Langston A, Tarantolo SR, Greinix H, Morais de Azevedo W, Reddy V, Boparai N, Pedicone L, Patino H, Durrant S (2007) Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med 356(4):335–347
Ullmann AJ, Akova M, Herbrecht R, Viscoli C, Arendrup MC, Arikan-Akdagli S, Bassetti M, Bille J, Calandra T, Castagnola E, Cornely OA, Donnelly JP, Garbino J, Groll AH, Hope WW, Jensen HE, Kullberg BJ, Lass-Florl C, Lortholary O, Meersseman W, Petrikkos G, Richardson MD, Roilides E, Verweij PE, Cuenca-Estrella M, ESCMID Fungal Infection Study Group (2012) ESCMID* guideline for the diagnosis and management of Candida diseases 2012: adults with haematological malignancies and after haematopoietic stem cell transplantation (HCT). Clin Microbiol Infect 18(Suppl 7):53–67
Vaden SL, Heit MC, Hawkins EC, Manaugh C, Riviere JE (1997) Fluconazole in cats: pharmacokinetics following intravenous and oral administration and penetration into cerebrospinal fluid, aqueous humour and pulmonary epithelial lining fluid. J Vet Pharmacol Ther 20(3):181–186
Van Cauteren H, Heykants J, De Coster R, Cauwenbergh G (1987) Itraconazole: pharmacologic studies in animals and humans. Rev Infect Dis 9(Suppl 1):S43–S46
Van Cutsem J, Van Gerven F, Geerts H, Rochette F (1985) Treatment with enilconazole spray of dermatophytosis in rabbit farms. Mykosen 28(8):400–407
Van Cutsem J, Van Gerven F, Janssen PA (1988) In vitro activity of enilconazole against Aspergillus spp. and its fungicidal efficacy in a smoke generator against Aspergillus fumigatus. Mycoses 31(3):143–147
Van Der Linden JW, Warris A, Verweij PE (2011) Aspergillus species intrinsically resistant to antifungal agents. Med Mycol 49(Suppl 1):S82–S89
Vanden Bossche H, Marichal P, Gorrens J, Bellens D, Moereels H, Janssen AJ (1990) Mutation in cytochrome P-450-dependent 14a-demethylase results in decreased affinity for azole antifungals. Biochem Soc Trans 18:56–59
Varga J, Houbraken J, Van Der Lee HA, Verweij PE, Samson RA (2008) Aspergillus calidoustus sp. nov., causative agent of human infections previously assigned to Aspergillus ustus. Eukaryot Cell 7(4):630–638
Vermeulen E, Lagrou K, Verweij PE (2013) Azole resistance in Aspergillus fumigatus: a growing public health concern. Curr Opin Infect Dis 26(6):493–500
Verweij PE, Mellado E, Melchers WJ (2007) Multiple-triazole-resistant aspergillosis. N Engl J Med 356(14):1481–1483
Verweij PE, Te Dorsthorst DT, Janssen WH, Meis JF, Mouton JW (2008) In vitro activities at pH 5.0 and pH 7.0 and in vivo efficacy of flucytosine against Aspergillus fumigatus. Antimicrob Agents Chemother 52(12):4483–4485
Verweij PE, Howard SJ, Melchers WJ, Denning DW (2009a) Azole-resistance in Aspergillus: proposed nomenclature and breakpoints. Drug Resist Updat 12(6):141–147
Verweij PE, Snelders E, Kema GH, Mellado E, Melchers WJ (2009b) Azole resistance in Aspergillus fumigatus: a side-effect of environmental fungicide use? Lancet Infect Dis 9(12):789–795
Verweij PE, Ananda-Rajah M, Andes D, Arendrup MC, Bruggemann RJ, Chowdhary A, Cornely OA, Denning DW, Groll AH, Izumikawa K, Kullberg BJ, Lagrou K, Maertens J, Meis JF, Newton P, Page I, Seyedmousavi S, Sheppard DC, Viscoli C, Warris A, Donnelly JP (2015) International expert opinion on the management of infection caused by azole-resistant Aspergillus fumigatus. Drug Resist Updat 21–22:30–40
Verweij PE, Chowdhary A, Melchers WJ, Meis JF (2016) Azole resistance in Aspergillus fumigatus: can we retain the clinical use of mold-active antifungal azoles? Clin Infect Dis 62(3):362–368
Walsh TJ, Melcher GP, Rinaldi MG, Lecciones J, McGough DA, Kelly P, Lee J, Callender D, Rubin M, Pizzo PA (1990) Trichosporon beigelii, an emerging pathogen resistant to amphotericin B. J Clin Microbiol 28(7):1616–1622
Walsh TJ, Karlsson MO, Driscoll T, Arguedas AG, Adamson P, Saez-Llorens X, Vora AJ, Arrieta AC, Blumer J, Lutsar I, Milligan P, Wood N (2004) Pharmacokinetics and safety of intravenous voriconazole in children after single- or multiple-dose administration. Antimicrob Agents Chemother 48(6):2166–2172
Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, Morrison VA, Segal BH, Steinbach WJ, Stevens DA, van Burik JA, Wingard JR, Patterson TF, Infectious Diseases Society of America (2008) Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 46(3):327–360
Wang DY, Gricourt M, Thierry S, Arné P, Seguin D, Deville M, Dannaoui E, Chermette R, Botterel F, Guillot J (2013) Mutations in the cyp51A gene and susceptibility to itraconazole in Aspergillus fumigatus isolated from avian farms in France and China. Med Mycol 93(1):12–15
Warn PA, Sharp A, Denning DW (2006) In vitro activity of a new triazole BAL4815, the active component of BAL8557 (the water-soluble prodrug), against Aspergillus spp. J Antimicrob Chemother 57(1):135–138
Warn PA, Sharp A, Parmar A, Majithiya J, Denning DW, Hope WW (2009) Pharmacokinetics and pharmacodynamics of a novel triazole, isavuconazole: mathematical modeling, importance of tissue concentrations, and impact of immune status on antifungal effect. Antimicrob Agents Chemother 53(8):3453–3461
Warrilow AG, Martel CM, Parker JE, Melo N, Lamb DC, Nes WD, Kelly DE, Kelly SL (2010) Azole binding properties of Candida albicans sterol 14-alpha demethylase (CaCYP51). Antimicrob Agents Chemother 54(10):4235–4245
White TC (1997) The presence of an R467K amino acid substitution and loss of allelic variation correlate with an azole-resistant lanosterol 14alpha demethylase in Candida albicans. Antimicrob Agents Chemother 41(7):1488–1494
Willard MD, Nachreiner RF, Howard VC, Fooshee SK (1986) Effect of long-term administration of ketoconazole in cats. Am J Vet Res 47(12):2510–2513
Williams K, Mansh M, Chin-Hong P, Singer J, Arron ST (2014) Voriconazole-associated cutaneous malignancy: a literature review on photocarcinogenesis in organ transplant recipients. Clin Infect Dis 58(7):997–1002
Wray JD, Sparkes AH, Johnson EM (2008) Infection of the subcutis of the nose in a cat caused by Mucor species: successful treatment using posaconazole. J Feline Med Surg 10(5):523–527
Yanong RP (2003) Fungal diseases of fish. Vet Clin North Am Exot Anim Pract 6(2):377–400
Zamos DT, Schumacher J, Loy JK (1996) Nasopharyngeal conidiobolomycosis in a horse. J Am Vet Med Assoc 208(1):100–101
Ziolkowska G, Tokarzewski S, Nowakiewicz A (2014) Drug resistance of Aspergillus fumigatus strains isolated from flocks of domestic geese in Poland. Poult Sci 93(5):1106–1112
Acknowledgement
The work of Seyedmojtaba Seyedmousavi was supported by the Intramural Research Program of the NIH, NIAID.
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Seyedmousavi, S., Wiederhold, N.P., Ebel, F., Hedayati, M.T., Rafati, H., Verweij, P.E. (2018). Antifungal Use in Veterinary Practice and Emergence of Resistance. In: Seyedmousavi, S., de Hoog, G., Guillot, J., Verweij, P. (eds) Emerging and Epizootic Fungal Infections in Animals. Springer, Cham. https://doi.org/10.1007/978-3-319-72093-7_16
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