The global problem of antifungal resistance: prevalence, mechanisms, and management

The Lancet Infectious Diseases

Volumn 17, Issue 12, 2017, Pages e383-e392

  Perlin, David S ^a   Rautemaa Richardson, Riina ^b   Alastruey Izquierdo, Ana ^c  

^a PUBLIC HEALTH RESEARCH INSTITUTE   (United States)

^b UNIVERSITY OF MANCHESTER   (United Kingdom)

^c INSTITUTO DE SALUD CARLOS III   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

AMPHOTERICIN B; ANTIFUNGAL AGENT; ECHINOCANDIN; ITRACONAZOLE; POLYENE; POSACONAZOLE; PYRROLE; VORICONAZOLE;

ANTIFUNGAL RESISTANCE; ASPERGILLUS FUMIGATUS; BIOFILM; CANDIDA; CANDIDA AURIS; CANDIDA GLABRATA; CELL STRESS; DRUG MECHANISM; HUMAN; MYCOSIS; NONHUMAN; PERMEABILITY BARRIER; PREVALENCE; PRIORITY JOURNAL; REVIEW; DRUG EFFECTS; FUNGUS; GLOBAL HEALTH; METABOLISM; MICROBIOLOGY;

ANTIFUNGAL AGENTS; DRUG RESISTANCE, FUNGAL; FUNGI; GLOBAL HEALTH; HUMANS; MYCOSES;

EID: 85026531535     PISSN: 14733099     EISSN: 14744457     Source Type: Journal    
DOI: 10.1016/S1473-3099(17)30316-X     Document Type: Review

References (114)

1. Brown, GD, Denning, DW, Gow, NA, Levitz, SM, Netea, MG, White, TC, Hidden killers: human fungal infections. Sci Transl Med, 4, 2012, 165rv13.
2. Odds, FC, Brown, AJ, Gow, NA, Antifungal agents: mechanisms of action. Trends Microbiol 11 (2003), 272–279.
3. Verweij, PE, Snelders, E, Kema, GH, Mellado, E, Melchers, WJ, Azole resistance in Aspergillus fumigatus: a side-effect of environmental fungicide use?. Lancet Infect Dis 9 (2009), 789–795.
4. Snelders, E, Melchers, WJ, Verweij, PE, Azole resistance in Aspergillus fumigatus: a new challenge in the management of invasive aspergillosis?. Future Microbiol 6 (2011), 335–347.
5. Brown, GD, Netea, MG, Exciting developments in the immunology of fungal infections. Cell Host Microbe 11 (2012), 422–424.
6. Shields, RK, Nguyen, MH, Press, EG, Clancy, CJ, Abdominal candidiasis is a hidden reservoir of echinocandin resistance. Antimicrob Agents Chemother 58 (2014), 7601–7615.
7. Shor, E, Perlin, DS, Coping with stress and the emergence of multidrug resistance in fungi. PLoS Pathog, 11, 2015, e1004668.
8. Pfaller, MA, Diekema, DJ, Andes, D, et al. Clinical breakpoints for the echinocandins and candida revisited: integration of molecular, clinical, and microbiological data to arrive at species-specific interpretive criteria. Drug Resist Updat 14 (2011), 164–176.
9. Arendrup, MC, Cuenca-Estrella, M, Lass-Florl, C, Hope, WW, Breakpoints for antifungal agents: an update from EUCAST focussing on echinocandins against Candida spp and triazoles against Aspergillus spp. Drug Resist Updat 16 (2013), 81–95.
10. Pfaller, MA, Andes, D, Arendrup, MC, et al. Clinical breakpoints for voriconazole and Candida spp revisited: review of microbiologic, molecular, pharmacodynamic, and clinical data as they pertain to the development of species-specific interpretive criteria. Diagn Microbiol Infect Dis 70 (2011), 330–343.
11. Turnidge, J, Kahlmeter, G, Kronvall, G, Statistical characterisation of bacterial wild-type MIC value distributions and the determination of epidemiological cut-off values. Clin Microbiol Infect 12 (2006), 418–425.
12. Espinel-Ingroff, A, Pfaller, MA, Bustamante, B, et al. Multilaboratory study of epidemiological cutoff values for detection of resistance in eight Candida species to fluconazole, posaconazole, and voriconazole. Antimicrob Agents Chemother 58 (2014), 2006–2012.
13. Espinel-Ingroff, A, Alvarez-Fernandez, M, Canton, E, et al. Multicenter study of epidemiological cutoff values and detection of resistance in Candida spp to anidulafungin, caspofungin, and micafungin using the Sensititre YeastOne colorimetric method. Antimicrob Agents Chemother 59 (2015), 6725–6732.
14. Espinel-Ingroff, A, Arendrup, MC, Pfaller, MA, et al. Interlaboratory variability of caspofungin MICs for Candida spp using CLSI and EUCAST methods: should the clinical laboratory be testing this agent?. Antimicrob Agents Chemother 57 (2013), 5836–5842.
15. Meletiadis, J, Geertsen, E, Curfs-Breuker, I, Meis, JF, Mouton, JW, Intra- and interlaboratory agreement in assessing the in vitro activity of micafungin against common and rare Candida species with the EUCAST, CLSI, and Etest methods. Antimicrob Agents Chemother 60 (2016), 6173–6178.
16. Peterson, JF, Pfaller, MA, Diekema, DJ, Rinaldi, MG, Riebe, KM, Ledeboer, NA, Multicenter comparison of the Vitek 2 antifungal susceptibility test with the CLSI broth microdilution reference method for testing caspofungin, micafungin, and posaconazole against Candida spp. J Clin Microbiol 49 (2011), 1765–1771.
17. Pappas, PG, Kauffman, CA, Andes, DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 62 (2016), e1–e50.
18. Pfaller, MA, Antifungal drug resistance: mechanisms, epidemiology, and consequences for treatment. Am J Med 125:suppl 1 (2012), S3–S13.
19. Howard, SJ, Arendrup, MC, Acquired antifungal drug resistance in Aspergillus fumigatus: epidemiology and detection. Med Mycol 49:suppl 1 (2011), S90–S95.
20. Hagen, F, Hare Jensen, R, Meis, JF, Arendrup, MC, Molecular epidemiology and in vitro antifungal susceptibility testing of 108 clinical Cryptococcus neoformans sensu lato and Cryptococcus gattii sensu lato isolates from Denmark. Mycoses 59 (2016), 576–584.
21. Pfaller, MA, Diekema, DJ, Gibbs, DL, et al. Results from the ARTEMIS DISK Global Antifungal Surveillance Study, 1997 to 2007: a 10·5-year analysis of susceptibilities of Candida species to fluconazole and voriconazole as determined by CLSI standardized disk diffusion. J Clin Microbiol 48 (2010), 1366–1377.
22. Pfaller, MA, Messer, SA, Hollis, RJ, et al. Variation in susceptibility of bloodstream isolates of Candida glabrata to fluconazole according to patient age and geographic location in the United States in 2001 to 2007. J Clin Microbiol 47 (2009), 3185–3190.
23. Castanheira, M, Messer, SA, Rhomberg, PR, Pfaller, MA, Antifungal susceptibility patterns of a global collection of fungal isolates: results of the SENTRY Antifungal Surveillance Program (2013). Diagn Microbiol Infect Dis 85 (2016), 200–204.
24. Guinea, J, Zaragoza, O, Escribano, P, et al. Molecular identification and antifungal susceptibility of yeast isolates causing fungemia collected in a population-based study in Spain in 2010 and 2011. Antimicrob Agents Chemother 58 (2014), 1529–1537.
25. Snelders, E, Camps, SM, Karawajczyk, A, et al. Triazole fungicides can induce cross-resistance to medical triazoles in Aspergillus fumigatus. PLoS One, 7, 2012, e31801.
26. Price, CL, Parker, JE, Warrilow, AG, Kelly, DE, Kelly, SL, Azole fungicides—understanding resistance mechanisms in agricultural fungal pathogens. Pest Manag Sci 71 (2015), 1054–1058.
27. van der Linden, JW, Arendrup, MC, Warris, A, et al. Prospective multicenter international surveillance of azole resistance in Aspergillus fumigatus. Emerg Infect Dis 21 (2015), 1041–1044.
28. Alanio, A, Denis, B, Hamane, S, et al. Azole resistance of Aspergillus fumigatus in immunocompromised patients with invasive aspergillosis. Emerg Infect Dis 22 (2016), 157–158.
29. Al-Hatmi, AM, Meis, JF, de Hoog, GS, Fusarium: molecular diversity and intrinsic drug resistance. PLoS Pathog, 12, 2016, e1005464.
30. Lackner, M, de Hoog, GS, Verweij, PE, et al. Species-specific antifungal susceptibility patterns of Scedosporium and Pseudallescheria species. Antimicrob Agents Chemother 56 (2012), 2635–2642.
31. Espinel-Ingroff, A, Chakrabarti, A, Chowdhary, A, et al. Multicenter evaluation of MIC distributions for epidemiologic cutoff value definition to detect amphotericin B, posaconazole, and itraconazole resistance among the most clinically relevant species of Mucorales. Antimicrob Agents Chemother 59 (2015), 1745–1750.
32. Ramos, LS, Figueiredo-Carvalho, MH, Barbedo, LS, et al. Candida haemulonii complex: species identification and antifungal susceptibility profiles of clinical isolates from Brazil. J Antimicrob Chemother 70 (2015), 111–115.
33. Chowdhary, A, Anil Kumar, V, Sharma, C, et al. Multidrug-resistant endemic clonal strain of Candida auris in India. Eur J Clin Microbiol Infect Dis 33 (2014), 919–926.
34. Chowdhary, A, Voss, A, Meis, JF, Multidrug-resistant Candida auris: ‘new kid on the block’ in hospital-associated infections?. J Hosp Infect 94 (2016), 209–212.
35. Cowen, LE, Sanglard, D, Howard, SJ, Rogers, PD, Perlin, DS, Mechanisms of antifungal drug resistance. Cold Spring Harb Perspect Med, 5, 2015, a019752.
36. Coste, A, Turner, V, Ischer, F, et al. A mutation in Tac1p, a transcription factor regulating CDR1 and CDR2, is coupled with loss of heterozygosity at chromosome 5 to mediate antifungal resistance in Candida albicans. Genetics 172 (2006), 2139–2156.
37. Morschhauser, J, Barker, K, Liu, T, Bla, B, Homayouni, R, Rogers, P, The transcription factor Mrr1p controls expression of the MDR1 efflux pump and mediates multidrug resistance in Candida albicans. PLoS Pathog, 3, 2007, e164.
38. Vermitsky, J-P, Earhart, KD, Smith, WL, Homayouni, R, Edlind, TD, Rogers, PD, Pdr1 regulates multidrug resistance in Candida glabrata: gene disruption and genome-wide expression studies. Mol Microbiol 61 (2006), 704–722.
39. Sagatova, AA, Keniya, MV, Wilson, RK, Monk, BC, Tyndall, JD, Structural insights into binding of the antifungal drug fluconazole to Saccharomyces cerevisiae lanosterol 14α-demethylase. Antimicrob Agents Chemother 59 (2015), 4982–4989.
40. Flowers, SA, Barker, KS, Berkow, EL, et al. Gain-of-function mutations in UPC2 are a frequent cause of ERG11 upregulation in azole-resistant clinical Isolates of Candida albicans. Eukaryotic Cell 11 (2012), 1289–1299.
41. Vale-Silva, LA, Coste, AT, Ischer, F, et al. Azole resistance by loss of function of the sterol Δ(5),(6)-desaturase gene (ERG3) in Candida albicans does not necessarily decrease virulence. Antimicrob Agents Chemother 56 (2012), 1960–1968.
42. Selmecki, A, Forche, A, Berman, J, Aneuploidy and isochromosome formation in drug-resistant Candida albicans. Science 313 (2006), 367–370.
43. Ramage, G, Rajendran, R, Sherry, L, Williams, C, Fungal biofilm resistance. Int J Microbiol, 2012, 2012, 528521.
44. Nett, JE, Crawford, K, Marchillo, K, Andes, DR, Role of Fks1p and matrix glucan in Candida albicans biofilm resistance to an echinocandin, pyrimidine, and polyene. Antimicrob Agents Chemother 54 (2010), 3505–3508.
45. Desai, JV, Mitchell, AP, Candida albicans biofilm development and its genetic control. Microbiol Spectr, 3, 2015 MB-0005-2014.
46. Mellado, E, Garcia-Effron, G, Alcazar-Fuoli, L, et al. A new Aspergillus fumigatus resistance mechanism conferring in vitro cross-resistance to azole antifungals involves a combination of cyp51A alterations. Antimicrob Agents Chemother 51 (2007), 1897–1904.
47. Verweij PE, Chowdhary A, Melchers WJ, Meis JF. Azole resistance in Aspergillus fumigatus: can we retain the clinical use of mold-active antifungal azoles? Clin Infect Dis; 62: 362–68.
48. Verweij, PE, Kema, GH, Zwaan, B, Melchers, WJ, Triazole fungicides and the selection of resistance to medical triazoles in the opportunistic mould Aspergillus fumigatus. Pest Manag Sci 69 (2013), 165–170.
49. Krishnan Natesan, S, Wu, W, Cutright, JL, Chandrasekar, PH, In vitro-in vivo correlation of voriconazole resistance due to G448S mutation (cyp51A gene) in Aspergillus fumigatus. Diagn Microbiol Infect Dis 74 (2012), 272–277.
50. Paul, RA, Rudramurthy, SM, Meis, JF, Mouton, JW, Chakrabarti, A, A novel Y319H substitution in CYP51C associated with azole resistance in Aspergillus flavus. Antimicrob Agents Chemother 59 (2015), 6615–6619.
51. Arendrup, MC, Jensen, RH, Grif, K, et al. In vivo emergence of Aspergillus terreus with reduced azole susceptibility and a Cyp51a M217I alteration. J Infect Dis 206 (2012), 981–985.
52. Le Pape, P, Lavergne, RA, Morio, F, Alvarez-Moreno, C, Multiple fungicide-driven alterations in azole-resistant Aspergillus fumigatus, Colombia, 2015. Emerg Infect Dis 22 (2016), 156–157.
53. Hodiamont, CJ, Dolman, KM, Ten Berge, IJ, Melchers, WJ, Verweij, PE, Pajkrt, D, Multiple-azole-resistant Aspergillus fumigatus osteomyelitis in a patient with chronic granulomatous disease successfully treated with long-term oral posaconazole and surgery. Med Mycol 47 (2009), 217–220.
54. Moye-Rowley, WS, Multiple mechanisms contribute to the development of clinically significant azole resistance in Aspergillus fumigatus. Front Microbiol, 6, 2015, 70.
55. Camps, SM, Dutilh, BE, Arendrup, MC, et al. Discovery of a HapE mutation that causes azole resistance in Aspergillus fumigatus through whole genome sequencing and sexual crossing. PLoS One, 7, 2012, e50034.
56. Bueid, A, Howard, SJ, Moore, CB, et al. Azole antifungal resistance in Aspergillus fumigatus: 2008 and 2009. J Antimicrob Chemother 65 (2010), 2116–2118.
57. Ramage, G, Mowat, E, Jones, B, Williams, C, Lopez-Ribot, J, Our current understanding of fungal biofilms. Crit Rev Microbiol 35 (2009), 340–355.
58. Alastruey-Izquierdo, A, Alcazar-Fuoli, L, Cuenca-Estrella, M, Antifungal susceptibility profile of cryptic species of Aspergillus. Mycopathologia 178 (2014), 427–433.
59. Alastruey-Izquierdo, A, Gomez-Lopez, A, Arendrup, MC, et al. Comparison of dimethyl sulfoxide and water as solvents for echinocandin susceptibility testing by the EUCAST methodology. J Clin Microbiol 50 (2012), 2509–2512.
60. Alastruey-Izquierdo, A, Cuenca-Estrella, M, Monzon, A, Rodriguez-Tudela, JL, Prevalence and susceptibility testing of new species of Pseudallescheria and Scedosporium in a collection of clinical mold isolates. Antimicrob Agents Chemother 51 (2007), 748–751.
61. Alastruey-Izquierdo, A, Castelli, MV, Cuesta, I, et al. In vitro activity of antifungals against zygomycetes. Clin Microbiol Infect 15:suppl 5 (2009), 71–76.
62. Taj-Aldeen, SJ, Salah, H, Al-Hatmi, AM, et al. In vitro resistance of clinical Fusarium species to amphotericin B and voriconazole using the EUCAST antifungal susceptibility method. Diagn Microbiol Infect Dis 85 (2016), 438–443.
63. Espinel-Ingroff, A, Johnson, E, Hockey, H, Troke, P, Activities of voriconazole, itraconazole and amphotericin B in vitro against 590 moulds from 323 patients in the voriconazole phase III clinical studies. J Antimicrob Chemother 61 (2008), 616–620.
64. Onishi, J, Meinz, M, Thompson, J, et al. Discovery of novel antifungal (1,3)-β-D-glucan synthase inhibitors. Antimicrob Agents Chemother 44 (2000), 368–377.
65. Cleveland, AA, Farley, MM, Harrison, LH, et al. Changes in incidence and antifungal drug resistance in candidemia: results from population-based laboratory surveillance in Atlanta and Baltimore, 2008–2011. Clin Infect Dis 55 (2012), 1352–1361.
66. Lortholary, O, Desnos-Ollivier, M, Sitbon, K, et al. Recent exposure to caspofungin or fluconazole influences the epidemiology of candidemia: a prospective multicenter study involving 2,441 patients. Antimicrob Agents Chemother 55 (2011), 532–538.
67. Pfaller, MA, Messer, SA, Woosley, LN, Jones, RN, Castanheira, M, 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 (2013), 2571–2581.
68. Balajee, SA, Gribskov, JL, Hanley, E, Nickle, D, Marr, KA, Aspergillus lentulus sp nov, a new sibling species of A fumigatus. Eukaryot Cell 4 (2005), 625–632.
69. Jensen, RH, Astvad, KM, Silva, LV, et al. Stepwise emergence of azole, echinocandin and amphotericin B multidrug resistance in vivo in Candida albicans orchestrated by multiple genetic alterations. J Antimicrob Chemother 70 (2015), 2551–2555.
70. Arendrup, MC, Perlin, DS, Echinocandin resistance: an emerging clinical problem?. Curr Opin Infect Dis 27 (2014), 484–492.
71. Pham, CD, Iqbal, N, Bolden, CB, et al. Role of FKS mutations in Candida glabrata: MIC values, echinocandin resistance, and multidrug resistance. Antimicrob Agents Chemother 58 (2014), 4690–4696.
72. Vallabhaneni, S, Cleveland, AA, Farley, MM, et al. Epidemiology and risk factors for echinocandin nonsusceptible Candida glabrata bloodstream infections: data from a large multisite population-based candidemia surveillance program, 2008–2014. Open Forum Infect Dis, 2, 2015, ofv163.
73. Alexander, BD, Johnson, MD, Pfeiffer, CD, et al. Increasing echinocandin resistance in Candida glabrata: clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations. Clin Infect Dis 56 (2013), 1724–1732.
74. Farmakiotis, D, Tarrand, JJ, Kontoyiannis, DP, Drug-resistant Candida glabrata infection in cancer patients. Emerg Infect Dis 20 (2014), 1833–1840.
75. Klotz, U, Schmidt, D, Willinger, B, et al. Echinocandin resistance and population structure of invasive Candida glabrata isolates from two university hospitals in Germany and Austria. Mycoses 59 (2016), 312–318.
76. Fekkar, A, Dannaoui, E, Meyer, I, et al. Emergence of echinocandin-resistant Candida spp in a hospital setting: a consequence of 10 years of increasing use of antifungal therapy?. Eur J Clin Microbiol Infect Dis 33 (2014), 1489–1496.
77. Perlin, DS, Current perspectives on echinocandin class drugs. Future Microbiol 6 (2011), 441–457.
78. Niimi, K, Maki, K, Ikeda, F, et al. Overexpression of Candida albicans CDR1, CDR2, or MDR1 does not produce significant changes in echinocandin susceptibility. Antimicrob Agents Chemother 50 (2006), 1148–1155.
79. Garcia-Effron, G, Park, S, Perlin, DS, Correlating echinocandin MIC and kinetic inhibition of fks1 mutant glucan synthases for Candida albicans: implications for interpretive breakpoints. Antimicrob Agents Chemother 53 (2009), 112–122.
80. Slater, JL, Howard, SJ, Sharp, A, et al. Disseminated candidiasis caused by Candida albicans with amino acid substitutions in Fks1 at position Ser645 cannot be successfully treated with micafungin. Antimicrob Agents Chemother 55 (2011), 3075–3083.
81. Arendrup, MC, Perlin, DS, Jensen, RH, Howard, SJ, Goodwin, J, Hope, W, Differential in vivo activities of anidulafungin, caspofungin, and micafungin against Candida glabrata isolates with and without FKS resistance mutations. Antimicrob Agents Chemother 56 (2012), 2435–2442.
82. Garcia-Effron, G, Lee, S, Park, S, Cleary, JD, Perlin, DS, Effect of Candida glabrata FKS1 and FKS2 mutations on echinocandin sensitivity and kinetics of 1,3-β-D-glucan synthase: implication for the existing susceptibility breakpoint. Antimicrob Agents Chemother 53 (2009), 3690–3699.
83. Shields, RK, Nguyen, MH, Press, EG, et al. The presence of an FKS mutation rather than MIC is an independent risk factor for failure of echinocandin therapy among patients with invasive candidiasis due to Candida glabrata. Antimicrob Agents Chemother 56 (2012), 4862–4869.
84. Beyda, ND, John, J, Kilic, A, Alam, MJ, Lasco, TM, Garey, KW, FKS mutant Candida glabrata: risk factors and outcomes in patients with candidemia. Clin Infect Dis 59 (2014), 819–825.
85. Pfaller, MA, Espinel-Ingroff, A, Bustamante, B, et al. Multicenter study of anidulafungin and micafungin MIC distributions and epidemiological cutoff values for eight Candida species and the CLSI M27-A3 broth microdilution method. Antimicrob Agents Chemother 58 (2014), 916–922.
86. Kale-Pradhan, PB, Morgan, G, Wilhelm, SM, Johnson, LB, Comparative efficacy of echinocandins and nonechinocandins for the treatment of Candida parapsilosis infections: a meta-analysis. Pharmacotherapy 30 (2010), 1207–1213.
87. Forrest, GN, Weekes, E, Johnson, JK, Increasing incidence of Candida parapsilosis candidemia with caspofungin usage. J Infect 56 (2008), 126–129.
88. Stevens, DA, Espiritu, M, Parmar, R, Paradoxical effect of caspofungin: reduced activity against Candida albicans at high drug concentrations. Antimicrob Agents Chemother 48 (2004), 3407–3411.
89. Healey, KR, Zhao, Y, Perez, WB, et al. Prevalent mutator genotype identified in fungal pathogen Candida glabrata promotes multi-drug resistance. Nat Commun, 7, 2016, 11128.
90. Mitchell, KF, Taff, HT, Cuevas, MA, Reinicke, EL, Sanchez, H, Andes, DR, Role of matrix β-1,3 glucan in antifungal resistance of non-albicans candida biofilms. Antimicrob Agents Chemother 57 (2013), 1918–1920.
91. Cheng, S, Clancy, C, Hartman, D, Hao, B, Nguyen, M, Candida glabrata intra-abdominal candidiasis is characterized by persistence within the peritoneal cavity and abscesses. Infect Immun 82 (2014), 3015–3022.
92. Anderson, TM, Clay, MC, Cioffi, AG, et al. Amphotericin forms an extramembranous and fungicidal sterol sponge. Nat Chem Biol 10 (2014), 400–406.
93. Pfaller, MA, Diekema, DJ, Rare and emerging opportunistic fungal pathogens: concern for resistance beyond Candida albicans and Aspergillus fumigatus. J Clin Microbiol 42 (2004), 4419–4431.
94. Alastruey-Izquierdo, A, Cuesta, I, Houbraken, J, Cuenca-Estrella, M, Monzon, A, Rodriguez-Tudela, JL, In vitro activity of nine antifungal agents against clinical isolates of Aspergillus calidoustus. Med Mycol 48 (2010), 97–102.
95. Krcmery, V Jr, Spanik, S, Kunova, A, Trupl, J, Breakthrough fungemia appearing during empiric therapy with amphotericin B. Chemotherapy 43 (1997), 367–370.
96. Hull, CM, Bader, O, Parker, JE, et al. Two clinical isolates of Candida glabrata exhibiting reduced sensitivity to amphotericin B both harbor mutations in ERG2. Antimicrob Agents Chemother 56 (2012), 6417–6421.
97. Colombo, AL, Melo, AS, Crespo Rosas, RF, et al. Outbreak of Candida rugosa candidemia: an emerging pathogen that may be refractory to amphotericin B therapy. Diagn Microbiol Infect Dis 46 (2003), 253–257.
98. Atkinson, BJ, Lewis, RE, Kontoyiannis, DP, Candida lusitaniae fungemia in cancer patients: risk factors for amphotericin B failure and outcome. Med Mycol 46 (2008), 541–546.
99. Woods, RA, Bard, M, Jackson, IE, Drutz, DJ, Resistance to polyene antibiotics and correlated sterol changes in two isolates of Candida tropicalis from a patient with an amphotericin B-resistant funguria. J Infect Dis 129 (1974), 53–58.
100. Espinel-Ingroff, A, Cuenca-Estrella, M, Fothergill, A, et al. Wild-type MIC distributions and epidemiological cutoff values for amphotericin B and Aspergillus spp for the CLSI broth microdilution method (M38-A2 document). Antimicrob Agents Chemother 55 (2011), 5150–5154.
101. Perfect, JR, Cox, GM, Drug resistance in Cryptococcus neoformans. Drug Resist Updat 2 (1999), 259–269.
102. Vazquez, JA, Arganoza, MT, Boikov, D, Yoon, S, Sobel, JD, Akins, RA, Stable phenotypic resistance of Candida species to amphotericin B conferred by preexposure to subinhibitory levels of azoles. J Clin Microbiol 36 (1998), 2690–2695.
103. Kelly, SL, Lamb, DC, Taylor, M, Corran, AJ, Baldwin, BC, Powderly, WG, Resistance to amphotericin B associated with defective sterol delta 8–>7 isomerase in a Cryptococcus neoformans strain from an AIDS patient. FEMS Microbiol Lett 122 (1994), 39–42.
104. Schuts, EC, Hulscher, ME, Mouton, JW, et al. Current evidence on hospital antimicrobial stewardship objectives: a systematic review and meta-analysis. Lancet Infect Dis 16 (2016), 847–856.
105. Ruhnke, M, Antifungal stewardship in invasive candida infections. Clin Microbiol Infect 20:suppl 6 (2014), 11–18.
106. Valerio, M MP, Rodríguez-González, C, Sanjurjo, M, Guinea, J, Bouza, E, Training should be the first step toward an antifungal stewardship program. Enferm Infecc Microbiol Clin 33 (2015), 221–227.
107. Micallef, C, Aliyu, SH, Santos, R, Brown, NM, Rosembert, D, Enoch, DA, Introduction of an antifungal stewardship programme targeting high-cost antifungals at a tertiary hospital in Cambridge, England. J Antimicrob Chemother 70 (2015), 1908–1911.
108. Munoz, P, Valerio, M, Vena, A, Bouza, E, Antifungal stewardship in daily practice and health economic implications. Mycoses 58:suppl 2 (2015), 14–25.
109. Schuetz, AN, Invasive fungal infections: biomarkers and molecular approaches to diagnosis. Clin Lab Med 33 (2013), 505–525.
110. Morrissey, CO, Chen, SC, Sorrell, TC, et al. Galactomannan and PCR versus culture and histology for directing use of antifungal treatment for invasive aspergillosis in high-risk haematology patients: a randomised controlled trial. Lancet Infect Dis 13 (2013), 519–528.
111. Bertz, H, Drognitz, K, Finke, J, Analysis of the efficiency and costs of antifungal prophylaxis and mycological diagnostics in patients undergoing allogeneic haematopoietic cell transplantation: “real life” evaluation. Ann Hematol 95 (2016), 457–463.
112. Barnes, RA, White, PL, Bygrave, C, Evans, N, Healy, B, Kell, J, Clinical impact of enhanced diagnosis of invasive fungal disease in high-risk haematology and stem cell transplant patients. J Clin Pathol 62 (2009), 64–69.
113. Andes, D, Pascual, A, Marchetti, O, Antifungal therapeutic drug monitoring: established and emerging indications. Antimicrob Agents Chemother 53 (2009), 24–34.
114. Ashbee, HR, Barnes, RA, Johnson, EM, Richardson, MD, Gorton, R, Hope, WW, Therapeutic drug monitoring (TDM) of antifungal agents: guidelines from the British Society for Medical Mycology. J Antimicrob Chemother 69 (2014), 1162–1176.