Current Fungal Infection Reports

, Volume 13, Issue 1, pp 33–43 | Cite as

Usefulness of Antifungal Reference In Vitro Susceptibility Tests as a Guide in Therapeutic Management

  • A. Espinel-IngroffEmail author
  • M. Sanguinetti
  • Brunella Posteraro
Clinical Mycology Lab Issues (S Cordoba, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Clinical Mycology Lab Issues


Purpose of Review

This review provides information on the utility of reference antifungal susceptibility testing methods in the clinical setting.

Recent Findings

Clinical and Laboratory Standards Institute (CLSI)/European Committee for Antimicrobial Susceptibility Testing breakpoints (BPs) as predictors of therapy response (reported as either “cured” or “failure”) and epidemiological cutoff endpoints (ECVs/ECOFFS) of mutants (harboring specific resistance mechanisms) have been established.


Although ECVs are available for other species and agents and for commercial methods, only reference triazole and echinocandin BPs have been established. Therefore, correlations of in vitro/in vivo results in this review were based on BPs or ECVs for Candida spp. and/or Aspergillus fumigatus. We also included CLSI ECVs for the Cryptococcus neoformans complex and tentative values for Candida auris. Overall, BPs/ECVs appear to be useful, but most available data are for correlations between BPs and minimal inhibitory concentrations (MICs) for susceptible isolates. Although ECVs can discriminate between MICs for WT (wild type) and mutants (non-WT), an MIC overlap could be present.


Antifungal reference methods Clinical breakpoint for reference methods ECVs for reference methods Clinical utility of reference triazole and echinocandin BPs Clinical utility of reference ECVs 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    • Bongomin F, Gago S, Oladele RO, Denning DW. Global and multinational prevalence of fungal diseases-estimate precision. J Fungi (Basel). 2017;3:E57. A paper interrogating the accuracy of the serious fungal infection burden estimates in 43 papers published within the Leading International Fungal Education (LIFE) initiative. CrossRefGoogle Scholar
  2. 2.
    Bassetti M, Righi E, Montravers P, Cornely OA. What has changed in the treatment of invasive candidiasis? A look at the past 10 years and ahead. J Antimicrob Chemother. 2018;73:i14–25. Scholar
  3. 3.
    • Kontoyiannis DP. Antifungal resistance: an emerging reality and a global challenge. J Infect Dis. 2017;216:S431–5. An overview on different aspects of a complex area dealing with the emerging and global problem of the antifungal resistance in pathogenic fungi. CrossRefGoogle Scholar
  4. 4.
    Kosmidis C, Denning DW. The clinical spectrum of pulmonary aspergillosis. Thorax. 2015;70:270–7. Scholar
  5. 5.
    Andes DR, Safdar N, Baddley JW, Playford G, Reboli AC, Rex JH, et al. Impact of treatment strategy on outcomes in patients with candidemia and other forms of invasive candidiasis: a patient-level quantitative review of randomized trials. Clin Infect Dis. 2012;54:1110–22.CrossRefGoogle Scholar
  6. 6.
    Clancy CJ, Nguyen MH. Emergence of Candida auris: an international call to arms. Clin Infect Dis. 2017;64(2):141–3.CrossRefGoogle Scholar
  7. 7.
    •• Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner, et al. Clinical practice guidelines for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62:1–50. An advice to physicians for applying the current IDSA guidelines for the management of candidiasis in the light of each patient’s individual circumstances. CrossRefGoogle Scholar
  8. 8.
    •• Patterson TF, Thompson GR III, Denning DW, Fishman JA, Hadley S, Herbrecht R, et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;63:e1–e60. An advice to physicians for applying the current IDSA guidelines for the management of aspergillosis in the light of each patient’s individual circumstances.CrossRefGoogle Scholar
  9. 9.
    Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR Jr, Hamill RJ, et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2010;50:291–322.CrossRefGoogle Scholar
  10. 10.
    Clinical and Laboratory Standards Institute. Reference method for broth dilution antifungal susceptibility testing of yeasts. In: CLSI standard M27. 4th ed. Wayne: Clinical and Laboratory Standards Institute; 2017.Google Scholar
  11. 11.
    Clinical and Laboratory Standards Institute. Reference method for broth dilution antifungal susceptibility testing of filamentous fungi. In: CLSI standard M38. 3rd ed. Wayne: Clinical and Laboratory Standards Institute; 2017.Google Scholar
  12. 12.
    •• Clinical and Laboratory Standards Institute. Performance standards for antifungal susceptibility testing of yeasts. In: CLSI standard M60. 1st. ed. Wayne: Clinical and Laboratory Standards Institute; 2017. An update on the CLSI clinical breakpoints (BPs) and QC data for the broth microdilution reference M27 method. Google Scholar
  13. 13.
    Rex JH, Bennett JE, Sugar AM, Pappas PG, van der Horst CM, Edwards JE, et al. A randomized trial comparing fluconazole and amphotericin B for the treatment of candidemia in patients without neutropenia. N Engl J Med. 1994;331:1325–30.CrossRefGoogle Scholar
  14. 14.
    Clancy CJ, Yu VL, Morris AJ, Snydman DR, Nguyen MH. Fluconazole MIC and the fluconazole dose/MIC ratio correlate with therapeutic response among patients with candidemia. Antimicrob Agents Chemother. 2005;49:3171–7.CrossRefGoogle Scholar
  15. 15.
    Pfaller MA, Andes D, Diekema DJ, Espinel-Ingroff A, Sheehan D, The CLSI Subcommittee for Antifungal Testing. Wild-type MIC distributions, epidemiological cutoff values and species-specific clinical break-points for fluconazole and Candida: time for harmonization of CLSI and EUCAST broth microdilution methods. Drug Resist Updat. 2010;13:180–95.CrossRefGoogle Scholar
  16. 16.
    Kuhlberg BJ, Sobel JD, Ruhnke M, Pappas PG, Viscoli C, Rex JD, et al. Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidemia in nonneutropenic patients: a randomized non-inferiority trial. Lancet. 2005;366:1435–42.CrossRefGoogle Scholar
  17. 17.
    Pfaller MA, Andes D, Arendrup MC, Diekema DJ, Espinel-Ingroff A, Alexander BD, 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. 2011;70:330–43.CrossRefGoogle Scholar
  18. 18.
    Kuse ERP, Chutchotisakd CA, da Cunha RM, Barrios C, Raghunadharao D, Sekhon JS, et al. Micafungin versus liposomal amphotericin B for candidemia and invasive candidiasis: a phase III randomized double-blind trial. Lancet. 2007;369:1519–27.CrossRefGoogle Scholar
  19. 19.
    Pappas PG, Rotstein CMF, Betts RF, Nucci M, Talwar D, De Waele JJ, et al. Micafungin versus caspofungin for treatment of candidemia and other forms of invasive candidiasis. Clin Infect Dis. 2007;45:883–93.CrossRefGoogle Scholar
  20. 20.
    Reboli AC, Rotstein C, Pappas PG, Chapman SW, Kett DH, Kumar D, et al. Anidulafungin versus fluconazole for invasive candidiasis. N Engl J Med. 2007;356:2472–82.CrossRefGoogle Scholar
  21. 21.
    Pfaller MA, Diekema DJ, Andes, D, Arendrup MC, Rodriguez-Tudela J-T, the CLSI Subcommittee for Antifungal Testing. Clinical breakpoints for the echinocandins and Candida revisited: Integration of molecular, clinical, and microbiological data to arrive at species-specific interpretive criteria. Drugs Resist Updates 2011:14:164-176.Google Scholar
  22. 22.
    Espinel-Ingroff A, Pfaller MA, Bustamante B, Canton E, Fothergill A, Fuller J, et al. Multilaboratory study of epidemiological cutoff values for detection of resistance in eight Candida species to fluconazole, posaconazole, and voriconazole. Antimicrob Agents Chemother. 2014;58:2006–12. Scholar
  23. 23.
    Pfaller MA, Espinel-Ingroff A, Bustamante B, Canton E, Diekema DJ, Fothergill A, 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. 2014;58:916–22. Scholar
  24. 24.
    Espinel-Ingroff A, Diekema DJ, Fothergill A, Johnson E, Pelaez T, Pfaller MA, et al. Wild-type MIC distributions and epidemiological cutoff values for the triazoles and six Aspergillus spp. for the CLSI broth microdilution method (M38-A2 document). J Clin Microbiol. 2010;48:3251–7. Scholar
  25. 25.
    Espinel-Ingroff A, Chowdhary A, Gonzalez GM, Guinea J, Hagen F, Meis JF, et al. Multicenter study of isavuconazole MIC distributions and epidemiological cutoff values for the Cryptococcus neoformansCryptococcus gattii species complex using the microdilution method. Antimicrob Agents Chemother. 2015;59:666–8.CrossRefGoogle Scholar
  26. 26.
    Espinel-Ingroff A, Chowdhary A, Gonzalez GM, Lass-Flörl C, Martin-Mazuelos E, Meis J, et al. Multicenter study of isavuconazole MIC distributions and epidemiological cutoff values for Aspergillus spp. for the CLSI M38-A2 broth microdilution method. Antimicrob Agents Chemother. 2013;57:3823–8.CrossRefGoogle Scholar
  27. 27.
    •• Clinical and Laboratory Standards Institute. Epidemiological cutoff values for antifungal susceptibility testing. In: CLSI supplement M59. 2nd ed. Wayne: Clinical and Laboratory Standards Institute; 2018. An updated document by the CLSI that summarizes the approved epidemiological cutoff values for antifungal susceptibility testing Google Scholar
  28. 28.
    • Espinel-Ingroff A, Turnidge J. The role of epidemiological cutoff values (ECVs/ECOFFs) in antifungal susceptibility testing and interpretation for uncommon yeasts and moulds. Rev Iberoam Micol. 2016;33:63–75 This review summarizes the ECVs that are not listed in the M59 document, as well as detailed information about ECV calculation.CrossRefGoogle Scholar
  29. 29.
    Clinical and Laboratory Standards Institute. Principles and procedures for the development of epidemiological cutoff values for antifungal susceptibility testing. In: CLSI M57 document. 1st ed. Wayne: Clinical and Laboratory Standards Institute; 2016.Google Scholar
  30. 30.
    Turnidge J, Kahmeter G, Kronvall G. Statistical characterization of bacterial wild-type MIC value distributions and the determination of epidemiological cut-off values. Clin Microbiol Infect. 2006;12:418–25.CrossRefGoogle Scholar
  31. 31.
    Espinel-Ingroff A, Arendrup MC, Pfaller MA, Bonfietti LX, Bustamante B, Canton, 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. 2013.
  32. 32.
    Rodriguez-Tudela JL, Almirante B, Rodriguez-Pardo D, Laguna F, Donnelly JP, Mouton JW, et al. Correlation of the MIC and dose/MIC ratio of fluconazole to the therapeutic response of patients with mucosal candidiasis and candidemia. Antimicrob Agents Chemother. 2007;51:3599–604.CrossRefGoogle Scholar
  33. 33.
    Rodriguez-Tudela JL, Donnelly JP, Pfaller MA, Chryssantou E, Warn P, Denning DW, et al. Statistical analyses of correlation between fluconazole MICs for Candida spp. assessed by standard methods set forth by the European Committee on Antimicrobial Susceptibility Testing (E.Dis. 7.1) and CLSI (M27-A2). J Clin Microbiol. 2007;45:109–11.CrossRefGoogle Scholar
  34. 34.
    Arendrup MC, Meletiadis J, Mouton JW, Guinea J, Cuenca-Estrella M, Lagrou K, et al. EUCAST technical note on isavuconazole breakpoints for Aspergillus, itraconazole breakpoints for Candida and updates for the antifungal susceptibility testing method documents. Clin Microbiol Infect. 2016;22:571.e1–4.CrossRefGoogle Scholar
  35. 35.
    Alastruey-Izquierdo A, Melhem MSC, Bonfieti LX, Rodriguez-Tudela JL. Susceptibility test for fungi: clinical and laboratorial correlations in medical mycology Revista do Instituto de Medicina Tropical de São Paulo. 2015
  36. 36.
    Arendrup MC, Prakash A, Meletiadis J, Sharmav C, Chowdhary A. Candida auris: comparison of the EUCAST and CLSI reference microdilution MICs for eight antifungal compounds and associated tentative ECOFFs. Antimicrob Agents Chemother. 2017;61:e00485–17. Scholar
  37. 37.
    Trek Diagnostic Systems. Sensititre Yeast One: Yeast One susceptibility, v1.8. 2012: Trek Diagnostic Systems, ClevelandGoogle Scholar
  38. 38.
    bioMérieux SA. Etest antifungal susceptibility testing package insert. Chemin: bioMérieux SA; 2013.Google Scholar
  39. 39.
    bioMérieux SA. Etest performance, interpretive criteria and quality control ranges table. Chemin: bioMérieux SA; 2013.Google Scholar
  40. 40.
    Espinel-Ingroff A, Alvarez-Fernandez M, Cantón E, Carver PL, Chen SC-A, et al. A multi-center study of epidemiological cutoff values and detection of resistance in Candida spp. to anidulafungin, caspofungin and micafungin using the Sensititre Yeast One colorimetric method. Antimicrob Agents Chemother. 2015;59:6725–32. Scholar
  41. 41.
    Espinel-Ingroff A, Arendrup M, Cantón E, Cordoba S, Dannaoui E, García-Rodríguez J, et al. Multicenter study of method-dependent epidemiological cutoff value for detection of resistance in Candida spp. and Aspergillus spp. to amphotericin B and echinocandins for the Etest agar diffusion method. Antimicrob Agents Chemother. 2017;61:e01792–16. Scholar
  42. 42.
    •• Espinel-Ingroff A, Turnidge J, Alastruey-Izquierdo A, Dannaoui E, Garcia-Effron G, Guinea J, et al. Posaconazole MIC distributions for Aspergillus fumigatus species complex by four methods: impact of cyp51A mutations on estimation of epidemiological cutoff values. Antimicrob Agents Chemother. 2018;62:e01916–7. This paper provides the impact of mutations in A. fumigatus MICs by four methods with a large number of mutant isolates.CrossRefGoogle Scholar
  43. 43.
    •• Espinel-Ingroff A, Turnidge J, Alastruey-Izquierdo F, Botterel F, Canton E, Castro C, et al. Method-dependent epidemiological cutoff values (ECVs) for detection of triazole resistance in Candida, other yeast and Aspergillus species for the SYO colorimetric broth and Etest agar diffusion methods. Antimicrob Agents Chemother. 2019;63:e01651–18. This paper provides triazole ECVs for commercial methods and provides MICs by these methods for a substantial number of mutants.
  44. 44.
    •• Sanglard D, Coste AT. Activity of isavuconazole and other azoles against Candida clinical isolates and yeast model systems with known azole resistance mechanisms. Antimicrob Agents Chemother. 2016;60:229–38. An in-depth investigation on the molecular mechanisms of resistance to isavuconazole in Candida clinical isolates using the Saccharomyces cerevisiae model.CrossRefGoogle Scholar
  45. 45.
    Grossman NT, Pham CD, Cleveland AA, Lockhart SR. Molecular mechanisms of fluconazole resistance in Candida parapsilosis isolates from a U.S. surveillance system. Antimicrob Agents Chemother. 2015;59:1030–7. Scholar
  46. 46.
    Souza ACR, Fuchs BB, Pinhati HMS, Siqueira RA, Hagen F, Meis JF, et al. Candida parapsilosis resistance to fluconazole: molecular mechanisms and in vivo impact in infected Galleria mellonella larvae. Antimicrob Agents Chemother. 2015;59:6581–7. Scholar
  47. 47.
    Berkow EL, Manigaba K, Parker JE, Barker KS, Kelly SL, Rogers PD. Multidrug transporters and alterations in sterol biosynthesis contribute to azole antifungal resistance in Candida parapsilosis. Antimicrob Agents Chemother. 2015;59:5942–50. Scholar
  48. 48.
    •• Healey KR, Kordalewska M, Jiménez Ortigosa C, Singh A, Berrío I, Chowdhary A, et al. Limited ERG11 mutations identified in isolates of Candida auris directly contribute to reduced azole susceptibility. Antimicrob Agents Chemother. 2018;62:e01427–18. An interesting paper showing for the first time that specific ERG11 mutations directly contributes to reduced azole susceptibility in Candida auris. CrossRefGoogle Scholar
  49. 49.
    Garcia-Effron G, Kontoyiannis DP, Lewis RE, Perlin DS. Caspofungin-resistant Candida tropicalis strains causing breakthrough fungemia in patients at high risk for hematologic malignancies. Antimicrob Agents Chemother. 2008;52:4181–3.CrossRefGoogle Scholar
  50. 50.
    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-D-glucan synthase: implication for the existing susceptibility breakpoint. Antimicrob Agents Chemother. 2009;53:3690–9.CrossRefGoogle Scholar
  51. 51.
    Pfeiffer CD, Garcia-Effron G, Zaas AK, Perfect JR, Perlin DS, Alexander A. Breakthrough invasive candidiasis in patients on micafungin. J Clin Microbiol. 2010;53:2373–80.CrossRefGoogle Scholar
  52. 52.
    Alexander BD, Johnson MD, Pfeiffer CD, Jimenez-Ortigosa C, Catania J, Booker R, et al. Increasing echinocandin resistance in Candida glabrata: clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations. Clin Infect Dis. 2013;56:1724–32.CrossRefGoogle Scholar
  53. 53.
    Shields RK, Hong Nguyen M, Press EG, Updike CL, Clancy CJ. Anidulafungin and micafungin MIC breakpoints are superior to that of caspofungin for identifying FKS mutant Candida glabrata strains and echinocandin resistance. Antimicrob Agents Chemother. 2013;57:6361–5.CrossRefGoogle Scholar
  54. 54.
    Ostrosky-Zeichner L, Andes D. The role of in vitro susceptibility testing in the management of Candida and Aspergillus. J Infect Dis. 2017;216(S3):S452–7.CrossRefGoogle Scholar
  55. 55.
    Lausch KR, Søgaard M, Rosenvinge FS, Johansen HK, Boysen T, Roder BL, et al. Treatment of candidemia in a nationwide setting: increased survival with primary echinocandin treatment. Infect Drug Resist. 2018;11:2449–59.CrossRefGoogle Scholar
  56. 56.
    Mora-Duarte J, Betts R, Rotstein C, Lopes-Colombo A, Thompson-Moya L, Smietana J, et al. Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med. 2002;547:2020–9.CrossRefGoogle Scholar
  57. 57.
    Lepak A, Castanheira M, Daniel Diekema D, Pfaller M, Andes D. Optimizing echinocandin dosing and susceptibility breakpoint determination via in vivo pharmacodynamic evaluation against Candida glabrata with and without fks mutations. Antimicrob Agents Chemother. 2012;52:5875–82.CrossRefGoogle Scholar
  58. 58.
    • Boonstra JM, van der Elst KC, Veringa A, Jongedijk EM, Brüggemann RJ, Koster RA, et al. Pharmacokinetic properties of micafungin in critically ill patients diagnosed with invasive candidiasis. Antimicrob Agents Chemother. 2017;61:e01398–17. An interesting paper highlighting the risk for inappropriate micafungin exposure and potentially inadequate antifungal treatment in critically ill patients diagnosed with invasive candidiasis. CrossRefGoogle Scholar
  59. 59.
    Garcia-Effron G, Dilger A, Alcazar-Fuoli L, Park S, Mellado E, Perlin DS. Rapid detection of triazole antifungal resistance in Aspergillus fumigatus. J Clin Microbiol. 2008;46:1200–6. Scholar
  60. 60.
    Mavridou E, Bruggemann RJM, Melchers WJG, Mouton JW, Verweij PE. Efficacy of posaconazole against three clinical Aspergillus fumigatus isolates with mutations in the cyp51A gene. Antimicrob Agents Chemother. 2010;54:860–5.CrossRefGoogle Scholar
  61. 61.
    Meletiadis J, Mavridou E, Melchers WJG, Mouton JW, Verweij PE. Epidemiological cutoff values for azoles and Aspergillus fumigatus based on a novel mathematical approach incorporating cyp51A sequence analysis. Antimicrob Agents Chemother. 2012;56:2524–9.CrossRefGoogle Scholar
  62. 62.
    Burgel P-R, Baixench M-T, Amsellem M, Audureau E, Chapron J, Kanaan R, et al. High prevalence of azole-resistant Aspergillus fumigatus in adults with cystic fibrosis exposed to itraconazole. Antimicrob Agents Chemother. 2012;56:869–74. Scholar
  63. 63.
    Jeans AR, Howard SJ, Al-Nakeeb Z, Goodwin J, Gregson L, Majithiya JB, et al. Pharmacodynamics of voriconazole in a dynamic in vitro model of invasive pulmonary apergillosis: implications for in vitro susceptibility breakpoints. J Infect Dis. 2012;206:442–52.CrossRefGoogle Scholar
  64. 64.
    Gregson L, Goodwin J, Johnson A, McEntee L, Moore CB, Richardson M, et al. In vitro susceptibility of Aspergillus fumigatus to isavuconazole: correlation with itraconazole, voriconazole, and posaconazole. Antimicrob Agents Chemother. 2013;57:5778–6578.CrossRefGoogle Scholar
  65. 65.
    Lepak AJ, Marchillo K, VanHecker J, Andes DR. Posaconazole pharmacodynamic target determination against wild type and Cyp51 mutant isolates of Aspergillus fumigatus in an in vivo model of invasive pulmonary aspergillosis. Antimicrob Agents Chemother. 2013;57:579–85.CrossRefGoogle Scholar
  66. 66.
    Lepak AJ, Marchillo K, VanHecker J, Andes DR. Isavuconazole (BAL4815) pharmacodynamic target determination in an in vivo murine model of invasive pulmonary aspergillosis against wild-type and cyp51 mutant isolates of Aspergillus fumigatus. Antimicrob Agents Chemother. 2013;57:6284–9.CrossRefGoogle Scholar
  67. 67.
    Patel TS, Carver PL, Eschenauer GA. Are in vitro susceptibilities to azole antifungals predictive of clinical outcome in the treatment of candidemia? J Clin Microbiol. 2018;56:e01072–18. Scholar
  68. 68.
    Thompson GR III, Rendon A, dos Santos RR, Queiroz-Telles F, Ostrosky-Zeichner L, Azie N, et al. Isavuconazole treatment of cryptococcosis and dimorphic mycoses. Clin Infect Dis. 2016;63:356–62.CrossRefGoogle Scholar
  69. 69.
    Aller AI, Martin-Mazuelos E, Lozano F, Gomez-Mateos J, Steele-Moore L, Espinel-Ingroff A, et al. Correlation of fluconazole MICs with clinical outcome in cryptococcal infection. Antimicrob Agents Chemother. 2000;44:1544–8.CrossRefGoogle Scholar
  70. 70.
    Isla G, Leonardelli F, Tiraboschi IN, Refojo N, Hevia A, Vivot W, et al. First clinical isolation of an azole-resistant 2 Aspergillus fumigatus harboring a TR46/Y121F/T289A mutation in South America. Antimicrob Agents Chemother. 2018;62.
  71. 71.
    Zhang M, Feng C-L, Chen F, He Q, Su X, Shi Y. Triazole resistance in Aspergillus fumigatus clinical isolates obtained in Nanjing, China. Chin Med J (Engl). 2017;20:130. Scholar
  72. 72.
    Rodriguez-Tudela L, Alcazar-Fuoli L, Mellado E, Alastruey-Izquierdo A, Monzon A, Cuenca-Estrella M. Epidemiological endpoints to azole drugs in Aspergillus fumigatus. Antimicrob Agents Chemother. 2008;52:2468–72.CrossRefGoogle Scholar
  73. 73.
    Andes DR, Ghannoum MA, Mukherjee PK, Kovanda LL, Lu Q, Jones ME, et al. Outcomes by minimum inhibitory concentrations for patients treated with isavuconazole or voriconazole for invasive aspergillosis in the phase 3 SECURE and VITAL trials. Antimicrobial Agents and Chemotherapy 2019;63:e01634–18.
  74. 74.
    Dannaoui E, Desnos-Ollivier M, Garcia-Hermoso D, Grenouillet F, Cassaing S, Baixench M-T, et al. Candida spp. with acquired echinocandin resistance, France, 2004–2010. Emerg Infect Dis. 2012.

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • A. Espinel-Ingroff
    • 1
    Email author
  • M. Sanguinetti
    • 2
  • Brunella Posteraro
    • 3
  1. 1.VCU Medical CenterRichmondUSA
  2. 2.Istituto di MicrobiologiaFondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro CuoreRomeItaly
  3. 3.Istituto di Patologia Speciale Medica e Semeiotica MedicaFondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro CuoreRomeItaly

Personalised recommendations