mycoses
Diagnosis,Therapy and Prophylaxis of Fungal Diseases
Original article
EUCAST Technical Note on Candida and micafungin, anidulafungin and fluconazole € rl,3 William W. Hope4 and Maiken Cavling Arendrup,1 Manuel Cuenca-Estrella,2 Cornelia Lass-Flo The European Committee on Antimicrobial Susceptibility Testing – Subcommittee on Antifungal Susceptibility Testing (EUCAST-AFST)* 1 Unit of Mycology, Department of Microbiology & Infection Control, Statens Serum Institute, Copenhagen, Denmark, 2Mycology, National Center for Microbiology, Madrid, Spain, 3Division of Hygiene and Medical Microbiology, Innsbruck Medical University, Innsbruck, Austria and 4Department of Molecular and Clinical Pharmacology, The University of Liverpool, Liverpool, UK
Summary
The European Committee on Antimicrobial Susceptibility Testing Subcommittee on Antifungal Susceptibility Testing has determined breakpoints for micafungin and revised breakpoints for anidulafungin and fluconazole for Candida spp. This Technical Note is based on the corresponding rationale documents (http://www.eucast.org). The micafungin breakpoints are based on PK data, animal PK/PD data, microbiological data and clinical experience. The anidulafungin breakpoints for C. parapsilosis and fluconazole breakpoints for C. glabrata have been modified to species-specific values that categorise the wild-type as intermediate to accommodate use of these compounds in some clinical situations.
Key words: EUCAST breakpoints, Candida, susceptibility testing, MIC, microdilution.
The EUCAST-AFST (European Committee on Antimicrobial Susceptibility Testing Subcommittee on Antifungal Susceptibility Testing) has determined breakpoints for micafungin and Candida and has revised breakpoints for anidulafungin and fluconazole for Candida spp. This Technical Note is based on the EUCAST micafungin, anidulafungin and fluconazole rationale documents (available on the EUCAST website: http://www.eucast.org). The rationale documents
Correspondence: M. C. Arendrup, Unit of Mycology, Department of Microbiology & Infection Control, Statens Serum Institute, Artillerivej 5, DK-2300 Copenhagen, Denmark. Tel.: (+45) 22632785. Fax: (+45) 32683130. E-mail: [email protected] or [email protected] *EUCAST-AFST: MC Arendrup (Chairman, Denmark), WW Hope (Secre€rl, Steering Committee (Austria), M Cuenca-Estrella, Steertary), C Lass-Flo ing Committee (Spain), S Arikan-Akdagli (Turkey), F Barchiesi (Italy), J Bille (Switzerland), E Chryssanthou (Sweden), P Gaustad (Norway), A Groll € l€ (Germany), H J€arv (Estonia), N Klimko (Russia), P Koukila-K€ ahko a (Finland), K Lagrou (Belgium), O Lortholary (France), C Moore (United Kingdom), A Velegraki (Greece), PV Verweij (The Netherlands). Submitted for publication 19 November 2013 Revised 19 December 2013 Accepted for publication 19 December 2013
© 2014 Blackwell Verlag GmbH Mycoses, 2014, 57, 377–379
include more detail and published references related to the selection of EUCAST-AFST breakpoints. Micafungin is an echinocandin antifungal agent active against the majority of Candida species. It is licensed for treatment of invasive candidiasis, and prophylaxis of Candida infection in patients undergoing allogeneic haematopoietic stem cell transplantation or patients who are expected to have neutropenia (absolute neutrophil count < 500 cells ll 1) for 10 or more days (adults and children, including neonates). Micafungin is also licensed for treatment of oesophageal candidiasis in adult patients for whom intravenous therapy is appropriate. The epidemiological cut-off values (ECOFFs, Table 1) were established using minimum inhibitory concentration (MIC) distributions from many sources. Clinical studies have suggested that micafungin is efficacious in treatment of oesophageal candidiasis in adults and candidaemia in adults and children. For oesophageal candidiasis, micafungin and fluconazole were equally efficacious in a study of 523 patients, the majority of whom had C. albicans infection.1 Success rates for treatment of candidaemia with micafungin have been similar to those for liposomal amphotericin B and caspofungin and across the various Candida species.2–4 Breakthrough infections in patients with
doi:10.1111/myc.12170
M. C. Arendrup et al.
invasive candidiasis receiving micafungin have been reported. In one study summarising 12 cases, half of these involved C. parapsilosis, which harbours a naturally occurring alteration in the FKS1 target gene, and the other half involved C. glabrata, C. tropicalis, C. albicans, C. dubliniensis or an unspecified yeast (6/9 available isolates with a hot spot target gene mutation).5 The main conclusion was that C. parapsilosis, which harbours a naturally occurring alteration in the target gene, was over-represented in breakthrough cases, but these cases were not associated with acquired resistance. The majority of other cases involved isolates with acquired resistance and hot spot Fksp alterations.5 Pharmacodynamic data and preclinical to clinical bridging studies for C. albicans and C. glabrata suggest that wild-type isolates are covered by standard dosing with success rate estimates of 89.2% and 96.3% respectively. A notable drop in predicted response rates is predicted for isolates with elevated MICs.6–8 Similar estimates have been obtained using clinical data and the CLSI MIC method.9 These data suggest that infections caused by isolates with Fks1 mutations and elevated MICs cannot be adequately treated with micafungin. Breakpoints were established using PK data, animal PK/PD data, microbiological data and clinical experience. EUCAST breakpoints apply only to licensed treatment regimens. The breakpoints will be reviewed when more data are available for the Candida species that were not assigned breakpoints during the present review.
EUCAST breakpoints were established for anidulafungin and Candida species in 2012.10 At that time a conservative approach was adopted, categorising C. parapsilosis as a poor target for anidulafungin. C. parapsilosis harbours an intrinsic alteration in the target gene, which is the likely mechanism for the higher MICs than with other Candida species. In a clinical trial the outcome for anidulafungin with C. parapsilosis was not statistically different from other species (23 patients: 64% success for anidulafungin vs. 83% for fluconazole, P = 0.37).11 The PK/PD target is lower for C. parapsilosis than for other Candida species.12 This may be due to C. parapsilosis being less virulent than C. albicans and C. glabrata.13 Echinocandins are generally not recommended as first-line agents for serious infections caused by C. parapsilosis. However, echinocandins can be used if the patient is clinically stable and/or has responded to initial echinocandin therapy, and/or if the use of other agents is not appropriate.14 –16 Therefore, the clinical breakpoints have been revised to categorise the entire wild-type population of C. parapsilosis as intermediate (Table 1). EUCAST breakpoints for fluconazole and Candida species were established in 2007.17 A significant number of infections involve C. glabrata, which exhibits fluconazole MICs of 2–32 mg l 1 when without resistance mechanisms.18–20 Any reasonable susceptibility breakpoint based on PK data would divide wild-type C. glabrata, obviating reproducible susceptibility testing. Therefore, EUCAST-AFST at that time refrained from
Table 1 Candida species-specific micafungin, anidulafungin and fluconazole EUCAST ECOFFs and breakpoints. Species-related ECOFFs and breakpoints2(mg/l) Micafungin
Anidulafungin Breakpoint
Species C. C. C. C. C.
1
albicans glabrata krusei parapsilosis tropicalis
Fluconazole Breakpoint
Breakpoint
ECOFF
S≤
R>
ECOFF
S≤
R>
ECOFF
S≤
R>
0.016 0.03 0.25 2 0.06
0.016 0.03 IE3 0.002 IE3
0.016 0.03 IE3 2 IE3
0.03 0.06 0.06 4 0.06
0.03 0.06 0.06 0.002 0.06
0.03 0.06 0.06 4 0.06
1 32 128 2 2
2 0.002 – 2 2
4 32 – 4 4
1
There is insufficient evidence (IE) to set non-species–related breakpoints.
2
To simplify the EUCAST tables, the intermediate category is not listed. It is readily interpreted as the values between the S and the R breakpoint. For example, for MIC breakpoints listed as S ≤ 2 and R > 4, the intermediate category is 4 (technically >2–4). For MIC breakpoints listed as S ≤ 0.002 and R > 4, the intermediate category includes the entire wild-type population, and for breakpoints listed as S ≤ 0.016 and R > 0.016, there is no intermediate category. There is insufficient clinical evidence to set breakpoints for other species than those listed. 3
The MIC values are in general higher than those for C. albicans. Whether this translates into a poorer clinical response remains unknown. There is IE to set breakpoints for these species. “–” indicates that susceptibility testing is not recommended as the species is a poor target for therapy with the drug. Isolates may be reported as R without prior testing.
378
© 2014 Blackwell Verlag GmbH Mycoses, 2014, 57, 377–379
EUCAST breakpoints for Candida
giving C. glabrata breakpoints for fluconazole. As there are, however, few agents suitable for the treatment of urinary tract infections and mucosal infections managed in the primary health care setting, fluconazole may be a suitable choice provided the infecting strain has no acquired resistance mechanisms. In such cases where fluconazole is the only available antifungal agent for treating C. glabrata infections, the use of fluconazole at higher dosage may be required. Therefore, the clinical breakpoints have been revised to categorise the entire wild-type population of C. glabrata as intermediate (Table 1), thereby facilitating discrimination between wild-type and isolates with elevated MICs and acquired resistance mechanisms.
Acknowledgment
2
3
4
5
6
7
William W. Hope is supported by a National Institute of Health Clinician Scientist Award.
8
Disclosures
9
The authors do not have any potential conflicts of interests related particularly to this study. MCA: has received research grants and acted as speaker for Astellas, Gilead, MSD and Pfizer, and been a consultant for Gilead, MSD and Pcovery. MCE: has received grant support from Astellas Pharma, bioMerieux, Gilead Sciences, Merck Sharp and Dohme, Pfizer, Schering Plough, Soria Melguizo SA, Ferrer International, the European Union, the ALBAN programme, the Spanish Agency for International Cooperation, the Spanish Ministry of Culture and Education, The Spanish Health Research Fund, The Instituto de Salud Carlos III, The Ramon Areces Foundation and The Mutua Madrile~ na Foundation. He has been an advisor/consultant to the Panamerican Health Organization, Gilead Sciences, Merck Sharp and Dohme, Pfizer and Schering Plough. He has been paid for talks on behalf of Gilead Sciences, Merck Sharp and Dohme, Pfizer and Schering Plough. CLF: has research grants, consultant and/or speakers bureau, for Pfizer, Astellas, Gilead and Merck. WWH: has research grants, consultant and/or speakers bureau, for Pfizer, Astellas, Gilead, Merck, Vectura, F2G. CBM: has received travel grants from Astellas, been paid for talks on behalf of Pfizer and has received grant support from Pfizer.
References 1
de Wet NT, Bester AJ, Viljoen JJ et al. A randomized, double blind, comparative trial of micafungin (FK463) vs. fluconazole for the
© 2014 Blackwell Verlag GmbH Mycoses, 2014, 57, 377–379
10
11 12
13
14
15
16
17
18
19
20
treatment of oesophageal candidiasis. Aliment Pharmacol Ther 2005; 21: 899–907. Kuse ER, Chetchotisakd P, da Cunha CA et al. Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial. Lancet 2007; 369: 1519– 27. Pappas PG, Rotstein CM, Betts RF et al. Micafungin versus caspofungin for treatment of candidemia and other forms of invasive candidiasis. Clin Infect Dis 2007; 45: 883–93. Queiroz-Telles F, Berezin E, Leverger G et al. Micafungin versus liposomal amphotericin B for pediatric patients with invasive candidiasis: substudy of a randomized double-blind trial. Pediatr Infect Dis J 2008; 27: 820–6. Pfeiffer CD, Garcia-Effron G, Zaas AK, Perfect JR, Perlin DS, Alexander BD. Breakthrough invasive candidiasis in patients on micafungin. J Clin Microbiol 2010; 48: 2373–80. 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 2011; 55: 3075–83. Howard SJ, Livermore J, Sharp A et al. Pharmacodynamics of echinocandins against Candida glabrata: requirement for dosage escalation to achieve maximal antifungal activity in neutropenic hosts. Antimicrob Agents Chemother 2011; 55: 4880–7. Arendrup MC, Perlin DS, Jensen RH, Howard SJ, Goodwin J, Hope W. Differential in vivo activity of anidulafungin, caspofungin and micafungin against C. glabrata with and without FKS resistance mutations. Antimicrob Agents Chemother 2012; 56: 2435–42. Andes D, Ambrose PG, Hammel JP et al. Use of pharmacokineticpharmacodynamic analyses to optimize therapy with the systemic antifungal micafungin for invasive candidiasis or candidemia. Antimicrob Agents Chemother 2011; 55: 2113–21. Arendrup MC, Rodriguez-Tudela JL, Lass-Fl€ orl C et al. EUCAST technical note on anidulafungin. Clin Microbiol Infect 2011; 17: E18–E20. Reboli AC, Rotstein C, Pappas PG et al. Anidulafungin versus fluconazole for invasive candidiasis. N Engl J Med 2007; 356: 2472–82. Andes D, Diekema DJ, Pfaller MA, Bohrmuller J, Marchillo K, Lepak A. In vivo comparison of the pharmacodynamic targets for echinocandin drugs against Candida species. Antimicrob Agents Chemother 2010; 54: 2497–506. Arendrup M, Horn T, Frimodt-Moller N. In vivo pathogenicity of eight medically relevant Candida species in an animal model. Infection 2002; 30: 286–91. Cornely OA, Bassetti M, Calandra T et al. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect 2012; 18: 19–37. Ullmann AJ, Akova M, Herbrecht R et al. 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 2012; 18: 53–67. Pappas PG, Kauffman CA, Andes D et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 2009; 48: 503–35. The European Committee on Antimicrobial Susceptibility TestingSubcommittee on AntifungalSusceptibility Testing (EUCAST-AFST). EUCAST Technical Note on fluconazole. Clin Microbiol Infect 2008; 14: 193–5. Arendrup MC; The Danish Fungaemia Study Group. National Surveillance of Fungemia in Denmark 2010–11. ICAAC 2012; abstract M318. Lee I, Fishman NO, Zaoutis TE et al. Risk factors for fluconazole-resistant Candida glabrata bloodstream infections. Arch Intern Med 2009; 169: 379–83. Tsai HF, Sammons LR, Zhang X et al. Microarray and molecular analyses of the azole resistance mechanism in Candida glabrata oropharyngeal isolates. Antimicrob Agents Chemother 2010; 54: 3308–17.
379
Diagnosis,Therapy and Prophylaxis of Fungal Diseases
Original article
EUCAST Technical Note on Candida and micafungin, anidulafungin and fluconazole € rl,3 William W. Hope4 and Maiken Cavling Arendrup,1 Manuel Cuenca-Estrella,2 Cornelia Lass-Flo The European Committee on Antimicrobial Susceptibility Testing – Subcommittee on Antifungal Susceptibility Testing (EUCAST-AFST)* 1 Unit of Mycology, Department of Microbiology & Infection Control, Statens Serum Institute, Copenhagen, Denmark, 2Mycology, National Center for Microbiology, Madrid, Spain, 3Division of Hygiene and Medical Microbiology, Innsbruck Medical University, Innsbruck, Austria and 4Department of Molecular and Clinical Pharmacology, The University of Liverpool, Liverpool, UK
Summary
The European Committee on Antimicrobial Susceptibility Testing Subcommittee on Antifungal Susceptibility Testing has determined breakpoints for micafungin and revised breakpoints for anidulafungin and fluconazole for Candida spp. This Technical Note is based on the corresponding rationale documents (http://www.eucast.org). The micafungin breakpoints are based on PK data, animal PK/PD data, microbiological data and clinical experience. The anidulafungin breakpoints for C. parapsilosis and fluconazole breakpoints for C. glabrata have been modified to species-specific values that categorise the wild-type as intermediate to accommodate use of these compounds in some clinical situations.
Key words: EUCAST breakpoints, Candida, susceptibility testing, MIC, microdilution.
The EUCAST-AFST (European Committee on Antimicrobial Susceptibility Testing Subcommittee on Antifungal Susceptibility Testing) has determined breakpoints for micafungin and Candida and has revised breakpoints for anidulafungin and fluconazole for Candida spp. This Technical Note is based on the EUCAST micafungin, anidulafungin and fluconazole rationale documents (available on the EUCAST website: http://www.eucast.org). The rationale documents
Correspondence: M. C. Arendrup, Unit of Mycology, Department of Microbiology & Infection Control, Statens Serum Institute, Artillerivej 5, DK-2300 Copenhagen, Denmark. Tel.: (+45) 22632785. Fax: (+45) 32683130. E-mail: [email protected] or [email protected] *EUCAST-AFST: MC Arendrup (Chairman, Denmark), WW Hope (Secre€rl, Steering Committee (Austria), M Cuenca-Estrella, Steertary), C Lass-Flo ing Committee (Spain), S Arikan-Akdagli (Turkey), F Barchiesi (Italy), J Bille (Switzerland), E Chryssanthou (Sweden), P Gaustad (Norway), A Groll € l€ (Germany), H J€arv (Estonia), N Klimko (Russia), P Koukila-K€ ahko a (Finland), K Lagrou (Belgium), O Lortholary (France), C Moore (United Kingdom), A Velegraki (Greece), PV Verweij (The Netherlands). Submitted for publication 19 November 2013 Revised 19 December 2013 Accepted for publication 19 December 2013
© 2014 Blackwell Verlag GmbH Mycoses, 2014, 57, 377–379
include more detail and published references related to the selection of EUCAST-AFST breakpoints. Micafungin is an echinocandin antifungal agent active against the majority of Candida species. It is licensed for treatment of invasive candidiasis, and prophylaxis of Candida infection in patients undergoing allogeneic haematopoietic stem cell transplantation or patients who are expected to have neutropenia (absolute neutrophil count < 500 cells ll 1) for 10 or more days (adults and children, including neonates). Micafungin is also licensed for treatment of oesophageal candidiasis in adult patients for whom intravenous therapy is appropriate. The epidemiological cut-off values (ECOFFs, Table 1) were established using minimum inhibitory concentration (MIC) distributions from many sources. Clinical studies have suggested that micafungin is efficacious in treatment of oesophageal candidiasis in adults and candidaemia in adults and children. For oesophageal candidiasis, micafungin and fluconazole were equally efficacious in a study of 523 patients, the majority of whom had C. albicans infection.1 Success rates for treatment of candidaemia with micafungin have been similar to those for liposomal amphotericin B and caspofungin and across the various Candida species.2–4 Breakthrough infections in patients with
doi:10.1111/myc.12170
M. C. Arendrup et al.
invasive candidiasis receiving micafungin have been reported. In one study summarising 12 cases, half of these involved C. parapsilosis, which harbours a naturally occurring alteration in the FKS1 target gene, and the other half involved C. glabrata, C. tropicalis, C. albicans, C. dubliniensis or an unspecified yeast (6/9 available isolates with a hot spot target gene mutation).5 The main conclusion was that C. parapsilosis, which harbours a naturally occurring alteration in the target gene, was over-represented in breakthrough cases, but these cases were not associated with acquired resistance. The majority of other cases involved isolates with acquired resistance and hot spot Fksp alterations.5 Pharmacodynamic data and preclinical to clinical bridging studies for C. albicans and C. glabrata suggest that wild-type isolates are covered by standard dosing with success rate estimates of 89.2% and 96.3% respectively. A notable drop in predicted response rates is predicted for isolates with elevated MICs.6–8 Similar estimates have been obtained using clinical data and the CLSI MIC method.9 These data suggest that infections caused by isolates with Fks1 mutations and elevated MICs cannot be adequately treated with micafungin. Breakpoints were established using PK data, animal PK/PD data, microbiological data and clinical experience. EUCAST breakpoints apply only to licensed treatment regimens. The breakpoints will be reviewed when more data are available for the Candida species that were not assigned breakpoints during the present review.
EUCAST breakpoints were established for anidulafungin and Candida species in 2012.10 At that time a conservative approach was adopted, categorising C. parapsilosis as a poor target for anidulafungin. C. parapsilosis harbours an intrinsic alteration in the target gene, which is the likely mechanism for the higher MICs than with other Candida species. In a clinical trial the outcome for anidulafungin with C. parapsilosis was not statistically different from other species (23 patients: 64% success for anidulafungin vs. 83% for fluconazole, P = 0.37).11 The PK/PD target is lower for C. parapsilosis than for other Candida species.12 This may be due to C. parapsilosis being less virulent than C. albicans and C. glabrata.13 Echinocandins are generally not recommended as first-line agents for serious infections caused by C. parapsilosis. However, echinocandins can be used if the patient is clinically stable and/or has responded to initial echinocandin therapy, and/or if the use of other agents is not appropriate.14 –16 Therefore, the clinical breakpoints have been revised to categorise the entire wild-type population of C. parapsilosis as intermediate (Table 1). EUCAST breakpoints for fluconazole and Candida species were established in 2007.17 A significant number of infections involve C. glabrata, which exhibits fluconazole MICs of 2–32 mg l 1 when without resistance mechanisms.18–20 Any reasonable susceptibility breakpoint based on PK data would divide wild-type C. glabrata, obviating reproducible susceptibility testing. Therefore, EUCAST-AFST at that time refrained from
Table 1 Candida species-specific micafungin, anidulafungin and fluconazole EUCAST ECOFFs and breakpoints. Species-related ECOFFs and breakpoints2(mg/l) Micafungin
Anidulafungin Breakpoint
Species C. C. C. C. C.
1
albicans glabrata krusei parapsilosis tropicalis
Fluconazole Breakpoint
Breakpoint
ECOFF
S≤
R>
ECOFF
S≤
R>
ECOFF
S≤
R>
0.016 0.03 0.25 2 0.06
0.016 0.03 IE3 0.002 IE3
0.016 0.03 IE3 2 IE3
0.03 0.06 0.06 4 0.06
0.03 0.06 0.06 0.002 0.06
0.03 0.06 0.06 4 0.06
1 32 128 2 2
2 0.002 – 2 2
4 32 – 4 4
1
There is insufficient evidence (IE) to set non-species–related breakpoints.
2
To simplify the EUCAST tables, the intermediate category is not listed. It is readily interpreted as the values between the S and the R breakpoint. For example, for MIC breakpoints listed as S ≤ 2 and R > 4, the intermediate category is 4 (technically >2–4). For MIC breakpoints listed as S ≤ 0.002 and R > 4, the intermediate category includes the entire wild-type population, and for breakpoints listed as S ≤ 0.016 and R > 0.016, there is no intermediate category. There is insufficient clinical evidence to set breakpoints for other species than those listed. 3
The MIC values are in general higher than those for C. albicans. Whether this translates into a poorer clinical response remains unknown. There is IE to set breakpoints for these species. “–” indicates that susceptibility testing is not recommended as the species is a poor target for therapy with the drug. Isolates may be reported as R without prior testing.
378
© 2014 Blackwell Verlag GmbH Mycoses, 2014, 57, 377–379
EUCAST breakpoints for Candida
giving C. glabrata breakpoints for fluconazole. As there are, however, few agents suitable for the treatment of urinary tract infections and mucosal infections managed in the primary health care setting, fluconazole may be a suitable choice provided the infecting strain has no acquired resistance mechanisms. In such cases where fluconazole is the only available antifungal agent for treating C. glabrata infections, the use of fluconazole at higher dosage may be required. Therefore, the clinical breakpoints have been revised to categorise the entire wild-type population of C. glabrata as intermediate (Table 1), thereby facilitating discrimination between wild-type and isolates with elevated MICs and acquired resistance mechanisms.
Acknowledgment
2
3
4
5
6
7
William W. Hope is supported by a National Institute of Health Clinician Scientist Award.
8
Disclosures
9
The authors do not have any potential conflicts of interests related particularly to this study. MCA: has received research grants and acted as speaker for Astellas, Gilead, MSD and Pfizer, and been a consultant for Gilead, MSD and Pcovery. MCE: has received grant support from Astellas Pharma, bioMerieux, Gilead Sciences, Merck Sharp and Dohme, Pfizer, Schering Plough, Soria Melguizo SA, Ferrer International, the European Union, the ALBAN programme, the Spanish Agency for International Cooperation, the Spanish Ministry of Culture and Education, The Spanish Health Research Fund, The Instituto de Salud Carlos III, The Ramon Areces Foundation and The Mutua Madrile~ na Foundation. He has been an advisor/consultant to the Panamerican Health Organization, Gilead Sciences, Merck Sharp and Dohme, Pfizer and Schering Plough. He has been paid for talks on behalf of Gilead Sciences, Merck Sharp and Dohme, Pfizer and Schering Plough. CLF: has research grants, consultant and/or speakers bureau, for Pfizer, Astellas, Gilead and Merck. WWH: has research grants, consultant and/or speakers bureau, for Pfizer, Astellas, Gilead, Merck, Vectura, F2G. CBM: has received travel grants from Astellas, been paid for talks on behalf of Pfizer and has received grant support from Pfizer.
References 1
de Wet NT, Bester AJ, Viljoen JJ et al. A randomized, double blind, comparative trial of micafungin (FK463) vs. fluconazole for the
© 2014 Blackwell Verlag GmbH Mycoses, 2014, 57, 377–379
10
11 12
13
14
15
16
17
18
19
20
treatment of oesophageal candidiasis. Aliment Pharmacol Ther 2005; 21: 899–907. Kuse ER, Chetchotisakd P, da Cunha CA et al. Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial. Lancet 2007; 369: 1519– 27. Pappas PG, Rotstein CM, Betts RF et al. Micafungin versus caspofungin for treatment of candidemia and other forms of invasive candidiasis. Clin Infect Dis 2007; 45: 883–93. Queiroz-Telles F, Berezin E, Leverger G et al. Micafungin versus liposomal amphotericin B for pediatric patients with invasive candidiasis: substudy of a randomized double-blind trial. Pediatr Infect Dis J 2008; 27: 820–6. Pfeiffer CD, Garcia-Effron G, Zaas AK, Perfect JR, Perlin DS, Alexander BD. Breakthrough invasive candidiasis in patients on micafungin. J Clin Microbiol 2010; 48: 2373–80. 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 2011; 55: 3075–83. Howard SJ, Livermore J, Sharp A et al. Pharmacodynamics of echinocandins against Candida glabrata: requirement for dosage escalation to achieve maximal antifungal activity in neutropenic hosts. Antimicrob Agents Chemother 2011; 55: 4880–7. Arendrup MC, Perlin DS, Jensen RH, Howard SJ, Goodwin J, Hope W. Differential in vivo activity of anidulafungin, caspofungin and micafungin against C. glabrata with and without FKS resistance mutations. Antimicrob Agents Chemother 2012; 56: 2435–42. Andes D, Ambrose PG, Hammel JP et al. Use of pharmacokineticpharmacodynamic analyses to optimize therapy with the systemic antifungal micafungin for invasive candidiasis or candidemia. Antimicrob Agents Chemother 2011; 55: 2113–21. Arendrup MC, Rodriguez-Tudela JL, Lass-Fl€ orl C et al. EUCAST technical note on anidulafungin. Clin Microbiol Infect 2011; 17: E18–E20. Reboli AC, Rotstein C, Pappas PG et al. Anidulafungin versus fluconazole for invasive candidiasis. N Engl J Med 2007; 356: 2472–82. Andes D, Diekema DJ, Pfaller MA, Bohrmuller J, Marchillo K, Lepak A. In vivo comparison of the pharmacodynamic targets for echinocandin drugs against Candida species. Antimicrob Agents Chemother 2010; 54: 2497–506. Arendrup M, Horn T, Frimodt-Moller N. In vivo pathogenicity of eight medically relevant Candida species in an animal model. Infection 2002; 30: 286–91. Cornely OA, Bassetti M, Calandra T et al. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect 2012; 18: 19–37. Ullmann AJ, Akova M, Herbrecht R et al. 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 2012; 18: 53–67. Pappas PG, Kauffman CA, Andes D et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 2009; 48: 503–35. The European Committee on Antimicrobial Susceptibility TestingSubcommittee on AntifungalSusceptibility Testing (EUCAST-AFST). EUCAST Technical Note on fluconazole. Clin Microbiol Infect 2008; 14: 193–5. Arendrup MC; The Danish Fungaemia Study Group. National Surveillance of Fungemia in Denmark 2010–11. ICAAC 2012; abstract M318. Lee I, Fishman NO, Zaoutis TE et al. Risk factors for fluconazole-resistant Candida glabrata bloodstream infections. Arch Intern Med 2009; 169: 379–83. Tsai HF, Sammons LR, Zhang X et al. Microarray and molecular analyses of the azole resistance mechanism in Candida glabrata oropharyngeal isolates. Antimicrob Agents Chemother 2010; 54: 3308–17.
379
