Susceptibility to echinocandins of Candida spp. strains isolated in Italy assessed by European Committee for Antimicrobial Susceptibility Testing and Clinical Laboratory Standards Institute broth microdilution methods

BMC Microbiology

Giuseppina Caggiano²  Antonio Rosato¹  Stella Balbino²  Roberta Iatta⁴  Osvalda De Giglio²  Domenico Martinelli³  Caterina Coretti²  Grazia Lovero²  Maria Teresa Montagna² 

[1] Department of Pharmacy-Drug Sciences, University of Bari Aldo Moro, Campus-Via Orabona, 4, Bari, Italy;Department of Biomedical Science and Human Oncology, Hygiene Section, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, Bari, Italy;Department of Medical and Surgical Sciences, Hygiene Section, University of Foggia, Via Gramsci 89-91, Foggia, 71100, Italy;Department of Veterinary Medicine, University of Bari Aldo Moro, Str. Prov. per Casamassima Km 3, Valenzano, Bari, Italy

关键词: Antifungal;    Micafungin;    Caspofungin;    Anidulafungin;    CLSI;    EUCAST;    Candida spp.;   

Others  :  1212037
DOI  :  10.1186/s12866-015-0442-4

 received in 2015-01-09, accepted in 2015-05-11,  发布年份 2015

【 摘 要 】

Background

The echinocandins are recommended as first-line therapy for Candida species infections, but drug resistance, especially among Candida glabrata, is becoming more frequent. We investigated the antifungal susceptibility of anidulafungin, caspofungin, and micafungin against 584 isolates of Candida spp. (bloodstream, other sterile sites) collected from patients admitted to an Italian university hospital between 2000 and 2013. The susceptibility was evaluated using the broth microdilution method according to both the European Committee for Antimicrobial Susceptibility Testing (EUCAST EDef 7.2) and the Clinical Laboratory Standards Institute (CLSI M27-A3). The echinocandin susceptibilities were assessed on the basis of the species-specific clinical breakpoints proposed by the EUCAST version 6.1 and CLSI M27-S4 documents. The two methods were comparable by assessing essential agreement (EA), categorical agreement (CA), and Spearman’s correlation analysis (rho, r).

Results

The modal minimum inhibitory concentrations (MICs; μg ⋅ mL ⁻¹) values by both methods (EUCAST/CLSI) for anidulafungin, caspofungin, and micafungin for each species were, respectively, as follows: C. albicans, 0.03/0.12, 0.016/0.5, and 0.016/0.008; C. parapsilosis complex, 2/1, 2/2, and 2/1; C. tropicalis, 0.06/0.12, 0.06/0.12, and 0.06/0.12; C. glabrata complex, 0.03/0.25, 0.06/0.12, and 0.03/0.06; C. guilliermondii, 2/1, 2/2, and 2/2; and C. krusei, 0.06/0.12, 0.12/0.5, and 0.06/0.12. The overall resistance rates for EUCAST/CLSI were as follows: anidulafungin, 2.5/0.9 %; caspofungin, breakpoint not available/3.8 %; micafungin, 2.7/1.5 %.

Candida glabrata complex was the least susceptible to all three echinocandins, and the percentages of resistant isolates by EUCAST/CLSI were as follows: anidulafungin, 13.5/2.7 %; caspofungin, breakpoint not available/16.2 %; micafungin, 18.9/13.5 %. The overall EA was 93 % for micafungin, 92 % for anidulafungin, and 90 % for caspofungin. The CA was >90 % for all organism-drug combinations with the exception of C. glabrata and anidulafungin (89 %). Spearman’s rho for EUCAST/CLSI was 0.89 (p < 0.001) for caspofungin, 0.85 (p < 0.001) for anidulafungin, and 0.83 for micafungin (p < 0.001).

Conclusions

Independent of the procedure applied, no alarming resistance to the tested agents was found, although a reduced susceptibility was detected for C. glabrata complex. The EUCAST and CLSI methods produce similar MICs, indicating that using one method or the other should not result in susceptibilities different enough to affect treatment decisions.

【 授权许可】

   
2015 Montagna et al.; licensee BioMed Central.

【 参考文献 】

• [1]Perlin DS. Current perspectives on echinocandin class drugs. Future Microbiol. 2011; 6:441-57.
• [2]Pfaller MA, Diekema DJ, Andes D, Arendrup MC, Brown SD, Lockhart SR 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. 2011; 14:164-76.
• [3]Spreghini E, Orlando F, Sanguinetti M, Posteraro B, Giannini D, Manso E et al.. Comparative effects of micafungin, caspofungin, and anidulafungin against a difficult-to-treat fungal opportunistic pathogen, Candida glabrata. Antimicrob Agents Chemother. 2012; 56:1215-22.
• [4]Spreghini E, Orlando F, Tavanti A, Senesi S, Giannini D, Manso E et al.. In vitro and in vivo effects of echinocandins against Candida parapsilosis sensu stricto, Candida orthopsilosis and Candida metapsilosis. J Antimicrob Chemother. 2012; 67:2195-202.
• [5]Perlin DS. Echinocandin resistance, susceptibility testing and prophylaxis: implications for patient management. Drugs. 2014; 74:1573-85.
• [6]Pappas PG, Kauffman CA, Andes D, Benjamin DK, Calandra TF, Edwards JE et al.. Clinical practice guidelines for the managementof candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. 2009; 48:503-35.
• [7]Ullmann AJ, Akova M, Herbrecht R, Viscoli C, Arendrup MC, Arikan-Akdagli S et al.. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: adults with haematological malignancies and after haematopoietic stemcell transplantation (HCT). Clin Microbiol Infect. 2012; 18 Suppl 7:53-67.
• [8]Leroux S, Ullmann AJ. Management and diagnostic guidelines for fungal diseases in infectious diseases and clinical microbiology: critical appraisal. Clin Microbiol Infect. 2013; 19:1115-21.
• [9]Reference method for broth dilution antifungal susceptibility testing of yeasts; third edition, M27-A3. CLSI, Wayne, PA, USA; 2008.
• [10]Reference method for broth dilution antifungal susceptibility testing of yeasts; fourth informational supplement, M27-S4. CLSI, Wayne, PA, USA; 2012.
• [11]EUCAST definitive document EDef 7.1: method for the determination of broth dilution MICs of antifungal agents for fermentative yeasts. Clin Microbiol Infect. 2008; 14:398-405.
• [12]Arendrup MC, Cuenca-Estrella M, Lass-Florl C, Hope WW. EUCAST-AFST. EUCAST technical note on the EUCAST definitive document EDef 7.2: method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for yeasts EDef 7.2 (EUCAST-AFST). Clin Microbiol Infect. 2012; 18:E246-7.
• [13]Arendrup MC, Cuenca-Estrella M, Lass-Flörl C, Hope WW. EUCAST technical note on Candida and micafungin, anidulafungin and fluconazole. Mycoses. 2014; 57:377-9.
• [14]Tortorano AM, Prigitano A, Lazzarini C, Passera M, Deiana ML, Cavinato S et al.. A 1-year prospective survey of candidemia in Italy and changing epidemiology over one decade. Infection. 2013; 41:655-62.
• [15]Beyda ND, Lewis RE, Garey KW. Echinocandin resistance in Candida species: mechanisms of reduced susceptibility and therapeutic approaches. Ann Pharmacother. 2012; 46:1086-96.
• [16]Faria-Ramos I, Neves-Maia J, Ricardo E, Santos-Antunes J, Silva AT, Costa-de-Oliveira S et al.. Species distribution and in vitro antifungal susceptibility profiles of yeast isolates from invasive infections during a Portuguese multicenter survey. Eur J Clin Microbiol Infect Dis. 2014; 33:2241-7.
• [17]Guinea J, Zaragoza O, Escribano P, Martín-Mazuelos E, Pemán J, Sánchez-Reus F 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. 2014; 58:1529-37.
• [18]Matsumoto E, Boyken L, Tendolkar S, McDanel J, Castanheira M, Pfaller M et al.. Candidemia surveillance in Iowa: emergence of echinocandin resistance. Diagn Microbiol Infect Dis. 2014; 79:205-8.
• [19]Pham CD, Iqbal N, Bolden CB, Kuykendall RJ, Harrison LH, Farley MM et al.. Role of FKS Mutations in Candida glabrata: MIC values, echinocandin resistance, and multidrug resistance. Antimicrob Agents Chemother. 2014; 58:4690-6.
• [20]Espinel-Ingroff A, Arendrup MC, Pfaller MA, Bonfietti LX, Bustamante B, Canton E et al.. Interlabo-ratory variability of caspofungin MICs for Candida spp. using CLSI and EUCAST methods: should the clinical laboratory be testing this agent? Antimicrob Agents Chemother. 2013; 57:5836-42.
• [21]Arendrup MC, Perlin DS. Echinocandin resistance: an emerging clinical problem? Curr Opin Infect Dis. 2014; 27:484-92.
• [22]Garcia-Effron G, Katiyar SK, Park S, Edlind TD, Perlin DS. A naturally occurring proline-to-alanine amino acid change in Fks1p in Candida parapsilosis, Candida orthopsilosis, and Candida metapsilosis accounts for reduced echinocandin susceptibility. Antimicrob Agents Chemother. 2008; 52:2305-12.
• [23]Pfaller MA, Castanheira M, Lockhart SR, Ahlquist AM, Messer SA, Jones RN. Frequency of decreased susceptibility and resistance to echinocandins among fluconazole-resistant bloodstream isolates of Candida glabrata: results from the SENTRY Antimicrobial Surveillance Program (2006–2010) and the Centers for Disease Control and Prevention Population-Based Surveillance (2008–2010). J Clin Microbiol. 2012; 50:1199-203.
• [24]Alexander BD, Johnson MD, Pfeiffer CD, Jiménez-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.
• [25]Thompson GR, Wiederhold NP, Vallor AC, Villareal NC, Lewis JS, Patterson TF. Development of caspofungin resistance following prolonged therapy for invasive candidiasis secondary to Candida glabrata infection. Antimicrob Agents Chemother. 2008; 52:3783-5.
• [26]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.
• [27]Cleary JD, Garcia-Effron G, Chapman SW, Perlin DS. Reduced Candida glabrata susceptibility secondary to an FKS1 mutation developed during candidemia treatment. Antimicrob Agents Chemother. 2008; 52:2263-5.
• [28]Cuenca-Estrella M, Díaz-Guerra TM, Mellado E, Rodríguez-Tudela JL. Influence of glucose supplementation and inoculum size on growth kinetics and antifungal susceptibility testing of Candida spp. J Clin Microbiol. 2001; 39:525-32.
• [29]Pfaller MA, Castanheira M, Diekema DJ, Messer SA, Moet GJ, Jones RN. Comparison of European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Etest methods with the CLSI broth microdilution method for echinocandin susceptibility testing of Candida species. J Clin Microbiol. 2010; 48:1592-9.
• [30]Pfaller MA, Castanheira M, Messer SA, Rhomberg PR, Jones RN. Comparison of EUCAST and CLSI broth microdilution methods for the susceptibility testing of 10 systemically active antifungal agents when tested against Candida spp. Diagn Microbiol Infect Dis. 2014; 79:198-204.
• [31]Arendrup MC, Cuenca-Estrella M, Lass-Flörl 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. 2013; 16:81-95.