Posttreatment Antifungal Resistance among Colonizing Candida Isolates in Candidemia Patients: Results from a Systematic Multicenter Study
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The prevalence of intrinsic and acquired resistance among colonizing Candida isolates from patients after candidemia was investigated systematically in a 1-year nationwide study. Patients were treated at the discretion of the treating physician. Oral swabs were obtained after treatment. Species distributions and MIC data were investigated for blood and posttreatment oral isolates from patients exposed to either azoles or echinocandins for <7 or ≥ 7 days. Species identification was confirmed using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and internal transcribed spacer (ITS) sequencing, susceptibility was examined by EUCAST EDef 7.2 methodology, echinocandin resistance was examined by FKS sequencing, and genetic relatedness was examined by multilocus sequence typing (MLST). One hundred ninety-three episodes provided 205 blood and 220 oral isolates. MLST analysis demonstrated a genetic relationship for 90% of all paired blood and oral isolates. Patients exposed to azoles for ≥ 7 days (n = 93) had a significantly larger proportion of species intrinsically less susceptible to azoles (particularly Candida glabrata) among oral isolates than among initial blood isolates (36.6% versus 12.9%; P < 0.001). A similar shift toward species less susceptible to echinocandins among 85 patients exposed to echinocandins for ≥ 7 days was not observed (4.8% of oral isolates versus 3.2% of blood isolates; P > 0.5). Acquired resistance in Candida albicans was rare (<5%). However, acquired resistance to fluconazole (29.4%; P < 0.05) and anidulafungin (21.6%; P < 0.05) was common in C. glabrata isolates from patients exposed to either azoles or echinocandins. Our findings suggest that the colonizing mucosal microbiota may be an unrecognized reservoir of resistant Candida species, especially C. glabrata, following treatment for candidemia. The resistance rates were high, raising concern in general for patients exposed to antifungal drugs.
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Prolonged administration of antifungal drugs for treatment and prevention is the primary cause of the emergence of resistant strains.
“Moreover, Jensen et al. [82] supported the view that prolonged administration of antifungal drugs for treatment and prevention is the primary cause of the emergence of resistant strains.”
From Candida glabrata: pathogenicity and resistance mechanisms for adaptation and survival (2021) · cites this paper as [82]
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Schoch, C. L., Seifert, K. A., Huhndorf, S. M., Robert, V., Spouge, J. L., Lévesque, C. A., Chen, W., Bolchacova, E., Voigt, K., Crous, P. W., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1117018109 · Cited by 5,176 · see citing works
Silva, S., Negri, M., Henriques, M., Oliveira, R., Williams, D. W., & Azeredo, J. (2012) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2011.00278.x · Cited by 969 · see citing works
Alexander, B. D., Johnson, M. D., Pfeiffer, C. D., Jiménez-Ortigosa, C., Catania, J., Booker, R., Castanheira, M., Messer, S. A., Perlin, D. S., & Pfaller, M. A. (2013) · Clinical Infectious Diseases · doi:10.1093/cid/cit136 · Cited by 778 · see citing works
Trick, W. E., Fridkin, S. K., Edwards, J. R., Hajjeh, R. A., Gaynes, R. P., & Hospitals, T. N. N. I. S. S. (2002) · Clinical Infectious Diseases · doi:10.1086/342300 · Cited by 660 · see citing works
Arendrup, M. C., Cuenca-Estrella, M., Lass-Flörl, C., & Hope, W. (2012) · Clinical Microbiology and Infection · doi:10.1111/j.1469-0691.2012.03880.x · Cited by 451 · see citing works
Self-citationLortholary, O., Desnos-Ollivier, M., Sitbon, K., Fontanet, A., Bretagne, S., & Dromer, F. (2011) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01128-10 · Cited by 362 · see citing works
The Ins and Outs of DNA Fingerprinting the Infectious Fungi
Soll, D. R. (2000) · Clinical Microbiology Reviews · doi:10.1128/cmr.13.2.332-370.2000 · Cited by 348 · see citing works
The changing epidemiology of healthcare-associated candidemia over three decades
Diekema, D., Arbefeville, S., Boyken, L., Kroeger, J., & Pfaller, M. (2012) · Diagnostic Microbiology and Infectious Disease · doi:10.1016/j.diagmicrobio.2012.02.001 · Cited by 309 · see citing works
Echinocandin resistance: an emerging clinical problem?
Arendrup, M. C., & Perlin, D. S. (2014) · Current Opinion in Infectious Diseases · doi:10.1097/qco.0000000000000111 · Cited by 299 · see citing works
Self-citationLockhart, S. R., Iqbal, N., Cleveland, A. A., Farley, M. M., Harrison, L. H., Bolden, C. B., Baughman, W., Stein, B., Hollick, R., Park, B. J., et al. (2012) · Journal of Clinical Microbiology · doi:10.1128/jcm.01283-12 · Cited by 299 · see citing works
Sipsas, N. V., Lewis, R. E., Tarrand, J., Hachem, R., Rolston, K. V., Raad, I. I., & Kontoyiannis, D. P. (2009) · Cancer · doi:10.1002/cncr.24507 · Cited by 269 · see citing works
Candida glabrata: A review of its features and resistance
Rodrigues, C. F., Silva, S., & Henriques, M. (2014) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/s10096-013-2009-3 · Cited by 268 · see citing works
Pfaller, M. A., Moet, G. J., Messer, S. A., Jones, R. N., & Castanheira, M. (2011) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01079-10 · Cited by 238 · see citing works
Bougnoux, M., Morand, S., & d'Enfert, C. (2002) · Journal of Clinical Microbiology · doi:10.1128/jcm.40.4.1290-1297.2002 · Cited by 216 · see citing works
Arendrup, M. C., Dzajic, E., Jensen, R. H., Johansen, H. K., Kjaldgaard, P., Knudsen, J. D., Kristensen, L., Leitz, C., Lemming, L. E., Nielsen, L., et al. (2013) · Clinical Microbiology and Infection · doi:10.1111/1469-0691.12212 · Cited by 206 · see citing works
Self-citationMultilocus Sequence Typing of Candidaglabrata Reveals Geographically EnrichedClades
Dodgson, A. R., Pujol, C., Denning, D. W., Soll, D. R., & Fox, A. J. (2003) · Journal of Clinical Microbiology · doi:10.1128/jcm.41.12.5709-5717.2003 · Cited by 191 · see citing works
Diagnostic Issues, Clinical Characteristics, and Outcomes for Patients with Fungemia
Arendrup, M. C., Sulim, S., Holm, A., Nielsen, L. B., Nielsen, S. D., Knudsen, J. D., Drenck, N. E., Christensen, J. J., & Johansen, H. K. (2011) · Journal of Clinical Microbiology · doi:10.1128/jcm.00179-11 · Cited by 177 · see citing works
Self-citationOne year prospective survey of Candida bloodstream infections in Scotland
Odds, F. C., Hanson, M. F., Davidson, A. D., Jacobsen, M. D., Wright, P., Whyte, J. A., Gow, N. A. R., & Jones, B. L. (2007) · Journal of Medical Microbiology · doi:10.1099/jmm.0.47239-0 · Cited by 176 · see citing works
Update on Antifungal Drug Resistance
Perlin, D. S., Shor, E., & Zhao, Y. (2015) · Current Clinical Microbiology Reports · doi:10.1007/s40588-015-0015-1 · Cited by 174 · see citing works
Shields, R. K., Nguyen, M. H., Press, E. G., Kwa, A. L., Cheng, S., Du, C., & Clancy, C. J. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00027-12 · Cited by 171 · see citing works
Drug-Resistant<i>Candida glabrata</i>Infection in Cancer Patients
Farmakiotis, D., Tarrand, J. J., & Kontoyiannis, D. P. (2014) · Emerging Infectious Diseases · doi:10.3201/eid2011.140685 · Cited by 152 · see citing works
Multilocus Sequence Typing for Differentiation of Strains of Candida tropicalis
Tavanti, A., Davidson, A. D., Johnson, E. M., Maiden, M. C. J., Shaw, D. J., Gow, N. A. R., & Odds, F. C. (2005) · Journal of Clinical Microbiology · doi:10.1128/jcm.43.11.5593-5600.2005 · Cited by 148 · see citing works
Clinical Significance of Azole Antifungal Drug Cross-Resistance in Candida glabrata
Panackal, A. A., Gribskov, J. L., Staab, J. F., Kirby, K. A., Rinaldi, M. G., & Marr, K. A. (2006) · Journal of Clinical Microbiology · doi:10.1128/jcm.44.5.1740-1743.2006 · Cited by 144 · see citing works
Increasing incidence of Candida parapsilosis candidemia with caspofungin usage.
Forrest, G. N., Weekes, E., & Johnson, J. K. (2008) · Journal of Infection · doi:10.1016/j.jinf.2007.10.014 · Cited by 144 · see citing works
Multilocus Sequence Typing of Pathogenic Candida Species
Odds, F. C., & Jacobsen, M. D. (2008) · Eukaryotic Cell · doi:10.1128/ec.00062-08 · Cited by 139 · see citing works
Lockhart, S. R., Fritch, J. J., Meier, A., Schröppel, K., Srikantha, T., Galask, R. P., & Soll, D. R. (1995) · Journal of Clinical Microbiology · doi:10.1128/jcm.33.6.1501-1509.1995 · Cited by 137 · see citing works
Arendrup, M. C., Cuenca-Estrella, M., Lass-Flörl, C., & Hope, W. W. (2013) · Drug Resistance Updates · doi:10.1016/j.drup.2014.01.001 · Cited by 129 · see citing works
Self-citationAbdominal candidiasis is a hidden reservoir of echinocandin resistance
Shields, R. K., Nguyen, M. H., Press, E. G., & Clancy, C. J. (2014) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.04134-14 · Cited by 118 · see citing works
Arendrup, M. C., Perlin, D. S., Jensen, R. H., Howard, S. J., Goodwin, J., & Hope, W. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.06369-11 · Cited by 117 · see citing works
Self-citationA 1-year prospective survey of candidemia in Italy and changing epidemiology over one decade
Tortorano, A. M., Prigitano, A., Lazzarini, C., Passera, M., Deiana, M. L., Cavinato, S., De Luca, C., Grancini, A., Lo Cascio, G., Ossi, C., et al. (2013) · Infection · doi:10.1007/s15010-013-0455-6 · Cited by 110 · see citing works
Jensen, R. H., Astvad, K. M. T., Silva, L. V., Sanglard, D., Jørgensen, R., Nielsen, K. F., Mathiasen, E. G., Doroudian, G., Perlin, D. S., & Arendrup, M. C. (2015) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkv140 · Cited by 95 · see citing works
Self-citationTwenty-two years of candidaemia surveillance: results from a Norwegian national study
Hesstvedt, L., Gaustad, P., Andersen, C. T., Haarr, E., Hannula, R., Haukland, H. H., Hermansen, N. O., Larssen, K. W., Mylvaganam, H., Ranheim, T. E., et al. (2015) · Clinical Microbiology and Infection · doi:10.1016/j.cmi.2015.06.008 · Cited by 94 · see citing works
Impact of Antifungal Prophylaxis on Colonization and Azole Susceptibility of Candida Species
Mann, P. A., McNicholas, P. M., Chau, A. S., Patel, R. J., Mendrick, C. A., Ullmann, A. J., Cornely, O. A., Patino, H., & Black, T. A. (2009) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01031-09 · Cited by 81 · see citing works
Jacobsen, M. D., Gow, N. A. R., Maiden, M. C. J., Shaw, D. J., & Odds, F. C. (2006) · Journal of Clinical Microbiology · doi:10.1128/jcm.01549-06 · Cited by 78 · see citing works
Lau, A. F., Kabir, M., Chen, S. C. ‐., Playford, E. G., Marriott, D. J. E., Jones, M., Lipman, J., McBryde, E. S., Gottlieb, T., Cheung, W., et al. (2015) · Journal of Clinical Microbiology · doi:10.1128/jcm.03239-14 · Cited by 74 · see citing works
Multilocus Sequence Typing for Analyses of Clonality of Candida albicans Strains in Taiwan
Chen, K.-W., Chen, Y., Lo, H., Odds, F. C., Wang, T.-H., Lin, C.-Y., & Li, S.-Y. (2006) · Journal of Clinical Microbiology · doi:10.1128/jcm.00320-06 · Cited by 64 · see citing works
McManus, B. A., Coleman, D. C., Moran, G. P., Pinjon, E., Diogo, D., Bougnoux, M., Borecká, S., Bujdáková, H., Murphy, P. G., d’Enfert, C., et al. (2007) · Journal of Clinical Microbiology · doi:10.1128/jcm.01574-07 · Cited by 62 · see citing works
Shah, D. N., Yau, R. C. H., Lasco, T. M., Weston, J. S., Salazar, M. J., Palmer, H. R., & Garey, K. W. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00019-12 · Cited by 59 · see citing works
Lott, T. J., Frade, J. P., & Lockhart, S. R. (2010) · Eukaryotic Cell · doi:10.1128/ec.00002-10 · Cited by 58 · see citing works
Diab‐Elschahawi, M., Forstner, C., Hagen, F., Meis, J. F. G. M., Lassnigg, A. M., Presterl, E., & Klaassen, C. H. W. (2012) · Journal of Clinical Microbiology · doi:10.1128/jcm.01179-12 · Cited by 57 · see citing works
Shields, R. K., Nguyen, M. H., Press, E. G., Updike, C. L., & Clancy, C. J. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01451-13 · Cited by 56 · see citing works
Jensen, R. H., Johansen, H. K., & Arendrup, M. C. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01193-12 · Cited by 47 · see citing works
Self-citationBlanchard, É., Lortholary, O., Sitbon, K., Desnos‐Ollivier, M., Dromer, F., Guillemot, D., & the French Mycosis Study Group (2011) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00690-11 · Cited by 47 · see citing works
<scp>EUCAST</scp> Technical Note on <i>Candida</i> and micafungin, anidulafungin and fluconazole
Cavling Arendrup, M., Cuenca‐Estrella, M., Lass‐Flörl, C., Hope, W. W., & The European Committee on Antimicrobial Susceptibility Testing – Subcommittee on Antifungal Susceptibility Testing (EUCAST‐AFST) (2014) · Mycoses · doi:10.1111/myc.12170 · Cited by 43 · see citing works
Colonization by Candida in children with cancer, children with cystic fibrosis, and healthy controls
Gammelsrud, K. W., Sandven, P., Høiby, E. A., et al. (2011) · Clinical Microbiology and Infection · doi:10.1111/j.1469-0691.2011.03528.x · Cited by 38 · see citing works
Angoulvant, A., Bourget, M., Brisse, S., Stockman-Pannier, C., Diancourt, L., François, N., Rimek, D., Fairhead, C., Poulain, D., & Hennequin, C. (2010) · Journal of Clinical Microbiology · doi:10.1128/jcm.02140-09 · Cited by 38 · see citing works
Zhang, L., Zhou, S., Pan, A., Li, J., & Liu, B. (2014) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2014.12.033 · Cited by 37 · see citing works
Hattori, H., Iwata, T., Nakagawa, Y., Kawamoto, F., Tomita, Y., Kikuchi, A., & Kanbe, T. (2006) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2005.12.003 · Cited by 28 · see citing works
Multilocus sequence typing of oenological Saccharomyces cerevisiae strains
Múñoz, R., Gómez, A., Robles, V., Rodriguez‐Rodriguez, P., Cebollero, E., Tabera, L., Carrascosa, A. V., & Gonzalez, R. (2009) · Food Microbiology · doi:10.1016/j.fm.2009.05.009 · Cited by 28 · see citing works
Lott, T. J., Frade, J. P., Lyon, G. M., Iqbal, N. J., & Lockhart, S. R. (2012) · Medical Mycology · doi:10.3109/13693786.2011.592153 · Cited by 28 · see citing works
Typing of Candida isolates from patients with invasive infection and concomitant colonization
Brillowska‐Dąbrowska, A., Bergmann, O. J., Jensen, I. M., Jarløv, J. O., & Arendrup, M. C. (2009) · Scandinavian Journal of Infectious Diseases · doi:10.3109/00365540903348336 · Cited by 21 · see citing works
Self-citationMolecular Fingerprints to IdentifyCandidaSpecies
Spampinato, C. P., & Leonardi, D. (2013) · BioMed Research International · doi:10.1155/2013/923742 · Cited by 16 · see citing works
Gammelsrud, K. W., Lindstad, B. L., Gaustad, P., Ingebretsen, A., Høiby, E. A., Brandtzaeg, P., & Sandven, P. (2012) · Medical Mycology · doi:10.3109/13693786.2012.675088 · Cited by 12 · see citing works
Long‐term oropharyngeal colonization by C. albicans in children with cystic fibrosis
Karaman, M., Fırıncı, F., Karaman, Ö., et al. (2013) · Yeast · doi:10.1002/yea.2977 · Cited by 5 · see citing works
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Self-citationTabah, A., Bassetti, M., Kollef, M. H., Zahar, J.-R., Paiva, J.-A., Timsit, J.-F., Roberts, J. A., Schouten, J., Giamarellou, H., Rello, J., et al. (2020) · Intensive Care Medicine · doi:10.1007/s00134-019-05866-w · Cited by 191 · see citing works
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Hassan, Y., Chew, S. Y., & Than, L. T. L. (2021) · Journal of Fungi · doi:10.3390/jof7080667 · Cited by 170 · see citing works
Astvad, K. M. T., Johansen, H. K., Røder, B. L., Rosenvinge, F. S., Knudsen, J. D., Lemming, L., Schønheyder, H. C., Hare, R. K., Kristensen, L., Nielsen, L., et al. (2018) · Journal of Clinical Microbiology · doi:10.1128/jcm.01564-17 · Cited by 125 · see citing works
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- Authors
- Jensen, R. H., Johansen, H. K., Søes, L. M., Lemming, L. E., Rosenvinge, F. S., Nielsen, L., Olesen, B., Kristensen, L., Dzajic, E., Astvad, K. M. T., & Arendrup, M. C.
- Affiliations
- Statens Serum Institut (DK)
- Copenhagen University Hospital (DK)
- Hvidovre Hospital (DK)
- Aarhus University Hospital (DK)
- Odense University Hospital (DK)
- Herlev Hospital (DK)
- Nordsjællands Hospital (DK)
- Regionshospitalet Viborg (DK)
- Hospital South West Jutland (DK)
- ORCID
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2016-03
- Volume
- 60
- Issue
- 3
- Pages
- 1500-1508
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC4775986
- OpenAlex
- W2216779599
- Cited by
- 77
- References
- 54
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 14 · 2023: 5 · 2022: 7 · 2021: 9 · 2020: 5 · 2019: 4 · 2018: 9 · 2017: 11 · 2016: 5
- FWCI
- 6.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion, other-oa)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Gilead Sciences (IX-DK-131-0286)
- European Society of Clinical Microbiology and Infectious Diseases (Research Grant 2013)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Yeasts and Rust Fungi Studies
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Keywords
- candidemia, antifungal resistance, Candida colonization, Candida glabrata, Candida albicans, azole resistance, echinocandin resistance, fluconazole resistance, mucosal microbiota, antifungal susceptibility, Candida species distribution
- MeSH terms
- Aged, Antifungal Agents, Candida, Denmark, Female, Humans, Male, Microbial Sensitivity Tests, Fluconazole, Drug Resistance, Fungal, Candidemia, Multilocus Sequence Typing
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