Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Implications of the EUCAST Trailing Phenomenon in Candida tropicalis for the In Vivo Susceptibility in Invertebrate and Murine Models

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. In-vivo gentamicin susceptibility test for prevention of bacterial biofilms in bone tissue and on implants

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. APX001A In Vitro Activity against Contemporary Blood Isolates and Candida auris Determined by the EUCAST Reference Method

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Population Pharmacokinetics of the Antimalarial Amodiaquine: a Pooled Analysis To Optimize Dosing

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Erratum for Hertz et al., "Antibiotic Selection of Escherichia coli Sequence Type 131 in a Mouse Intestinal Colonization Model"

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Would you like to purchase a rodent with dermatophytes?

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Pediatric Candidemia Epidemiology and Morbidities: A Nationwide Cohort

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Treatment of candidemia in a nationwide setting: increased survival with primary echinocandin treatment

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

Candida tropicalis isolates often display reduced but persistent growth (trailing) over a broad fluconazole concentration range during EUCAST susceptibility testing. Whereas weak trailing (<25% of the positive growth control) is common and found not to impair fluconazole efficacy, we investigated if more pronounced trailing impacted treatment efficacy. Fluconazole efficacy against two weakly (≤25% growth), two moderately (26% to 50% growth), and one heavily (>70% growth) trailing resistant isolate and one resistant (100% growth) isolate were investigated in vitro and in vivo (in a Galleria mellonella survival model and two nonlethal murine models). CDR1 expression levels and ERG11 sequences were characterized. The survival in fluconazole-treated G. mellonella was inversely correlated with the degree of trailing (71% to 9% survival in treatment groups). In mice, resistant and heavily trailing isolates responded poorly to fluconazole treatment. CDR1 expression was significantly higher in trailing and resistant isolates than in wild-type isolates (1.4-fold to 10-fold higher). All isolates exhibited ERG11 wild-type alleles. Heavily trailing isolates were less responsive to fluconazole in all in vivo models, indicating an impact on fluconazole efficacy. CDR1 upregulation may have contributed to the observed differences. Moderately trailing isolates responded less well to fluconazole in larvae only. This confirms clinical data suggesting fluconazole is effective against infections with such isolates in less severely ill patients and supports the current 50% growth endpoint for susceptibility testing. However, it is still unclear if the gradual loss of efficacy observed for moderately trailing isolates in the larva model may be a reason for concern in selected vulnerable patient populations.

OriginalsprogEngelsk
TidsskriftAntimicrobial Agents and Chemotherapy
Vol/bind62
Udgave nummer12
Sider (fra-til)e01624-18
ISSN0066-4804
DOI
StatusUdgivet - dec. 2018

ID: 56272833