title: Activity of a Long-Acting Echinocandin (CD101) and Seven Comparator Antifungal Agents Tested against a Global Collection of Contemporary Invasive Fungal Isolates in the SENTRY 2014 Antifungal Surveillance Program.
abstract: The activity of CD101 and comparator antifungal agents against 606 invasive fungal isolates collected worldwide during 2014 was evaluated using the Clinical and Laboratory Standards Institute (CLSI) method. AllCandida albicans(n= 251),Candida tropicalis(n= 51),Candida krusei(n= 16), andCandida dubliniensis(n= 11) isolates were inhibited by ≤0.12 μg/ml of CD101 and were susceptible or showed wild-type susceptibility to the other echinocandins tested. FiveC. glabrataisolates (n= 100) displayed CD101 MIC values of 1 to 4 μg/ml, had elevated MICs of caspofungin (2 to >8 μg/ml), anidulafungin (2 to 4 μg/ml), and micafungin (2 to 4 μg/ml), and carried mutations onfks1andfks2Candida parapsilosis(n= 92) andCandida orthopsilosis(n= 10) displayed higher CD101 MIC values (ranges, 0.5 to 4 μg/ml and 0.12 to 2 μg/ml, respectively), and similar results were observed for the other echinocandins tested. Fluconazole resistance was noted among 11.0% ofCandida glabrataisolates, 4.3% ofC. parapsilosisisolates, and 2.0% ofC. albicansandC. tropicalisisolates. The activity of CD101 againstAspergillus fumigatus(n= 56) was similar to that of micafungin and 2-fold greater than that of caspofungin but less than that of anidulafungin. These isolates had wild-type susceptibility to itraconazole, voriconazole, and posaconazole. The echinocandins had limited activity againstCryptococcus neoformans(n= 19). CD101 was as active as the other echinocandins against common fungal organisms recovered from patients with invasive fungal infections. The long half-life profile is very desirable for the prevention and treatment of serious fungal infections, especially in patients who can then be discharged from the hospital to complete antifungal therapy on an outpatient basis.
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA.|University of Iowa, Iowa City, Iowa, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pfaller
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA.
authors.forename: Shawn A
authors.initials: SA
authors.lastname: Messer
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Rhomberg
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA mariana-castanheira@jmilabs.com.
authors.forename: Mariana
authors.initials: M
authors.lastname: Castanheira
mesh_terms: D000077612:Anidulafungin; D000935:Antifungal Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001208:Asia / Q000453:epidemiology; D001228:Aspergillosis / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000254:growth & development; D002175:Candida / Q000187:drug effects* / Q000254:growth & development; D058365:Candidiasis, Invasive / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D000077336:Caspofungin; D003453:Cryptococcosis / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000254:growth & development; D025141:Drug Resistance, Fungal; D054714:Echinocandins / Q000493:pharmacokinetics / Q000494:pharmacology*; D062665:Epidemiological Monitoring; D005060:Europe / Q000453:epidemiology; D015725:Fluconazole / Q000493:pharmacokinetics / Q000494:pharmacology; D006207:Half-Life; D006801:Humans; D017964:Itraconazole / Q000493:pharmacokinetics / Q000494:pharmacology; D007843:Latin America / Q000453:epidemiology; D055666:Lipopeptides / Q000493:pharmacokinetics / Q000494:pharmacology; D000077551:Micafungin; D008826:Microbial Sensitivity Tests; D009656:North America / Q000453:epidemiology; D014230:Triazoles / Q000493:pharmacokinetics / Q000494:pharmacology; D065819:Voriconazole / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; C000621306:CD101 echinocandin; D054714:Echinocandins; D055666:Lipopeptides; D014230:Triazoles; D017964:Itraconazole; C101425:posaconazole; D015725:Fluconazole; D000077612:Anidulafungin; D000077336:Caspofungin; D065819:Voriconazole; D000077551:Micafungin
keywords: Candida; antifungal susceptibility; echinocandins