Risk factors of mortality and comparative in-vitro efficacy of anidulafungin, caspofungin, and micafungin for candidemia.
BACKGROUND
Although echinocandins have high in vitro antifungal efficacy according to prior reports, comparative studies on the clinical cure rates of anidulafungin, caspofungin, and micafungin in systemic candida infections have not yet been reported.


METHODS
Interpretation of clinical and microbiological responses to anidulafungin, caspofungin, and micafungin in 109 cases of candidemia was done according to the published criteria. The clinical cure rates between patients treated with echinocandins and patients treated with fluconazole were also compared. The minimal inhibitory concentrations (MICs) of anidulafungin, caspofungin, micafungin, and fluconazole for these 109 blood isolates of candida were determined with the Clinical and Laboratory Standards Institute M27-A reference microdilution method. Logistic regression with forward selection was used to determine the important factors of prognosis with variables such as age, underlying diseases, acute physiology and chronic health evaluation (APACHE) III score, persistent candidemia, and antimicrobial therapy.


RESULTS
Among the 109 cases of candidemia, 70 were treated with echinocandins, azoles, or amphotericin B for ≥7 days. The clinical cure rate of cases treated with antifungal agents adequately (≥7 days) and inadequately (<7 days) were 44/70 (62.9%) and 4/39 (10.2%), respectively, with significant difference (p < 0.0001). Clinical cure rates of anidulafungin, caspofungin, micafungin, and fluconazole were 18/30 (60.0%), 8/9 (88.9%), 5/7 (71.4%), and 9/18 (50%), respectively. The difference in APACHE III score between treatment success and failure cases was significant. The MIC50/MIC90 of anidulafungin, caspofungin, and micafungin for all Candida spp. were 0.03/1 μg/mL, 0.06/0.5 μg/mL, and 0.008/1 μg/mL, respectively.


CONCLUSIONS
Adequate antifungal therapy and APACHE III score are both independent factors affecting the clinical outcome. The clinical cure rate of the echinocandins group was higher than that of the fluconazole group without significant difference. Although caspofungin had the best clinical cure rate in this study, there was no significant difference between the clinical cure rates among these three echinocandins. All Candida spp. were susceptible in vitro to these three echinocandins.
Division of Infectious Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan; Division of Infectious Diseases, Chang Gung University, Kwei-Shan, Taoyuan, Taiwan. Electronic address: Lee.sch@msa.hinet.net.
Sai-Cheong
SC
Lee
Department of General Surgery, Chang Gung Memorial Hospital, Kwei-Shan, Taoyuan, Taiwan.
Chao-Wei
CW
Lee
Division of Infectious Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan.
Hsiang-Ju
HJ
Shih
Department of Laboratory Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan.
Shu-Huan
SH
Huang
Department of Public Health, Chang Gung University, Kwei-Shan, Taoyuan, Taiwan.
Meng-Jiun
MJ
Chiou
Department of Public Health, Chang Gung University, Kwei-Shan, Taoyuan, Taiwan; Biostatistics Core laboratory, Molecular Medicine Research Center, Chang Gung University, Kwei-Shan, Taoyuan, Taiwan.
Lai-Chu
LC
See
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002175:Candida / Q000187:drug effects; D058387:Candidemia / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology / Q000401:mortality; D002648:Child; D054714:Echinocandins / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D012307:Risk Factors; D055815:Young Adult
D000935:Antifungal Agents; D054714:Echinocandins
Anidulafungin; Candidemia; Caspofungin; Echinocandin; Fluconazole; Micafungin