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Session: P085 resistance

Category: 6d. Antifungal resistance & susceptibility testing

25 April 2017, 12:30 - 13:30 P1760

Synergistic activity of micafungin plus against multidrug-resistant

Hamed Fakhim*1, Anuradha Chowdhary2, Jacques F. Meis3, Afsane Vaezi4, Hamid Badali5

1Invasive Fungi Research Center, Mazandaran University of Medical Sciences; Department of Medical Mycology and Parasitology

2Department of Medical Microbiology, Division of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi

3Canisius Wilhelmina Hospital; Medical Microbiology and Infectious Diseases

4Student Research Committee, Mazandaran University of Medical Sciences

5Invasive Fungi Research Centre (Ifrc), School of Medicine, Mazandaran University of Medical Sciences; Department of Medical Mycology and Parasitology, Fungal Biodiversity Centre

Background: Blood stream infections due to Candida auris are related to a high mortality rate and treatment failure attributed to resistance to , voriconazole, , and . Thus, the precise identification of agents and in vitro antifungal susceptibility testing is highly recommended. Novel therapeutic strategies, such as combination therapy, are essential for increasing the efficacy and reducing the toxicity of antifungal agents. Therefore, we investigated the in vitro combination of micafungin plus voriconazole against multidrug-resistant C. auris isolated from cases of candidemia. Material/methods: A total of ten clinical isolates were obtained from tertiary care hospitals in Delhi, North India. Isolate identities were done by MALDI-TOF MS and sequencing of ITS region. The interactions of micafungin with voriconazole were investigated using a microdilution checkerboard technique in 96-well microtitre plates. The range of the concentration depended on the MIC results for each isolate; the maximum concentration was twofold the MIC and then serial diluted. Data obtained by visual reading were further analyzed using the fractional inhibitory concentration index (FICI).

Results: Results revealed that MICs range for voriconazole and micafungin were 0.5-8 and 0.25–8 mg/L, respectively. The checkerboard analysis revealed that the combination of micafungin with voriconazole exhibited synergistic activity against all 10 multidrug-resistant C. auris isolates (FICI range: 0.15-0.5). Overall, no antagonistic effects were observed in this experiments.

Conclusions: In vitro studies have previously suggested that among isavuconazole and are more active drugs against C. auris. In addition, the majority of isolates reported are resistant to fluconazole. Remarkably, unsuccessful treatment of C. auris infections with fluconazole, voriconazole, amphotericin B, caspofungin, and has been already on record. Here in we demonstrates that interaction between micafungin with voriconazole exhibited synergistic activity against multidrug-resistant C. auris isolates. It seems that lower concentrations of drugs cause fewer side-effects and improve the treatment outcomes. However, in vivo studies with suitable animal models of C. auris infection is highly recomended.