Antifungal susceptibility profile of invasive Candida glabrata isolates (2009-2020) from a tertiary care hospital laboratory in Pakistan

Introduction. Invasive infections with Candida glabrata are a global concern due to poor clinical outcomes and propensity to acquire resistance to antifungal agents. Hypothesis/Gap Statement. Monitoring emerging resistance and trends in Candida glabrata, an important agent of candidemia in Pakistan, is critical for patient management; data that is missing from Pakistan. Aim. Thus, this study evaluated antifungal resistance and MICs) distribution in invasive C. glabrata isolates from Pakistan. Methods. This cross-sectional and retrospective study was conducted from January 2009 to March 2020 at a clinical laboratory in Pakistan that has a nation-wide network. Antifungal susceptibility data of 277 candidemia, deep organ and soft tissue (invasive) C. glabrata sensu lato isolates against fluconazole, itraconazole, voriconazole, posaconazole, anidulafungin, micafungin, caspofungin and amphotericin B was retrieved. Susceptibility testing was performed using colorimetric broth microdilution and interpreted using CLSI criteria. Demographics, clinical history and outcome were studied. Chi-square test was used to demonstrate association between antifungal resistance and clinical characteristics of the patients.Results. We identified 277 patients with invasive C. glabrata infection. Of which 48 (18.4%) isolates were resistant to fluconazole (MIC ≥64 mg l-1), one isolate each was resistant to amphotericin (MIC=2 mg l-1), anidulafungin (MIC=1 mg l-1) and micafungin (MIC=0.5 mg l-1). MIC90 for fluconazole was 64 mg l-1 and other triazoles 2 mg l-1, caspofungin 0.12 mg l-1, anidulafungin 0.06 mg l-1, micafungin 0.03 mg l-1 and amphotericin 0.5 mg l-1. Fluconazole MIC ≥64 mg l-1, caspofungin MIC \u3e0.06 mg l-1 and amphotericin MIC \u3e0.25 mg l-1 (above MIC50) were significantly associated with patient being alive at the time of reporting, no use of healthcare devices, nor infection with other fungi. Fluconazole resistance was significantly associated with prior antifungal use by the patient.Conclusion. Surveillance data of antifungal resistance among common Candida species should be monitored closely for identification of resistant strains