Alarming Increase of Azole-Resistant Candida Causing Blood Stream Infections in Oncology Patients in Egypt

Abstract

Candidemia is a life-threatening invasive fungal infection in immunocompromised patients. The widespread use of azoles and the shift toward non-albicans Candida (NAC) species remarkably increase azole resistance in developing countries. We aimed to study candidemia trends and associated risk factors in oncology patients since they vary geographically, and rapid and appropriate treatment improves outcomes. Vitek 2 was used to identify the Candida species, and the E-test determined their susceptibility to azoles. Candida was the cause of 3.1% (n = 53/1701) of bloodstream infections (BSIs) during a 1-year study. Candida tropicalis was the most predominant species among the 30 candidemia episodes studied (36.7%), followed by C. albicans (33.3%). However, C. krusei, C. guilliermondii, C. pelliculosa, C. parapsilosis, C. famata, and C. inconspicua accounted for 30.0% of the isolates. An increased risk of NAC BSI was significantly associated with chemotherapy and leucopenia (P = 0.036 and 0.016, respectively). However, the multivariable analysis revealed that leucopenia was the only independent risk factor (P = 0.048). Fluconazole and voriconazole resistance were 58.3% and 16.7%, with NAC species showing higher resistance rates than C. albicans. Both fluconazole and voriconazole minimum inhibitory concentration (MIC) median values were higher in NAC than in C. albicans, but only voriconazole was significantly higher (0.220 versus 0.048 μg/ml, P = 0.047). In conclusion, the increased prevalence of NAC BSIs and incredibly high fluconazole resistance rates in cancer patients emphasize the necessity of antifungal stewardship to preserve voriconazole effectiveness, continued surveillance of candidemia, and future studies into azole resistance molecular mechanisms.

Fig. 1

Frequency of Candida species identified by Vitek 2 causing bloodstream infections in cancer patients at the National Cancer Institute. The percentages of all identified species are shown. Candida tropicalis was the most prevalent species (n = 11/30, 36.7%), followed by C. albicans (n = 10, 33.3%). Less isolated were C. krusei, C. guilliermondii, C. pelliculosa (each with 2 isolates, 6.7%), C. parapsilosis, C. famata, and C. inconspicua (each with 1 isolate, 3.3%)

Fig. 2

Voriconazole and fluconazole MIC₅₀ and MIC₉₀ in Candida albicans and non-albicans Candida species causing bloodstream infections in cancer patients at the National Cancer Institute. NAC species exhibited higher MIC₅₀ and MIC₉₀ values for voriconazole and fluconazole than C. albicans. Voriconazole MIC₅₀ and MIC₉₀ values for NAC and C. albicans species were 0.19 versus 0.032 and 24 versus 0.25 μg/ml, respectively; fluconazole MIC₅₀ was > 256 versus 3 μg/ml, respectively, and MIC₉₀ was > 256 μg/ml in both NAC and C. albicans species. The MIC₅₀ and MIC₉₀ represent the lowest concentration of the antifungal agent that inhibits 50% and 90% of the isolates, and based on the formulae, MIC₅₀ = number of isolates × 0.5 and MIC₉₀ = number of isolates × 0.9, respectively. MIC minimum inhibitory concentration, NAC non-albicans Candida