Ketorolac-fluconazole: A New Combination Reverting Resistance in Candida albicans from Acute Myeloid Leukemia Patients on Induction Chemotherapy: In vitro Study

Abstract

Background and Objectives Candida albicans is a significant source of morbidity and mortality for patients with acute myeloid leukemia (AML). Prolonged use of fluconazole as empirical antifungal prophylaxis in AML patients leads to overexpression of efflux pump genes that resulted in the emergence of azole-resistant species. Consequently, the introduction of a new strategy to improve the management of C. albicans infections is an urgent need. Nonsteroidal anti-inflammatory drug (NSAID) ketorolac is associated with a reduction in cancer relapses. The present study was performed to investigate the use of ketorolac-fluconazole combination to reverse fluconazole resistance in C. albicans isolated from AML patients on induction chemotherapy. Patients and Methods One hundred and seventy AML patients were evaluated. Fifty C. albicans were isolated and subjected to disc diffusion assay and broth microdilution for fluconazole alone and combined with different concentrations of ketorolac. Efflux pump gene ( CDR1, CDR2 , and MDR1 ) expressions were quantified by real-time PCR. Results The tested ketorolac acted synergistically with fluconazole against resistant C. albicans with the minimum inhibitory concentration (MIC) of fluconazole decreased from >160 μg/mL to 0.3–1.25 μg/mL in (93.8%) of resistant isolates with fractional inhibitory concentration index (FICI) value of 0.25. The majority of the resistant isolates overexpressed CDR1 (71.1%) and MDR1 (60%). Conclusion Ketorolac-fluconazole in vitro combination would be a promising strategy for further clinical in vivo trials to overcome fluconazole resistance in AML patients on induction chemotherapy.

T-Lymphocytes Expression of Toll-Like Receptors 2 and 4 in Acute Myeloid Leukemia Patients With Invasive Fungal Infections

“…In An Egyptian study reported that 75 (44.1%) Candida spp (25 (33.3%) non-albicans Candida spp and 50 (66.6%) C. albicans) were isolated from AML patients on induction chemotherapy. 37 The common site of IFI was the lower respiratory tracts (47.5%, 19/40), and oral mucosa (mucositis grade ӀӀ or ӀѴ) (37.5%, 15/40) followed by mixed infection sites (bloodstream, oral and LRTI) (15%, 6/40). Pagano et al 38 and Tang et al 33 reported that lower respiratory tract was the most common site for IFIs (80% and 75.4% respectively); also EL-mahallawy et al 35 and Kurosawa et al 30 found an incidence of (35.7% and 55.3% respectively) for IFIs affecting the lung.…”

Potential Anti-fungal Activity of Lactobacilli Probiotic Against Fluconazole Resistant Candida albicans Clinical Isolates

“…This could be as a result of limited use of this drug in the current scenario. However, other studies reported elevated level of resistance 40,42 .…”

“…However, recent studies reported extremely high FLZ resistance rate of 86.2% and 94% among C. albicans isolates 34,40 . This high level of FLZ resistance might be due to extensive and prolonged use of this antifungal drug especially as prophylactic in cancer patients and in intensive care units 40 . In our scenario, the use of FLZ as an empirical therapy in the treatment of different forms of candidiasis contributes to FLZ resistance.…”

The Effect of Essential Oils of Selected Plants on Clinical Isolates of Candida Species Growth, Transition and Biofilm Formation

“…Unfortunately, resistance to these conventional treatments is progressively rising. [11][12][13][14] . Due to the existence of phytochemicals that can result in the development of new drugs, medicinal plants are currently regarded as a possible source for new therapeutic agents.…”