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

• Published in: Journal of blood medicine Vol. 12; pp. 465 - 474
• Main Authors: Sayed, Shereen A, Hassan, Ehsan A B, Abdel Hameed, Muhamad R, Agban, Michael N, Mohammed Saleh, Mostafa F, Mohammed, Hayam H, Abdel-Aal, Abu-Baker M, Elgendy, Sherein G
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2021; Taylor & Francis Ltd; Dove; Dove Medical Press
• Subjects: acute myeloid leukemia; Analgesics; Antifungal agents; Antimitotic agents; Antineoplastic agents; Bone marrow; Cancer; Cancer therapies; cdr1; Chemotherapy; Disease prevention; Egypt; Enzymes; Fluconazole; fluconazole resistance; Genes; Health aspects; Hepatitis; Infection; Infections; Ketorolac; Leukemia; mdr1; Mortality; Neutropenia; Nonsteroidal anti-inflammatory drugs; Oncology, Experimental; Original Research; Vagina; Egypt; France; United States > US; Germany; India; MDR1; acute myeloid leukemia; ketorolac; fluconazole resistance; CDR1
• ISSN: 1179-2736; 1179-2736
• DOI: 10.2147/JBM.S302158

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 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 isolated from AML patients on induction chemotherapy. One hundred and seventy AML patients were evaluated. Fifty were isolated and subjected to disc diffusion assay and broth microdilution for fluconazole alone and combined with different concentrations of ketorolac. Efflux pump gene ( , and ) expressions were quantified by real-time PCR. The tested ketorolac acted synergistically with fluconazole against resistant 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 (71.1%) and (60%). 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.