Unlocking New Strategies: Reversing Fluconazole Resistance In Candida Species With Efflux Pump Inhibitors Like Aspirin And Ibuprofen

Background: Inadvertent use of broad-spectrum antibiotics and rise in immunocompromised patients are contributing to in-creased prevalence of fungal infections. While Candida albicans is the most prevalent yeast infection, Non-albicans Candida(NAC) are emerging opportunistic pathogens that are more resistant to antifungal agents[1,2]. Thus, we tried to determine candidemia profile and ascertain if efflux pump inhibitors Aspirin and Ibuprofen could elicit re-versal of Fluconazole resistance. Methods: Candida speciation was performed manually and using the VITEK 2 system[3]. Antifungal susceptibility was deter-mined by the broth microdilution method[4,5]. The effect of aspirin and ibuprofen on fluconazole-resistant isolates was also assessed using the broth microdilution method. Results: Of 126 Candida sp., 15(11.90%) were Candida albicans and 111(88.10%) were NAC. Candida sp. showed maximum susceptibility to Flucytosine(111/88.10%). 32 isolates were Fluconazole resistant(14 inherently resistant). 16 of 18 remaining isolates that were not inherently but resistant to Fluconazole, concurrent administration of Aspirin or Ibuprofen with Fluconazole caused reversal of resistance, with significant drop in minimum inhibitory concentration(< =0.125µg/ml), indicating 88.89% conversion rate[6]. Conclusion: Emergence of drug-resistant NAC as opportunistic pathogen necessitates species-level identification of isolates to initiate appropriate antifungal as empirical treatment[7]. Common mechanism for azole resistance is reduction of intracellular antifungal concentration by overexpression of efflux pump encoded by CDR1, CDR2, and MDR1 genes[8]. Our study shows concomitant use of efflux pump inhibitors Aspirin and Ibuprofen as suitable therapeutic alternative that may be effective for most Candida species that are Fluconazole resistant[9,10].