Meta-Analysis of Antifungal Resistance Pattern in Aspergillus Species

Abstract

Abstract Backgrounds and Objectives: Aspergillus infection has several manifestations from non-invasive aspergillosis to invasive pulmonary and cerebral aspergillosis. Prophylaxis and treatment regimens for aspergillosis are limited to triazoles, echinocandins, and polyenes, each with different efficacy, complications, and resistance patterns. Drug selection presents challenges, including differences in resistance rates, drug interactions, and concerns about side effects with long-term use. Aspergillus resistance to antifungal agents is an international concern and shows an increasing trend. Each region worldwide has a resistance pattern affecting prevention and treatment regimens. Therefore, we examined the susceptibility rates of Aspergillus species to different antifungal drugs and their gene mutation rates in Iran. Methods: This meta-analysis started with a systematic search that was reported based on the Preferred Reporting Items for Systematic and Meta-analyses (PRISMA), yielding 1631 articles, of which 29 articles were included. Resistance rates were extracted, and a meta-analysis was done on 18 species-drug pairs. Results: Pooled resistance rate of Aspergillus fumigatus was 1.39% to amphotericin B, 17.77% to itraconazole, 2.63% to posaconazole, and 9.17% to voriconazole. For Aspergillus flavus it was 2.43% to amphotericin B, 7.64% to caspofungin, 3.60% to itraconazole, 1.48% to posaconazole, and 1.443% to voriconazole. Conclusion: Our meta-analysis showed that amphotericin B has superior effects on aspergillosis caused by A. fumigatus isolated from patients with unknown minimum inhibitory concentrations (MICs). The next most effective drugs are posaconazole and voriconazole, respectively. For the same problem in A.flavus, our analysis suggests voriconazole, posaconazole, and amphotericin B, respectively. This study also points to increased azole resistance, which should be of concern in clinical practice.