ArticleMycopathologia2025
Antifungal Susceptibility of Melanized Fungi Isolated from CARD9 Deficient Patients: Implications for Treatment of Refractory Infections.
Article in Mycopathologia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundInherited genetic deficiencies in the Caspase-associated recruitment domain-containing protein 9 (CARD9) lead to increased susceptibility of patients to opportunistic melanized fungi. Such infections are recalcitrant, and the fungus possibly acquires resistance under therapy.
objectiveTo evaluate differences of in vitro antifungal susceptibility of strains of melanized fungi originating from patients with CARD9 deficiency versus strains from chronic patients with unclear genetic background.
methodsWe analyzed a total of 118 isolates, including 33 from patients with CARD9 deficiency, 80 from chronic patients with other undefined immunological features, and 5 environmental strains, all collected between 1997 and 2021. All isolates were identified by sequencing the ITS spacer of the rDNA operon. Broth microdilution susceptibility tests were performed according to CLSI guidelines (M38-A3document).
resultsMIC ranges of strains from infected patients having CARD9 deficiency and other individuals were mostly similar. However, comparing these two groups, the GM MICs of posaconazole, amphotericin B and fluconazole in the CARD9 group were statistically higher and the GM MICs of terbinafine lower than those of undefined genetic background group. The FICI of the CARD9 group were higher than those of the undefined group in the combination of caspofungin plus amphotericin B and amphotericin B plus fluconazole, but lower than the undefined group in the combination of itraconazole plus terbinafine.
conclusionsThe GM MICs for posaconazole, amphotericin B, and fluconazole were significantly elevated in the CARD9 group compared to the group with undefined chronic infections. For patients with refractory infections, conducting susceptibility testing before treatment can optimize the selection of the most effective therapeutic agent, and the combination therapy of caspofungin with amphotericin B or itraconazole may be considered the preferred treatment option.
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