Overall, 25% and 13% of isolates were MDR and multi-azole resistant, respectively. The most common resistance combination was azoles and 5-flucytosine in 14% followed by azoles and amphotericin B in 7% and azoles and echinocandins in 2% of isolates.

infections are increasing worldwide and exhibit greater rates of antifungal resistance than those with other species. DNA mismatch repair (MMR) gene deletions, such as , in resulting in a mutator phenotype have recently been reported to facilitate rapid acquisition of antifungal resistance. This study determined the antifungal susceptibility profiles of 210 isolates in 10 hospitals in India and investigated the impact of novel polymorphisms on mutation potential. No echinocandin- or azole-resistant strains and no mutations in hot spot regions were detected among the isolates, supporting our susceptibility testing results. CLSI antifungal susceptibility data showed that the MICs of anidulafungin (geometric mean [GM], 0.12 μg/ml) and micafungin (GM, 0.01 μg/ml) were lower and below the susceptibility breakpoint compared to that of caspofungin (CAS) (GM, 1.31 μg/ml). Interestingly, 69% of the strains sequenced contained six nonsynonymous mutations in , i.e., V239L and the novel mutations E459K, R847C, Q386K, T772S, and V239/D946E. Functional analysis of mutations revealed that 49% of the tested strains (40/81) contained a partial loss-of-function mutation. The novel substitution Q386K produced higher frequencies of CAS-resistant colonies upon expression in the mutant. However, expression of two other novel alleles, i.e., E459K or R847C, did not confer selection of resistant colonies, confirming that not all mutations in the MMR pathway affect its function or generate a phenotype of resistance to antifungal drugs. The lack of drug resistance prevented any correlations from being drawn with respect to genotype.

No abstract

Penicillium species are rarely reported agents of infections in immunocompromised patients. We report 3 cases of invasive mycosis caused by voriconazole-resistant Penicillium oxalicum in patients with acute myeloid leukemia, diabetes mellitus, and chronic obstructive pulmonary disease, while on voriconazole therapy. Penicillium oxalicum has not been previously recognized as a cause of invasive mycoses.

These results on microbiologic profile and antibiotic sensitivity pattern of the isolates will be extremely helpful in revision of antibiotic guidelines for our patients and in developing strategies for coping with high prevalence of multi-drug resistance. Antibiotic stewardship and strict implementation of infection control practices will be important components of this effort.