Candidiasis, which includes both superficial infections and invasive disease, is the most common cause of fungal infection worldwide. Candida bloodstream infections (BSI) cause significant mortality and elicit a major threat to intensive care unit (ICU) patients [1]. The annual global burden of Candida spp. BSIs is about 400,000 cases, with most cases reported from the developed world. Although Candida albicans remains the most frequently isolated Candida species in the clinical setting, in some countries, a marked shift towards species of Candida that have increased resistance to azoles such as fluconazole (FLU), the standard antifungal drug of choice in many countries, and to the recently introduced antifungals known as echinocandins, is reported. Several species of non-albicans Candida, such as C. tropicalis, C. glabrata, and C. parapsilosis, are well-recognized pathogens in BSIs in different geographic locations. More recently, Candida auris, a multidrug-resistant (MDR) yeast that exhibits resistance to FLU and markedly variable susceptibility to other azoles, amphotericin B (AMB), and echinocandins, has globally emerged as a nosocomial pathogen (Fig 1) [2-20]. Alarmingly, in a span of only 7 years, this yeast, which is difficult to treat and displays clonal inter-and intra-hospital transmission, has become widespread across several countries, causing a broad range of healthcare-associated invasive infections [4, 5, 10, 12, 21, 22].

Candida auris has emerged globally as an MDR nosocomial pathogen in ICU patients. We studied the antifungal susceptibility of C. auris isolates (n = 350) from 10 hospitals in India collected over a period of 8 years. To investigate azole resistance, ERG11 gene sequencing and expression profiling was conducted. In addition, echinocandin resistance linked to mutations in the C. auris FKS1 gene was analysed. CLSI antifungal susceptibility testing of six azoles, amphotericin B, three echinocandins, terbinafine, 5-flucytosine and nystatin was conducted. Screening for amino acid substitutions in ERG11 and FKS1 was performed. Overall, 90% of C. auris were fluconazole resistant (MICs 32 to ≥64 mg/L) and 2% and 8% were resistant to echinocandins (≥8 mg/L) and amphotericin B (≥2 mg/L), respectively. ERG11 sequences of C. auris exhibited amino acid substitutions Y132 and K143 in 77% (n = 34/44) of strains that were fluconazole resistant whereas WT genotypes, i.e. without substitutions at these positions, were observed in isolates with low fluconazole MICs (1–2 mg/L) suggesting that these substitutions confer a phenotype of resistance to fluconazole similar to that described for Candida albicans. No significant expression of ERG11 was observed, although expression was inducible in vitro with fluconazole exposure. Echinocandin resistance was linked to a novel mutation S639F in FKS1 hot spot region I. 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.

Candida auris is a multidrug-resistant yeast that causes a wide spectrum of infections, especially in intensive care settings. We investigated C. auris prevalence among 102 clinical isolates previously identified as Candida haemulonii or Candida famata by the Vitek 2 system. Internal transcribed spacer region (ITS) sequencing confirmed 88.2% of the isolates as C. auris , and matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) easily separated all related species, viz ., C. auris ( n = 90), C. haemulonii ( n = 6), C. haemulonii var. vulnera ( n = 1), and Candida duobushaemulonii ( n = 5). The in vitro antifungal susceptibility was determined using CLSI broth microdilution (CLSI-BMD), the Vitek 2 antifungal susceptibility test, and the Etest method. C. auris isolates revealed uniformly elevated fluconazole MICs (MIC ₅₀ , 64 μg/ml), and an alarming percentage of isolates (37%) exhibited elevated caspofungin MICs by CLSI-BMD. Notably, 34% of C. auris isolates had coexisting elevated MICs (≥2 μg/ml) for both fluconazole and voriconazole, and 10% of the isolates had elevated coexisting MICs (≥2 μg/ml) to two additional azoles, i.e., posaconazole and isavuconazole. In contrast to reduced amphotericin B MICs by CLSI-BMD (MIC ₅₀ , 1 μg/ml) for C. auris , elevated MICs were noted by Vitek 2 (MIC ₅₀ , 8 μg/ml), which were statistically significant. Candida auris remains an unnoticed pathogen in routine microbiology laboratories, as 90% of the isolates characterized by commercial identification systems are misidentified as C. haemulonii . MALDI-TOF MS proved to be a more robust diagnostic technique for rapid identification of C. auris . Considering that misleading elevated MICs of amphotericin B by the Vitek AST-YS07 card may lead to the selection of inappropriate therapy, a cautionary approach is recommended for laboratories relying on commercial systems for identification and antifungal susceptibility testing of rare yeasts.

A new clonal strain of Candida auris is an emerging etiologic agent of fungemia in Delhi, India. In 12 patients in 2 hospitals, it was resistant to fluconazole and genotypically distinct from isolates from South Korea and Japan, as revealed by M13 and amplified fragment length polymorphism typing.

Aspergillus fumigatus remains the most common species in all pulmonary syndromes, followed by Aspergillus flavus which is a common cause of allergic rhinosinusitis, postoperative aspergillosis and fungal keratitis. The manifestations of Aspergillus infections include invasive aspergillosis, chronic pulmonary aspergillosis and bronchitis. Allergic manifestations of inhaled Aspergillus include allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization. Triazoles are the mainstay of therapy against Aspergillus infections for treatment and prophylaxis. Lately, increased azole resistance in A. fumigatus has become a significant challenge in effective management of aspergillosis. Earlier studies have brought to light the contribution of non-cyp51 mutations along with alterations in cyp51A gene resulting in azole-resistant phenotypes of A. fumigatus. This review highlights the magnitude of azole-resistant aspergillosis and resistance mechanisms implicated in the development of azole-resistant A. fumigatus and address the therapeutic options available.