Candidemia, the commonest invasive fungal infection, is associated with high morbidity and mortality in developing countries, though the exact prevalence is not known due to lack of systematic epidemiological data from those countries. The limited studies report a very high incidence of candidemia and unique epidemiology with a different spectrum of Candida species. The recent global emergence of multi-drug resistant Candida auris is looming large as an important threat in hospitalized patients of developing countries. While managing candidemia cases in those countries several challenges are faced, which include poor infrastructure; compromised healthcare and infection control practices; misuse and overuse of antibiotics and steroids; lack of awareness in fungal infections; non-availability of advance diagnostic tests and antifungal drugs in many areas; poor compliance to antifungal therapy and stewardship program. Considering the above limitations, innovative strategies are required to reduce mortality due to candidemia in adults and neonates. In the present review, we have unraveled the challenges of candidemia faced by low resource countries and propose a ten part strategy to reduce mortality due candidemia.

Allergic fungal rhinosinusitis (AFRS) is a unique variety of chronic polypoid rhinosinusitis usually in atopic individuals, characterized by presence of eosinophilic mucin and fungal hyphae in paranasal sinuses without invasion into surrounding mucosa. It has emerged as an important disease involving a large population across the world with geographic variation in incidence and epidemiology. The disease is surrounded by controversies regarding its definition and etiopathogenesis. A working group on “Fungal Sinusitis” under the International Society for Human and Animal Mycology (ISHAM) addressed some of those issues, but many questions remain unanswered. The descriptions of “eosinophilic fungal rhinosinusitis” (EFRS), “eosinophilic mucin rhinosinusitis” (EMRS) and mucosal invasion by hyphae in few patients have increased the problem to delineate the disease. Various hypotheses exist for etiopathogenesis of AFRS with considerable overlap, though recent extensive studies have made certain in depth understanding. The diagnosis of AFRS is a multi-disciplinary approach including the imaging, histopathology, mycology and immunological investigations. Though there is no uniform management protocol for AFRS, surgical clearing of the sinuses with steroid therapy are commonly practiced. The role of antifungal agents, leukotriene antagonists and immunomodulators is still questionable. The present review covers the controversies, recent advances in pathogenesis, diagnosis, and management of AFRS.

Candidaemia is a major cause of morbidity and mortality of hospitalised patients, especially in developing countries. This study was conducted to monitor any change in species distribution and antifungal susceptibility pattern of Candida species causing candidaemia over the last 20 years. The candidaemia cases reported during January 1999 and December 2018 at our centre were reviewed. The yeasts were identified by phenotypic characters (during 1999-2014) and matrix-assisted laser desorption ionisation-time of flight mass spectrometry (MALDI-TOF MS) (during 2014-2018). Antifungal susceptibility testing (AFST) was performed in accordance with the Clinical and Laboratory Standards Institute guidelines. A total of 602,963 blood samples from patients with suspected sepsis were processed. Candidaemia was diagnosed in 7927 (1.31%) cases. The frequency of cases rose significantly (P = 0.000) in the last quarter of the study. Candida tropicalis (40.1%) was the most common species, followed by Candida albicans (15.2%), Wickerhamomyces anomalus (13.1%), Candida krusei (6.6%), Candida parapsilosis (4.7%) and others. Rare species such as Candida auris, Candida lambica, Candida orthopsilosis, Candida vishwanathii were identified after the introduction of MALDI-TOF. The minimum inhibitory concentrations of amphotericin B rose significantly from the first to last quarter (0.5%-4.9%). Fluconazole resistance was fairly constant at 7.4%-8.8%. Local epidemiology of candidaemia at our centre was distinct regarding prevalence and change of spectrum of species. The identification of rare species was possible after the introduction of MALDI-TOF. With the emergence of multidrug-resistant C. auris and resistance in other species, routine AFST has become imperative.

Wickerhamomyces anomalus, previously known as Candida pelliculosa, occasionally causes candidemia in humans, primarily infecting neonates, and infants. The mortality rate of these invasive infections is high, and isolates with a reduced susceptibility to fluconazole have been reported. W. anomalus outbreaks are regularly reported in healthcare facilities, especially in neonatal intensive care units (NICUs). In order to rapidly genotype isolates with a high-resolution, we developed and applied a short tandem repeat (STR) typing scheme for W. anomalus. Six STR markers were selected and amplified in two multiplex PCRs, M3 and M6, respectively. In total, 90 W. anomalus isolates were typed, leading to the identification of 38 different genotypes. Four large clusters were found, unveiling simultaneous outbreak events spread across multiple units within the same hospital. STR typing results of 11 isolates were compared to whole-genome sequencing (WGS) single nucleotide polymorphism (SNP) calling, and the identified genotypic relationships were highly concordant. We performed antifungal susceptibility testing of these isolates, and a reduced susceptibility to fluconazole was found for two (2.3%) isolates. ERG11 genes of these two isolates were examined using WGS data, which revealed a novel I469L substitution in one isolate. By constructing a homology model for W. anomalus ERG11p, the substitution was found in close proximity to the fluconazole binding site. In summary, we showed multiple W. anomalus outbreak events by applying a novel STR genotyping scheme.