Invasive fungal infections (IFI) are an emerging problem worldwide with invasive candidiasis and candidemia responsible for the majority of cases. This is predominantly driven by the widespread adoption of aggressive immunosuppressive therapy among certain patient populations (e.g., chemotherapy, transplants) and the increasing use of invasive devices such as central venous catheters (CVCs). The use of new immune modifying drugs has also opened up an entirely new spectrum of patients at risk of IFIs. While the epidemiology of candida infections has changed in the last decade, with a gradual shift from C. albicans to non-albicans candida (NAC) strains which may be less susceptible to azoles, these changes vary between hospitals and regions depending on the type of population risk factors and antifungal use. In certain parts of the world, the incidence of IFI is strongly linked to the prevalence of other disease conditions and the ecological niche for the organism; for instance cryptococcal and pneumocystis infections are particularly common in areas with a high prevalence of HIV disease. Poorly controlled diabetes is a major risk factor for invasive mould infections. Environmental factors and trauma also play a unique role in the epidemiology of mould infections, with well-described hospital outbreaks linked to the use of contaminated instruments and devices. Blastomycosis is associated with occupational exposure (e.g., forest rangers) and recreational activities (e.g., camping and fishing).The true burden of IFI is probably an underestimate because of the absence of reliable diagnostics and lack of universal application. For example, the sensitivity of most blood culture systems for detecting candida is typically 50 %. The advent of new technology including molecular techniques such as 18S ribosomal RNA PCR and genome sequencing is leading to an improved understanding of the epidemiology of the less common mould and dimorphic fungal infections. Molecular techniques are also providing a platform for improved diagnosis and management of IFI.Many factors affect mortality in IFI, not least the underlying medical condition, choice of therapy, and the ability to achieve early source control. For instance, mortality due to pneumocystis pneumonia in HIV-seronegative individuals is now higher than in seropositive patients. Of significant concern is the progressive increase in resistance to azoles and echinocandins among candida isolates, which appears to worsen the already significant mortality associated with invasive candidiasis. Mortality with mould infections approaches 50 % in most studies and varies depending on the site, underlying disease and the use of antifungal agents such as echinocandins and voriconazole. Nevertheless, mortality for most IFIs has generally fallen with advances in medical technology, improved care of CVCs, improved diagnostics, and more effective preemptive therapy and prophylaxis.

Objectives: Effluents contain a diverse abundance of antibiotic resistance genes that augment the resistome of receiving aquatic environments. However, uncertainty remains regarding their temporal persistence, transcription and response to anthropogenic factors, such as antibiotic usage. We present a spatiotemporal study within a river catchment (River Cam, UK) that aims to determine the contribution of antibiotic resistance gene-containing effluents originating from sites of varying antibiotic usage to the receiving environment. Methods: Gene abundance in effluents (municipal hospital and dairy farm) was compared against background samples of the receiving aquatic environment (i.e. the catchment source) to determine the resistome contribution of effluents. We used metagenomics and metatranscriptomics to correlate DNA and RNA abundance and identified differentially regulated gene transcripts. Results: We found that mean antibiotic resistance gene and transcript abundances were correlated for both hospital (ρ = 0.9, two-tailed P <0.0001) and farm (ρ = 0.5, two-tailed P  <0.0001) effluents and that two β-lactam resistance genes (blaGES and blaOXA) were overexpressed in all hospital effluent samples. High β-lactam resistance gene transcript abundance was related to hospital antibiotic usage over time and hospital effluents contained antibiotic residues. Conclusions: We conclude that effluents contribute high levels of antibiotic resistance genes to the aquatic environment; these genes are expressed at significant levels and are possibly related to the level of antibiotic usage at the effluent source.

Using a multidisciplinary team, antifungal stewardship can achieve significant improvements in patient management and it may reduce costs.