The Austrian landscape of diagnostic capacity and access to treatment for invasive fungal infections

Immunosuppression after chemotherapy, stem cell transplantation or solid organ transplantation are the main risk factors for invasive fungal infections in Austria. Here, we aim to describe the status of laboratory mycology and the access to antifungal treatment in Austria.


| INTRODUC TI ON
Austria is a Central European country located partially in the Alps with a population of 9 million inhabitants. 1 Based on macroeconomic data from the International Monetary Fund, Austria is ranked in the top 15 of the world's highest income countries, with a gross domestic product per capita of US$ 64,750 in April 2022. 2 Austria's healthcare system provides universal coverage for its citizens, with broad access to all levels of care.In addition, its healthcare system is above the European average in terms of funding. 3This is likely to ensure adequate clinical management of the various diseases in the country, including invasive fungal infections.
In Austria like other countries in the region, the largest groups of patients at high risk for invasive fungal infections are the severely immunosuppressed after chemotherapy for malignancy treatment, stem cell transplant or solid organ transplantation. 4,5Cases of endemic fungal infections have been reported from Austrian institutions, such as emergomycosis 6 or histoplasmosis. 5,7In the case of histoplasmosis, although the cases reported so far were imported, potential for endemicity in Austria has been described, especially in the Alpine federal states. 8Moreover, the incidence of multidrug resistant moulds and yeasts has also been depicted in the country.
Despite azole-resistance has still been described as low, [9][10][11] as of March 2022, five cases of Candida auris infections have already been reported. 12re, we aim to describe the current landscape of laboratory diagnosis and treatment capacity of invasive fungal infections in Austria.This will allow us to highlight the potential weaknesses of Austrian institutions and provide guidance to policymakers and medical teams to improve the situation where necessary.Frequencies and percentages are used to present data.No comparison was made in the light of the small sample size and uniformity of the responses given by the various institutions, as this could be prejudiced and not be informative.

| General overview
Responses from the university hospitals of Graz, Innsbruck, Linz and Vienna were collected between October and November 2021 (Figure 1).The four hospitals provide tertiary care and are highly specialised, with the possibility to perform both stem cell and solid organ transplantation.Although all institutions have onsite microbiology laboratories, including mycological diagnostics, in Linz some procedures are outsourced (Table 1).
The overall self-perceived expert incidence of invasive fungal infections is considered moderate, with the self-perceived expert incidence of mucormycosis ranging from low (Graz and Innsbruck) All sites consider the incidence of invasive fungal infections to be moderate.Access to microscopy, culture, serology, antigen detection and molecular testing is provided regardless of laboratory.The maximum capacity to identify fungi varies from institution to institution.All currently marketed antifungal agents are available at the four sites.

Conclusion:
Austria is currently well equipped to deal with the emerging threat of invasive fungal infections.However, hospitals may consider preparing for the potential endemicity of certain infections in the near future.
antifungal agents, antigen test, antifungal susceptibility, antimycotic chemotherapy, deep fungal infection, fungemia, microdilution, PCR to very low (Linz and Vienna).Aspergillus spp.and Candida spp.are contemplated as the most relevant pathogens in all institutions.In the case of Graz and Vienna, Fusarium spp.and Mucorales are also described as of concern (Table 1).

| Access to diagnostic tools
China/India ink and silver stains are available for microscopic examination when needed in all sites.The first is widely used for direct examination in body fluids when cryptococcosis is suspected.Silver stain could be employed in all institutions when pneumocystosis is suspected (Table 1).
Fungaemia can always be detected by culture, regardless of the laboratory, with wide access to all existing fungal culture methods.Specifically for further identification, matrix-assisted laser desorption/ionisation-time-of-flight-mass spectrometry is a procedure available in all institutions.The maximum level of fungal identification capacity differed between institutions: Graz, Innsbruck and Vienna can identify moulds up to cryptic species, whereas yeast identification to species level is possible at all sites.Broth microdilution, mainly using instructions and break points of the European Committee on Antimicrobial Susceptibility Testing as reference, gradient strip tests and automated testing system methods are widely used (Table 1).
Although Graz, Innsbruck and Linz report access to serologies for either Aspergillus spp., Candida spp. or Histoplasma spp., testing for the latter is outsourced in all of them.Candida spp.serology is also outsourced to external laboratories in the case of Linz (Table 1

| Access to antifungals and therapeutic drug monitoring
All the antifungals currently in the market are available at the four sites.TDM for voriconazole is available to the teams in all hospitals, while TDM for flucytosine, itraconazole and posaconazole is available in Graz, Innsbruck and Vienna.In addition, isavuconazole TDM is available in Graz (Table 1).

| DISCUSS ION
Here, we describe the current diagnostic and treatment capacity for invasive fungal infections in Austria.Our study collected data from the major institutions in the country.We found that, overall, all centres are well prepared for such tasks, with subtle variation.
Only four university hospitals and their respective laboratories took part in our survey.However, it must be considered that these are the hospitals with the largest number of beds and the largest experience in treating invasive fungal infections.Although this may have biased our results towards a better situation than the actual one, it should also be remembered that every citizen in Austria is free to choose their treatment facility. 3It is therefore quite likely that a patient with a serious illness, including an invasive fungal infection, requires to be transferred, if not already admitted, to these larger facilities with more experience in treating invasive fungal infections.
The self-perceived expert incidence of invasive fungal infections in Austria is considered moderate by all participating institutions.The presence of well-established and adequate prophylactic strategies for patients at risk, [13][14][15] together with the perceived good general status of the Austrian healthcare system, 3 may facilitate such expert-based self-perception of moderate incidence.All institutions were most concerned about Aspergillus spp.and Candida spp., while Fusarium spp.and Mucorales were only mentioned in two.This is in line with the data previously described for Europe in general, 16 as well as with the recently published World Health Organization (WHO) priority list of fungal pathogens, where certain Aspergillus spp.and Candida spp.were identified as critical priority pathogens. 179][20][21][22][23][24][25][26][27][28][29] Nevertheless, it should be noted that all Austrian hospitals are above the European average for each of the parameters analysed, both for diagnosis and treatment. 16is puts Austria in one of the best situations to fight invasive fungal infections properly.The analysed institutions not only have access to all diagnostic tests described as essential by the WHO, but also go beyond such a list. 30Nonetheless, factors such as turnaround time hold significant importance, and subsequent publications should  consider incorporating these variables to draw more precise conclusions.Additionally, the diversity of diagnostic and treatment options might be contingent on independent factors related to each patient's-specific circumstances.Albeit Austria has not yet been described as a country with autochthonous endemic mycoses, tourism to endemic areas has already been observed as a risk factor for the acquisition of endemic mycoses. 7Now may therefore be a good time to promote the availability of onsite testing for endemic mycoses in every facility.The availability of appropriate diagnostic tools in clinics and laboratories is of paramount importance to provide the best treatment for patients with these life-threatening acute infections.
October and November 2021, tertiary care facilities from the Republic of Austria were contacted by email between October and November 2021 and asked to complete an electronic case report form (eCRF) about their establishments' capacity for diagnosing and treating fungal infections.The eCRF was online available at www.clini calsu rveys.net/uc/IFI_management_capac ity/ (EFS Summer 2021, TIVIAN GmbH, Cologne, Germany).At least one clinical or laboratory mycologist from each of the nine Austrian Federal States was invited to participate in the online survey.The potential participants were selected from major institutions responsible for managing invasive fungal infections in the country, including hospitals distributed as follows: two hospitals each in Lower Austria (Krems and Sankt Pölten), Salzburg, Styria (Graz) and Upper Austria (Linz and Wels), and one hospital each in Burgenland (Oberwart), Carinthia (Klagenfurt), Tyrol (Innsbruck), Vienna and Vorarlberg (Felkirch).The eCRF gathered pertinent information in several dimensions, including institutional profile, self-perception of the prevalence of local invasive fungal infections by local experts in medical mycology, access to commonly used diagnostic tools, including microscopy, culture, serology, antigen detection, molecular testing and onsite antifungal repertoire and therapeutic drug monitoring (TDM).The submitted responses were scrutinised for consistency and completeness before being utilised for data analysis.
TA B L E 1 (Continued)