This part of the EFISG guidelines focuses on non-neutropenic adult patients. Only a few of the numerous recommendations can be summarized in the Prophylactic usage of fluconazole is supported in patients with recent abdominal surgery and recurrent gastrointestinal perforations or anastomotic leakages. Candida isolation from respiratory secretions alone should never prompt treatment. For the targeted initial treatment of candidaemia, echinocandins are strongly recommended while liposomal amphotericin B and voriconazole are supported with moderate, and fluconazole with marginal strength. Treatment duration for candidaemia should be a minimum of 14 days after the end of candidaemia, which can be determined by one blood culture per day until negativity. Switching to oral treatment after 10 days of intravenous therapy has been safe in stable patients with susceptible Candida species. In candidaemia, removal of indwelling catheters is strongly recommended. If catheters cannot be removed, lipid-based amphotericin B or echinocandins should be preferred over azoles. Transoesophageal echocardiography and fundoscopy should be performed to detect organ involvement. Native valve endocarditis requires surgery within a week, while in prosthetic valve endocarditis, earlier surgery may be beneficial. The antifungal regimen of choice is liposomal amphotericin B +/- flucytosine. In ocular candidiasis, liposomal amphotericin B +/- flucytosine is recommended when the susceptibility of the isolate is unknown, and in susceptible isolates, fluconazole and voriconazole are alternatives. Amphotericin B deoxycholate is not recommended for any indication due to severe side effects.

The burden of human disease related to medically important fungal pathogens is substantial. An improved understanding of antifungal pharmacology and antifungal pharmacokinetics–pharmacodynamics has resulted in therapeutic drug monitoring (TDM) becoming a valuable adjunct to the routine administration of some antifungal agents. TDM may increase the probability of a successful outcome, prevent drug-related toxicity and potentially prevent the emergence of antifungal drug resistance. Much of the evidence that supports TDM is circumstantial. This document reviews the available literature and provides a series of recommendations for TDM of antifungal agents.

Mucormycosis is a very aggressive invasive fungal disease [ 1 x 1 Christopeit, M, Lindner, A, Surov, A et al. Right flank pain and high fever in a neutropenic patient with acute lymphoblastic leukaemia. Mycoses. 2013; 56: 90–92 Crossref | PubMed | Scopus (0) | Google Scholar See all References , 2 x 2 Neblett Fanfair, R, Benedict, K, Bos, J et al. Necrotizing cutaneous mucormycosis after a tornado in Joplin, Missouri, in 2011. N Engl J Med. 2012; 367: 2214–2225 Crossref | PubMed | Scopus (107) | Google Scholar See all References ]. It is a fungal emergency that affects a variety of patient groups [ 3 x 3 Roden, MM, Zaoutis, TE, Buchanan, WL et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis. 2005; 41: 634–653 Crossref | PubMed | Scopus (1104) | Google Scholar See all References 3 ]. The disease, previously termed zygomycosis [ 4 x 4 Ajello, L, Dean, DF, and Irwin, RS. The zygomycete Saksenaea vasiformis as a pathogen of humans with a critical review of the etiology of zygomycosis. Mycologia. 1976; 68: 52–62 Crossref | PubMed | Google Scholar See all References 4 ], is caused by mucoralean fungi, which have collectively also been called Mucormycetes [ 5 x 5 Gomes, MZ, Lewis, RE, and Kontoyiannis, DP. Mucormycosis caused by unusual mucormycetes, non-Rhizopus, -Mucor, and -Lichtheimia species. Clin Microbiol Rev. 2011; 24: 411–445 Crossref | PubMed | Scopus (138) | Google Scholar See all References , 6 x 6 Kwon-Chung, KJ. Taxonomy of fungi causing mucormycosis and entomophthoramycosis (zygomycosis) and nomenclature of the disease: molecular mycologic perspectives. Clin Infect Dis. 2012; 54: S8–S15 Crossref | PubMed | Scopus (0) | Google Scholar See all References ]. However, we prefer to use the name of the order, i.e. Mucorales.

The frequency and diversity of serious fungal infections is increasing [ 1 x 1 Nucci, M, Garnica, M, Gloria, AB et al. Invasive fungal diseases in haematopoietic cell transplant recipients and in patients with acute myeloid leukaemia or myelodysplasia in Brazil. Clin Microbiol Infect. 2013; 19: 745–751 Abstract | Full Text | Full Text PDF | PubMed | Scopus (43) | Google Scholar See all References , 2 x 2 Nucci, M and Anaissie, E. Fusarium infections in immunocompromised patients. Clin Microbiol Rev. 2007; 20: 695–704 Crossref | PubMed | Scopus (413) | Google Scholar See all References , 3 x 3 Nucci, M and Anaissie, E. Emerging fungi. Infect Dis Clin North Am. 2006; 20: 563–579 Abstract | Full Text | Full Text PDF | PubMed | Scopus (0) | Google Scholar See all References ]. Severely immunocompromised patients are particularly vulnerable to infection from unusual moulds and yeasts, which are present in the environment. Clinical manifestations range from colonization to chronic localized lesions to acute invasive and/or disseminated diseases. Localized infections may occur following penetrating trauma in healthy individuals; dissemination usually occurs among immunocompromised patients and the outcome is closely related to the degree and persistence of immunosuppression [ 4 x 4 Nucci, M, Anaissie, EJ, Queiroz-Telles, F et al. Outcome predictors of 84 patients with hematologic malignancies and Fusarium infection. Cancer. 2003; 98: 315–319 Crossref | PubMed | Scopus (163) | Google Scholar See all References 4 ]. Diagnosis usually requires isolation and identification of the infecting pathogen; however, serology, imaging techniques and clinical manifestations are not specific, and pan-fungal and species-specific PCR are useful investigational tools. Many of the emerging opportunistic moulds demonstrate in vitro and in vivo resistance to various antifungals. As a result, successful treatment may require adjunctive surgical debridement and, when possible, reconstitution of the host immune system.

Antifungal susceptibility tests are performed on fungi that cause disease, especially if they belong to a species exhibiting resistance to commonly used antifungal agents. Antifungal susceptibility testing is also important for resistance surveillance, for epidemiological studies and for comparing the in-vitro activity of new and existing agents.