# Duration of systemic antifungal therapy for patients with invasive fungal diseases: A reassessment

Simon B Gressens, Claire Rouzaud, Frederic Lamoth, Thierry Calandra,
Fanny Lanternier, Olivier Lortholary

► To cite this version:

Simon B Gressens, Claire Rouzaud, Frederic Lamoth, Thierry Calandra, Fanny Lanternier, et al. Duration of systemic antifungal therapy for patients with invasive fungal diseases: A reassessment. Molecular Aspects of Medicine, 2025, 103, pp.101347. 10.1016/j.mam.2025.101347. hal-05105992

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Submitted on 10 Jun 2025

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## Review

# Duration of systemic antifungal therapy for patients with invasive fungal diseases: A reassessment

Simon B. Gressens<sup>a, b</sup>, Claire Rouzaud<sup>a, b</sup>, Frederic Lamoth<sup>c, d</sup>, Thierry Calandra<sup>c</sup>, Fanny Lanternier<sup>a, b</sup>, Olivier Lortholary<sup>a, b, *</sup>

<figure><img src="image_3.png" /></figure>

## ARTICLE INFO

**Keywords:**

invasive fungal diseases therapy duration
biomarkers
PET-Scanner

## ABSTRACT

Invasive fungal diseases are associated with significant morbidity and mortality, especially among immunocompromised patients, and often prompt for rapid and aggressive treatment aiming cure. Due to the expanding magnitude of patients burdened by chronic immunosuppression and affected by fungal diseases, the diversity of clinical settings has risen. This often results in prolonged therapy (induction, consolidation and maintenance) associated with potentially severe side effects, and clinicians face the challenging decisions of when and how to stop anti-fungal therapy. Adequate duration of therapy is poorly defined, hampered by the lack of dedicated trials to the question, the heterogeneity of cases (type of fungal pathogen, localization of infection, underlying host conditions) and various confounding factors that may influence the clinical response (e.g. persistence vs recovery of immunosuppression, impact of surgery). In this review, we aim to evaluate the existing data underlying the guidelines and recommendations of treatment duration for the most frequent invasive fungal diseases (cryptococcal meningitis, *Pneumocystis pneumonia*, invasive aspergillosis, invasive candidiasis and mucormycosis), as well as specific localizations of deep-seated diseases (osteo-articular or central nervous system diseases and endocarditis) and emerging considerations and strategies.

With an estimated incidence of around 4.5 million cases annually worldwide (Denning, 2024), invasive fungal diseases (IFD) can result in significant morbidity and mortality, especially among immunocompromised patients (Webb et al., 2018; Brown et al., 2012). Historically, IFD were primarily associated with patients suffering from hematologic malignancies. However, over time, the population of immunocompromised and at-risk individuals has become more diverse, with certain groups now exhibiting heightened susceptibility to IFD. We have observed the emergence of new at-risk populations, including solid organ transplant recipients and intensive care unit patients with predisposing factors such as central catheters or infections like influenza and SARS-CoV-2. Additionally, the broader use of immunosuppressive or immunomodulatory therapies beyond hematology—such as in rheumatology (e.g., rheumatoid arthritis and ANCA-associated vasculitis, often treated with high doses of steroids and other immunosuppressants), gastroenterology (where inflammatory bowel disease contributes

to significant cases of fungemia), neurology (with recent multiple scle-rosis treatments linked to IFD), and dermatology (where anti-IL17 therapies have been associated with a marked rise in candidiasis)—has expanded the at-risk patient population. Moreover, recent advances in immunology should encourage clinicians to conduct a thorough immunological assessment when an IFD occurs in an apparently healthy patient with no classical risk factors (Puerta-Alcalde and Garcia-Vidal, 2021; Poissy et al., 2022; Galmiche et al., 2023; Scotto et al., 2021; Davidson et al., 2022; Lionakis, 2019). So far, basic and clinical research has focused on improving early diagnosis and effective therapies, but less attention has been paid to the duration of treatment (Fernández-Cruz et al., 2020; Portillo and Neofytos, 2023). The paradigm for treatment of bacterial diseases has shifted to “shorter is better” (Lee et al., 2022; Imlay and Spellberg, 2022). Given the nature of IFD (ie their overall mortality, with over 3.5 million deaths estimated annually worldwide (Denning, 2024)), the frequency of central nervous system

<footnote><sup>a</sup> Department of Infectious Diseases and Tropical Medicine, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique -Hôpitaux de Paris, Université de Paris Cité, Paris, France</footnote>

<footnote><sup>b</sup> Institut Pasteur, Centre d'Infectiologie Necker-Pasteur, National Reference Center for Invasive Mycoses and Antifungals, France</footnote>

<footnote><sup>c</sup> Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland</footnote>

<footnote><sup>d</sup> Institute of Microbiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland</footnote>

<footnote>* Corresponding author. Service de Maladies Infectieuses et tropicales, Hôpital Necker Enfants Malades, 149, rue de Sèvres, Cedex 15, 75743, PARIS, France. E-mail address: olivier.lortholary@aphp.fr (O. Lortholary).</footnote>
involvement, the characteristics of immunocompromised patients (such as the type and intensity of immunosuppression, the capacity to restore a proper immune response) and the pharmacokinetic/pharmacodynamic characteristics of antifungal agents (in vitro activity, bioavailability, rate of tissue penetration) therapy can sometimes be pursued for months or even years, some being life-long prescribed (for example coccidioides-induced meningitis, diseases of prosthetic materials). The emergence of resistant fungi and degree of drug toxicity (Benitez and Carver, 2019; Perlin et al., 2017; Orasch et al., 2018) point to the need to re-evaluate the duration of systemic antifungal treatment for patients who developed IFD.

Treatment duration is a function of treatment goals. Ideally, treatment should restore the patient's pre-infection clinical status, resolve radiologic abnormalities, and achieve negative fungal cultures—or at minimum, reduce the fungal burden to undetectable levels. Theoretically, the latter could be approached by molecular or antigenic biomarkers especially for IFD with a well described and dedicated biomarker, ie cryptococcal antigen and cryptococcal meningitis, galactomannan antigen and aspergillosis ... Unfortunately, persistently immunocompromised patients are unlikely to reach all these goals, at least simultaneously. Indeed, the type and intensity of the

immunosuppression will not only influence the type of IFD but also its evolution. (Galmiche et al., 2023). Their treatment goal may be achieving a less aggressive form of IFD rather than total eradication, at least in the initial phase of treatment. Thus, the treatment regimen for immunocompromised patients must be tailored for each individual and monitored for continued efficacy (Slavin et al., 2021; Heinz et al., 2019; Neofytos et al., 2021).

Below, we review the current evidence guiding treatment duration for the IFDs, organized by the strength of evidence supporting the recommended treatment durations: Cryptococcal meningitis, *Pneumocystis* pneumonia, invasive aspergillosis, invasive candidiasis, and invasive mucormycosis. Current guidelines and level of evidence supporting them are summarized in Table 1, and the main clinical trials providing the most robust evidence have been summarized in Supplementary Table 1.

## 1. Cryptococcal meningitis

Cryptococcal meningitis is associated with high rates of fatality in early-stage infection and severe sequelae among survivors (Rajasingham et al., 2017). The epidemiology of this infection changed dramatically

<table><caption>**Table 1**
Level of evidence supporting current guidelines for IFI therapy duration.</caption><thead><tr><th rowspan="2"></th><th rowspan="2">IFI</th><th rowspan="2">Current Guidelines</th><th colspan="2">Treatment regimens</th><th colspan="4">Available tools to adjust therapy duration</th></tr><tr><th>Induction therapy</th><th>Maintenance therapy</th><th colspan="2">Biomarkers</th><th>Conventional imaging</th><th>Nuclear imaging</th></tr></thead><tbody><tr><td rowspan="2">Cryptococcal meningitis</td><td rowspan="2">HIV-infected patients</td><td>Induction<br>AmB-L 1 dose + [FCZ+5FU] 2w<br>OR AmB + 5FU 7d then FCZ 7d</td><td>Prophylaxis<br>12 months post-CD4&gt;200/mm³</td><td></td><td>CrAg /<br>GM</td><td>BDG</td><td>NAAT</td><td></td></tr><tr><td>Non-HIV patients</td><td>Induction<br>AmB-L + 5FU ≥2w</td><td>Prophylaxis<br>6-12 months FCZ</td><td></td><td>CrAg<br>-</td><td></td><td></td><td></td></tr><tr><td>Pneumocystis pneumonia</td><td></td><td>Induction<br>SXT-TMP 21 d<br>(ECIL for hematological malignancies ≥14d)</td><td></td><td></td><td>/</td><td>-</td><td></td><td></td></tr><tr><td>Invasive Aspergillosis</td><td></td><td>≥ 6-12 w (total duration of therapy: tailored to each patient)</td><td></td><td></td><td>GM<br>±</td><td>-</td><td></td><td></td></tr><tr><td>Candida blood stream infection</td><td></td><td>≥ 14d (after first negative blood culture)</td><td></td><td>/</td><td>/</td><td>±</td><td>/</td><td></td></tr><tr><td>Mucormycosis</td><td></td><td>AmB-L (Isavuconazole if pre-existing renal impairment) with undefined generic duration (until permanent reversal of immunosuppression and complete response on imaging)</td><td></td><td></td><td>/</td><td>/</td><td></td><td></td></tr></tbody></table>

<table><caption>**Table 1.** Level of evidence supporting current guidelines for IFI therapy duration.</caption><thead><tr><th>RCT comparing therapy duration between arms</th><th>Non-dedicated to therapy duration RCT<br>Non-randomized prospective cohorts</th><th>Retrospective studies</th><th>Small series<br>Case reports</th><th>No data</th></tr></thead></table>

AmB: deoxycholate amphotericin B; AmB-L: liposomal amphotericin B; FCZ: Fluconazole; 5FU: 5-Fluorouracile; SXT-TMP: Sulfamethoxazole-Trimethoprim; w: week(s); d: day(s); CrAg: Cryptococcus antigen; BDG: beta-D-glucan; GM: galactomannan antigen; NAAT: nucleic acid amplification tests
The current consensus for biomarkers usage in guiding therapy duration is summarized via the following symbols: “-” not useful/not recommended, “±” could be useful in some situations but need further dedicated research.

AmB: deoxycholate amphotericin B; AmB-L: liposomal amphotericin B; FCZ: Fluconazole; 5FU: 5-Fluorouracile; SXT-TMP: Sulfamethoxazole-Trimethoprim; w: week(s); d: day(s); CrAg: Cryptococcus antigen; BDG: beta-D-glucan; GM: galactomannan antigen; NAAT: nucleic acid amplification tests
The current consensus for biomarkers usage in guiding therapy duration is summarized via the following symbols: “-” not useful/not recommended, “±” could be useful in some situations but need further dedicated research.
with the HIV pandemic and is now the primary cause of meningitis in high prevalence HIV regions and is responsible to up to 25% of deaths related to HIV(Rajasingham et al., 2022). In contrast, its epidemiology in Western countries has evolved, with cryptococcosis now more commonly occurring in patients without HIV than in those living with the virus (Paccoud et al., 2023). Clinical research to mitigate mortality has divided treatment into 3 phases: induction, consolidation and maintenance.

## 1.1. Induction treatment

### 1.1.1. HIV-infected patients

Over the past four decades, clinical trials have tested several combination drug therapies as well as different doses of drugs (Supplementary Table 1). Guidelines and clinical practice have broadly adopted the duration of the induction phase applied in these trials. Early trials during the HIV-pandemic used a 6–10 weeks induction period with conventional deoxycholate amphotericin B as backbone (Bennett et al., 1979; Dismukes et al., 1987; Larsen, 1990). Shorter periods were not found to be effective in a small RCT in the USA (1 week of daily administration, total of 14 patients in 1990) (Larsen, 1990), although the dose of conventional amphotericin B may have been too low and not sufficiently active alone (van der Horst et al., 1997). A decade ago, a randomized clinical trial in people living with HIV (PLWH) patients in Vietnam found a combination of conventional amphotericin B and fluycytosine to reduce mortality at all time points studied compared with conventional amphotericin B plus fluconazole combination or conventional amphotericin B alone (Day et al., 2013). This protocol called for combinations to be given for two weeks before switching to maintenance therapy while conventional amphotericin B alone was given for four weeks.

The combination of conventional amphotericin B plus flucytosine as induction treatment for two weeks has successfully reduced mortality rates among PLWH with cryptococcal meningitis. Of note, less than 14 days of flucytosine was shown to be inferior to the full duration of induction using this combination (Dromer et al., 2008). However, there remain several concerns about these agents. Conventional amphotericin B has known toxicity problems, and flucytosine is not readily available in low-income countries. Scientists hoped to identify alternative drugs or shorter treatment regimens. The African ACTA trial (2018) conducted in 721 HIV infected subjects compared a shorter combination regimen (1 week of conventional amphotericin B plus flucytosine followed by 1 week of high-dose oral fluconazole) to a longer regimen (2 weeks of amphotericin B plus flucytosine). The study was designed to test non-inferiority, not superiority. Mortality was measured at week 2, week 4 and week 10. The shorter regimen demonstrated non-inferiority at both week 4 (Hazard ratio (HR) 0.5, 95% confidence interval (CI) [0.29; 0.86]) and week 10 (HR 0.56, 95%CI [0.35; 0.91]) (Molloy et al., 2018).

As a result of these findings, WHO guidelines (World Health Organization, 2018) adopted the shorter induction regimen (i.e., 1 week of conventional amphotericin B plus flucytosine followed by 1 week of high dose [1200 mg/day] fluconazole). However, in the absence of superiority data (and with available drug monitoring), higher income countries continue to use the two-weeks combination induction regimen, as recently recommended by the ECMM/ISHAM/ASM(Ryom et al., 2022; National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and Infectious Diseases Society of America, 2021; Chang et al., 2024). In addition, one should remember that exclusive oral therapy associating fluconazole high dose and flucytosine during 2 weeks was also validated (Molloy et al., 2018) and is still recommended by WHO guidelines when no amphotericin B formulations are available (14 days of fluconazole 1200 mg daily with flucytosine 100 mg/kg daily).

Investigators continue to test different regimens to optimize resources and minimize toxicity. A recent non-inferiority randomized trial (2022, Africa) compared a single dose of liposomal amphotericin B

combined with two weeks of flucytosine and fluconazole to one week of conventional amphotericin B combined with flucytosine, before switching for fluconazole with flucytosine (Jarvis et al., 2022). The regimen that included liposomal amphotericin B demonstrated non-inferiority with respect to mortality at week 10 as well as moderately less severe adverse events (50% vs 62%). Again, WHO modified its guidelines to recommend this shortened regimen as first line therapy for cryptococcal meningitis (Guidelines for Diagnosing, Preventing and Managing Cryptococcal Disease among Adults, Adolescents and Children Living with HIV, 2022). These non-inferiority trials conducted in low-income settings are useful for allocating limited resources. However, higher income regions have the availability of flucytosine and capacity to monitor for and administer liposomal amphotericin B to manage its toxicity (Rothenbühler et al., 2018; Dreyfuss et al., 2013) and international societies therefore recommend two weeks of lower dose amphotericin B (3 mg/kg daily for liposomal formulation or 0.7 mg/kg daily for deoxycholate formulation). Current guidelines and level of evidence supporting them are summarized in Table 1.

Most clinical trials of treatment for cryptococcal meningitis have been conducted in samples of PLWH. We know considerably less about relative treatment effectiveness and tolerance in other populations, such as solid organ transplant recipients.

### 1.1.2. Prolonged induction therapy

It may be necessary to adapt induction therapy for Cryptococcal meningitis in immunocompromised patients to achieve fungal clearance from the cerebrospinal fluid (CSF) (Jarvis et al., 2014; Rolfes et al., 2014). Adaptations can include different doses or duration of treatment. In patients who fail to improve or deteriorate neurologically, who continue to have high or increasing CSF opening pressure, or who have positive CSF cultures or predicted to be persistently positive (ie large lesions on neurological imagery), extending the 2-week induction period should be considered. It should be noted that prolonged induction regimens have not been systematically evaluated. Patients receiving extended therapy require close monitoring, including repeated and systematic lumbar punctures (Kagimu et al., 2022) and CSF cultures, to tailor treatment to the evolving clinical situation.

### 1.1.3. Solid organ transplant recipients

Cryptococcal meningitis among immunocompromised patients without HIV has received relatively little research attention. There are no randomized trials to guide the choice of drug or duration of administration despite higher mortality rate in some studies, highlighting the need for dedicated management strategies (Paccoud et al., 2023). Existing guidelines rely mainly on retrospective data, expert opinions, and data extrapolated from HIV trials (Baddley, Forrest, and the AST Infectious Diseases Community of Practice, 2019; Nina Singh et al., 2008). One exception is a multi-site cohort study of 75 transplant recipients with cryptococcal meningitis (Sun et al., 2009). In this study, subjects received either conventional amphotericin B or liposomal amphotericin B. Approximately 40% of subjects in the first group and 67.3% of the second group also received flucytosine. The duration of induction therapy was approximately 3 weeks (median of 20 days in conventional amphotericin B group and 25 days in liposomal amphotericin B group). Of the 75 subjects enrolled, 61 survived the induction period. Less than half of the first group (40%) survived 90 days while only 11.5% of the second group survived that long.

One might expect the addition of flucytosine to significantly reduce the time to CSF sterilization. This has been demonstrated in HIV-positive patients (Dromer et al., 2007). This finding may apply to solid organ transplant recipients if the fungal burden is adequately reduced by the initial treatment, but dedicated data is missing in this population.

Similarly, the duration of induction therapy could be modified if net immunosuppression state (Roberts and Fishman, 2020) is reduced in transplant patients. Current guidelines advise that whenever feasible the immunosuppression therapy is gradually reduced while treatment is
initiated to reduce the fungal burden of these patients (Baddley, Forrest, and the AST Infectious Diseases Community of Practice, 2019; Henao-Martínez et al., 2018). However, the best step-down strategy to reduce immunosuppression is not clear. A drastic reduction of immunosuppression could expose the patient to a risk of immune reconstitution inflammatory syndrome. Moreover, calcineurin inhibitors have been shown to have intrinsic anti-cryptococcal activity (Nina Singh et al., 2007; Kontoyiannis et al., 2008) which may explain a different outcome and risk of immune reconstitution inflammatory syndrome (IRIS) in the group of patients receiving calcineurin-inhibitors.

The current recommendation for treatment of cryptococcal meningitis in immunocompromised patients without HIV is at least a two-week induction regimen with liposomal amphotericin B and flucytosine. The duration can be extended to 4–6 weeks if optimal improvement has not been achieved (Baddley and Forrest, 2020).

## 1.2. Consolidation and maintenance treatment

Current recommendations for treatment following induction therapy call for 8 weeks of fluconazole (800 mg/day). This extended regimen following induction therapy is referred to as consolidation treatment. The research base for consolidation treatment is thin. Most treatment recommendations rely on expert opinion (Guidelines for Diagnosing, Preventing and Managing Cryptococcal Disease among Adults, Adolescents and Children Living with HIV, 2022). The results of two clinical trials have been reported (Mootsikapun et al., 2003; van der Horst et al., 1997). Both were conducted before trials of antiretroviral drugs and compared fluconazole to itraconazole for 8–10 weeks following induction therapy, proving superiority of the former. It should be noted that neither trial specifically evaluated the duration of consolidation treatment.

Maintenance therapy has received more research attention among HIV-infected patients, including several trials for interruption of such treatment after immune restoration (Mussini et al., 2004; Soriano et al., 2000; Lortholary et al., 2006). These studies support the current recommendation of 12 months maintenance treatment (as most relapses occurred during the first year) with fluconazole in HIV-infected patients with undetectable viral loads and CD4 counts greater than 200/mm³ for 3 consecutive months.

## 1.3. Assessment of therapeutic response

The patient population with cryptococcal meningitis is not homogeneous. Each patient can vary with respect to immunocompromised history and comorbidities. Surrogate markers to guide the intensity and duration of therapy have some limitations but can be useful, nonetheless.

There are several ways to monitor Cryptococcal antigen (CrAg) titer. Latex agglutination, ELISA, and more recently lateral flow assays have been used for initial diagnosis using either serum or CSF(Temfack et al., 2021). Both tests detect an antigen from the cryptococcal polysaccharide capsule. High titers at baseline are associated with a worse prognosis in HIV-infected patients, which is likely to reflect a higher fungal burden (Kabanda et al., 2014). There have been several studies of CrAg titers kinetics to assess optimal treatment duration. Unfortunately, CrAg kinetics in serum have been shown to be imperfectly predictive (Powderly et al., 1994) or completely uncorrelated with recurrent infection rates and treatment success (Aberg et al., 2000; Antinori et al., 2005; Brouwer et al., 2005; Skripuletz et al., 2014). However, older studies in patients without HIV have demonstrated a correlation between low or negative CrAg titers at the end of treatment and treatment success (Dismukes et al., 1987; Diamond, 1974). The clearance of CrAg among PLWH with cryptococcal meningitis who restore their immunity may require up to 4 years (Lortholary et al., 2006). This discrepancy in the literature has not been resolved even though PLWH have a higher fungal load. Moreover, CrAg clearance from the CSF is achieved by macrophages, is a slow process, and may be independent of yeast killing (Grinsell et al., 2001).

Thus, serum CrAg is not an appropriate biomarker for cryptococcal meningitis and treatment duration, especially in patients with a high fungal burden.

CrAg titers in CSF may be useful when relapse is suspected, although the sensitivity might be low, particularly with first generation kits. One study found that 43% of patients who relapsed had an elevated CrAg titer when compared to baseline titers and the 5% of patients who did not relapse (Powderly et al., 1994). However, there is no available extensive data regarding the CrAg kinetics in the CSF, which limits its utility for monitoring treatment efficiency. Recurrence of symptoms after initial improvement presents diagnostic challenges. Symptoms may reflect an IRIS rather than a relapse of infection (Lortholary et al., 2005; N. Singh et al., 2005). Thus, recurring symptoms call for a differential diagnostic work up to spare patients from toxicity associated with drug re-initiation.

One study found CSF beta-D-glucan (BDG) to be higher among PLWH with cryptococcal meningitis than patients without this fungal infection (Rhein et al., n.d.; Lyons et al., 2015). Moreover, BDG titers decreased more rapidly than CrAg titers and normalized faster as well. This study found approximately a 50% reduction of BDG 4 days after therapy was initiated. BDG is not commonly used to detect cryptococcal infection. The concentration of BDG in *Cryptococcus* sp. cell wall is lower than that found in other fungi (Miyazaki et al., 1995; Davis et al., 2020). Nevertheless, high yeast concentrations seen in meningitis patients may permit detection of BDG in CSF. BDG may be able to distinguish IRIS from relapse infection and spare patients prolonged induction or consolidation treatments and their toxicities, but this should be carefully studied in prospective studies. Thus, this biomarker may hold promise to monitor treatment efficacy and therefore duration.

# 2. Pneumocystis pneumonia

The incidence of *Pneumocystis* pneumonia increased dramatically during the first years of the HIV pandemic (Kaplan et al., 2000). Historically found among malnourished people or premature infants (Goldman et al., 2005), it was then described in cancer patients receiving myelotoxic chemotherapy, and eventually became one of the most prevalent opportunistic diseases in PLWH (Morris et al., 2004; Denis et al., 2014). Recently, patients who were not previously considered in prophylactic measures are increasingly affected by *Pneumocystis* pneumonia (as recently evaluated by the French National Reference Center for Invasive Mycoses and Antifungals – unpublished data: between 2012 and 2022, 3323 *Pneumocystis* pneumonia cases have been reported, with only 14.9% of them among people living with HIV, while most of the cases occurred in patients with hematological (27.3%) or solid (20.4%) malignancies and patients with solid organ transplants (15.5%)) (Kolbrink et al., 2022).

## 2.1. Antifungal therapy

Several induction regimens have been used to treat *Pneumocystis* pneumonia. A summary of randomized trials is provided in *Supplementary Table 1*. One trial in pre-HIV era (USA, 1978) among pediatric cancer patients compared 14 days of trimethoprim-sulfamethoxazole (TMP-SMZ) vs pentamidine (Hughes et al., 1978). They found success rates of 77% and 75% in the respective treatment groups. While it is difficult to compare pediatric patients to adult ones, adult therapeutic regimens were adapted during the rise of the HIV-pandemic based on this available pediatric trial, and one early study of HIV-infected adult subjects used longer treatment duration (21 days) due to concern of relapse in severely immunocompromised patients (Haverkos, 1984). However, even though another study conducted at that time in a similar patient population used a 14-day treatment duration (and found no difference in mortality rates when comparing PLWH and others) (Kovacs et al., 1984), subsequent studies adopted the longer 21-day induction period (Wharton et al., 1986; Sattler et al., 1988; Medina et al., 1990;
Safrin et al., 1996). Interestingly, the Sattler trial planned a 17-to-21-day therapeutic regimen, but the actual median duration of treatment was 16 days. Even with this shortened induction period, the survival rate was 86% in the TMP-SMZ group. Despite some success with shorter 2-week induction period, international guidelines for *Pneumocystis pneumonia* have adopted the 21-day regimen, including in transplant recipients where optimal treatment duration has not been studied (Ryom et al., 2022; Fishman, Gans, and the AST Infectious Diseases Community of Practice, 2019). In contrast, the European Conference on Infection in Leukemia (ECIL) has recommended treating patients with hematological malignancies for at least 14 days (Maschmeyer et al., 2016).

## 2.2. Assessment of therapeutic response

Like other fungal diseases, *Pneumocystis pneumonia* presents in diverse forms with varying severity and different fungal loads (Kaplan et al., 2000; Morris et al., 2004). Moreover, individual patients have different immune profiles (Kovacs et al., 1984; Fishman, Gans, and the AST Infectious Diseases Community of Practice, 2019). Thus, clinicians are faced with multiple decision points to adapt treatment on a case-by-case basis.

The standard treatment guidelines for *Pneumocystis pneumonia* in immunocompromised patients is based on TMP-SMZ for 21 days. It is common for patient's disease to progress during the first five days of treatment (National Institutes of Health-University of California Expert Panel for Corticosteroids as Adjunctive Therapy for Pneumocystis Pneumonia, 1990). Clinicians should resist the urge to modify the treatment regimen. Clinical failure is a rare event and should not be considered until day 8 of full-dose therapy (Helweg-Larsen et al., 2009). A differential diagnostic work-up should be used to identify co-existing diseases (Baughman et al., 1994). If none is found and the patient is not improving, salvage therapy can be considered (Smego et al., 2001).

Beta-D-glucan is mainly used for *Pneumocystis pneumonia* diagnosis for its predictive negative. The literature does not support the use of BDG as a biomarker to evaluate treatment response. The existing studies have produced conflicting results. At least one study reported a good correlation between a decrease in serum BDG and a favorable treatment outcome (Held and Wagner, 2011). However, other studies have failed to find this association (Koo et al., 2012; Marty et al., 2007; Koga et al., 2011).

On the other hand, *Pneumocystis immuno-fluorescence assay* requires bronchoalveolar fluid. Because *Pneumocystis* cysts can persist in lung airways for a considerable period of time in patients who have made a full recovery (O'Donnell et al., 1998), this assay should not be used to make decisions about prolonging treatment or to assess status of infection under treatment. The questionable predictive value of this test does not warrant the invasiveness of the procedure to obtain an appropriate specimen.

*Pneumocystis* PCR have been included in several diagnosis algorithms (Robert-Gangneux et al., 2014; Veintimilla et al., 2023; "Prevention and Treatment of Opportunistic Infections Among Adults and Adolescents," n.d.). To our knowledge, there are no data on kinetics under treatment using this assay.

Serial pulmonary imaging can provide useful information for decisions concerning prolongation of treatment. One study of non-HIV immunocompromised patients with *Pneumocystis pneumonia* found that the characteristic ground-glass opacity seen in CT scans improves rapidly as subjects progressed through treatment (Vogel et al., 2012). Earlier studies in PLWH using X-ray imaging found that lesions improve at a slower rate (Datta et al., 2003; DeLorenzo et al., 1987). This difference may reflect a decrease in sensitivity to dimmer images on X-ray than seen on CT scans. While the vast majority of *Pneumocystis pneumonia* cases do not require serial radiological evaluations to guide treatment duration, complex cases with intricated causes for respiratory symptoms and/or difficult clinical evaluation (ie ICU settings), serial CT scans could provide valuable information regarding treatment

efficiency.

# 3. Invasive pulmonary aspergillosis

Aspergillosis presents in several forms, depending on host immune status and underlying conditions (Kosmidis and Denning, 2015). Invasive aspergillosis (IA) is one of the most severe forms on this disease spectrum. It is primarily found in patients who are severely immunocompromised, especially those with prolonged, severe neutropenia or long-term steroid therapy (Denning, 2024).

## 3.1. Antifungal therapy

Current treatment guidelines for invasive pulmonary aspergillosis calls for induction therapy consisting of voriconazole or isavuconazole for 6–12 weeks (Neofytos et al., 2021; Frederic Tissot et al., 2017; Patterson et al., 2016; Ullmann et al., 2018). The range of treatment duration reported in the literature is wide, from 2 to 3 weeks to multiple months (Fanny Lanternier et al., 2020). While some clinical trials have been conducted to identify first line drugs (voriconazole, isavuconazole, amphotericin B), no randomized studies have been conducted to evaluate optimal therapy duration in any specific patient population. These studies are the basis of current treatment guidelines for Aspergillosis (Herbrecht et al., 2002; Bowden et al., 2002; J. A. Maertens et al., 2016, 2021).

Defining optimal duration of treatment relies on a clear definition of expected treatment outcome. However, optimal treatment outcome must be balanced against toxicity in immunocompromised patients as well as disturbance of underlying conditions, such as a relapse of hematologic malignancies. Toxicity and relapse of disease can confound analyses when mortality is the endpoint; this is particularly relevant when autopsy rates are low (Anaissie, 2007). Therefore, findings from such studies may result in unnecessary escalation or extension of therapy by incorrectly attributing the harmful effects of the underlying disease or treatment toxicity to aspergillosis infection. Moreover, establishing clear treatment guidelines is hampered by a lack of a clear definition of treatment failure (Slavin et al., 2021) and an absence of well-defined treatment assessment measures that are consistent with clinical practice for caring for these patients (Segal et al., 2008).

## 3.2. Assessment of therapeutic response

Galactomannan is frequently used to diagnose IA. It is a polysaccharide antigen that is found primarily in cell walls of *Aspergillus* species. It is released into the bloodstream during invasive infection but the kinetics of this biomarker are complex and not completely elucidated to date (Mercier et al., 2018). Multiple studies have reported a correlation between galactomannan levels and treatment outcomes for aspergillosis (François et al., 2002; Woods et al., 2007; J. Maertens et al., 2009; S. H. Park et al., 2011; Simone A. Nouér et al. 2011). Monitoring galactomannan levels over the first two weeks of antifungal therapy can be useful in assessing induction therapy efficacy. Woods and colleagues (Woods et al., 2007) have proposed a definition of treatment success to be survival with repeatedly negative serum galactomannan indexes (GMI) for 2 or more weeks after the first negative GMI with an absence of new extrapulmonary IAs lesions. Neutropenia status did not appear to affect the usefulness of this definition. This was confirmed by a reanalysis of SECURE trial (2015) data (Kovanda et al., 2017). Agreement between GMI defined outcome and survival at week 6, the classical trial outcome, was confirmed independently by Nouer and colleagues (kappa correlation coefficient = 0.819, p < 0.001) (Simone Aranha Nouér et al. 2012).

While very promising, further prospective research is needed to confirm the usefulness of this biomarker under common clinical conditions and to further define therapeutic rules, especially considering that IA with a positive serum GM might represent only a fraction of
commonly managed IA cases (Couchepin et al., 2018). A recent retro-
spective study (Mercier et al., 2020) looked at galactomannan kinetics in
the six weeks prior to death from IA using two independent cohorts.
Authors were able to identify different risk groups based on the evolu-
tion of GMI. However, these findings did not reproduce the results of
previously published GMI-based classification strategies to predict
clinical outcome for IA (Woods et al., 2007; Chai Louis Y. A. et al., 2020).
Moreover, a negative test for serum GMI does not exclude a poor
treatment outcome and cessation of treatment cannot rely only on this
biomarker evolution (Simone A. Nouér et al. 2011). Thus, additional
prospective research using parallel clinical and computed tomography
(CT) scan findings is needed to provide a sound empirical basis for
prognostic value of GMI levels in assessing treatment efficacy and
duration.

BDG has also been used as a biomarker for IA, but it is less useful than GMI. Studies have found that BDG is poorly or not correlated with IA outcome (Koo et al., 2012; Pini et al., 2016; Angebault et al., 2016). One prospective study used a composite marker of GMI plus BDG to predict IA outcome (Neofytos et al., 2015). Decline in this composite marker was correlated with mortality at week 12 but not at week 6. The predictive value in this study appears to be carried by GMI alone as GMI level was correlated with mortality at both weeks 12 and 6.

Biomarkers based on molecular biology are now being developed and tested, but there are little data on the underlying kinetics. Nonetheless, PCR techniques have been included in the latest EORTC diagnosis guidelines for IA (Donnelly et al., 2020). One retrospective study used *Aspergillus* PCR to look at 51 cases of probable or proven IA (Imbert et al., 2016). Cases included, among other immunocompromised patients, subjects with hematological conditions (59.2%) and solid organ transplant recipients (27.6%). *Aspergillus* DNA PCR levels during the first week of treatment were not associated with mortality on day 30 or day 90 after treatment initiation. However, subjects who were still PCR positive during the third week of treatment had an 80% increase in risk of mortality at day 30 and 100% risk of death at day 90, while patients who were negative after the first two weeks of treatment (n = 9) survived. Another study did not find any correlation between *Aspergillus* blood DNA and outcomes (Bergeron Anne et al., 2020).

In immunocompromised patients, clinical signs of IA are frequently nonspecific. Early diagnosis relies on CT images to identify characteristic pulmonary lesions. Thus, this type of imaging is included in current diagnostic guidelines (Neofytos et al., 2021; Donnelly et al., 2020). Descriptions of characteristic lesions and their evolution through progression of disease or resolution by treatment have largely relied on studies of hematological patients (Brodoefel et al., 2006; Caillot et al., 2001). In neutropenic patients, lesion volume can increase up to 4-fold during the first week of treatment and remain stable during the second week without indicating treatment failure (Caillot et al., 2010). This evolution is thought to be a consequence of an inflammatory response within the lesion as well as cavitation concomitant with neutropenia recovery. A recent study re-evaluated chest CT scans from earlier clinical trials (Vehreschild et al., 2017). The authors reported that lesion volume can increase between day 7 and day 14 after introduction of treatment. Such an increase was found to have a significant association with mortality (OR 20.01, 95% CI 1.62–157.32). However, it is not clear if this association is related to treatment failure or deleterious inflammatory response (Rhee et al., 2009).

Therefore, even if the optimal chest CT frequency is not well defined, follow-up exams should probably be performed at 1 and 2 weeks after treatment introduction and subsequent exams should be driven by changes in clinical status of the patient and changes in GMI(Alexander et al., 2021). It should be noted that the kinetics of lesion resolution as seen by radiological assessment can be slow, even after neutropenia resolution (Brodoefel et al., 2006; Kuhlman et al., 1988). The delineation of a clear radiological target for therapy cessation remains elusive, likely contingent upon the initial lesion's extensivity and the host's immune status. A pragmatic approach to radiological evolution into

therapeutic decision algorithms could involve setting multiple thresh-
olds tailored to distinct clinical scenarios. Complete resolution might be
considered for non-extensive lesions accompanied by robust immune
reconstitution in the host. Alternatively, near-complete resolution (with
residual scarring) could be expected in cases of initially extensive le-
sions. On the other hand, when immune resolution remains severely
impaired, stability of lesions observed across successive chest CT scans
may further guide decisions.

Radiological evaluation of IA in the presence of cavitation presents challenges. In non-neutropenic patients, the pattern and timing of lesion changes are less clear, especially when patients are diagnosed at a later stage of infection. And the prognostic value of radiological evaluation in these patients is unknown (Alexander et al., 2021; S. Y. Park et al., 2011). The contribution of positive emission tomography (PET) scan during the follow-up of IA and particularly when treatment can be stopped safely is under investigation and coordinated by one of us (F. Lanternier) in interaction with the trend of biomarkers in plasma (OPTIFIL, NCT02955966).

The subset of IA associated with viral diseases (influenza or SARS-CoV-2), especially in an intensive care context, represents a specific pathophysiological and clinical entity. The dysregulated immune response in this entity differs from the immunosuppression state observed in more classically observed IA cases. Therefore, treatment duration should be tailored to the evolution of these patients as discussed elsewhere (Lamoth, 2022). Despite the absence of dedicated clinical trials, antifungal therapy should be continued for at least 4–6 weeks in these settings if IA is highly suspected (probable or proven) or could be interrupted following extubation in other cases (possible or putative IA).

4. Invasive candidiasis

Invasive candidiasis (IC) presents in several forms and can be asso-
ciated with high mortality rates (Pappas et al., 2018). Candidemia is
diagnosed with at least one positive blood culture. It can occur with and
without complications reflecting deep-seated foci of infection. Existing
treatment guidelines emphasize early initiation of treatment for at least
14 days (echinocandins first line ± switch) and source control (Pappas
et al., 2016).

4.1. Antifungal therapy

Treatment guidelines indicate that standard treatment for uncom-
plicated IC calls for 14 days after the first negative blood culture of
treatment with echinocandins or triazoles (Pappas et al., 2016). How-
ever, the empirical evidence underlying this duration of therapy is
limited. The 14-day period post negative culture has been used in several
clinical trials evaluating first line therapy for candidemia (Rex et al.,
1994; Abele-Horn et al., 1996; Mora-Duarte et al., 2002; Rex et al., 2003;
B. Kullberg et al., 2005; Kuse et al., 2007; Reboli et al., 2007; Kullberg
et al., 2019). Unfortunately, these studies did not evaluate different
schedules for administering drug. Observational studies have reported
that longer duration of treatment did not result in fewer microbiological
failures (Nguyen et al., 1995). Nonetheless, compliance to current
guidelines and involvement of an infectious diseases specialist have
been associated with reduced mortality when compared to
non-standardized practices. It remains to be seen if shorter treatment
time could be safe and effective in specific populations as hinted by a
retrospective analysis of real-life practice in 2007 showing that even
though 12% of treated candidemia received shorter treatment, no sig-
nificant difference in mortality at 4 weeks was detected (Horn et al.,
2007; Mejia-Chew et al., 2019; Junco et al., 2021; Vena et al., 2020;
Murakami et al., 2018). A retrospective monocentric study in
Switzerland showed an increased mortality of candidemia associated
with a reduced duration (16 days vs 19 days) of antifungal treatment
over the period of a decade, although multiple confounding factors
could explain such association (candidemia population also shifted to more frail populations, namely elderly and ICU patients) (Battistolo et al., 2021). Oude Lashof and colleagues studied 81 patients with uncomplicated candidemia (Oude Lashof et al., 2003). One quarter (25%) were treated for less than 7 days (while the others were treated at least 2 weeks, or even >4 weeks for 38% of them). Of the 3 cases of delayed complications of infection, none occurred in the short treatment group. Another study tied duration of antifungal therapy to the duration of blood culture positivity (Fichtenbaum et al., 1999). The short-term therapy subjects (n = 29) had a positive blood culture for a day or less; the longer treatment group (n = 28) had positive blood cultures for more than one day. Short term therapy consisted of conventional AmB for 5-7 days, and longer therapy group received conventional AmB for 14-20 days. The difference in mortality rates across the two groups (10% vs 25%) was not statistically significant, although the study may have been underpowered to detect such difference. No relapses were observed in the short treatment group while one relapse was reported in the longer-term group (median follow up of 272 days). A recent retrospective study evaluated short-course treatments among 114 patients with non-complicated candidemia (Vena et al., 2023). Authors showed that receiving a short-course treatment (5-11 days, n = 35), when compared to a prolonged-course treatment (12-24 days, n = 79), was not significantly associated with 90-day mortality (22.9% vs 22.8%, p = 0.997) and 1-year mortality (p = 0.95), nor recurrent candidemia (8.6% vs 7.0%, p = 0.63).

## 4.2. Assessment of therapeutic response

No prospective study has evaluated a biomarkers-driven strategy to guide therapy among patients with confirmed IC. The only available trials using decisional biomarkers concern probabilistic or preemptive strategies of anti-fungal therapy introduction/cessation among severe patients in the ICU settings (Rouzé et al., 2017; Bloos et al., 2022) and are beyond the scope of this review.

However, BDG and other biomarkers are promising and should be evaluated in future prospective trials.

Overall, serum BDG kinetics are difficult to relate to clinical outcome (Angebault et al., 2016). Upon antifungal therapy, BDG has been shown in retrospective studies to decrease sharply among patients who responded to treatment whereas non-responders had stable or increased levels over the course of the infection (Jaijakul et al., 2012; Guitard et al., 2018). Interestingly, Agnelli and colleagues showed that among 148 patients with candidemia, a persistently negative serum BDG was significantly associated with lower rates of complications (2 vs 41), mortality (1 vs 29) and shorter hospitalization stay (34 vs 51 days) (Agnelli et al., 2020). In response to the latter study, Giacobbe and colleagues confirmed the protective effect of a persistently negative BDG among 213 patients with candidemia (mortality OR 0.3 (95%CI [0.1; 0.9]) but also showed that outcome was not statistically different between patients with persistently negative BDG and patients with negative baseline that subsequently turned positive (Giacobbe et al., 2020). These studies, in combination with the pilot trial cited earlier, could help characterize a low-risk population that could benefit from shorter and/or oral treatment.

However, caution is advised when interpreting these studies, as mechanisms regulating BDG kinetics in treated IC are poorly understood and may be influenced by various factors. Various factors, such as the type of treatment employed (echinocandins could theoretically induce an initial BDG flare (Sims et al., 2012)), the *Candida* species (Angebault et al., 2016) and the underlying medical condition contribute to this complexity. For instance, in a recent study, BDG in *C. auris* culture supernatant was shown to be significantly less concentrated than with *C. albicans* (Mikulska et al., 2022). Additionally, a limited retrospective study among hematological stem cell transplant recipients showed that BDG remained positive for a median of 48 days, even in responders (Mikulska M. et al., 2011). The presence of a deep-seated infection (ie

*Candida* endocarditis is associated with a slow, if any, decrease in serum BDG (Angebault et al., 2016; Lefort et al., 2012). Other confounding factors further complicate the interpretation (Tschopp et al., 2022; Isnard et al., 2021).

Other promising biomarkers include T2MR *Candida* and emerging sepsis markers such as presepsin.

T2MR *Candida*, an FDA-approved non-culture-based platform for candidemia diagnosis using T2 magnetic resonance measurements coupled with DNA amplification, has been shown to be more sensitive than blood cultures in candidemia (Monday et al., 2021). Munoz and colleagues evaluated the prognostic value of this marker. Among 30 patients with candidemia, a positive T2MR in the first 5 days after initial diagnosis was associated with a high risk of complications (OR 36.5 (95%CI [1.7; 779.2])) and kept good predicting performances for complication after 7 days (Se 85.7%, Sp 94.7%) even though not better than BDG at this timepoint (Muñoz et al., 2018).

## 4.3. Source control and deep-seated candidiasis

As reviewed recently (Bassetti et al., 2020), source control is mandatory to eradicate IC (Pappas et al., 2016; Martin-Loeches et al., 2019). Multiple studies have reported a correlation between poor outcomes and failure to control the infection source (central catheter not removed, persistent intra-abdominal collection ...) (Martínez et al., 2017; Nucci et al., 2010; Agnelli et al., 2019; Junco et al., 2021; Vena et al., 2020). Prompt source control is probably mandatory to be able to reduce antifungal therapy duration, even though the literature is disparate. Early catheter removal after antifungal therapy (24-48h) did not change prognosis (Nucci et al., 2010; Damonti et al., 2017), but a recent study showed that earlier catheter removal (in the first 72h of candidemia onset) was associated with a reduction in mortality (Papadimitriou-Olivgeris et al., 2022). When source control is delayed or not possible, a prolonged (but not codified) therapy duration should be discussed, as this situation is associated with complications, including secondary deep-seated IC, such as endocarditis, endophthalmitis, joint/bone infection or CNS infection, which are rare but difficult to treat diseases (Thompson et al., 2023; Pappas et al., 2018).

# 5. Mucormycosis

Invasive mucormycosis remains one of the deadliest IFD, despite recent advances in diagnosis and anti-fungal therapies (Sigera et al., 2024). The most frequent forms of the disease are rhino-orbital and pulmonary mucormycosis (Dailey et al., 2023). Survival of infected patients depends on multiple and often intricate factors such as the correction of the predisposing factor(s), efficient and tolerable anti-fungal therapy as well as optimal surgical debridement (Vironneau et al., 2014), which is often debilitating if even possible. This tripartite therapy shapes the duration of the antifungal therapy and underscores the need to tailor therapy to individual patients.

## 5.1. Antifungal therapy

Antifungal regimens mainly rely on liposomal amphotericin B at least as first line therapy. The literature to support the standard dose or duration of treatment is limited (Bergeron et al., 2020; O.A. Cornely et al., 2014) and available prospective trials were not dedicated to duration evaluation. Available trials cannot be easily compared to determine an efficient treatment duration as they combined multiple treatment strategies and molecules associations, resulting in wide induction treatment duration ranges (4-21 days) (Spellberg et al., 2012; Lanternier et al., 2015; Marty et al., 2016; Skiada et al., 2013). Other observational studies have reported a wide range of treatment duration. Overall, polyenes are generally used for 2-4 weeks (Roden et al., 2005; Skiada et al., 2011; Shoham et al., 2010; Xhaard et al., 2012) and then switched to oral triazole (isavuconazole or posaconazole) after surgery
and at the time of hospital discharge. Treatment duration with triazoles is typically prolonged, lasting from several months to years (Rüping et al., 2010; Greenberg R. N. et al., 2006; van Burik et al., 2006). Moreover, despite the variety of Mucorales species implicated in human disease, there is currently no specific data or recommendation supporting modifications to treatment duration based on the species or the measured minimum inhibitory concentration of effective antifungal agents.

As is the case with other fungal diseases, identifying a definite therapy duration for all patients is illusive and end of treatment strategies should be considered with multiple evaluated modalities as suggested by recent international guidelines (Segal et al., 2008; Cornely et al., 2019).

A step-down therapy, or maintenance therapy, could be considered once clinical status and imagery lesions have improved while the predisposing factor(s) is still present (Kontoyiannis and Lewis, 2011). This strategy often relies on triazoles (posaconazole or isavuconazole), because of their better long-term tolerance than polyenes and depending on the predisposing factor, such therapy can be pursued for months or even life-long in selected cases (Kontoyiannis and Lewis, 2011). Nevertheless, these strategies have not been carefully evaluated either, and guidance through multimodal evaluation should be considered.

## 5.2. Available biomarkers

In contrast to other fungi, *Mucorales* do not produce significant levels of BDG to be detectable, even though they have been shown to have the appropriate genetic material to produce it (Ibrahim et al., 2005; Ma et al., 2009). Similarly, Aspergillus galactomannan is not detected, as *Mucorales* spp. do not expose gluconic cell wall sugars on the surface of their hyphae (Pickering et al., 2005). Relatively little is known about the cell wall composition of *Mucorales* spp. (Lecointe et al., 2019). This has hampered the development of specific biomarkers for this fungus. However, we do know that *Mucorales'* cell wall contains uncommon monosaccharides which hold promise for the development of specific diagnostic biomarkers (Lecointe et al., 2019, 2022). This is currently under investigation (NCT05406037).

Another promising strategy includes the use of molecular biology tools to diagnose *Mucorales* diseases and evaluate fungal load. A study of the MODIMUCOR trial is looking at the use of these tools to assess fungal load (Dannaoui, 2022). Thirty patients with a positive baseline serum qPCR were retested at regular intervals (at least twice per week). The qPCR turned negative in 70% of the patients in a median time of 4 days. These subjects were significantly more likely to survive than those with persistent positive serum qPCR for 7 or more days after initiation of anti-fungal therapy (adjusted hazard ratio 0.15 and 0.12 at 30 days and 6 months respectively, p = 0.02 and p = 0.001). However, these results are yet to be replicated in other populations and reproducibility must be ensured before designing effective clinical strategies based on molecular biology.

## 5.3. Radiological assessment of infection evolution

Most radiologic studies of pulmonary mucormycosis have been conducted in hematological patients with neutropenia. In this very specific population, a reverse halo sign is reported to be suggestive of pulmonary mucormycosis (Legouge et al., 2014; Bourcier et al., 2017). However, Marchoiri and colleagues caution that careful evaluation of images for diagnostic purpose should be done by a trained radiologists as characteristics of such lesion can point towards differential diagnosis (Marchiori et al., 2020). Few studies have looked at the kinetics of pulmonary mucormycosis lesions with CT (Legouge et al., 2014; Choo et al., 2013). They found progression of lesions up to day 26 after symptom onset. However, it is unclear whether changes in lesions correlate with treatment response or neutropenia status or overall outcome. Nam and colleagues reported a non-significant trend of

increasing peripheral neutrophils with lesion pattern evolution towards central necrosis and air-crescent sign (Nam et al., 2018).

Angio-invasion monitoring through high resolution computed tomography angiography is a promising addition to the regular computed tomography tools for diagnosis (Stanzani et al., 2015, 2021), including in non-neutropenic patients (Henzler et al., 2017). However, to incorporate it in future therapy duration algorithms, vessel occlusion evolution on serial exams needs to be carefully evaluated under treatment. Henzler and colleagues did not find significant differences in vessel occlusion between subjects receiving anti-fungal therapy and those not treated (Henzler et al., 2017). It should be noted that this study included a limited number of patients.

Magnetic resonance imaging is crucial in defining rhino-orbital cerebral extension (Mazzai et al., 2022) and should be performed regularly in the follow-up of patients to detect further progression (guiding surgical interventions). Nonetheless, surgical procedures can result in distortion of lesions or even create artifact lesion-like images. The best timing of imaging in patient follow-up is not well defined. Some recommend a delay of up to 4 weeks post induction treatment (Lanternier et al., 2015). In rhino-orbital presentations, regular specialized evaluations through minimal invasive endoscopy should probably be performed to correlate radiological findings and post-operative aspects and avoid overseeing relapse or progressing infection (NCT02226705).

# 6. Future considerations

## 6.1. Current challenges and limitations

Establishing applicable recommendations for treatment duration for IFI has frustrated and eluded clinicians. The rarity of such diseases, the heterogeneity of patients and of practices have challenged the elaboration of universal guidelines, and common practice is often to associate prolonged (sometimes life-long) antifungal therapy associated with source control when possible (including surgery if required). Evidence supporting current guidelines for treatment duration is limited by the lack of dedicated trials (with the notable exception of cryptococcal meningitis among people living with HIV) and difficulty to compare the highly variable populations across studies. Therefore, the required treatment duration is unlikely to be the same in every case, and should be personalized, once again emphasizing the crucial multi-disciplinary and frequent evaluations for prompt adjustments (and subsequent surgical procedures when appropriate) such as recently suggested in updated algorithms (Portillo and Neofytos, 2023). Future treatment trials should include evaluation of treatment efficacy and duration in specific sub populations of immunocompromised patients; establishment of biomarker kinetics as well as use of serial imaging to assess course of treatment response; and the impact of treatment on underlying conditions and their treatment, as well as pragmatic desirability of outcome ranking (DOOR) designs (Evans et al., 2015). Pragmatic goals for future trials are summarized in Table 2.

All future strategies designed to be tailored to individuals and their evolution are destined to be relying heavily on state-of-the-art technologies and dedicated infrastructures. As recently highlighted by a series of studies conducted by the ECMM, there are major disparities in diagnostic capacity and treatment accessibility around the globe (Salmanton-García et al., 2023; Salmanton-García et al., 2023; Salmanton-García et al., 2023; Driemeyer et al., 2022; Riera et al., 2023). Therefore, future guidelines will have to include dedicated algorithms for different types of infrastructures. Moreover, disparities in accessibility to treatment will face renewed challenges as new molecules are getting approved, such as ibrexafungerp, penconazole, rezafungin, olorofim, and manogepix. These molecules, which diversify the spectrum of fungal infections to be treated, as well as their administration routes, should be properly evaluated to understand how their usage will modify the treatment duration of these infections (Pfaller et al., 2021;
<caption>**Table 2**
Future research directions.</caption>

*   **Cryptococcal meningitis:**
    -   Prospectively evaluate therapeutic strategies among non-HIV-infected patients (ie solid organ transplant recipients)
    -   Evaluate prospectively the contribution of beta-D-glucan and quantitative PC in monitoring CSF fungal clearance
*   **Pneumocystis jirovecii pneumonia**
    -   Evaluate prospectively (in randomized controlled trials) the minimally required duration (and dose) of induction therapy in both HIV-infected and non infected patients
*   **Invasive Aspergillosis and Mucormycosis**
    -   Evaluate in randomized controlled trials the contribution of predefined algorithms guiding antifungal therapy duration (clinical status, biomarker kinetics and radiologically evaluated lesions)
    -   Evaluate inclusion of new technologies in antifungal treatment efficacy evaluation (ie nuclear imaging and quantitative molecular tools)
*   **Candida blood stream infection**
    -   Evaluate in randomized controlled trials shorter treatment course for uncomplicated infections

Feuss et al., 2024; Angulo et al., 2022; Thompson et al., 2023a,b).

## 6.2. Novel imaging strategies

Classical imaging strategies bear limitations such as slow evolution and difficulties to differentiate worsening disease from the impact of immune status restauration, or from post-surgical aspects. To overcome these obstacles, a marked interest for nuclear imaging has been observed in the past decade. The most clinically used radionuclide in PET is 18-fluoro-2-deoxyglucose (FDG). This radionuclide uptake by cells with high metabolic activities have been evaluated for the diagnosis and measure of residual infection in invasive fungal diseases in small retrospective studies (Hot et al., 2011; Xu et al., 2010; Franzius et al., 2001). A study of 28 patients with serial PET-CTs showed that metabolic activity imaging changed the antifungal management (changed or stopped treatment) in 50% of patients (Ankrah et al., 2019, 2021). Although not designed to tailor antifungal therapy duration to treatment response, a recent randomized trial among high-risk hematological patients with prolonged fever showed that FDP-PET-CT was superior to regular CT for adapting antimicrobial treatment (82% vs 65%, p = 0.033).

A recent pilot trial with FDG-PET/CT 3 months after therapy initiation in chronic disseminated candidiasis showed valuable insights for anti-fungal therapy efficacy assessment in a complex infectious and inflammatory disease (Rammaert et al., 2022). Prospective studies evaluating strategies incorporating PET/CT in invasive fungal diseases would hopefully provide essential tools to guide therapy duration based on the nucleotide uptake at the infection foci (NCT02955966).

However, FDG-PET/CT lacks specificity and high metabolic uptake can be observed in other diseases (ie bacterial co-diseases) and malignant processes (Baxter et al., 2011; Sonet et al., 2007). Its performances are also limited by the physiological uptake of the radionuclide in a significant number of tissues of interest such as brain, myocardium, and kidneys.

Hence, more specific imaging technologies have been under development. Using the iron-scavenging necessity of invasive fungal diseases such as aspergillosis, radiolabeled-siderophores have shown promising performances in animal models (Thornton, 2018) but need further investigations in clinical human studies (especially in potentially iron-overloaded patients such as multi-transfused leukemic patients). The uptake of the available siderophores by other pathogens limits their specificity and warrants further development of chemically engineered siderophores to increase specificity (Gunzer et al., 2020).

Monoclonal-directed in vivo imaging is an imaging technique on the rise, with promising specificity and sensitivity in animal models (Henneberg et al., 2021). These radiolabeled monoclonal antibodies combined with classical PET/CT techniques (so called immunoPET) could provide resolution and specificity (including in tissues difficult to assess with FDG-PET/CT) desperately needed for early diagnosis and therapy assessment for residual disease (Lian et al., 2022) if their pre-clinical performances were to be confirmed.

## 6.3. Future biomarkers

As stated before, biomarkers-guided strategies to steer anti-fungal therapy are to be evaluated in prospective trials. Nevertheless, none of the available biomarkers is suitable for universal application across immunocompromised patients nor to be a reliable reflection of the host immune system ability to control the fungal infection.

New biological strategies using mass-spectrometry (MS) have been developed to detect disaccharides (DS) common to most fungi. A recent European study validated the performances of the MS-DS platform when compared to classical biomarkers for diagnosis purposes (Cornu et al., 2019). This study found a persistent increase in disaccharide detection during the first weeks and even months of infection while the classical biomarkers tended to decline during this period. This dichotomy highlights the need for further research on the kinetics of biomarkers over the course of infection.

There are few - if any - biomarkers for some fungal diseases, such as mucormycosis. New biomarkers for this fungus are currently being developed, but they are in preclinical stages of development and are not currently available in clinical practice, nor is their kinetics under treatment unraveled (Shibata et al., 2020).

On the other hand, assessing the host specific immune response to the fungal pathogen would be of great help to stop safely anti-fungal therapies. Analogous to existing T cell responses assays for Cytomega-lovirus in solid organ transplant recipients, evaluating host T cell cytokine production to specific fungal components could reflect its ability to control the pathogenic process in addition to diagnostic values (Camargo and Shahid, 2014; Potenza et al., 2016; Steinbach et al., 2019). Serum cytokines profiles have recently been evaluated in a Spanish pilot study of patients with hematological malignancies and associated with both diagnosis and prognosis values (mortality associated with high levels of serum IL-6) (Puerta-Alcalde et al., 2022). Further studies confirming these results and exploring such strategies in different populations should be conducted.

## 7. Conclusion

Invasive fungal diseases remain difficult to treat diseases, due to the frailty of the patients, the often-prolonged associated immunosuppression and the scarcity of clinical trials that thoroughly evaluate optimal treatment durations. The literature on treatment duration is inconsistent in terms of patient numbers and types, with few studies specifically addressing this issue. Notable exceptions include research on cryptococcal meningitis in people living with HIV. The decision to pursue or stop anti-fungal therapy is challenging and must be individualized. This decision requires balancing the risk of relapse and treatment failure against drug-induced toxicity or paradoxical immune reactions. Current guidelines for antifungal therapy and its cessation are based on multidisciplinary evaluations involving clinical, and imaging endpoints. Overall, there is a critical need for prospective studies and clinical trials to evaluate strategies for the management of fungal diseases based on predefined endpoints including duration of therapy. And this in turn calls for prospective studies of existing biomarkers and imaging tools as
well as the development of new ones to learn more about the kinetics across the course of infection, from initial diagnosis through drug treatment to cessation of therapy. We recognize that this represents an ambitious research agenda, but one that is perhaps more complex given the huge variation in settings where patients receive care. Pragmatic considerations, such as the availability of technologies and therapeutic agents, underscore the necessity for carefully crafted local guidelines on the follow-up and treatment duration of these infections. Whatever biomarkers are developed, and endpoints defined, they need to be able to be implemented under real-life conditions where these fungal diseases are diagnosed and treated.

## CREDIT authorship contribution statement

**Simon B. Gressens:** Conceptualization, Data curation, Investigation, Visualization, Writing – original draft, Writing – review & editing.
**Claire Rouzaux:** Data curation, Writing – review & editing.
**Frederic Lamoth:** Conceptualization, Formal analysis, Supervision, Writing – review & editing.
**Thierry Calandra:** Conceptualization, Formal analysis, Writing – review & editing.
**Fanny Lanternier:** Formal analysis, Writing – review & editing.
**Olivier Lortholary:** Conceptualization, Formal analysis, Investigation, Methodology, Project administration, Supervision, Writing – review & editing.

## Appendix A. Supplementary data

Supplementary data to this article can be found online at https://doi.org/10.1016/j.mam.2025.101347.

## References

Abele-Horn, Marianne, Kopp, A., Sternberg, U., Ohly, A., Nagengast, O., Dauber, A., Russwurm, W., Büchinger, W., Emmerling, P., 1996. A randomized study comparing fluconazole with amphotericin B/5-Flucytosine for the treatment of systemic Candida infections in intensive care patients. Infection 24 (6), 426-432. https://doi.org/10.1007/BF01713042.

Aberg, Judith A., Watson, Jessica, Segal, Mark, Chang, Larry W., 2000. Clinical utility of monitoring serum cryptococcal antigen (sCRAG) titers in patients with AIDS-related cryptococcal disease. HIV Clin. Trials 1 (1), 1-6. https://doi.org/10.1310/NQXR-ULMG-MM1B-3T2B.

Agnelli, Caroline, Valerio, Maricela, Bouza, Emilio, Vena, Antonio, Guinea, Jesús, Martínez-Jiménez, María del Carmen, Marcos-Zambrano, Laura Judith, Escribano, Pilar, Muñoz, Patricia, COMIC Study Group (Collaborative Group on Mycosis), 2019. Persistent candidemia in adults: underlying causes and clinical significance in the antifungal stewardship era. Eur. J. Clin. Microbiol. Infect. Dis. 38 (3), 607-614. https://doi.org/10.1007/s10096-019-03477-3.

Agnelli, Caroline, Bouza, Emilio, Martínez-Jiménez, María del Carmen, Navarro, Raquel, Valerio, Maricela, Machado, Marina, Guinea, Jesús, et al., 2020. Clinical relevance and prognostic value of persistently negative (1,3)-β-D-glucan in adults with candidemia: a 5-year experience in a tertiary hospital. Clin. Infect. Dis. 70 (9), 1925-1932. https://doi.org/10.1093/cid/ciz555.

Alexander, Barbara D., Lamoth, Frédéric, Heussel, Claus Peter, Prokop, Cornelia Schaefer, Desai, Sujal R., Morrissey, C Orla, Baddley, John W., 2021. Guidance on imaging for invasive pulmonary aspergillosis and mucormycosis: from the imaging working group for the revision and update of the consensus definitions of fungal disease from the EORTC/MSGERC. Clin. Infect. Dis. 72 (Suppl. ment. 2), S79-S88. https://doi.org/10.1093/cid/cia1855.

Anaissie, E.J., 2007. Trial design for mold-active agents: time to break the mold-aspergillosis in neutropenic adults. Clin. Infect. Dis. 44 (10), 1298-1306. https://doi.org/10.1086/514352.

Angebault, Cécile, Lanternier, Fanny, Dalle, Frédéric, Schrimpf, Cécile, Roupie, Anne-Laure, Dupuis, Aurélie, Agathine, Aurélie, et al., 2016. Prospective evaluation of serum β-glucan testing in patients with probable or proven fungal diseases. Open Forum Infect. Dis. 3 (3), ofw128. https://doi.org/10.1093/ofid/ofw128.

Angulo, David A., Alexander, Barbara, Rautema-Richardson, Riina, Alastruey-Izquierdo, Ana, Hoenigl, Martin, Ibrahim, Ashraf S., Ghannoum, Mahmoud A., King, Thomas R., Azie, Nkechi E., Walsh, Thomas J., 2022. Ibrexafung器, a novel triterpenoid antifungal in development for the treatment of mold infections. J. Fungi 8 (11), 1121. https://doi.org/10.3390/jof8111121.

Ankrah, Alfred O., Lambert, F. R. Span, Klein, Hans C., de Jong, Pim A., Dierckx, Rudi A. J. O., Kwee, Thomas C., Sathekge, Mike M., Glaudemans, Andor W.J. M., 2019. Role of FDG PET/CT in monitoring treatment response in patients with invasive fungal infections. Eur. J. Nucl. Med. Mol. Imag. 46 (1), 174-183. https://doi.org/10.1007/s00259-018-4192-z.

Ankrah, Alfred O., Creemers-Schild, Dina, de Keizer, Bart, Klein, Hans C., Dierckx, Rudi A.J. O., Kwee, Thomas C., Span, Lambert F.R., de Jong, Pim A., Sathekge, Mike M., Glaudemans, Andor W.J. M., 2021. The added value of [18F]FDG PET/CT in the

management of invasive fungal infections. Diagnostics 11 (1). https://doi.org/10.3390/diagnostics11010137.

Anne, Bergeron, Raphaël, Porcher, Jean, Menotti, Jean Louis, Poirot, Karine, Chagnon, Anne, Vekhoff, Muriel, Cornet, et al., 2020. Prospective evaluation of clinical and biological markers to predict the outcome of invasive pulmonary aspergillosis in hematological patients. J. Clin. Microbiol. 50 (3), 823-830. https://doi.org/10.1128/JCM.43.11.5828-5829.2005.

Antinori, Spinello, Radice, Anna, Galimberti, Laura, Magni, Carlo, Fasan, Marco, Parravicini, Carlo, 2005. The role of cryptococcal antigen assay in diagnosis and monitoring of cryptococcal meningitis. J. Clin. Microbiol. 43 (11), 5828-5829. https://doi.org/10.1128/JCM.43.11.5828-5829.2005.

Baddley, John W., Forrest, Graeme N., the AST Infectious Diseases Community of Practice, 2019. Cryptococcosis in solid organ transplantation—guidelines from the American society of transplantation infectious diseases community of practice. Clin. Transplant. 33 (9). https://doi.org/10.1111/citr.13543.

Baddley, John W., Forrest, Graeme N., 2020. Management of cryptococcosis in transplant candidates and recipients. In: Morris, Michele I., Nelson Kotton, Camille, Wolfe, Camille (Eds.), Emerging Transplant Infections. Springer International Publishing, Cham, pp. 1-28. https://doi.org/10.1007/978-3-030-01751-4_47-1.

Bassetti, Matteo, Giacobbe, Daniele R., Berruti, Marco, Del Puente, Filippo, Vena, Antonio, 2020. Adequate duration of therapy in severe fungal infections. Curr. Opin. Crit. Care 26 (5). https://journals.lw.com/co-criticalcare/fulltext/2020/10000/Adequate duration of therapy in severe fungal 6.aspx.

Battistolo, Julien, Glampedakis, Emmanouil, Damonti, Lauro, Poissy, Julien, Grandbastien, Bruno, Kalbermatter, Laetitia, Pagani, Jean-Luc, et al., 2021. Increasing morbidity and mortality of candidemia over one decade in a Swiss university hospital. Mycoses 64 (12), 1512-1520. https://doi.org/10.1111/myc.13376.

Baughman, R.P., Dohn, M.N., Frame, P.T., 1994. The continuing utility of bronchoalveolar lavage to diagnose opportunistic infection in AIDS patients. Am. J. Med. 97 (6), 515-522. https://doi.org/10.1016/0002-9343(94)90346-8.

Baxter, Caroline G., Bishop, Paul, Low, Su Enn, Baiden-Amissah, Kweku, Denning, David W., 2011. Pulmonary aspergillosis: an alternative diagnosis to lung cancer after positive [¹⁸F]FDG positron emission tomography. Thorax 66 (7), 638. https://doi.org/10.1136/thx.2010.155515.

Benitez, Lydia L., Carver, Peggy L., 2019. Adverse effects associated with long-term administration of azole antifungal agents. Drugs 79 (8), 833-853. https://doi.org/10.1007/s40265-019-01127-8.

Bennett, John E., Dismukes, William E., Duma, Richard J., Medoff, Gerald, Sande, Merle A., Gallis, Harry, Leonard, John, et al., 1979. A comparison of amphotericin B alone and combined with flucytosine in the treatment of cryptococcal meningitis. N. Engl. J. Med. 301 (3), 126-131. https://doi.org/10.1056/NEJM197907193010303.

Bloos, Frank, Held, Jürgen, Kluge, Stefan, Simon, Philipp, Kogelmann, Klaus, de Heer, Geraldine, Kuhn, Sven-Olaf, et al., 2002. (1 → 3)-β-D-Glucan-Guided antifungal therapy in adults with sepsis: the CandiSep randomized clinical trial. Intensive Care Med. 47 (8), 865-875. https://doi.org/10.1007/s00134-022-06733-x.

Bourcier, Jessie, Heudes, Pierre-Marie, Morio, Florent, Gastineau, Thomas, Chevallier, Patrice, Rialland-Battisti, Fanny, Garandeau, Claire, et al., 2017. Prevalence of the reversed halo sign in neutropenic patients compared with non-neutropenic patients: data from a single-centre study involving 27 patients with pulmonary mucormycosis (2003-2016). Mycoses 60 (8), 526-533. https://doi.org/10.1111/myc.12624.

Bowden, Raleigh, Chandrasekar, Pranatharthi, White, Mary H., Li, Xin, Pietrelli, Larry, Gurwith, Marc, Burik, Jo-Anne van, Laverdiere, Michel, Safrin, Sharon, Wingard, John R., 2002. A double-blind, randomized, controlled trial of amphotericin B colloidal dispersion versus amphotericin B for treatment of invasive aspergillosis in immunocompromised patients. Clin. Infect. Dis. 35 (4), 359-366. https://doi.org/10.1086/341401.

Brodeefel, Harald, Vogel, Monika, Hebart, Holger, Einsele, Hermann, Vonth Hein, Reinhard, Claussen, Claus, Horger, Marius, 2006. Long-term CT follow-up in 40 non-HIV immunocompromised patients with invasive pulmonary aspergillosis: kinetics of CT morphology and correlation with clinical findings and outcome. Am. J. Roentgenol. 187 (2), 404-413. https://doi.org/10.2214/AJR.05.0513.

Brouwer, Annemarie E., Teparrukkul, Paprit, Pinpraphaporn, Supraphada, Larsen, Robert A., Chierakul, Wirongrong, Peacock, Sharon, Day, Nicholas, White, Nicholas J., Harrison, Thomas S., 2005. Baseline correlation and comparative kinetics of cerebrospinal fluid colony-forming unit counts and antigen titers in cryptococcal meningitis. J. Infect. Dis. 192 (4), 681-684. https://doi.org/10.1086/432073.

Brown, Gordon D., Denning, David W., Gow, Neil A.R., Levitz, Stuart M., Netea, Mihai G., White, Theodore C., 2012. Hidden killers: human fungal infections. Sci. Transl. Med. 4 (165). https://doi.org/10.1126/scitranslmed.3004404.

Burik, Jo-Anne H. van, Hare, Roberta S., Solomon, Howard F., Corrado, Michael L., Kontoyiannis, Dimitrios P., 2006. Posaconazole is effective as salvage therapy in zygomycosis: a retrospective summary of 91 cases. Clin. Infect. Dis. 42 (7), e61-e65. https://doi.org/10.1086/500212.

Caillot, Denis, Couaillier, Jean-François, Bernard, Alain, Casasnovas, Olivier, Denning, David W., Mannone, Lionel, Lopez, Jose, et al., 2001. Increasing volume and changing characteristics of invasive pulmonary aspergillosis on sequential thoracic computed tomography scans in patients with neutropenia. J. Clin. Oncol. 19 (1), 253-259. https://doi.org/10.1200/JCO.2001.19.1253.

Caillot, Denis, Latrabe, Valérie, Thiébaut, Anne, Herbrecht, Raoul, De Botton, Stéphane, Pigneux, Arnaud, Monchecourt, Françoise, Mahi, Lamine, Alfandari, Serge, Couaillier, Jean-François, 2010. Computer tomography in pulmonary invasive aspergillosis in hematological patients with neutropenia: an useful tool for diagnosis
and assessment of outcome in clinical trials. Eur. J. Radiol. 74 (3), e172-e175.
https://doi.org/10.1016/j.ejrad.2009.05.058.

Camargo, Jose F., Shahid, Husain, 2014. Immune correlates of protection in human invasive aspergillosis. Clin. Infect. Dis. 59 (4), 569-577. https://doi.org/10.1093/
cid/ciu337.

Chai Louis, Y.A., Bart-Jan, Kullberg, Johnson, Elizabeth M., Steven, Teerenstra, Lay
Wai, Khin, Vonk, Alieke G., Johan, Maertens, et al., 2020. Early serum
galactomannan trend as a predictor of outcome of invasive aspergillosis. J. Clin.
Microbiol. 50 (7), 2330-2336. https://doi.org/10.1128/jcm.06513-11.

Chang, Christina C., Harrison, Thomas S., Bicanic, Tihana A., Chayakuleree, Methee, Sorrell, Tania C., Warris, Adilia, Hagen, Ferry, et al., 2024. Global guideline for the diagnosis and management of cryptococcosis: an initiative of the ECMC and ISHAM in cooperation with the ASM. Lancet Infect. Dis. S1473309923007314 https://doi.org/10.1016/S14733099(23)00731-4. February.

Choo, Ji Yung, Park, Chang Min, Lee, Hyun-Ju, Lee, Chang Hyun, Goo, Jin Mo, Im, Jung-Gi, 2013. Sequential morphological changes in follow-up CT of pulmonary mucormycosis. Diagn. Interv. Radiol. https://doi.org/10.5152/dir.2013.13183.
September.

Cornely, O.A., Cuenca-Estrella, M., Meis, J.F., Ullmann, A.J., 2014. European society of clinical microbiology and infectious diseases (ESCMID) fungal infection study group (EFISG) and European confederation of medical mycology (ECMM) 2013 joint guidelines on diagnosis and management of rare and emerging fungal diseases. Clin. Microbiol. Infection 20 (April), 1-4. https://doi.org/10.1111/1469-0691.12569.

Cornely, Oliver A., Alastruey-Izquierdo, Ana, Arenz, Dorothee, Chen, Sharon C.A., Dannaoui, Eric, Hochhegger, Bruno, Hoenigl, Martin, et al., 2019. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European confederation of medical mycology in cooperation with the Mycese study group education and research consortium. Lancet Infect. Dis. 19 (12), e405-e421. https://doi.org/10.1016/S14733099(19)30123-2.

Couchepin, Jade, Brunel, Anne-Sophie, Jaton, Katia, Meylan, Pascal, Bochud, Pierre-Yves, Lamoth, Frédéric, 2018. Role of Bi-weekly serum galactomannan screening for the diagnosis of invasive aspergillosis in haematological cancer patients. Myceses 61 (6), 350-354. https://doi.org/10.1111/myc.12755.

Dailey, Garnes, Natalie J.M., Kontoyiannis, Dimitrios P., 2023. Mucormycosis: update on clinical presentation, diagnosis, and treatment. Curr. Opin. Infect. Dis. 36 (6), 427-435. https://doi.org/10.1097/QCO.0000000000000976.

Damonti, Lauro, Erard, Véronique, Garbino, Jorge, Schrenzel, Jacques, Zimmerli, Stefan, Mühlethaler, Konrad, Imhof, Alexander, et al., 2017. Catheter retention as a consequence rather than a cause of unfavorable outcome in candidemia. Intensive Care Med. 43 (6), 935-939. https://doi.org/10.1007/s00134-017-4737-9.

Dannaoui, Eric, 2022. Recent developments in the diagnosis of mucormycosis. J. Fungi 8 (5). https://doi.org/10.3390/jof0805457.

Datta, Debapriya, Ali, Syed Abbas, Henken, E.M., Kellet, Helen, Brown, Susan, Metersky, Mark L., 2003. Pneumocystis carinii pneumonia*: the time course of clinical and radiographic improvement. Chest 124 (5), 1820-1823. https://doi.org/
10.1016/S0012-3692(15)33416-4.

Davidson, Linda, van den Reek, Juul M.P. A., Bruno, Mariolina, van Hunsel, Florence, Herings, Ron M.C., Matzaraki, Vasiliki, Boahen, Collins K., et al., 2022. Risk of candidiasis associated with interleukin-17 inhibitors: a real-world observational study of multiple independent sources. Lancet Region. Health - Europe 13 (February). https://doi.org/10.1016/j.lanepe.2021.100266.

Davis, Christian, Joseph Wheat, L., Myint, Thein, Boulware, David R., Bahr, Nathan C., 2020. Efficacy of cerebrospinal fluid beta-d-glucan diagnostic testing for fungal meningitis: a systematic review. Edited by Kimberly E. Hanson J. Clin. Microbiol. 58 (4), e02094. https://doi.org/10.1128/JCM.02094-19.

Day, Jeremy N., Tran, T.H. Chau, Wolbers, Marcel, Mai, Pham P., Dung, Nguyen T., Mai, Nguyen H., Phu, Nguyen H., et al., 2013. Combination antifungal therapy for cryptococcal meningitis. N. Engl. J. Med. 368 (14), 1291-1302. https://doi.org/
10.1056/NEJMoa1110404.

DeLorenzo, Lawrence J., Huang, Chin Tang, Maguire, George P., Stone, Daniel J., 1987. Roentgenographic patterns of Pneumocystis carinii pneumonia in 104 patients with AIDS. Chest 91 (3), 323-327. https://doi.org/10.1378/chest.91.3.323.

Denis, Blandine, Guiguet, Marguerite, Castro, Nathalie de, Mechaï, Frédéric, Revest, Matthieu, Mahamat, Aba, Garioire, Giovanna Melica, Lortholary, Olivier, Costagliola, Dominique, 2014. Critical importance of long-term adherence to care in HIV infected patients in the cART era: new insights from Pneumocystis jirovecii pneumonia cases over 2004-2011 in the FHDH-ANRS CO4 cohort. PLoS One 9 (4), e94183. https://doi.org/10.1371/journal.pone.0094183.

Denning, David W., 2024. Global incidence and mortality of severe fungal disease. Lancet Infect. Dis. https://doi.org/10.1016/S1473-3099(23)00692-8. January.

Diamond, Richard D., 1974. Prognostic factors in cryptococcal meningitis: a study in 111 cases. Ann. Intern. Med. 80 (2), 176. https://doi.org/10.7326/0003-4819-80-2-176.

Dismukes, William E., Cloud, Gretchen, Gallis, Harry A., Kerkering, Thomas M., Medoff, Gerald, Craven, Philip C., Kaplowitz, Lisa G., et al., 1987. Treatment of cryptococcal meningitis with combination amphotericin B and flucytosine for four as compared with six weeks. N. Engl. J. Med. 317 (6), 334-341. https://doi.org/
10.1056/NEJM198708063170602.

Donnelly, J Peter, Chen, Sharon C., Kauffman, Carol A., Steinbach, William J., Baddley, John W., Verweij, Paul E., Clancy, Cornelius J., et al., 2020. Revision and update of the consensus definitions of invasive fungal disease from the European organization for research and treatment of cancer and the Myceses study group education and research consortium. Clin. Infect. Dis. 71 (6), 1367-1376. https://doi.org/
10.1093/cid/ciz1008.

Dreyfuss, Didier, Ricard, Jean-Damien, Gaudry, Stéphane, 2013. Reply: continuous infusion of amphotericin B deoxycholate for the treatment of life-threatening

Candida infections. Am. J. Respir. Crit. Care Med. 188 (8), 1033-1034. https://doi.org/
10.1164/rccm.201305-0884LE.

Driemeyer, Candida, Falci, Diego R., Hoenigl, Martin, Cornely, Oliver A., Chakrabarti, Arunaloke, Gangneux, Jean Pierre, Segal, Esther, et al., 2022. The current state of clinical mycology in eastern and South-Eastern Europe. Med. Mycol. 60 (4), myac017. https://doi.org/10.1093/mmy/myac017.

Dromer, Françoise, Mathoulin-Pélissier, Simone, Launay, Odile, Lortholary, Olivier, the French Cryptococcosis Study Group, 2007. Determinants of disease presentation and outcome during cryptococcosis: the CryptoA/D study. PLoS Med. 4 (2), e21. https://doi.org/10.1371/journal.pmed.0040021. Edited by John R Perfect.

Dromer, Françoise, Bernede-Bauduin, Claire, Guillemot, Didier, Lortholary, Olivier, for the French Cryptococcosis Study Group, 2008. Major role for amphotericin B-flucytosine combination in severe cryptococcosis. PLoS One 3 (8), e2870. https://doi.org/10.1371/journal.pone.0002870.

Evans, Scott R., Rubin, Daniel, Follmann, Dean, Pennello, Gene, Charles Huskins, W., Powers, John H., Schoenfeld, David, et al., 2015. Desirability of outcome ranking (DOOR) and response adjusted for duration of antibiotic risk (RADAR). Clin. Infect. Dis. 61 (5), 800-806. https://doi.org/10.1093/cid/civ495.

Fernández-Cruz, Ana, Lewis, Russell E., Kontoyiannis, Dimitrios P., 2020. How long do we need to treat an invasive mold disease in hematology patients? Factors influencing duration of therapy and future questions. Clin. Infect. Dis. 71 (3), 685-692. https://doi.org/10.1093/cid/ciz1195.

Feuss, Aliosha, Bougnoux, Marie-Elisabeth, Dannaoui, Eric, 2024. The role of olorifim in the treatment of filamentous fungal infections: a review of in vitro and in vivo studies. J. Fungi (Basel, Switzerland) 10 (5), 345. https://doi.org/10.3390/jof10050345.

Fichtenbaum, Carl J., German, Matthew, Claiborne Dunagan, W., Fraser, Victoria J., Medoff, Gerald, Diego, Jorge, Powderly, William G., 1999. A pilot study of the management of uncomplicated candidemia with a standardized protocol of amphotericin B. Clin. Infect. Dis. 29 (6), 1545-1550. https://doi.org/10.1086/313499.

Fishman, Jay A., Gans, Hayley, the AST Infectious Diseases Community of Practice, 2019. Pneumocystis jirovecii in solid organ transplantation: guidelines from the American society of transplantation infectious diseases community of practice. Clin. Transplant. 33 (9), e13587. https://doi.org/10.1111/ctr.13587.

François, Boutboul, Corinne, Alberti, Thierry, Leblanc, Annie, Sulahian, Eliane, Gluckman, Francis, Derouin, Patricia, Ribaud, 2002. Invasive aspergillosis in allogeneic stem cell transplant recipients: increasing antigenemia is associated with progressive disease. Clin. Infect. Dis. 34 (7), 939-943. https://doi.org/10.1086/339324.

Franzius, Christiane, Biermann, Martin, Hülskamp, Georg, Frosch, Michael, Roth, Johannes, Sciuk, Joachim, Schober, Otmar, 2001. Therapy monitoring in aspergillosis using F-18 FDG positron emission tomography. Clin. Nucl. Med. 26 (3). https://journals.lww.com/nuclearmed/Fulltext/2001/03000/Therapy_Monitoring_i_n_Aspergillosis_Using_F_18_FDG.11.aspx.

Galmiche, Simon, Thoreau, Benjamin, Bretagne, Stéphane, Alanio, Alexandre, Paugam, André, Letscher-Bru, Valérie, Cassaina, Sophie, et al., 2023. Invasive fungal diseases in patients with autoimmune diseases: a case series from the French RESSIF network. RMD Open 9 (3), e003281. https://doi.org/10.1136/rmdopen-2023-003281.

Giacobbe, Daniele Roberto, Berruti, Marco, Mikulska, Malgorzata, 2020. Prognostic impact of negative serum (1,3)-β-D-glucan in patients with candidemia. Clin. Infect. Dis. 71 (4), 1124-1126. https://doi.org/10.1093/cid/ciz1051.

Goldman, Armond S., Goldman, Lynn R., Goldman, Daniel A., 2005. What caused the epidemic of Pneumocystis pneumonia in European premature infants in the Mid-20th Century? Pediatrics 115 (6), e725-e736. https://doi.org/10.1542/peds.2004-2157.

Greenberg, R.N., Mullane, K., van Burik, J.-A.H., Raad, I., Abzug, M.J., Anstead, G., Herbrecht, R., et al., 2006. Poxaconazole as salvage therapy for Zygomycosis. Antimicrob. Agents Chemother. 50 (1), 126-133. https://doi.org/10.1128/acm.50.1.126-133.2006.

Grinsell, Matthew, Weinhold, Leanne C., Cutler, Jim E., Han, Yongmoon, Kozel, Thomas R., 2001. In vivo clearance of Glucuronoxylomannan, the major Capsular polysaccharide of *Cryptococcus neoformans*: a critical role for tissue macrophages. J. Infect. Dis. 184 (4), 479-487. https://doi.org/10.1086/322787.

Guidelines for Diagnosing, 2022. Preventing and Managing Cryptococcal Disease Among Adults, Adolescents and Children Living with HIV. World Health Organization, Geneva.

Guitard, J., Isnard, F., Tabone, M.-D., Antignac, M., Brissot, E., Senghor, Y., Petit, A., Leverger, G., Hennequin, C., 2018. Usefulness of SS-D-Glucan for diagnosis and follow-up of invasive candidiasis in onco-haematological patients. J. Infect. 76 (5), 483-488. https://doi.org/10.1016/j.jinf.2018.01.011.

Gunzer, Matthias, Thornton, Christopher R., Nicolas, Beziere, 2020. Advances in the in vivo molecular imaging of invasive aspergillosis. J. Fungi 6 (4). https://doi.org/
10.3390/jof6040338.

Haverkos, Harry W., 1984. Assessment of therapy for Pneumocystis carinii pneumonia: PCP therapy Project group. Am. J. Med. 76 (3), 501-508. https://doi.org/10.1016/
0002-9343(84)90670-3.

Heinz, Werner J., Verheschild, Jörg J., Buchheit, Dieter, 2019. Diagnostic work up to assess early response indicators in invasive pulmonary aspergillosis in adult patients with haematologic malignancies. Myceses 62 (6), 486-493. https://doi.org/
10.1111/myc.12860.

Held, J., Wagner, D., 2011. β-d-Glucan kinetics for the assessment of treatment response in Pneumocystis jirovecii pneumonia. Clin. Microbiol. Infection 17 (7), 1118-1122. https://doi.org/10.1111/j.1469-0691.2010.03452.x.
Helweg-Larsen, Jannik, Benfield, Thomas, Atzori, Chiara, Miller, Robert F., 2009. Clinical efficacy of first- and second-line treatments for HIV-associated Pneumocystis jirovecii pneumonia: A Tri-centre cohort study. J. Antimicrob. Chemother. 64 (6), 1282-1290. https://doi.org/10.1093/jac/dkp372.

Henao-Martínez, Andrés F., Chastain, Daniel B., Franco-Paredes, Carlos, 2018. Treatment of cryptococcosis in non-HIV immunocompromised patients. Curr. Opin. Infect. Dis. 31 (4), 278-285. https://doi.org/10.1097/QCO.10000000000000458.

Henneberg, Sophie, Hasenberg, Anja, Maurer, Andreas, Neumann, Franziska, Bornemann, Lea, Gonzalez-Menendez, Irene, Kraus, Andreas, et al., 2021. Antibody-guided in vivo imaging of Aspergillus fumigatus lung infections during antifungalazole treatment. Nat. Commun. 12 (1), 1707. https://doi.org/10.1038/s41467-021-21965-z.

Henzler, C., Henzler, T., Buchheidt, D., Nance, John W., Weis, C.A., Vogelmann, R., Benck, U., et al., 2017. Diagnostic performance of contrast enhanced pulmonary computed tomography angiography for the detection of angioinvasive pulmonary aspergillosis in immunocompromised patients. Sci. Rep. 7 (1), 4483. https://doi.org/10.1038/s41598-017-04470-6.

Herbrecht, Raoul, Denning, David W., Patterson, Thomas F., Bennett, John E., Greene, Reginald E., Oestmann, Jörg-W., Kern, Winfried V., et al., 2002. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N. Engl. J. Med. 347 (6), 408-415. https://doi.org/10.1056/NEJMoa020191.

Horn, D., Neofytos, D., Fishman, J., Steinbach, W., Anaisie, E., Pfaller, M., Olyaei, A., 2007. Use of the PATH alliance database to measure adherence to IDSA guidelines for the therapy of candidemia. Eur. J. Clin. Microbiol. Infect. Dis. 26 (12), 907-914. https://doi.org/10.1007/s10096-007-0383-4.

Hot, A., Maunoury, C., Poiree, S., Lanternier, F., Viard, J.P., Loulergue, P., Coignard, H., et al., 2011. Diagnostic contribution of positron emission tomography with [18F] fluorodeoxyglucose for invasive fungal infections. Clin. Microbiol. Infect. 17 (3), 409-417. https://doi.org/10.1111/j.1469-0691.2010.03301.x.

Hughes, Walter T., Feldman, Sandor, Chaudhary, Subhash A., Ossi, Michael J., Cox, Frederick, Sanyal, S.K., 1978. Comparison of pentamidine isethionate and trimethoprim-sulfamethoxazole in the treatment of Pneumocystis carinii pneumonia. J. Pediatr. 92 (2), 285-291. https://doi.org/10.1016/S0022-3476(78)80028-6.

Ibrahim, Ashraf S., Bowman, Joel C., Avanessian, Valentina, Brown, Keturah, Spellberg, Brad, Edwards, John E., Douglas, Cameron M., 2005. Caspofungin inhibits rhizopus oryzae 1,3-β-d-Glucan synthase, lowers burden in brain measured by quantitative PCR, and improves survival at a low but not a high dose during murine disseminated Zygomycosis. Antimicrob. Agents Chemother. 49 (2), 721-727. https://doi.org/10.1128/aac.49.2.721-727.2005.

Imbert, S., Gauthier, L., Joly, I., Brossas, J.-Y., Uzunov, M., Touafek, F., Brun, S., et al., 2016. Aspergillus PCR in serum for the diagnosis, follow-up and prognosis of invasive aspergillosis in neutropenic and Nonneutropenic patients. Clin. Microbiol. Infect. 22 (6), 562.e1-562.e8. https://doi.org/10.1016/j.cmi.2016.01.027.

Imlay, Hannah, Spellberg, Brad, 2022. Shorter is better: the case for short antibiotic courses for common infections in short organ transplant recipients. Transpl. Infect. Dis. 24 (5). https://doi.org/10.1111/tid.13896.

Isnard, Stéphane, Lin, John, Bu, Simeng, Fombuena, Brandon, Royston, Léna, Routy, Jean-Pierre, 2021. Gut leakage of fungal-related products: turning up the heat for HIV infection. Front. Immunol. 12 (April), 656414. https://doi.org/10.3389/fimmu.2021.656414.

Jaijakul, Siraya, Vazquez, Jose A., Swanson, Robert N., Luis, Ostrosky-Zeichner, 2012. (1,3)-β-D-Glucan as a prognostic marker of treatment response in invasive candidiasis. Clin. Infect. Dis. 55 (4), 521-526. https://doi.org/10.1093/cid/cis456.

Jarvis, Joseph N., Bicanic, Tihana, Loyse, Angela, Namarika, Daniel, Jackson, Arthur, Nussbaum, Jesse C., Longley, Nicky, et al., 2014. Determinants of mortality in a combined cohort of 501 patients with HIV-associated cryptococcal meningitis: implications for improving outcomes. Clin. Infect. Dis. 58 (5), 736-745. https://doi.org/10.1093/cid/cit794.

Jarvis, Joseph N., Lawrence, David S., Meya, David B., Kagimu, Enock, Kasibante, John, Mpoza, Edward, Rutakingirwa, Morris K., et al., 2022. Single-dose liposomal amphotericin B treatment for cryptococcal meningitis. N. Engl. J. Med. 386 (12), 1109-1120. https://doi.org/10.1056/NEJMoa21111904.

Junco, Jacobson, Shauna, Chehab, Sarah, Giancarelli, Amanda, Bowman, Mary Catherine, Brigg Turner, R., 2021. Adherence to national consensus guidelines and association with clinical outcomes in patients with candidemia. Infect. Dis. 14. https://doi.org/10.1177/11786337211018722.

Kabanda, Taseera, Siedner, Mark J., Klausner, Jeffrey D., Muzoora, Conrad, Boulware, David R., 2014. Point-of-Care diagnosis and prognostication of cryptococcal meningitis with the cryptococcal antigen lateral flow assay on cerebrospinal fluid. Clin. Infect. Dis. 58 (1), 113-116. https://doi.org/10.1093/cid/cit641.

Kagimu, Enock, Engen, Nicole, Ssebambulidde, Kenneth, Kasibante, John, Kiiza, Tadeo K., Mpoza, Edward, Tugume, Lillian, et al., 2022. Therapeutic lumbar punctures in human immunodeficiency virus-associated cryptococcal meningitis: should opening pressure direct management? Open Forum Infect. Dis. 9 (9), ofac416. https://doi.org/10.1093/ofid/ofac416.

Kaplan, Jonathan E., Hanson, Debra, Holworkin, Mark S., Frederick, Toni, Bertolli, Jeanne, Lindegren, Mary Lou, Scott, Holmberg, Jones, Jeffrey L., 2000. Epidemiology of human immunodeficiency virus-associated opportunistic infections in the United States in the era of highly active antiretroviral therapy. Clin. Infect. Dis. 30 (Suppl. ment 1), S5-S14. https://doi.org/10.1086/313843.

Koga, Michiko, Koibuchi, Tomohiko, Kikuchi, Tadashi, Nakamura, Hitomi, Miura, Toshiyuki, Iwamoto, Aikichi, Fujii, Takeshi, 2011. Kinetics of serum β-D-glucan after Pneumocystis pneumonia treatment in patients with AIDS. Intern. Med. 50 (13), 1397-1401. https://doi.org/10.2169/internalmedicine.50.5296.

Kolbrink, Benedikt, Scheikholeslami-Sabzewari, Jubin, Borzikowsky, Christoph, von Samson-Himmelstjerna, Friedrich A., Ullmann, Andrew J., Ulrich, Kenzendorf, Schulte, Kevin, 2022. Evolving epidemiology of Pneumocystis pneumonia: findings from a longitudinal population-based study and a retrospective multi-center study in Germany. Lancet Region. Health - Europe 18 (July). https://doi.org/10.1016/j.lanepe.2022.100400.

Kontoyiannis, Dimitrios P., Lewis, Russell E., 2011. How I treat mucormycosis. Blood 118 (5), 1216-1224. https://doi.org/10.1182/blood-2011-03-316403.

Kontoyiannis, Dimitrios P., Lewis, Russell E., Alexander, Barbara D., Lortholary, Olivier, Rienart, Françoise, Gupta, Krishan L., John, George T., et al., 2008. Calcineurin inhibitor agents interact synergistically with antifungal agents in vitro against *Cryptococcus neoformans* isolates: correlation with outcome in solid organ transplant recipients with cryptococcosis. Antimicrob. Agents Chemother. 52 (2), 735-738. https://doi.org/10.1128/AAC.00990-07.

Koo, S., Baden, L.R., Marty, F.M., 2012. Post-diagnostic kinetics of the (1 → 3)-β-d-Glucan assay in invasive aspergillosis, invasive candidiasis and Pneumocystis jirovecii pneumonia. Clin. Microbiol. Infect. 18 (5), E122-E127. https://doi.org/10.1111/j.1469-0691.2012.03777.x.

Kosmidis, Chris, Denning, David W., 2015. The clinical spectrum of pulmonary aspergillosis. Thorax 70 (3), 270-277. https://doi.org/10.1136/thoraxjnl-2014-206291.

Kovacs, Joseph E., Hiemenz, John W., Macher, Abe M., Stover, Diane, Murray, Henry W., Shelhamer, James, Clifford Lane, H., et al., 1984. Pneumocystis carinii pneumonia: a comparison between patients with the acquired immunodeficiency syndrome and patients with other immunodeficiencies. Ann. Intern. Med. 100 (5), 663-671. https://doi.org/10.7326/0003-4819-100-5-663.

Kovanda, Laura L., Kolamunnage-Dona, Ruwantho, Neely, Michael, Maertens, Johan, Lee, Misun, Hope, William W., 2017. Pharmacodynamics of isavuconazole for invasive mold disease: role of galactomannan for real-time monitoring of therapeutic response. Clin. Infect. Dis. 64 (11), 1557-1563. https://doi.org/10.1093/cid/cix198.

Kuhlman, J.E., Fishman, E.K., Burch, P.A., Karp, J.E., Zerhouni, E.A., Siegelman, S.S., 1988. CT of invasive pulmonary aspergillosis. Am. J. Roentgenol. 150 (5), 1015-1020. https://doi.org/10.2214/ajr.150.5.1015.

Kullberg, B.J., Sobel, J.D., Ruhnke, M., Pappas, P.G., Viscoli, C., Rex, J.H., Cleary, J.D., et al., 2005. Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidemia in non-neutropenic patients: a randomised non-inferiority trial. Lancet 366 (9495), 1435-1442. https://doi.org/10.1016/S0140-6736(05)67490-9.

Kullberg, Bart Jan, Viscoli, Claudio, Pappas, Peter G., Vazquez, Jose, Ostrosky-Zeichner, Luis, Rotstein, Coleman, Sobel, Jack D., et al., 2019. Isavuconazole versus caspofungin in the treatment of candidemia and other invasive Candida infections: the ACTIVE trial. Clin. Infect. Dis. 68 (12), 1981-1989. https://doi.org/10.1093/cid/ciy827.

Kuse, Ernst-Rüdiger, Chetchotisakd, Ploenchan, Cunha, Clovis Arns da, Ruhnke, Markus, Barrios, Carlos, Raghunadharao, Digumarti, Singh Sekhon, Jagdev, et al., 2007. Micafungin versus liposomal amphotericin B for candidemia and invasive candidosis: a phase III randomised double-blind trial. Lancet 369 (9572), 1519-1527. https://doi.org/10.1016/S0140-6736(07)60605-9.

Lamoth, Frederic, 2022. Invasive aspergillosis in coronavirus disease 2019: a practical approach for clinicians. Curr. Opin. Infect. Dis. 35 (2). https://journals.lww.com/co-infectiousdiseases/fulltext/2022/04000/invasive_aspergillosis_in_coronavirus_dis_ease_14.aspxx.

Lanternier, F., Poiree, S., Elie, C., Garcia-Hermoso, D., Bakouboula, P., Sitbon, K., Herbrecht, R., et al., 2015. Prospective pilot study of high-dose (10 Mg/Kg/Day) liposomal amphotericin B (L-AMB) for the initial treatment of mucormycosis. J. Antimicrob. Chemother. 70 (11), 3116-3123. https://doi.org/10.1093/jac/dkv236.

Lanternier, Fanny, Seidel, Danila, Pagano, Livio, Styczynski, Jan, Mikulsa, Malgorzata, Pulcini, Celine, Maertens, Johan, et al., 2020. Invasive pulmonary aspergillosis treatment duration in haematology patients in Europe: an EFISG, IDWP-EBMT, EORTC-IDG and SEIFEM survey. Mycoses 63 (5), 420-429. https://doi.org/10.1111/myc.13056.

Larsen, Robert A., 1990. Fluconazole compared with amphotericin B plus flucytosine for cryptococcal meningitis in AIDS: a randomized trial. Ann. Intern. Med. 113 (3), 183. https://doi.org/10.7326/0003-4819-113-3-183.

Lecointe, Karine, Cornu, Marjorie, Leroy, Jordan, Coulon, Pauline, Sendid, Boualem, 2019. Polysaccharides cell wall architecture of Mucoreales. Front. Microbiol. 10. https://www.frontiersin.org/articles/10.3389/fmicb.2019.000496.

Lecointe, Karine, Coulon, Pauline, Krzewinski, Frédéric, Charlet, Rogatien, Bortolos, Clovis, Sendid, Boualem, Cornu, Marjorie, 2022. Parietal composition of Lichtheimia Corymbifera: differences between spore and germ tube stages and host-pathogen interactions. Med. Mycol. 61 (1), myac100. https://doi.org/10.1093/mmy/myac100.

Lee, Rachael A., Stripling, Joshua T., Spellberg, Brad, Centor, Robert M., 2022. Short course antibiotics for common infections: what do we know and where do we go from here? Clin. Microbiol. Infection, S1198743X2200461X. https://doi.org/10.1016/j.cmi.2022.08.024. September.

Lefort, A., Chartier, L., Sendid, B., Wolff, M., Mainardi, J.-L., Podglajen, I., Desnos-Ollivier, M., Fontanet, A., Bretagne, S., Lortholary, O., 2012. Diagnosis, management and outcome of Candida endocarditis. Clin. Microbiol. Infection 18 (4), E99-E109. https://doi.org/10.1111/j.1469-0691.2012.03764.x.

Legouge, C., Caillot, D., Chrétien, M.-L., Lafon, I., Ferrant, E., Audia, S., Pagés, P.-B., et al., 2014. The reversed halo sign: pathognomonic pattern of pulmonary mucormycosis in leukemic patients with neutropenia? Clin. Infect. Dis. 58 (5), 672-678. https://doi.org/10.1093/cid/cit929.
Lian, Xihua, Scott-Thomas, Amy, Lewis, John G., Bhatia, Madhav, MacPherson, Sean A., Zeng, Yiming, Chambers, Stephen T., 2022. Monoclonal antibodies and invasive aspergillosis: diagnostic and therapeutic perspectives. Int. J. Mol. Sci. 23 (10). https://doi.org/10.3390/ijms23105563.

Lionakis, Michael S., 2019. Primary immunodeficiencies and invasive fungal infection: when to suspect and how to diagnose and manage. Curr. Opin. Infect. Dis. 32 (6), 531. https://doi.org/10.1097/QCO.000000000000000593.

Lortholary, Olivier, Fontanet, Arnaud, Mémain, Nathalie, Martin, Antoine, Sitbon, Karine, Dromer, Françoise, 2005. Incidence and risk factors of immune reconstitution inflammatory syndrome complicating HIV-associated cryptococcosis in France. AIDS 19 (10), 1043–1049. https://doi.org/10.1097/01.aids.0000174450.7087430.

Lortholary, Olivier, Poizat, Gwendoline, Zeller, Valérie, Neuville, Séguélo, Boibieux, André, Alvarez, Muriel, Dellamonica, Pierre, Botterel, Françoise, Dromer, Françoise, Chêne, Geneviève, 2006. Long-term outcome of AIDS-associated cryptococcosis in the era of combination antiretroviral therapy. AIDS 20 (17), 2183–2191. https://doi.org/10.1097/01.aids.0000252060.80704.68.

Lyons, Jennifer L., Thakur, Kiran T., Lee, Rick, Watkins, Tonya, Pardo, Carlos A., Carson, Kathryn A., Markley, Barbara, et al., 2015. Utility of measuring (1,3)-β-d-glucan in cerebrospinal fluid for diagnosis of fungal central nervous system infection. J. Clin. Microbiol. 53 (1), 319–322. https://doi.org/10.1128/JCM.02301-14. Edited by D. J. Diekema.

Ma, Li-Jun, Ibrahim, Ashraf S., Skory, Christopher, Grabhahn, Manfred G., Burger, Gertraud, Butler, Margi, Elias, Marek, et al., 2009. Genomic analysis of the basal lineage fungus rhizopus oryzae reveals a whole-genome duplication. PLoS Genet. 5 (7), e1000549. https://doi.org/10.1371/journal.pgen.1000549.

Maertens, Johan, Buvé, Kristel, Theunissen, Koen, Meersseman, Wouter, Verbeken, Eric, Verhoef, Gregor, Eldere, Johan Van, Lagrou, Katrien, 2009. Galactomannan serves as a surrogate endpoint for outcome of pulmonary invasive aspergillosis in neutropenic hematology patients. Cancer 115 (2), 355–362. https://doi.org/10.1002/cncr.24022.

Maertens, Johan A., Raad, Issam I., Marr, Kieren A., Patterson, Thomas F., Kontoyiannis, Dimitrios P., Cornely, Oliver A., Bow, Eric J., et al., 2016. Isuvacunazole versus voriconazole for primary treatment of invasive mold disease caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial. Lancet 387 (10020), 760–769. https://doi.org/10.1016/S0140-6736(15)01159-9.

Maertens, Johan A., Rahav, Galia, Lee, Dong-Gun, Ponce-de-León, Alfredo, Sánchez, Isabel Cristina Ramírez, Klimko, Nikolay, Sonet, Anne, et al., 2021. Posaconazole versus voriconazole for primary treatment of invasive aspergillosis: a phase 3, randomised, controlled, non-inferiority trial. Lancet 397 (10273), 499–509. https://doi.org/10.1016/S0140-6736(21)00219-8.

Marchiori, Edson, Hochhegger, Bruno, Zanetti, Glàcia, 2020. Importance of the reversed halo sign for diagnosis of mucormycosis. Lancet Infect. Dis. 20 (5), 538. https://doi.org/10.1016/S1473-3099(20)30266-8.

Marjorie, Cornu, Boualem, Sendid, Alexandre, Mery, Nadine, François, Malgorzata, Mikulska, Valérie, Letsch-Bru, Elena, De Carolis, et al., 2019. Evaluation of mass spectrometry-based detection of panfungal serum disaccharide for diagnosis of invasive fungal infections: results from a collaborative study involving six European clinical Centers. J. Clin. Microbiol. 57 (5). https://doi.org/10.1128/jcm.01867-18.

Martin-Loeches, Ignacio, Antonelli, Massimo, Cuenca-Estrella, Manuel, Dimopoulos, George, Einav, Sharon, De Waele, Jan J., Garnacho-Montero, Jose, et al., 2019. ESICM/ECSMID task force on practical management of invasive candidiasis in critically ill patients. Intensive Care Med. 45 (6), 789–805. https://doi.org/10.1007/s00134-019-05599-w.

Martínez, María Luisa, Ferrer, Ricard, Torrents, Eva, Guillamat-Prats, Raquel, Gomà, Gemma, Suárez, David, Alvarez-Rocha, Luis, et al., 2017. Impact of source control in patients with severe sepsis and septic shock. Crit. Care Med. 45 (1) https://journals.lww.com/ccmjournal/Fulltext/2017/01000/Impact_of_Source-Control_iJ Clin Patients With Severe_2.aspx.

Marty, Francisco M., Koo, Sophia, Bryar, Julie, Baden, Lindsey R., 2007. (1→3)-β-d-Glucan assay positivity in patients with Pneumocystis (carinii) Jiroveci pneumonia. Ann. Intern. Med. 147 (1), 70–72. https://doi.org/10.7326/0003-4819-147-1-200707030-00018.

Marty, Francisco M., Ostrosky-Zeichner, Luis, Cornely, Oliver A., Mullane, Kathleen M., Perfect, John R., Thompson III, George R., Alangaden, George J., et al., 2016. Isuvacunazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis. Lancet Infect. Dis. 16 (7), 828–837. https://doi.org/10.1016/S1473-3099(16)00071-2.

Maschmeyer, Georg, Helweg-Larsen, Jannik, Pagano, Livio, Robin, Christine, Cordonnier, Catherine, Schellongowski, Peter, 2016. ECIL guidelines for treatment of Pneumocystis jirovecii pneumonia in non-HIV-infected haematology patients. J. Antimicrob. Chemother. 71 (9), 2405–2413. https://doi.org/10.1093/jac/dkw158.

Mazzai, Linda, Anglani, Mariagiulia, Giraudo, Chiara, Martucci, Matia, Cester, Giacomo, Causin, Francesco, 2022. Imaging features of rhinocerebral mucormycosis: from onset to vascular complications. Acta Radiol. 63 (2), 232–244. https://doi.org/10.1177/0284185120988828.

Medina, Ileana, Mills, John, Leoung, Gifford, Hopewell, Philip C., Lee, Belle, Modin, Gunnard, Neal, Benowitz, Wofsy, Constance B., 1990. Oral therapy for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. N. Engl. J. Med. 323 (12), 776–782. https://doi.org/10.1056/NEJM19909203231202.

Mejia-Chew, Carlos, O'Halloran, Jane A., Olsen, Margaret A., Stwalley, Dustin, Kronen, Ryan, Lin, Charlotte, Salazar, Ana S., et al., 2019. Effect of infectious disease

consultation on mortality and treatment of patients with Candida bloodstream infections: a retrospective, cohort study. Lancet Infect. Dis. 19 (12), 1336–1344. https://doi.org/10.1016/S1473-3099(19)30405-0.

Mercier, Toine, Guldentops, Ellen, Lagrou, Katrien, Maertens, Johan, 2018. Galactomannan, a surrogate marker for outcome in invasive aspergillosis: finally coming of age. Front. Microbiol. 9. https://www.frontiersin.org/articles/10.3389/fmicb.2018.000661.

Mercier, Toine, Wera, Joachim, Chai, Louis Y.A., Lagrou, Katrien, Maertens, Johan, 2020. A mortality prediction rule for hematology patients with invasive aspergillosis based on serum galactomannan kinetics. J. Clin. Med. 9 (2). https://doi.org/10.3390/jcm9020610.

Mikulska, M., Furfaro, E., Del Bono, V., Gualandi, F., Van Lint, M.T., Miletich, F., Bacigalupo, A., Viscoli, C., 2011. Persistence of a positive (1,3)-β-d-glucan test after clearance of candidemia in hematopoietic stem cell transplant recipients. Clin. Vaccine Immunol. 18 (3), 518–519. https://doi.org/10.1128/CVI.00513-10.

Mikulska, Malgorzata, Furfaro, Elisa, Magnasco, Laura, Codda, Giulia, Giacobbe, Daniele Roberto, Dentone, Chiara, Vena, Antonio, Marchese, Anna, Bassetti, Matteo, 2022. Levels of beta-D-glucan in Candida auris supernatants, an in vitro and in vivo preliminary study. Clin. Microbiol. Infection 28 (8), 1154.e1–1154.e3. https://doi.org/10.1016/j.cmi.2022.02.045.

Miyazaki, Takashige, Kohno, Shigeru, Mitsutake, Kotaro, Maesaki, Shigefumi, Tanaka, Ken-Ichi, Hara, Kohei, 1995. (1→3)-β-D-Glucan in culture fluid of fungi activates factor g, a limulus coagulation factor. J. Clin. Lab. Anal. 9 (5), 334–339. https://doi.org/10.1002/jcla.1860090509.

Molloy, Sfè F., Kanyama, Cecilia, Heyderman, Robert S., Loyse, Angela, Kouanackf, Charles, Duncan, Chanda, Mfinanga, Sayoki, et al., 2018. Antifungal combinations for treatment of cryptococcal meningitis in Africa. N. Engl. J. Med. 378 (11), 1004–1017. https://doi.org/10.1056/NEJMoa1710922.

Monday, Lea M., Acosta, Tommy Parraga, George, Alangaden, 2021. T2Candida for the diagnosis and management of invasive Candida infections. J. Fungi 7 (3). https://doi.org/10.3390/jof7030178.

Mootsikapun, Piroon, Chetchtotiskad, Ploenchan, Anunnatsiri, Siruluck, Choksawadphinyo, Kittiyaporn, 2003. The efficacy of fluconazole 600 Mg/day versus itraconazole 600 Mg/day as consolidation therapy of cryptococcal meningitis in AIDS patients. J. Med. Associat. Thailand = Chotmaihet Thangphaet. 86 (4), 293–298.

Mora-Duarte, Jorge, Betts, Robert, Rotstein, Coleman, Lopes Colombo, Arnaldo, Thompson-Moya, Luis, Smietana, Juanita, Lupinacci, Robert, Sable, Carole, Kartsonis, Nicholas, Perfect, John, 2002. Comparison of caspofungin and amphotericin B for invasive candidiasis. N. Engl. J. Med. 347 (25), 2020–2029. https://doi.org/10.1056/NEJMoa021585.

Morris, Alison, Lundgren, Jens D., Masur, Henry, Walzer, Peter D., Hanson, Debra L., Frederick, Toni, Huang, Laurence, Beard, Charles B., Kaplan, Jonathan E., 2004. Current epidemiology of Pneumocystis pneumonia. Emerg. Infect. Dis. 10 (10), 1713–1720. https://doi.org/10.3201/eid1010.030985.

Muñoz, Patricia, Vena, Antonio, Machado, Marina, Gioia, Francesca, Martínez-Jiménez, María Carmen, Gómez, Elia, Origia, et al., 2018. T2Candida MR as a predictor of outcome in patients with suspected invasive candidiasis starting empirical antifungal treatment: a prospective pilot study. J. Antimicrob. Chemother. 73 (Suppl. 1.4), iv6–12. https://doi.org/10.1093/jac/dky047.

Murakami, Minoru, Komatsu, Hirokazu, Sugiyama, Masahide, Ichikawa, Yuhei, Ide, Kyoko, Tsuchiya, Rumi, Kunieda, Kenji, et al., 2018. Antimicrobial stewardship without infectious disease physician for patients with candidemia: a before and after study. J. General Fam. Med. 19 (3), 82–89. https://doi.org/10.1002/jgf2.159.

Mussini, Cristina, Pezzotti, Patrizio, Miro, Jose M., Martinez, Esteban, De Quiros, Juan Carlos Lopez Bernaldo, Cinque, Paola, Borghi, Vanni, et al., 2004. Discontinuation of maintenance therapy for cryptococcal meningitis in patients with AIDS treated with highly active antiretroviral therapy: an international observational study. Clin. Infect. Dis. 38 (4), 565–571. https://doi.org/10.1086/381261.

Nam, Bo Da, Kim, Tae Jung, Lee, Kyung Soo, Kim, Tae Sung, Han, Joungho, Chung, Myung Jin, 2018. Pulmonary mucormycosis: serial morphologic changes on computed tomography correlate with clinical and pathologic findings. Eur. Radiol. 28 (2), 788–795. https://doi.org/10.1007/s00330-017-5007-5.

National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and Infectious Diseases Society of America, 2021. Panel on guidelines for the prevention and treatment of opportunistic infections in adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and Adolescents with HIV. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-opportunistic-infection.

Neofytos, Dionysios, Railkar, Radha, Mullane, Kathleen M., Fredricks, David N., Granwehr, Bruno, Marr, Kieren A., Almyroudis, Nikolaos G., et al., 2015. Correlation between circulating fungal biomarkers and clinical outcome in invasive aspergillosis. PLoS One 10 (6), e0129022. https://doi.org/10.1371/journal.pone.0129022.

Neofytos, Dionysios, Garcia-Vidal, Carolina, Lamoth, Frédéric, Lichtenstern, Christoph, Perrella, Alessandro, Vehreschild, Jörg Janne, 2021. Invasive aspergillosis in solid organ transplant patients: diagnosis, prophylaxis, treatment, and assessment of response. BMC Infect. Dis. 21 (1), 296. https://doi.org/10.1186/s12879-021-05958-3.

Nguyen, M. Hong, Peacock Jr., James E., Tanner, David C., Morris, Arthur J., Nguyen, Minh Ly, Snydman, David R., Wagener, Marilyn M., Yu, Victor L., 1995. Therapeutic approaches in patients with candidemia: evaluation in a multicenter, prospective, observational study. Arch. Intern. Med. 155 (22), 2429–2435. https://doi.org/10.1001/archinte.1995.0043022087009.

Nouér, Simone A., Nucci, Marcio, Kumar, Naveen Sanath, Graziutti, Monica, Barlogie, Bart, Anaissie, Elias, 2011. Earlier response assessment in invasive aspergillosis based on the kinetics of serum Aspergillus galactomannan: proposal for
a new definition. Clin. Infect. Dis. 53 (7), 671–676. https://doi.org/10.1093/cid/cir441.

Nouér, Simone Aranha, Nucci, Marcio, Sanath Kumar, Naveen, Graziotti, Monica, Restrepo, Alejandro, Elias, Anaissie, 2012. Baseline platelet count and creatinine clearance rate predict the outcome of neutropenia-related invasive aspergillosis. Clin. Infect. Dis. 54 (12), e173–e183. https://doi.org/cid/cis298.

Nucci, Marcio, Elias, Anaissie, Betts, Robert F., Dupont, Bertrand F., Wu, Chunzhang, Buell, Donald N., Kovanda, Laura, Lortholary, Olivier, 2010. Early removal of central venous catheter in patients with candidemia does not improve outcome: analysis of 842 patients from 2 randomized clinical trials. Clin. Infect. Dis. 51 (3), 295–303. https://doi.org/10.1086/653935.

null, 1990. Consensus statement on the use of corticosteroids as adjunctive therapy for Pneumocystis pneumonia in the acquired immunodeficiency syndrome. N. Engl. J. Med. 323 (21), 1500–1504. https://doi.org/10.1056/NEJM199011223232131.

Orasch, Christina, Mertz, Dominik, Garbino, Jorge, van Delden, Christian, Emonet, Stephane, Schrenzel, Jacques, Zimmerli, Stefan, et al., 2018. Fluconazole non-susceptible breakthrough candidemia after prolonged low-dose prophylaxis: a prospective FUNGINOS study. J. Infect. 76 (5), 489–495. https://doi.org/10.1016/j.jinf.2017.12.018.

Oude Lashof, A.M.L., Donnelly, J.P., Meis, J.F.G.M., van der Meer, J.W.M., Kullberg, B.J., 2003. Duration of antifungal treatment and development of delayed complications in patients with candidaemia. Eur. J. Clin. Microbiol. Infect. Dis. 22 (1), 43–48. https://doi.org/10.1007/s10096-002-0854-6.

O'Donnell, Walter J., Pieciak, Walter, Chertow, Glenn M., Sanabria, Jose, Lahive, Karen C., 1998. Clearance of Pneumocystis carinii cysts in acute P carinii pneumonia: assessment by serial sputum induction. Chest 114 (5), 1264–1268. https://doi.org/10.1378/chest.114.5.1264.

Paccoud, Olivier, Desnos-Ollivier, Marie, Cassaina, Sophie, Boukris-Sitbon, Karine, Alanio, Alexandre, Bellanger, Anne-Pauline, Bonnal, Christine, et al., 2023. Cryptococcus neoformans infections differ among HIV-seropositive and HIV-seronegative individuals: results from a nationwide surveillance program in France. Open Forum Infect. Dis. https://doi.org/10.1093/ofid/ofad658. December, ofad658.

Papadimitriou-Olivgeris, Matthaios, Battistolo, Julien, Poissy, Julien, Coste, Alix, Bochud, Pierre-Yves, Bellandra, Thierry, Senn, Laurence, Lamoth, Frédéric, 2022. Key role of early source control in candidemic patients with sepsis or septic shock. Open Forum Infect. Dis. 9 (8), ofac383. https://doi.org/10.1093/ofid/ofac383.

Pappas, Peter G., Kauffman, Carol A., Andes, David R., Clancy, Cornelius J., Marr, Kieren A., Ostrosky-Zeichner, Luis, Reboli, Annette C., et al., 2016. Clinical practice guideline for the management of candidiasis: 2016 update by the infectious diseases society of America. Clin. Infect. Dis. 62 (4), e1–e50. https://doi.org/10.1093/cid/civ933.

Pappas, Peter G., Lionakis, Michail S., Cavling Arendrup, Maiken, Ostrosky-Zeichner, Luis, Kullberg, Bart Jan, 2018. Invasive candidiasis. Nat. Rev. Dis. Primers 4 (1), 18026. https://doi.org/10.1038/nrdp.2018.26.

Park, Seong Yeon, Lim, Chaehun, Lee, Sang-Oh, Choi, Sang-Ho, Kim, Yang Soo, Woo, Jun Hee, Song, Jae-Woo, et al., 2011. Computed tomography findings in invasive pulmonary aspergillosis in non-neutropenic transplant recipients and neutropenic patients, and their prognostic value. J. Infect. 63 (6), 447–456. https://doi.org/10.1016/j.jinf.2011.08.007.

Park, Sun Hee, Choi, Su-Mi, Lee, Dong-Gun, Choi, Jung-Hyun, Kim, Si-Hyun, Kwon, Jae-Cheol, Yoo, Jin-Hong, et al., 2011. Serum galactomannan strongly correlates with outcome of invasive aspergillosis in acute leukaemia patients. Mycoses 54 (6), 523–530. https://doi.org/10.1111/j.1439-0507.2010.02009.x.

Patterson, Thomas F., Thompson III, George R., Denning, David W., Fishman, Jay A., Hadley, Susan, Herbrecht, Raoul, Kontoyianni, Dimitrios P., et al., 2016. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the infectious diseases society of America. Clin. Infect. Dis. 63 (4), e1–e60. https://doi.org/10.1093/cid/ciw326.

Perlin, David S., Rautemaa-Richardson, Riina, Alastruey-Izquierdo, Ana, 2017. The global problem of antifungal resistance: prevalence, mechanisms, and management. Lancet Infect. Dis. 17 (12), e383–e392. https://doi.org/10.1016/S1473-3099(17)30316-X.

Pfaller, Michael A., Huband, Michael D., Flamm, Robert K., Bien, Paul A., Castanheira, Mariana, 2021. Antimicrobial activity of managrepix, a first-in-class antifungal, and comparator agents tested against contemporary invasive fungal isolates from an international surveillance programme (2018-2019). J. Glob. Antimicrob. Resist. 26 (September), 117–127. https://doi.org/10.1016/j.jgar.2021.04.012.

Pickinger, Jerry W., Sant Howard, W., Bowles Catherine, A.P., Roberts, William L., Woods, Gail L., 2005. Evaluation of a (1→3)-β-D-glucan assay for diagnosis of invasive fungal infections. J. Clin. Microbiol. 43 (12), 5957–5962. https://doi.org/10.1128/jcm.43.12.5957-5962.2005.

Pini, P., Bettua, C., Orsi, C.F., Venturelli, C., Forghieri, F., Bigliardi, S., Faglioni, L., et al., 2016. Evaluation of serum (1 → 3)-β-D-Glucan clinical performance: kinetic assessment, comparison with galactomannan and evaluation of confounding factors. Infection 44 (2), 223–233. https://doi.org/10.1007/s15010-015-0849-8.

Poissy, Julien, Rouzé, Anahita, Cornu, Marjorie, Nseir, Saad, Sendid, Boualem, 2022. The changing landscape of invasive fungal infections in ICUs: a need for risk stratification to better target antifungal drugs and the threat of resistance. J. Fungi 8 (9), 946. https://doi.org/10.3390/jof8090946.

Portillo, Vera, Neofytos, Dionysios, 2023. Duration of antifungal treatment in mold infection: when is enough? Curr. Opin. Infect. Dis. 36 (6). https://journals.lww.com/co-infectiousdiseases/fulltext/2023/12000/duration_of_antifungal_treatment_in_mold_d.aspx.

Potenza, Leonardo, Vallerini, Daniela, Barozzi, Patrizia, Riva, Giovanni, Gilioli, Andrea, Forghieri, Fabio, Candoni, Anna, et al., 2016. Mucorales-specific T cells in patients

with hematologic malignancies. PLoS One 11 (2), e0149108. https://doi.org/10.1371/journal.pone.0149108.

Powderly, W.G., Cloud, G.A., Dismukes, W.E., Saag, M.S., 1994. Measurement of cryptococcal antigen in serum and cerebrospinal fluid: value in the management of AIDS-associated cryptococcal meningitis. Clin. Infect. Dis. 18 (5), 789–792. https://doi.org/10.1093/clinids/18.5.789.

Prevention and Treatment of Opportunistic Infections Among Adults and Adolescents. n. d. Accessed June 5, 2024. https://www.idsociety.org/practice-guideline/prevention-and-treatment-of-opportunistic-infections-among-adults-and-adolescents/.

Puerta-Alcalde, Pedro, Garcia-Vidal, Carolina, 2021. Changing epidemiology of invasive fungal disease in allogeneic hematopoietic stem cell transplantation. J. Fungi 7 (10), 848. https://doi.org/10.3390/jof7100848.

Puerta-Alcalde, Pedro, Ruiz-Camps, Isabel, Gudiol, Carlota, Salvart, Miquel, Barba, Pere, Morandeira, Francisco, Jarque, Isidro, et al., 2022. Cytokine response as a biomarker for early diagnosis and outcome prediction of stem cell transplant recipients and acute leukemia patients with invasive aspergillosis. Med. Mycol. 60 (7), myac038. https://doi.org/10.1093/mmy/myac038.

Rajasingham, Radha, Smith, Rachel M., Park, Benjamin J., Jarvis, Joseph N., Govender, Nelesh P., Chiller, Tom M., Denning, David W., Loyse, Angela, Boulware, David R., 2017. Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis. Lancet Infect. Dis. 17 (8), 873–881. https://doi.org/10.1016/S1473-3099(17)30243-8.

Rajasingham, Radha, Govender, Nelesh P., Jordan, Alexander, Loyse, Angela, Shroufi, Amir, Denning, David W., Meya, David B., Chiller, Tom M., Boulware, David R., 2022. The global burden of HIV-associated cryptococcal infection in adults in 2020: a modelling analysis. Lancet Infect. Dis., S1473309922004996 https://doi.org/10.1016/S1473-3099(22)00499-6. August.

Rammaert, Blandine, Maunoury, Christophe, Rabeony, Tioka, Correas, Jean-Michel, Elie, Caroline, Alfandari, Serge, Berger, Pierre, et al., 2022. Does 18F-fdg PET/CT Add value to conventional imaging in clinical assessment of chronic disseminated candidiasis? Front. Med. 9. https://www.frontiersin.org/articles/10.3389/fmed.2022.1026067.

Reboli, Annette C., Rotstein, Coleman, Pappas, Peter G., Chapman, Stanley W., Kett, Daniel H., Kumar, Deepali, Betts, Robert, et al., 2007. Anidulafungin versus fluconazole for invasive candidiasis. N. Engl. J. Med. 356 (24), 2472–2482. https://doi.org/10.1056/NEJMoa066906.

Rex, John H., Bennett, John E., Sugar, Alan M., Pappas, Peter G., van der Horst, Charles M., Edwards, John E., Washburn, Ronald G., et al., 1994. A randomized trial comparing fluconazole with amphotericin B for the treatment of candidemia in patients without neutropenia. N. Engl. J. Med. 331 (20), 1325–1330. https://doi.org/10.1056/NEJM199411173312001.

Rex, John H., Pappas, Peter G., Karchmer, Adolf W., Sobel, Jack, Edwards, John E., Hadley, Susan, Brass, Costiaian, et al., 2003. A randomized and blinded multicenter trial of high-dose fluconazole plus placebo versus fluconazole plus amphotericin B as therapy for candidemia and its consequences in nonneutropenic subjects. Clin. Infect. Dis. 36 (10), 1221–1228. https://doi.org/10.1086/374850.

Rhee, Chin Kook, Kang, Ji Young, Kim, Yong Hyun, Kim, Jin Woo, Yoon, Hyung Kyu, Kim, Seok Chan, Kwon, Soon Suk, et al., 2009. Risk factors for acute respiratory distress syndrome during neutropenia recovery in patients with hematologic malignancies. Crit. Care 13 (6), R173. https://doi.org/10.1186/cc8149.

Rhein, Joshua, Nathan C Bahr, Bozena M Morawski, Charlotte Schutz, Yonglong Zhang, Malcolm Finkelman, David B Meya, Graeme Meintjes, and David R Boulware. n.d. "Detection of High Cerebrospinal Fluid Levels of (1→3)-β-D-Glucan in Cryptococcal Meningitis.".

Riera, Fernando, Pablo Caeiro, Juan, Cornely, Oliver A., Salmanton-García, Jon, Argentinian IFI diagnostic and treatment capacity group, 2023. The argentinian landscape of mycological diagnostic capacity and treatment accessibility. Med. Mycol. 61 (6), myad058. https://doi.org/10.1093/mmy/myad058.

Robert-Gangneux, Florence, Belaz, Sorya, Revest, Matthieu, Tattеви, Pierre, Jouanne, Stéphane, Decaux, Olivier, Chevrier, Sylviane, Tulzo, Yves Le, Gangneux, Jean-Pierre, 2014. Diagnosis of Pneumocystis jirovecii pneumonia in immunocompromised patients by real-time PCR: a 4-year prospective study. J. Clin. Microbiol. 52 (9), 3370–3376. https://doi.org/10.1128/JCM.01480-14.

Roberts, Matthew B., Fishman, Jay A., 2020. Immunosuppressive agents and infectious risk in transplantation: managing the 'net state of immunosuppression. Clin. Infect. Dis. 73 (7), e1302-e1317. https://doi.org/10.1093/cid/ciaa1189.

Roden, Maureen M., Zaoutis, Theoklis E., Buchanan, Wendy L., Knudsen, Tena A., Sarkisova, Tatyana A., Schaufele, Robert L., Sein, Michael, et al., 2005. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin. Infect. Dis. 41 (5), 634–653. https://doi.org/10.1086/432579.

Rolfes, Melissa A., Hullsiek, Kathy Huppler, Rhein, Joshua, Nabeta, Henry W., Taseera, Kabanda, Schutz, Charlotte, Musubire, Abdu, et al., 2014. The effect of therapeutic lumbar punctures on acute mortality from cryptococcal meningitis. Clin. Infect. Dis. 59 (11), 1607–1614. https://doi.org/10.1093/cid/ciu596.

Rothenbühler, Christoph, Held, Ulrike, Manz, Markus G., Schanz, Urs, Gerber, Bernhard, 2018. Continuously infused amphotericin B deoxycholate for primary treatment of invasive fungal disease in acute myeloid leukaemia. Hematol. Oncol. 36 (2), 471–480. https://doi.org/10.1002/hon.2500.

Rouzé, Anahita, Loridant, Séverine, Poissy, Julien, Dervaux, Benoit, Sendid, Boualem, Cornu, Marjorie, Nseir, Saad, et al., 2017. Biomarker-based strategy for early discontinuation of empirical antifungal treatment in critically ill patients: a randomized controlled trial. Intensive Care Med. 43 (11), 1668–1677. https://doi.org/10.1007/s00134-017-4932-8.

Rüping, M.J.G.T., Heinz, W.J., Kindo, A.J., Rickerts, V., Lass-Flörl, C., Beisel, C., Herbrecht, R., et al., 2010. Forty-one recent cases of invasive Zygomycosis from a
global clinical registry. J. Antimicrob. Chemother. 65 (2), 296-302. https://doi.org/10.1093/jac/dkp430

Ryom, Lene, De Miguel, Rosa, Grace Cotter, Aoife, Podlekareva, Daria, Beguelin, Charles, Waalewijn, Hylke, Arribas, Josè R., et al., 2022. Major revision version 11.0 of the European AIDS clinical practice guidelines 2021. HIV Med. 23 (8), 849-858. https://doi.org/10.1111/hiv.13268

Safrin, Sharon, Finkelstein, Dianne M., Feinberg, Judith, Telegraph, Peter, Simpson, Gail, Wu, Albert, Cheung, Tony, Soiero, Ruy, Hojczyk, Peter, Black, John R., 1996. Comparison of three regimens for treatment of mild to moderate Pneumocystis carinii pneumonia in patients with AIDS: a double-blind, randomized trial of oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, and clindamycin-primaquine. Ann. Intern. Med. 124 (9), 792-802. https://doi.org/10.7326/0003-4819-124-9-199605010-00003

Salmanton-García, Jon, Au, Wing-Yan, Hoenigl, Martin, Chai, Louis Yi Ann, Badali, Hamid, Basher, Ariful, Brockhoff, Ronja A., et al., 2023a. The current state of laboratory mycology in Asia/Pacific: a survey from the European confederation of medical mycology (ECMM) and international society for human and animal mycology (ISHAM). Int. J. Antimicrob. Agents 61 (3), 106718. https://doi.org/10.1016/j.ijantimicag.2023.106718

Salmanton-García, Jon, Hoenigl, Martin, Gangneux, Jean-Pierre, Segal, Esther, Alastruey-Izquierdo, Ana, Akdagli, Sevtap Arikan, Lagrou, Katrien, Ozenci, Volkan, Vena, Antonio, Cornely, Oliver A., 2023b. The current state of laboratory mycology and access to antifungal treatment in Europe: a European confederation of medical mycology survey. Lancet. Microb. 4 (1), e47-e56. https://doi.org/10.1016/S2666-5247(22)00261-0

Salmanton-García, Jon, Hoenigl, Martin, Salzer, Helmut J.F., Lackner, Michaela, Prattes, Juergen, Dichtl, Karl, Winkler-Zamani, Markus, et al., 2023c. The Austrian landscape of diagnostic capacity and access to treatment for invasive fungal infections. Mycoses 66 (12), 1056-1063. https://doi.org/10.1111/myc.13650

Sattler, Fred R., Cowan, Robert, Nielsen, Donald M., Ruskin, Joel, 1988. Trimethoprim-sulfamethoxazole compared with pentamidine for treatment of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. Ann. Intern. Med. 109 (4), 280-287. https://doi.org/10.7326/0003-4819-109-4-280

Scotto, R., Reia, A., Buonomo, A.R., Mocca, M., Viceconte, G., Pisano, E., Zappulo, E., Brescia Morra, V., Gentile, I., 2021. Risk of invasive fungal infections among patients treated with disease modifying treatments for multiple sclerosis: a comprehensive review. Expet Opin Opin. Saf. 20 (8), 925-936. https://doi.org/10.1080/14740338.2021.1918673

Segal, Brahm H., Herbrecht, Raoul, Stevens, David A., Ostrosky-Zeichner, Luis, Jack, Sobel, Claudio, Viscoli, Walsh, Thomas J., et al., 2008. Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses study group and European organization for research and treatment of cancer consensus criteria. Clin. Infect. Dis. 47 (5), 674-683. https://doi.org/10.1086/590566

Shibata, Wataru, Niki, Mamiko, Sato, Kanako, Fujimoto, Hiroki, Yamada, Koichi, Watanabe, Tetsuya, Miyazaki, Yoshitsugu, et al., 2020. Detection of rhizopus-specific antigen in human and murine serum and bronchoalveolar lavage. Med. Mycol. 58 (7), 958-964. https://doi.org/10.1093/mmy/myaa001

Shoham, Shmuel, Magill, Niki, Mazzoni, B.D., Gupta, K.L., John, G.T., Pursell, K., Munoz, N., Buchanan, Wendy L., Knudsen, Tena A., Sarkisova, Tatyana A., Walsh, Thomas J., 2010. Primary treatment of zygomycosis with liposomal amphotericin B: analysis of 28 cases. Med. Mycol. 48 (3), 511-517. https://doi.org/10.3109/13693780903311944

Sigaer, L., Shamitha, M., Denning, David W., 2024. A systematic review of the therapeutic outcome of mucormycosis. Open Forum Infect. Dis. 11 (1), ofad704. https://doi.org/10.1093/ofid/ofad704

Sims, Charles R., Siraya, Jaijakul, John, Mohr, Jose, Rodriguez, Malcolm, Finkelman, Luis, Ostrosky-Zeichner, 2012. Correlation of clinical outcomes with β-glucan levels in patients with invasive candidiasis. J. Clin. Microbiol. 50 (6), 2104-2106. https://doi.org/10.1128/jcm.00773-12

Singh, N., Lortholary, O., Alexander, B.D., Gupta, K.L., John, G.T., Pursell, K., Munoz, P., et al., 2005. An immune reconstitution syndrome-like illness associated with Cryptococcus neoformans infection in organ transplant recipients. Clin. Infect. Dis. 40 (12), 1756-1761. https://doi.org/10.1086/430606

Singh, Nina, Alexander, Barbara D., Lortholary, Olivier, Dromer, Françoise, Gupta, Krishan L., John, George T., Busto, Ramon Del, et al., 2007. *Cryptococcus neoformans* in organ transplant recipients: impact of calcineurin-inhibitor agents on mortality. J. Infect. Dis. 195 (5), 756-764. https://doi.org/10.1086/511438

Singh, Nina, Dromer, Françoise, Perfect, John R., Lortholary, Olivier, 2008. Immunocompromised hosts: cryptococcosis in solid organ transplant recipients: current state of the science. Clin. Infect. Dis. 47 (10), 1321-1327. https://doi.org/10.1086/592690

Skiada, A., Pagano, L., Groll, A., Zimmerli, S., Dupont, B., Lagrou, K., Lass-Florl, C., et al., 2011. Zygomycosis in europe: analysis of 230 cases accrued by the registry of the European confederation of medical mycology (ECMM) working group on zygomycosis between 2005 and 2007. Clin. Microbiol. Infection 17 (12), 1859-1867. https://doi.org/10.1111/j.1469-0691.2010.03456.x

Skiada, A., Lanterier, F., Groll, A.H., Pagano, L., Zimmerli, S., Herbrecht, R., Lortholary, O., Petrikkos, G.L., 2013. Diagnosis and treatment of mucormycosis in patients with hematological malignancies: guidelines from the 3rd European conference on infections in leukemia (ECIL 3). Haematologia 98 (4), 492-504. https://doi.org/10.3324/haematol.2012.065110

Skripuletz, Thomas, Schwenkenbecher, Philipp, Pars, Kaweh, Stoll, Matthias, Conzen, Josef, Bolat, Seza, Pul, Refik, et al., 2014. Importance of follow-up cerebrospinal fluid analysis in cryptococcal meningoencephalitis. Dis. Markers 2014, 1-10. https://doi.org/10.1155/2014/162576

Slavin, Monica A., Chen, Yee-Chun, Cordonnier, Catherine, Cornely, Oliver W., Cuenca-Estrella, Manuel, Peter Donnelly, J., Groll, Andreas H., et al., 2021. When to change treatment of acute invasive aspergillosis: an expert viewpoint. J. Antimicrob. Chemother. 77 (1), 16-23. https://doi.org/10.1093/jac/dka317

Smego, Jr, Raymond, A., Nagar, Shashi, Maloba, Johanna, Popara, Mirjana, 2001. A meta-analysis of salvage therapy for Pneumocystis carinii pneumonia. Arch. Intern. Med. 161 (12), 1529. https://doi.org/10.1001/arch纪.161.12.1529

Sonet, Anne, Graux, Carlos, Nollevaux, Marie-Cécile, Krug, Bruno, Bosly, André, Borght, Thierry Vander, 2007. Unsuspected FDG-PE findings in the follow-up of patients with lymphoma. Ann. Hematol. 86 (1), 9-15. https://doi.org/10.1007/s00277-006-0167-4

Soriano, Vincent, Dana, Carmen, Rodríguez-Rosado, Rafael, Barreiro, Pablo, Lahoz, Juan González, 2000. Discontinuation of secondary prophylaxis for opportunistic infections in HIV-infected patients receiving highly active antiretroviral therapy. AIDS 14 (4), 383-386. https://doi.org/10.1097/00002030-20003100-00011

Spellberg, Brad, Ibrahim, Ashraf S., Chin-Hong, Peter V., Kontoyiannis, Dimitrios P., Morris, Michele I., Perfect, John R., Fredricks, David, Brass, Eric P., 2012. The deferasirox-AmBisome therapy for mucormycosis (DEFEAT mucor) study: a randomized, double-blinded, placebo-controlled trial. J. Antimicrob. Chemother. 67 (3), 715-722. https://doi.org/10.1093/jac/dkr375

Stanzani, Marta, Sassi, Claudia, Lewis, Russell E., Tolomelli, Giulia, Bazzocchi, Alberto, Cavo, Michele, Vianelli, Nicola, Battista, Giuseppe, 2015. High resolution computed tomography angiography improves the radiographic diagnosis of invasive mold disease in patients with hematological malignancies. Clin. Infect. Dis. 60 (11), 1603-1610. https://doi.org/10.1093/cid/civ154

Stanzani, Marta, Sassi, Claudia, Lewis, Russell, Sartor, Chiara, Rasetto, Gianluca, Cavo, Michele, Battista, Giuseppe, 2021. Early low-dose computed tomography with pulmonary angiography to improve the early diagnosis of invasive mold disease in patients with haematological malignancies: a pilot study. J. Infect. 83 (3), 371-380. https://doi.org/10.1016/j.jinf.2021.06.019

Steinbach, Angela, Cornely, Oliver A., Wispleringhoff, Hilmar, Schaus, Astrid C., Vehbrecht, Joerg J., Rybniker, Jan, Hampfner, Axel, et al., 2019. Mould-reactive T cells for the diagnosis of invasive mold infection—a prospective study. Mycoses 7 (7), 562-569. https://doi.org/10.1111/myc.12919

Sun, Hsin-Yun, Alexander, Barbara D., Lortholary, Olivier, Dromer, Francoise, Forrest, Graeme N., Marshall Lyon, G., Somani, Jyoti, et al., 2009. Lipid formulations of amphotericin B significantly improve outcome in solid organ transplant recipients with central nervous system cryptococcosis. Clin. Infect. Dis. 49 (11), 1721-1728. https://doi.org/10.1086/647948

Temfack, Elvis, Rim, Jean Joel Bigna, Spijker, Rene, Loyse, Angela, Chiller, Tom, Pappas, Peter G., Perfect, John, et al., 2021. Cryptococcal antigen in serum and cerebrospinal fluid for detecting cryptococcal meningitis in adults living with human immunodeficiency virus: systematic review and meta-analysis of diagnostic test accuracy studies. Clin. Infect. Dis. 72 (7), 1268-1278. https://doi.org/10.1093/cid/ciaa1243

Thompson, George R., Jenks Jeffrey, D., Baddley, John W., Lewis, James S., Egger, Matthias, Schwartz, Ilan S., Boyer, Johannes, et al., 2023a. Fungal endocarditis: pathophysiology, epidemiology, clinical presentation, diagnosis, and management. Clin. Microbiol. Rev. 36 (3), e00019. https://doi.org/10.1128/cmr.00019-23

Thompson, George R., Soriano, Alex, Cornely, Oliver A., Jan Kullberg, Bart, Kollef, Marin, Vazquez, Jose, Honore, Patrick M., et al., 2023b. Rezafungin versus caspofungin for treatment of candidaemia and invasive candidiasis (ReSTORE): a multicentre, double-blind, double-dummy, randomised phase 3 trial. Lancet 401 (10370), 49-59. https://doi.org/10.1016/S0140-6736(22)02324-8

Thornton, Christopher R., 2018. Molecular imaging of invasive pulmonary aspergillosis using ImmunPET/MRI: the future looks bright. Front. Microbiol. 9. https://www.frontiersin.org/articles/10.3389/fmicb.2018.00691

Tissot, Frederic, Agrawal, Samir, Pagano, Livio, Petrikkos, Georgios, Groll, Andreas H., Skiada, Anna, Lass-Florl, Cornelia, Calandra, Thierry, Viscoli, Claudio, Herbrecht, Raoul, 2017. ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica 102 (3), 433-444. https://doi.org/10.3324/haematol.2016.15290

Tschopp, Jonathan, Brunel, Anne Sophie, Spertini, Olivier, Croxatto, Anthony, Lamoth, Frederic, Bochud, Pierre Yves, 2022. High false-positive rate of (1,3)-β-D-glucan in onco-hematological patients receiving immunoglobulins and therapeutic antibodies. Clin. Infect. Dis. 75 (2), 330-333. https://doi.org/10.1093/cid/ciai028

Ullmann, A.J., Aguado, J.M., Arikan-Akdagli, S., Denning, D.W., Groll, A.H., Lagrou, K., Lass-Florl, C., et al., 2018. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin. Microbiol. Infection 24 (May), e1-e38. https://doi.org/10.1016/j.cmi.2018.01.002

van der Horst, Charles M., Saag, Michael S., Cloud, Gretchen J., Hamill, Richard J., Richard Graybill, J., Sobel, Jack D., Johnson, Philip C., et al., 1997. Treatment of cryptococcal meningitis associated with the acquired immunodeficiency syndrome. N. Engl. J. Med. 337 (1), 15-21. https://doi.org/10.1056/NEJM199707033370103

Vehreschild, J.J., Heussel, C.P., Groll, A.H., Vehreschild, M.J.G.T., Silling, G., Würthen, G., Brecht, A., Cornely, O.A., 2017. Serial assessment of pulmonary lesion volume by computed tomography allows survival prediction in invasive fungal aspergillosis. Eur. Radiol. 27 (8), 3275-3282. https://doi.org/10.1007/s00330-016-4717-4

Veintimilla, Cristina, Álvarez-Uría, Ana, Martín-Rabadán, Pablo, Valerio, Maricela, Machado, Marina, Padilla, Belén, Alonso, Roberto, Diez, Cristina, Muñoz, Patricia, Marín, Mercedes, 2023. Pneumocystis jirovecii pneumonia diagnostic approach:
real-life experience in a tertiary centre. J. Fungi 9 (4), 414. https://doi.org/10.3390/jof9040414.

Vena, Antonio, Bouza, Emilio, Corisco, Rafael, Machado, Marina, Valerio, Maricela, Sánchez, Carlos, Muñoz, Patricia, for the COMIC Study Group, 2020. Efficacy of a 'checklist' intervention bundle on the clinical outcome of patients with Candida bloodstream infections: a quasi-experimental pre-post study. Infect. Dis. Ther. 9 (1), 119-135. https://doi.org/10.1007/s40121-020-00281-x.

Vena, Antonio, Bovis, Francesca, Tutino, Stefania, Santagostino Barbone, Alessandro, Mezzogori, Laura, Ponzano, Marta, Taramasso, Lucia, et al., 2023. Short course of antifungal therapy in patients with uncomplicated *Candida* bloodstream infection: another case of less is more in the clinical setting? Open Forum Infect. Dis. 10 (1), ofac656. https://doi.org/10.1093/ofid/ofac656.

Vironneau, P., Kania, R., Herman, P., Morizot, G., Garcia-Hermoso, D., Lortholary, O., Lanternier, F., Elie, C., French Mycosis Study Group, 2014. Local control of rhino-orbito-cerebral mucormycosis dramatically impacts survival. Clin. Microbiol. Infection 20 (5), O336–O339. https://doi.org/10.1111/1469-0691.12408.

Vogel, M.N., Vatlach, M., Weissgerber, P., Goeppert, B., Claussen, C.D., Hetzel, J., Horger, M., 2012. HRCT-features of Pneumocystis Jiroveci pneumonia and their evolution before and after treatment in non-HIV immunocompromised patients. Eur. J. Radiol. 81 (6), 1315-1320. https://doi.org/10.1016/j.ejrad.2011.02.052.

Webb, Brandon J., Ferraro, Jeffrey P., Rea, Susan, Kaufusi, Stephanie, Goodman, Bruce E., Spalding, James, 2018. Epidemiology and clinical features of invasive fungal infection in a US Health care network. Open Forum Infect. Dis. 5 (8), ofy187. https://doi.org/10.1093/ofid/ofy187.

Wharton, J. Marcus, Lewis Coleman, Diana, Wofsy, Constance B., Luce, John M., Blumenfeld, Walter, Keith Hadley, W., Ingram-Drake, Leslie, Volberding, Paul A., Hopewell, Philip C., 1986. Trimethoprim-sulfamethoxazole or pentamidine for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. Ann. Intern. Med. 105 (1), 37-44. https://doi.org/10.7326/0003-4819-105-1-37.

Woods, Gail, Miceli, Marisa H., Grazziutti, Monica L., Zhao, Weizhi, Barlogie, Bart, Elias, Anaissie, 2007. Serum Aspergillus galactomannan antigen values strongly correlate with outcome of invasive aspergillosis. Cancer 110 (4), 830-834. https://doi.org/10.1002/cncr.22863.

World Health Organization, 2018. Guidelines for the Diagnosis, Prevention, and Management of Cryptococcal Disease in HIV-Infected Adults, Adolescents and Children, March 2018: Supplement to the 2016 Consolidated Guidelines of the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection. World Health Organization, Geneva. https://apps.who.int/iris/handle/10665/260399.

Xhaard, A., Lanternier, F., Porcher, R., Dannaoui, E., Bergeron, A., Clement, L., Lacroix, C., et al., 2012. Mucormycosis after allogeneic haematopoietic stem cell transplantation: a French multicentre cohort study (2003–2008). Clin. Microbiol. Infection 18 (10), E396–E400. https://doi.org/10.1111/j.1469-0691.2012.03908.x.

Xu, Bing, Shi, Pengcheng, Wu, Hubing, Guo, Xutao, Wang, Quanshi, Zhou, Shuyun, 2010. Utility of FDG PET/CT in guiding antifungal therapy in acute leukemia patients with chronic disseminated candidiasis. Clin. Nucl. Med. 35 (8). https://journals.lww.com/nuclearmed/Fulltext/2010/08000/Utility_of_FDG_PET_CT_in_Guiding_Antifungal.1.aspx.