What Do We Know About the Usefulness of 18f-fdg Pet-ct for the Management of Invasive Fungal Infection? An International Survey.

What Do We Know About the Usefulness of 18f-fdg Pet-ct for the Management of Invasive Fungal Infection? 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An International Survey. Andrea Gutiérrez-Villanueva, Jorge Calderón-Parra, Alejandro Callejas Diaz, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4242318/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 16 Sep, 2024 Read the published version in Mycopathologia → Version 1 posted 5 You are reading this latest preprint version Abstract Background Recent data support 18 F-FDG PET-CT for the management of infections in immunocompromised patients, including invasive fungal infection (IFI). However, its role is not well established in clinical practice. We performed an international survey to evaluate the knowledge of physicians about the usefulness of 18 F-FDG PET-CT in IFI, in order to define areas of uncertainty. Methods An online survey was distributed to infectious diseases working groups in December 2023-January 2024. It included questions regarding access to 18 F-FDG PET-CT, knowledge on its usefulness for IFI and experience of the respondents. A descriptive analysis was performed. Results 180 respondents answered; 60.5% were Infectious Diseases specialists mainly from Spain (52.8%) and Italy (23.3%). 84.4% had access to 18 F-FDG PET-CT at their own center. 85.6% considered that 18 F-FDG PET-CT could be better than conventional tests for IFI. In the context of IFI risk, 81.1% would consider performing 18 F-FDG PET-CT to study fever without a source and around 50% to evaluate silent lesions and assess response, including distinguishing residual from active lesions. Based on the results of the follow-up 18 F-FDG PET-CT, 56.7% would adjust antifungal therapy duration. 60% would consider a change in the diagnostic or therapeutic strategy in case of increased uptake or new lesions. Uncovering occult lesions (52%) and diagnosing/excluding endocarditis (52.7%) were the situations in which 18 F-FDG PET-CT was considered to have the most added value. Conclusion Although the majority considered that 18 F-FDG PET-CT may be useful for IFI, many areas of uncertainty remain: timing and indication in which it adds most value, duration of uptake, the threshold for discontinuing treatment or the influence of immune status. There is a need for protocolized research to improve IFI management. 18F-FDG PET-CT survey febrile neutropenia immunocompromised invasive fungal infection invasive fungal disease Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 INTRODUCTION Positron emission tomography/computed tomography with 18 F-fluorodeoxyglucose ( 18 F-FDG PET-CT) is an imaging Nuclear Medicine technique that provides functional information as well as anatomical data, in addition to having the ability to evaluate more than one body area in a single session [ 1 – 3 ]. Those are potential advantages over conventional imaging techniques that are the current standard for invasive fungal infection evaluation. In recent years, the contribution of 18 F-FDG PET-CT to the management of infectious complications in hematological patients has been studied [ 4 – 6 ]. Several studies suggest that 18 F-FDG PET-CT has the potential of improving the evaluation of patients with febrile neutropenia (FN) and invasive fungal infection (IFI) and also the assessment of the response to treatment [ 4 , 7 – 10 ]. On the other hand, it is known that the use of excessively broad-spectrum empirical therapies in febrile immunocompromised patients may lead to adverse effects, increasing antimicrobial resistance and unnecessary expenses; therefore, several authors have analyzed the usefulness of 18 F-FDG PET-CT for optimizing empirical antimicrobial therapy and allowing early de-escalation and withdrawal of antimicrobials, and specifically antifungals [ 5 , 7 , 11 , 12 , 13 ]. Despite the results of these publications supporting the use of 18 F-FDG PET-CT, in hematological patients its role has not been clearly defined and its use is not yet protocolized. This is even more true for other populations at risk for IFI, such as solid organ transplant recipients [(14]. Along the same lines, even if 18 F-FDG PET-CT for the diagnosis of infectious endocarditis is recommended in the guidelines [ 15 ], especially in prosthetic endocarditis (IB), experience in fungal endocarditis so far is scarce [ 14 ]. We performed an international online survey to evaluate the knowledge of clinicians who care for patients at risk for IFI about the usefulness of 18 F-FDG PET-CT for the management of IFI, and to clarify areas of uncertainty to guide further research. METHODS AND ANALYSIS Survey development A team of Infectious Diseases and Nuclear Medicine physicians developed an online survey that was initially tested on a small group of clinicians to ensure understanding, interpretability, and relevance to clinical practice, both in Spanish and English. The online survey (supplementary material 1) included questions related to the characteristics of the hospital facility, the physician's overall experience caring for immunocompromised patients, and access to 18 F-FDG PET-CT, and then focused on specific questions regarding 18 F-FDG PET-CT indications in IFI, and its added value in different clinical scenarios (diagnosis, staging and therapy of IFI). The physician's experience in using 18 F-FDG PET-CT specifically for the management of fungal infection was also queried. Once the correct functioning of the tool was verified, it was distributed during December 2023 and January 2024. The survey was administered to clinicians through an online link, allowing 28 days to respond. No financial incentives were provided for completing the survey. Study population The survey was distributed to clinicians from different countries who care for patients at risk for IFI, including infectious diseases specialists, hematologists, solid organ transplant clinicians and others, or who interpret 18 F-FDG PET-CT scans (Nuclear Medicine physicians). Members of Infectious Diseases and Nuclear Medicine work groups such as GEMICOMED, GESITRA-IC, GIM, ESGICH, EFISG, EANM and SITA were invited to participate, and, additionally, calls for participation were disseminated across various online platforms. Data analysis Before the analysis, the Spanish and English datasets were combined into a unified unit, ensuring meticulous consistency. Once the results were compiled, descriptive statistics were used to analyze the responses to the questions proposed in the survey. All questions were included and analyzed, specifying the denominator of responses whenever it did not reach 100%. The presentation of data involved organizing frequencies, percentages, and proportions into contingency tables. Ethics The Institutional Review Board (CEIm) at Hospital Universitario Puerta de Hierro (Majadahonda) approved the study as an opinion survey (EXE-01/24). RESULTS Out of 1863 physicians subscribing to the target email groups, 180 answered the survey (10.4% response rate). There were 31.1% complete responses and 68.9% partially complete. The results organized by questions can be checked in supplementary material 2. 1. Characteristics of the practitioners who responded to the survey Table 1 summarizes the characteristics of the clinicians who responded to the survey. Table 1 Characteristics of surveyed clinicians CHARACTERISTIC N % Specialties Internal Medicine 28 15.5 Infectious Diseases 109 60.5 Nuclear Medicine 12 6.6 Microbiology 5 2.6 Intensive Care 4 2.1 Pediatrics 4 2.1 Hematology 12 6.6 Geriatrics 1 0.5 Surgery 1 0.5 Nephrology 1 0.5 Pneumology 2 2.1 Liver transplant specialist 1 0.5 Category of the respondent Attending 66 36.7 Consultant 93 51.7 Fellow 20 11.1 Hospital characteristics: number of beds > 500 131 72.8 200–500 36 20 < 200 13 7.2 Hospital characteristics Public 161 89.4 Private 15 8.3 Departments Hematology Unit 167 92.8 Leukemia Unit 120 66.7 Autologous SCT 140 77.8 Allogenic SCT 119 66.1 CAR-T cell therapy 103 57.2 Oncology Unit 157 87.2 Lung transplantation 58 32.2 Heart transplantation 79 43.9 Liver transplantation 93 51.7 Kidney transplantation 123 68.3 Pancreas transplantation 34 18.9 Intestinal transplantation 22 12.2 Intensive Care Unit (ICU) 173 96.1 Specialized ICU (hemato-oncologic, cardiothoracic surgery, other) 99 55 The majority of the respondents (109; 60.5%) were Infectious Diseases specialists, notwithstanding there was a wide array of other specialties caring of different types of immunocompromised patients from different perspectives. Most of the respondents (93.5%) were consultants, 66 (36.7%) were attending and 20 (11.1%), fellows. The distribution by country of practice is shown in Fig. 1. The majority of responses came from European countries such as Spain (52.8%), Italy (23.3%) or Greece (3.9%), though there is a sample of respondents from all over the world. Of those who responded, 89.4% worked in a public center, generally a large hospital (> 500 beds), (72.8%). As such, most hospitals had Oncology (87.2%) and Hematology units (92.8%), which included leukemia unit in 66.7%, and performed autologous HSCT (hematopoietic stem cell transplantation) in 140 (77.8%), allogenic HSCT in 66.1% and CAR-T cell therapy in 57.2%. Among the solid organ transplantation units, more than 50% had a kidney transplantation program (68.3%), while the remaining types of solid organ transplantation programs were less common: lung, 32.2%; heart, 43.9%; liver, 51.7%; pancreas, 18.9%, and intestine 12.2%. Almost every center had an ICU (96.1%) but only 55% had specialized ICUs. 2. Access to 18 F-FDG PET/CT Although a vast majority of the respondents had onsite access to 18 F-FDG PET-CT (84.4%), as much as 7.9% were not authorized to use 18 F-FDG PET-CT for infection management. 18 F-FDG PET-CT was generally performed within a week since it was requested (30.8%), and even in less than 3 days in another 31.4%, but still in almost in half of the cases the clinicians considered that the delay between requesting and performing 18 F-FDG PET-CT was too long to be clinically useful. Other barriers to the use of 18 F-FDG PET-CT for the management of IFI were the disagreement regarding the indication in 49 (41.2%) or the lack of reimbursement in 22 (18.5%). 3. Usefulness of PET in invasive fungal infection Respondents considered that 18 F-FDG PET-CT could be better than conventional techniques in IFI diagnosis in 53.9% of the cases and for staging in 65%, and, above all, 85.6% for monitoring response to treatment Figure 2 summarizes the multiple indications where the respondents would consider ordering 18 F-FDG PET-CT and the one indication where it was deemed to add more value as compared with conventional imaging. Although 81.1% would consider performing 18 F-FDG PET-CT for the study of fever of unknown origin (FUO), only 52.8% believed this was the indication where 18 F-FDG PET-CT had more added value compared to conventional tests. In contrast, 18 F-FDG PET-CT was considered to add the most value in detecting silent sites of involvement (61.1%) and in differentiating active from residual lesions (60.6%). The question about the timing for performing a control 18 F-FDG PET-CT to monitor the response to antifungal therapy obtained variable responses (Fig. 3 ), although the majority considered it should be performed at 6 (53.7%) or 12 weeks (42.9%) after starting antifungals. Based on the results of the 18 F-FDG PET-CT follow-up, many clinicians agreed they would change the management of the patient. Clinicians would shorten antifungal therapy if there were no FDG uptake (56.7%) or if there were a clear decrease in FDG uptake (even if had not totally disappeared) (29.2%). However, if FDG uptake persisted, 55.6% would prolong antifungal therapy. If there were an increase in uptake or new lesions, 62.9% would consider performing new diagnostic tests and 61.2% would consider a change in the therapeutic strategy. Only 3.9% would not modify it. 4. Fungal endocarditis Regarding 18 F-FDG PET-CT usefulness in candidemia to diagnose or rule out Candida endocarditis in the event of inconclusive echocardiography, 61.5% would use 18 F-FDG PET-CT in case of prosthetic endocarditis, 59.8% in case of cardiac device-associated endocarditis and 50.3% to unveil septic metastasis. Only 31.3% would perform 18 F-FDG PET-CT in all cases of candidemia and 5% would not use 18 F-FDG PET-CT and would prefer a different imaging technique. 5. Technical aspects of 18F-FDG PET/CT uptake The responses regarding the duration of glucose uptake of fungal lesions in 18 F-FDG PET-CT when therapy is effective were very diverse, however, most respondents (44.8%) agreed on the influence of the patient's immunological status on persistence of uptake. In this sense, 91.6% believed that 18 F-FDG PET-CT could be useful in spite of the patient being neutropenic. The ability of 18 F-FDG PET-CT to discern between different etiologies was enquired. Almost 50% believed it is possible to differentiate malignancy from fungal infection according to FDG uptake, while almost 50% (48.9%) believed that it is not. When evaluating the ability of 18 F-FDG PET-CT to distinguish bacterial from fungal infection using 18 F-FDG PET-CT, the agreement was greater, with a vast majority (86.6%) of respondents considering this is not possible. Nevertheless, a similar agreement was not found when asking about the possibility of different FDG uptake by different fungal species in 18 -FDG PET-CT (46.9 versus 53.1%). Radiation exposure can be a matter of concern. Compared to high-resolution CT (HRCT), 39.7% were unsure of the degree of radiation exposure, while the remaining answers were distributed between 29.6% who thought that radiation exposure in 18 F-FDG PET-CT is significantly less than HRCT; and 22.9% who considered that it has a slightly higher or a significantly higher 13 (7.3%) radiation exposure than a standard chest HRCT. 6. Personal experience of the respondents with the use of 18-FDG PET-CT The most common use of 18 F-FDG PET-CT was for Oncology indications (85.8%). A large proportion of the respondents (57.3%) used it commonly for infection management, but only 16.7% used it commonly specifically for IFI management. However, up to 80.9% reported an occasional use in this indication. The experience in the use of 18 F-FDG PET-CT for the management of IFI is summarized in Figs. 4 and 5 . The main indications for requesting a 18 F-FDG PET-CT in this setting were FUO (58.7%) followed by assessment of the response to antifungal therapy (48%), while uncovering occult lesions (52%) and diagnosis/exclusion of endocarditis 92 (52.7%) were the situations in which 18 F-FDG PET-CT was considered to have been the most useful. The main barriers to the use of 18 F-FDG PET-CT for the management of IFI were the concern about cost-effectiveness (54.5%), ignorance of its added value as compared to conventional imaging (39.6%), on site unavailability (19%), authorization only for Oncology indications (13.2%) or the fear of exposing patients to additional radiation (10.7%). DISCUSSION The present survey sheds light on the areas of uncertainty regarding 18 F-FDG PET-CT usefulness for IFI management, underlines the need for spreading the available information to take advantage of its added value and reveals barriers to the use of 18 F-FDG PET-CT in this indication. 1. Demographics and access to 18 F-FDG PET/CT The majority of the respondents of the survey belong to the target population that takes care of patients with IFI: practitioners who work in third level hospitals with Oncology and Hematology units, or that care for solid organ transplantation recipients or manage ICU patients. A large proportion were senior specialists experienced with the use of 18 F-FDG PET-CT. Consequently, their answers reflect the current access to 18 F-FDG PET-CT, and the knowledge and experience of physicians on this indication in developed countries. 2. Access to 18 F-FDG PET/CT 18 F-FDG PET-CT was accessible to almost all the respondents, but there is a need to implement its use for infection, and to reduce the delay to get it done in a timely manner. This delay can lead to a decrease in its performance. Despite data from several studies increasingly supporting the usefulness of 18 F-FDG PET-CT for the management of infection in immunocompromised patients [ 2 , 5 , 16 – 18 ], practitioners encountered barriers such as disagreement regarding the indication and, in some cases, lack of reimbursement. Likewise, a survey conducted in Australia obtained similar results regarding access to 18 F-FDG PET-CT for the management of infection [ 19 ] in spite of the clinicians considering it useful. Cost-effectiveness studies are needed to clarify the role of 18 F-FDG PET-CT as compared to conventional imaging to overcome these limitations. 3. Indications of 18 F-FDG PET-CT in invasive fungal infection Diagnosis/ Exclusion and rationalization of antifungals Several studies, mostly retrospective, have demonstrated the usefulness of 18 F-FDG PET-CT for IFI diagnosis in high risk patients [ 12 , 20 ], in particular in non-neutropenic patients whose lower fungal burden and amount of necrosis hinder the diagnosis [ 18 ], or cases that are clinically silent or involve extrapulmonary sites [ 14 ]. A high proportion of respondents would consider performing 18 F-FDG PET-CT in this scenario. However, only a small percentage would consider performing 18 F-FDG PET-CT to distinguish colonization from invasion, in spite of some evidence in this area [ 21 ]. Regarding neutropenic patients, the vast majority of the respondents were aware of 18 F-FDG PET-CT usefulness in patients with neutropenia, in accordance with previous studies that demonstrate that it is a reliable technique even in patients with severe neutropenia [ 4 , 9 ]. In view of the growing evidence in this area, institutions should facilitate the use of 18 F-FDG PET-CT as part of the study of FN, and in particular to exclude IFI. Less than 40% of clinicians were aware that despite only a small proportion of high risk patients being eventually diagnosed with IFI, the negative 18 F-FDG PET-CT results allow to discontinue empirical antifungals, and so, rationalize antifungal use, as shown by a recent clinical trial that compares an 18 F-FDG PET-CT-based strategy to the standard imaging-based strategy [ 5 ]. So far, studies comparing 18 F-FDG PET-CT versus conventional techniques head to head in the same patient are lacking [ 12 ]. More prospective, comparative studies are needed to better determine its role. Staging (dissemination/endocarditis) IFI presentation varies depending on the host immune response. Dissemination with multiple organ involvement is not uncommon, especially in immunocompromised patients, often remaining clinically silent. The detection of these silent lesions can modify patient management. However, staging is not a clearly established practice in routine evaluation of IFI. Despite the available literature, less than half of those surveyed considered performing 18 F-FDG PET-CT at the time of diagnosis for staging the infection, and a large percentage did not consider that it provided an added value in this setting. Regarding both mold and yeast infections, several authors have shown the superiority of 18 F-FDG PET-CT over CT scan to detect silent lesions [ 10 ] or lesions outside the regions imaged by the anatomy-based studies in almost 50% of the cases [ 1 ]. In the case of fungemia, staging includes the evaluation for endocarditis. In this indication, only one third of those surveyed, and up to 62% in specific circumstances, would use 18 F-FDG PET-CT. According to the guidelines, 18 F-FDG PET-CT does have a role in patients with prosthetic valves [ 15 , 22 ]. It has proven useful to detect septic metastases [ 23 , 24 ], and especially helpful in cases with dubious or negative echocardiography [ 14 ], but the available evidence on 18 F-FDG PET-CT use in candidemia is still scarce and based in retrospective single center studies. Monitoring the response (duration/residual/active) The optimal antifungal treatment duration is a controversial issue [ 23 , 24 ]. The assessment of the response to antifungal therapy is typically based on clinical signs, fungal biomarkers and imaging. Conventional imaging can be confusing when it comes to differentiate active from residual lesions. There is data in favor of 18 F-FDG PET-CT for the assessment of the activity of residual lesions [ 1 , 2 , 10 , 14 ]. Although more than 80% of respondents considered that 18 F-FDG PET-CT could be of help for monitoring the response to antifungal therapy, and around 60% considered that one of its main contributions is precisely the ability to distinguish active from residual lesions, there was no consensus on when would be the optimal moment to perform a follow-up 18 F-FDG PET-CT to monitor response to treatment. The majority pointed to 6 or 12 weeks from the start of the antifungals. Two ongoing prospective studies that will perform systematic 18 F-FDG PET-CT at different time points in different subsets of patients with IFI will hopefully help clarify this issue (OPTIFIL study, https://ichgcp.net/es/clinical-trials-registry/NCT02955966 ; PETIFI PROJECT29, Clinical trials.gov identifier NCT05688592 [ 3 ]. More than half of the clinicians that answered the survey would take into account the results of the 18 F-FDG PET-CT to make changes in treatment or order new diagnostic tests. However, as validated by the answers of 45% of the respondents, the patient’s immunological status is likely to influence the duration of the glucose uptake, presumably reflecting the fungal activity [ 25 ]. Different duration of activity of fungal lesions has been observed in different types of hosts [ 14 ]. The natural history of the 18 F-FDG PET-CT imaging of IFI is still unknown, and the optimal uptake threshold to safely discontinue antifungal needs to be determined. 4. Other technical aspects of 18 F-FDG PET/CT uptake Cancer lesions present typically a high glucose uptake in 18 F-FDG PET-CT. Historically, a SUV of 2.5 or higher was considered to be indicative of malignant tissue; however, there has been a wide range of SUVs reported for other diseases [ 26 ]. Uncertainty about the different 18 F-FDG PET-CT uptake by lesions of diverse etiology was reflected in the responses to the survey, with 50% believing that it would be possible to differentiate neoplasia from infection, or considering that different fungal species could have different glucose uptake intensities. On the contrary, a large majority believed that it is not possible to distinguish bacterial from fungal infection based on glucose uptake. Interestingly, several publications suggest that glucose uptake by fungal lesions is often above the 2.5 SUV threshold, and that it could vary depending on the fungal species [ 2 , 14 ]. Further studies on IFI characteristics in 18 F-FDG PET-CT will improve evaluation of Oncology and Hematology patients at risk for IFI. 18 F-FDG PET-CT generates somewhat more radiation than CT since patients are receiving not only radiation from the CT component of the examination but also lingering radiation from the radiopharmaceutical, 18 F-FDG [ 27 , 28 ]. In this sense, inconsistent answers from the survey indicate ignorance of this issue by the majority of the respondents. Only 23% indicated the correct option, that is, that 18 F-FDG PET-CT has a slightly higher exposure than HRCT, similar to the answers in the survey carried out among Australian practitioners [ 19 ]. Awareness of this only small increase in radiation exposure might help eliminate barriers for the use of 18 F-FDG PET-CT. 5. Experience of participants in the use of 18 F-FDG PET-CT Despite the availability of 18 F-FDG PET-CT among the respondents, slightly more than half used it regularly for infection management, but only 17% specifically for IFI management, compared to a widespread use in Oncology indications. This results are similar to those of a European survey on the treatment of invasive aspergillosis [ 24 ] and the Australian survey [ 19 ]. Barriers to the use of 18 F-FDG PET-CT for IFI, in addition to the aforementioned access and funding difficulties, consist in unawareness of existing evidence in some aspects and insufficient evidence in others, reflected by the percentage of respondents who doubted about its added value as compared to conventional techniques or believed that it did not provide relevant information, and a great proportion who reported concerns about its cost-effectiveness in this indication. Additionally, the survey showed some concern of exposure to additional radiation. Evidence regarding 18 F-FDG PET-CT usefulness for IFI management is based mainly in retrospective single center studies. Although 18 F-FDG PET-CT has long been used in patients at high risk for IFI, and its results in monitoring the response to antifungals are promising, there are still many areas of uncertainty (Table 2 ). Prospective multicenter studies that compare head to head 18 F-FDG PET-CT to conventional imaging in the same patient are needed, especially regarding natural history of IFI from 18 F-FDG PET-CT perspective, follow-up timing and criteria to safely end antifungal therapy. Table 2 Areas of uncertainty regarding usefulness of 18 F-FDG PET-CT for IFI management to be addressed by future research Area Evidence gap/ Research question Required investigations Diagnosis Value of 18 F-FDG PET-CT for the differential diagnosis between colonization and infection in patients with positive cultures from non-sterile sites Prospective study that analyzes the results of performing 18 F-FDG PET-CT to assess active lesions in patients with fungal isolates and whether it determines modification of management Value of 18 F-FDG PET-CT for the differential diagnosis between bacterial and fungal infection Multicenter registry that compares the type of uptake of the different etiologies Value of 18 F-FDG PET-CT for the differential diagnosis between fungal species infection Multicenter registry that compares the type of uptake of the different fungal species Value of 18 F-FDG PET-CT for the differential diagnosis between cancer and fungal infection Multicenter registry that compares the type of uptake of the different etiologies Staging Added value of 18 F-FDG PET-CT performed at diagnosis to rule out or confirm dissemination Head to head comparison with conventional techniques Follow-up Normal duration of glucose uptake in 18 F-FDG PET-CT in the case of a good outcome, and to what extent is it influenced by immunological status Serial 18 F-FDG PET-CT at different time points in patients with different types of underlying immunocompromise and correlation with outcome Optimal timing of follow-up 18 F-FDG PET-CT Protocolized 18 F-FDG PET-CT at different time points of IFI follow-up Optimal glucose uptake threshold to stop antifungals Correlation of 18 F-FDG PET-CT SUV values with clinical parameters and fungal biomarkers Prognosis 18 F-FDG PET-CT parameters such as TLG (total lesion glycolysis) and MV (metabolic volume) showed the ability to predict whether a patient will achieve a complete metabolic response. Prospective study that analyzes patient´s outcome through these parameters. Efficiency Disagreement about the indication of 18 F-FDG PET-CT for IFI as compared to conventional imaging Lack of reimbursement of 18 F-FDG PET-CT in this indication Cost-effectiveness studies Limitations of the survey Only 10.4% of those to whom the survey was sent responded and, in 68.9% of the questions, the response rate was not 100%, in line with other surveys [ 19 ]. However, the characteristics of the respondents correspond to the target population of physicians managing patients with IFI, so that we can consider that the results are generalizable to clinicians working in hospitals of similar characteristics. The majority of the respondents come from southern European countries, though there was a considerable representation of a variety of other mainly western countries. CONCLUSION Although many clinicians consider that 18 F-FDG PET-CT could be better than conventional techniques for IFI management, there remain many areas of uncertainty to be resolved regarding its role in this indication. Unawareness of existing evidence, and lack of good quality evidence in other areas, hamper its generalized use. The present survey unveils the need to generate evidence to establish a protocolized use of 18 F-FDG PET-CT that helps clinicians in their day-to-day decision making to improve IFI management in a cost-effective way. Abbreviations 18 F-FDG PET-CT Positron emission tomography/computed tomography with 18 F-fluorodeoxyglucose FN febrile neutropenia IFI invasive fungal infection HSCT hematopoietic stem cell transplantation GEMICOMED Grupo de Estudio de Micología Médica dentro de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica GESITRA-IC Grupo de Estudio de Infección en el Trasplante y el Huésped Inmunocomprometido de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica GIM Grupo de Infectólogos de Madrid ESGICH European Society of Clinical Microbiology and Infectious Diseases. Study Group for Infections in Compromised Hosts EFISG European Society of Clinical Microbiology and Infectious Diseases. Fungal Infection Study Group EANM European Association of Nuclear Medicine SITA Società Italiana di Terapia Antinfettiva ICU Intensive Care Unit FUO fever of unknown origin HRCT high-resolution computed tomography FN Febrile neutropenia Declarations PATIENT AND PUBLIC INVOLVEMENT None ETHICAL ASPECTS The study has been approved by the Ethical Research Committee of the Puerta de Hierro-Majadahonda Hospital as an opinion survey (EXE-01/24). POTENTIAL CONFLICTS OF INTEREST The authors declare no conflicts of interest. ROLE OF FUNDING SOURCE Andrea Gutiérrez Villanueva is contracted by the Fundación para la Investigación Biomédica del Hospital Universitario Puerta de Hierro-Majadahonda and Fondo de Investigación Sanitaria (FIS) CM22/00248. ACKNOWLEDGMENTS We thank all the survey respondents for taking their time to answer the questions. 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Gutierrez-Villanueva A, Quintana-Reyes C, Martinez de Antonio E, Rodriguez-Alfonso B, Velasquez K, de la Iglesia A, et al. Usefulness of (18)F-FDG PET-CT in the Management of Febrile Neutropenia: A Retrospective Cohort from a Tertiary University Hospital and a Systematic Review. Microorganisms. 2024;12(2). 10.3390/microorganisms12020307 . Hess S. FDG-PET/CT in Fever of Unknown Origin, Bacteremia, and Febrile Neutropenia. PET Clin. 2020;15(2):175–85. 10.1016/j.cpet.2019.11.002 . Gutiérrez-Martín I G-PS, Velásquez K, et al. Usefulness of 18F-FDG PET-CT for the management of invasive fungal infections: a retrospective cohort from a tertiary university hospital. Mycoses. 2024;67(2):e13701. 10.1111/myc.13701 . Delgado V, Ajmone Marsan N, de Waha S, Bonaros N, Brida M, Burri H, et al. 2023 ESC Guidelines for the management of endocarditis. Eur Heart J. 2023. 10.1093/eurheartj/ehad193 . Guy SD, Tramontana AR, Worth LJ, Lau E, Hicks RJ, Seymour JF, et al. Use of FDG PET/CT for investigation of febrile neutropenia: Evaluation in high-risk cancer patients. Eur J Nucl Med Mol Imaging. 2012;39(8):1348–55. 10.1007/s00259-012-2143-7 . Koh KC, Slavin MA, Thursky KA, Lau E, Hicks RJ, Drummond E, et al. Impact of fluorine-18 fluorodeoxyglucose positron emission tomography on diagnosis and antimicrobial utilization in patients with high-risk febrile neutropenia. Leuk Lymphoma. 2012;53(10):1889–95. 10.3109/10428194.2012.677533 . Chamilos G, Macapinlac HA, Kontoyiannis DP. The use of 18F-fluorodeoxyglucose positron emission tomography for the diagnosis and management of invasive mould infections. Med Mycol. 2008;46(1):23–9. 10.1080/13693780701639546 . Douglas AP, Thursky KA, Worth LJ, Harrison SJ, Hicks RJ, Slavin MA. Access, knowledge and experience with fluorodeoxyglucose positron emission tomography/computed tomography in infection management: a survey of Australia and New Zealand infectious diseases physicians and microbiologists. Intern Med J. 2019;49(5):615–21. 10.1111/imj.14117 . Douglas A, Lau E, Thursky K, Slavin M. What, where and why: exploring fluorodeoxyglucose-PET's ability to localise and differentiate infection from cancer. Curr Opin Infect Dis. 2017;30(6):552–64. 10.1097/QCO.0000000000000405 . Kim JY, Yoo JW, Oh M, Park SH, Shim TS, Choi YY, et al. (18)F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography findings are different between invasive and noninvasive pulmonary aspergillosis. J Comput Assist Tomogr. 2013;37(4):596–601. 10.1097/RCT.0b013e318289aa31 . Salomaki SP, Saraste A, Jalava-Karvinen P, Pirila L, Hohenthal U. Prosthetic Valve Candida Endocarditis: A Case Report with 18F-FDG-PET/CT as Part of the Diagnostic Workup. Case Rep Cardiol. 2020;2020:4921380. 10.1155/2020/4921380 . Fernandez-Cruz A, Lewis RE, Kontoyiannis DP. 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. 2020;71(3):685–92. 10.1093/cid/ciz1195 . Lanternier F, Seidel D, Pagano L, Styczynski J, Mikulska M, Pulcini C, et al. Invasive pulmonary aspergillosis treatment duration in haematology patients in Europe: An EFISG, IDWP-EBMT, EORTC-IDG and SEIFEM survey. Mycoses. 2020;63(5):420–9. 10.1111/myc.13056 . Ankrah AO, Sathekge MM, Dierckx R, Glaudemans A. Radionuclide Imaging of Fungal Infections and Correlation with the Host Defense Response. J Fungi (Basel). 2021;7(6). 10.3390/jof7060407 . Kwee TC, Cheng G, Lam MG, Basu S, Alavi A. SUVmax of 2.5 should not be embraced as a magic threshold for separating benign from malignant lesions. Eur J Nucl Med Mol Imaging. 2013;40(10):1475–7. 10.1007/s00259-013-2484-x . Muzaffar R, Koester E, Frye S, Alenezi S, Sterkel BB, Osman MM. Development of Simple Methods to Reduce the Exposure of the Public to Radiation from Patients Who Have Undergone (18)F-FDG PET/CT. J Nucl Med Technol. 2020;48(1):63–7. 10.2967/jnmt.119.233296 . Leide-Svegborn S. Radiation exposure of patients and personnel from a PET/CT procedure with 18F-FDG. Radiat Prot Dosimetry. 2010;139(1–3):208–13. 10.1093/rpd/ncq026 . Supplementary Files Supplementarymaterial1.PETIFIsurvey.pdf Supplementarymaterial2.Resultsbyquestions.docx Cite Share Download PDF Status: Published Journal Publication published 16 Sep, 2024 Read the published version in Mycopathologia → Version 1 posted Reviewers agreed at journal 19 Apr, 2024 Reviewers invited by journal 19 Apr, 2024 Editor invited by journal 19 Apr, 2024 Editor assigned by journal 10 Apr, 2024 First submitted to journal 09 Apr, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4242318","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":293357620,"identity":"295b081a-d091-4324-b3bc-dbbfded82798","order_by":0,"name":"Andrea 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respondents\u0026nbsp;\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4242318/v1/89e6fa4596b9a8902e03fa88.png"},{"id":55517536,"identity":"8ee1f134-f722-402a-a0be-507a64011ef9","added_by":"auto","created_at":"2024-04-29 13:25:54","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":71967,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eUsefulness of PET for invasive fungal infection\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4242318/v1/a17ef01d2bd042cc21e9a35d.png"},{"id":55518388,"identity":"4903fa70-545a-4c54-ab07-7a0d12ff58b6","added_by":"auto","created_at":"2024-04-29 13:33:54","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":52069,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eWhen to perform \u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e18\u003c/strong\u003e\u003c/sup\u003e\u003cstrong\u003e-FDG PET-CT to monitor the response to therapy in a patient with IFI\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4242318/v1/e9d578567206b58e4c437d92.png"},{"id":55517534,"identity":"d672bc30-3e82-4f2f-8e5f-22632745842e","added_by":"auto","created_at":"2024-04-29 13:25:54","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":59650,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cu\u003e\u003cstrong\u003ePersonal experience on the use of \u003c/strong\u003e\u003c/u\u003e\u003csup\u003e\u003cu\u003e\u003cstrong\u003e18\u003c/strong\u003e\u003c/u\u003e\u003c/sup\u003e\u003cu\u003e\u003cstrong\u003e-FDG PET-CT: Indication\u003c/strong\u003e\u003c/u\u003e\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-4242318/v1/28bae65f5b32af8aa99a7c22.png"},{"id":55517537,"identity":"150895ae-c398-46c9-a7b2-2240515e9280","added_by":"auto","created_at":"2024-04-29 13:25:54","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":54990,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cu\u003e\u003cstrong\u003ePersonal experience on the use of 18-FDG PET-CT: Usefulness\u003c/strong\u003e\u003c/u\u003e\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-4242318/v1/3580367474fe36462325db13.png"},{"id":65104030,"identity":"ddae4efc-3431-4b7e-bcdc-967971653b30","added_by":"auto","created_at":"2024-09-23 16:10:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1342671,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4242318/v1/9b0a0d9f-6424-4bab-b318-3a067ff50d4a.pdf"},{"id":55517540,"identity":"7aa969eb-53d5-4083-8ebd-e70991baa5ad","added_by":"auto","created_at":"2024-04-29 13:25:54","extension":"pdf","order_by":12,"title":"","display":"","copyAsset":false,"role":"supplement","size":233455,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterial1.PETIFIsurvey.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4242318/v1/c4cff40570dc8b60830af5ea.pdf"},{"id":55519238,"identity":"1a9b99ab-c063-49e2-8bcb-1c399944ac7b","added_by":"auto","created_at":"2024-04-29 13:41:54","extension":"docx","order_by":13,"title":"","display":"","copyAsset":false,"role":"supplement","size":19871,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterial2.Resultsbyquestions.docx","url":"https://assets-eu.researchsquare.com/files/rs-4242318/v1/237568ca318672e061705e66.docx"}],"financialInterests":"","formattedTitle":"\u003cp\u003eWhat Do We Know About the Usefulness of 18f-fdg Pet-ct for the Management of Invasive Fungal Infection? An International Survey.\u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003ePositron emission tomography/computed tomography with \u003csup\u003e18\u003c/sup\u003eF-fluorodeoxyglucose (\u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT) is an imaging Nuclear Medicine technique that provides functional information as well as anatomical data, in addition to having the ability to evaluate more than one body area in a single session [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Those are potential advantages over conventional imaging techniques that are the current standard for invasive fungal infection evaluation.\u003c/p\u003e \u003cp\u003eIn recent years, the contribution of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT to the management of infectious complications in hematological patients has been studied [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Several studies suggest that \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT has the potential of improving the evaluation of patients with febrile neutropenia (FN) and invasive fungal infection (IFI) and also the assessment of the response to treatment [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan additionalcitationids=\"CR8 CR9\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. On the other hand, it is known that the use of excessively broad-spectrum empirical therapies in febrile immunocompromised patients may lead to adverse effects, increasing antimicrobial resistance and unnecessary expenses; therefore, several authors have analyzed the usefulness of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT for optimizing empirical antimicrobial therapy and allowing early de-escalation and withdrawal of antimicrobials, and specifically antifungals [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Despite the results of these publications supporting the use of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT, in hematological patients its role has not been clearly defined and its use is not yet protocolized. This is even more true for other populations at risk for IFI, such as solid organ transplant recipients [(14].\u003c/p\u003e \u003cp\u003eAlong the same lines, even if \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT for the diagnosis of infectious endocarditis is recommended in the guidelines [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], especially in prosthetic endocarditis (IB), experience in fungal endocarditis so far is scarce [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe performed an international online survey to evaluate the knowledge of clinicians who care for patients at risk for IFI about the usefulness of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT for the management of IFI, and to clarify areas of uncertainty to guide further research.\u003c/p\u003e"},{"header":"METHODS AND ANALYSIS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSurvey development\u003c/h2\u003e \u003cp\u003eA team of Infectious Diseases and Nuclear Medicine physicians developed an online survey that was initially tested on a small group of clinicians to ensure understanding, interpretability, and relevance to clinical practice, both in Spanish and English.\u003c/p\u003e \u003cp\u003eThe online survey (supplementary material 1) included questions related to the characteristics of the hospital facility, the physician's overall experience caring for immunocompromised patients, and access to \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT, and then focused on specific questions regarding \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT indications in IFI, and its added value in different clinical scenarios (diagnosis, staging and therapy of IFI). The physician's experience in using \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT specifically for the management of fungal infection was also queried.\u003c/p\u003e \u003cp\u003eOnce the correct functioning of the tool was verified, it was distributed during December 2023 and January 2024. The survey was administered to clinicians through an online link, allowing 28 days to respond. No financial incentives were provided for completing the survey.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eThe survey was distributed to clinicians from different countries who care for patients at risk for IFI, including infectious diseases specialists, hematologists, solid organ transplant clinicians and others, or who interpret \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT scans (Nuclear Medicine physicians). Members of Infectious Diseases and Nuclear Medicine work groups such as GEMICOMED, GESITRA-IC, GIM, ESGICH, EFISG, EANM and SITA were invited to participate, and, additionally, calls for participation were disseminated across various online platforms.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eData analysis\u003c/h2\u003e \u003cp\u003eBefore the analysis, the Spanish and English datasets were combined into a unified unit, ensuring meticulous consistency. Once the results were compiled, descriptive statistics were used to analyze the responses to the questions proposed in the survey. All questions were included and analyzed, specifying the denominator of responses whenever it did not reach 100%. The presentation of data involved organizing frequencies, percentages, and proportions into contingency tables.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eEthics\u003c/h2\u003e \u003cp\u003e The Institutional Review Board (CEIm) at Hospital Universitario Puerta de Hierro (Majadahonda) approved the study as an opinion survey (EXE-01/24).\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eOut of 1863 physicians subscribing to the target email groups, 180 answered the survey (10.4% response rate). There were 31.1% complete responses and 68.9% partially complete.\u003c/p\u003e \u003cp\u003eThe results organized by questions can be checked in supplementary material 2.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e1. Characteristics of the practitioners who responded to the survey\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e summarizes the characteristics of the clinicians who responded to the survey.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of surveyed clinicians\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCHARACTERISTIC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpecialties\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInternal Medicine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInfectious Diseases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e109\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNuclear Medicine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMicrobiology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntensive Care\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePediatrics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHematology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGeriatrics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNephrology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePneumology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLiver transplant specialist\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCategory of the respondent\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAttending\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConsultant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFellow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHospital characteristics: number of beds\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt; 500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e131\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e200\u0026ndash;500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt; 200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHospital characteristics\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePublic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e161\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e89.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrivate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDepartments\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHematology Unit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e167\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e92.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeukemia Unit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e120\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAutologous SCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e140\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e77.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAllogenic SCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e119\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCAR-T cell therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e103\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOncology Unit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e157\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLung transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeart transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLiver transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKidney transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e123\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePancreas transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntestinal transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntensive Care Unit (ICU)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e173\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e96.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpecialized ICU (hemato-oncologic, cardiothoracic surgery, other)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe majority of the respondents (109; 60.5%) were Infectious Diseases specialists, notwithstanding there was a wide array of other specialties caring of different types of immunocompromised patients from different perspectives.\u003c/p\u003e \u003cp\u003eMost of the respondents (93.5%) were consultants, 66 (36.7%) were attending and 20 (11.1%), fellows.\u003c/p\u003e \u003cp\u003eThe distribution by country of practice is shown in Fig.\u0026nbsp;1. The majority of responses came from European countries such as Spain (52.8%), Italy (23.3%) or Greece (3.9%), though there is a sample of respondents from all over the world. Of those who responded, 89.4% worked in a public center, generally a large hospital (\u0026gt;\u0026thinsp;500 beds), (72.8%). As such, most hospitals had Oncology (87.2%) and Hematology units (92.8%), which included leukemia unit in 66.7%, and performed autologous HSCT (hematopoietic stem cell transplantation) in 140 (77.8%), allogenic HSCT in 66.1% and CAR-T cell therapy in 57.2%. Among the solid organ transplantation units, more than 50% had a kidney transplantation program (68.3%), while the remaining types of solid organ transplantation programs were less common: lung, 32.2%; heart, 43.9%; liver, 51.7%; pancreas, 18.9%, and intestine 12.2%.\u003c/p\u003e \u003cp\u003eAlmost every center had an ICU (96.1%) but only 55% had specialized ICUs.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e2. Access to \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT\u003c/h2\u003e \u003cp\u003eAlthough a vast majority of the respondents had onsite access to \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT (84.4%), as much as 7.9% were not authorized to use \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT for infection management.\u003c/p\u003e \u003cp\u003e \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT was generally performed within a week since it was requested (30.8%), and even in less than 3 days in another 31.4%, but still in almost in half of the cases the clinicians considered that the delay between requesting and performing \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT was too long to be clinically useful.\u003c/p\u003e \u003cp\u003eOther barriers to the use of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT for the management of IFI were the disagreement regarding the indication in 49 (41.2%) or the lack of reimbursement in 22 (18.5%).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3. Usefulness of PET in invasive fungal infection\u003c/h2\u003e \u003cp\u003eRespondents considered that \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT could be better than conventional techniques in IFI diagnosis in 53.9% of the cases and for staging in 65%, and, above all, 85.6% for monitoring response to treatment\u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e2\u003c/span\u003e summarizes the multiple indications where the respondents would consider ordering \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT and the one indication where it was deemed to add more value as compared with conventional imaging. Although 81.1% would consider performing \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT for the study of fever of unknown origin (FUO), only 52.8% believed this was the indication where \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT had more added value compared to conventional tests. In contrast, \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT was considered to add the most value in detecting silent sites of involvement (61.1%) and in differentiating active from residual lesions (60.6%).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe question about the timing for performing a control \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT to monitor the response to antifungal therapy obtained variable responses (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e3\u003c/span\u003e), although the majority considered it should be performed at 6 (53.7%) or 12 weeks (42.9%) after starting antifungals.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eBased on the results of the \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT follow-up, many clinicians agreed they would change the management of the patient. Clinicians would shorten antifungal therapy if there were no FDG uptake (56.7%) or if there were a clear decrease in FDG uptake (even if had not totally disappeared) (29.2%). However, if FDG uptake persisted, 55.6% would prolong antifungal therapy. If there were an increase in uptake or new lesions, 62.9% would consider performing new diagnostic tests and 61.2% would consider a change in the therapeutic strategy. Only 3.9% would not modify it.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e4. Fungal endocarditis\u003c/h2\u003e \u003cp\u003eRegarding \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT usefulness in candidemia to diagnose or rule out \u003cem\u003eCandida\u003c/em\u003e endocarditis in the event of inconclusive echocardiography, 61.5% would use \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT in case of prosthetic endocarditis, 59.8% in case of cardiac device-associated endocarditis and 50.3% to unveil septic metastasis. Only 31.3% would perform \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT in all cases of candidemia and 5% would not use \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT and would prefer a different imaging technique.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e5. Technical aspects of 18F-FDG PET/CT uptake\u003c/h2\u003e \u003cp\u003eThe responses regarding the duration of glucose uptake of fungal lesions in \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT when therapy is effective were very diverse, however, most respondents (44.8%) agreed on the influence of the patient's immunological status on persistence of uptake. In this sense, 91.6% believed that \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT could be useful in spite of the patient being neutropenic.\u003c/p\u003e \u003cp\u003eThe ability of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT to discern between different etiologies was enquired. Almost 50% believed it is possible to differentiate malignancy from fungal infection according to FDG uptake, while almost 50% (48.9%) believed that it is not. When evaluating the ability of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT to distinguish bacterial from fungal infection using \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT, the agreement was greater, with a vast majority (86.6%) of respondents considering this is not possible. Nevertheless, a similar agreement was not found when asking about the possibility of different FDG uptake by different fungal species in \u003csup\u003e18\u003c/sup\u003e-FDG PET-CT (46.9 versus 53.1%).\u003c/p\u003e \u003cp\u003eRadiation exposure can be a matter of concern. Compared to high-resolution CT (HRCT), 39.7% were unsure of the degree of radiation exposure, while the remaining answers were distributed between 29.6% who thought that radiation exposure in \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT is significantly less than HRCT; and 22.9% who considered that it has a slightly higher or a significantly higher 13 (7.3%) radiation exposure than a standard chest HRCT.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e6. Personal experience of the respondents with the use of 18-FDG PET-CT\u003c/h2\u003e \u003cp\u003eThe most common use of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT was for Oncology indications (85.8%). A large proportion of the respondents (57.3%) used it commonly for infection management, but only 16.7% used it commonly specifically for IFI management. However, up to 80.9% reported an occasional use in this indication.\u003c/p\u003e \u003cp\u003eThe experience in the use of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT for the management of IFI is summarized in Figs.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e4\u003c/span\u003e and \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e5\u003c/span\u003e. The main indications for requesting a \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT in this setting were FUO (58.7%) followed by assessment of the response to antifungal therapy (48%), while uncovering occult lesions (52%) and diagnosis/exclusion of endocarditis 92 (52.7%) were the situations in which \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT was considered to have been the most useful.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe main barriers to the use of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT for the management of IFI were the concern about cost-effectiveness (54.5%), ignorance of its added value as compared to conventional imaging (39.6%), on site unavailability (19%), authorization only for Oncology indications (13.2%) or the fear of exposing patients to additional radiation (10.7%).\u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThe present survey sheds light on the areas of uncertainty regarding \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT usefulness for IFI management, underlines the need for spreading the available information to take advantage of its added value and reveals barriers to the use of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT in this indication.\u003c/p\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e1. Demographics and access to \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT\u003c/h2\u003e \u003cp\u003eThe majority of the respondents of the survey belong to the target population that takes care of patients with IFI: practitioners who work in third level hospitals with Oncology and Hematology units, or that care for solid organ transplantation recipients or manage ICU patients. A large proportion were senior specialists experienced with the use of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT. Consequently, their answers reflect the current access to \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT, and the knowledge and experience of physicians on this indication in developed countries.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003e2. Access to \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT\u003c/h2\u003e \u003cp\u003e \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT was accessible to almost all the respondents, but there is a need to implement its use for infection, and to reduce the delay to get it done in a timely manner. This delay can lead to a decrease in its performance. Despite data from several studies increasingly supporting the usefulness of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT for the management of infection in immunocompromised patients [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], practitioners encountered barriers such as disagreement regarding the indication and, in some cases, lack of reimbursement. Likewise, a survey conducted in Australia obtained similar results regarding access to \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT for the management of infection [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] in spite of the clinicians considering it useful. Cost-effectiveness studies are needed to clarify the role of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT as compared to conventional imaging to overcome these limitations.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003e3. Indications of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT in invasive fungal infection\u003c/h2\u003e \u003cdiv id=\"Sec18\" class=\"Section3\"\u003e \u003ch2\u003eDiagnosis/ Exclusion and rationalization of antifungals\u003c/h2\u003e \u003cp\u003eSeveral studies, mostly retrospective, have demonstrated the usefulness of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT for IFI diagnosis in high risk patients [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], in particular in non-neutropenic patients whose lower fungal burden and amount of necrosis hinder the diagnosis [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], or cases that are clinically silent or involve extrapulmonary sites [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. A high proportion of respondents would consider performing \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT in this scenario. However, only a small percentage would consider performing \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT to distinguish colonization from invasion, in spite of some evidence in this area [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRegarding neutropenic patients, the vast majority of the respondents were aware of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT usefulness in patients with neutropenia, in accordance with previous studies that demonstrate that it is a reliable technique even in patients with severe neutropenia [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In view of the growing evidence in this area, institutions should facilitate the use of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT as part of the study of FN, and in particular to exclude IFI.\u003c/p\u003e \u003cp\u003eLess than 40% of clinicians were aware that despite only a small proportion of high risk patients being eventually diagnosed with IFI, the negative \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT results allow to discontinue empirical antifungals, and so, rationalize antifungal use, as shown by a recent clinical trial that compares an \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT-based strategy to the standard imaging-based strategy [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. So far, studies comparing \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT versus conventional techniques head to head in the same patient are lacking [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. More prospective, comparative studies are needed to better determine its role.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eStaging (dissemination/endocarditis)\u003c/h2\u003e \u003cp\u003eIFI presentation varies depending on the host immune response. Dissemination with multiple organ involvement is not uncommon, especially in immunocompromised patients, often remaining clinically silent. The detection of these silent lesions can modify patient management. However, staging is not a clearly established practice in routine evaluation of IFI. Despite the available literature, less than half of those surveyed considered performing \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT at the time of diagnosis for staging the infection, and a large percentage did not consider that it provided an added value in this setting. Regarding both mold and yeast infections, several authors have shown the superiority of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT over CT scan to detect silent lesions [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] or lesions outside the regions imaged by the anatomy-based studies in almost 50% of the cases [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the case of fungemia, staging includes the evaluation for endocarditis. In this indication, only one third of those surveyed, and up to 62% in specific circumstances, would use \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT. According to the guidelines, \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT does have a role in patients with prosthetic valves [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. It has proven useful to detect septic metastases [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], and especially helpful in cases with dubious or negative echocardiography [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], but the available evidence on \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT use in candidemia is still scarce and based in retrospective single center studies.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003eMonitoring the response (duration/residual/active)\u003c/h2\u003e \u003cp\u003eThe optimal antifungal treatment duration is a controversial issue [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The assessment of the response to antifungal therapy is typically based on clinical signs, fungal biomarkers and imaging. Conventional imaging can be confusing when it comes to differentiate active from residual lesions. There is data in favor of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT for the assessment of the activity of residual lesions [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAlthough more than 80% of respondents considered that \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT could be of help for monitoring the response to antifungal therapy, and around 60% considered that one of its main contributions is precisely the ability to distinguish active from residual lesions, there was no consensus on when would be the optimal moment to perform a follow-up \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT to monitor response to treatment. The majority pointed to 6 or 12 weeks from the start of the antifungals. Two ongoing prospective studies that will perform systematic \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT at different time points in different subsets of patients with IFI will hopefully help clarify this issue (OPTIFIL study, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://ichgcp.net/es/clinical-trials-registry/NCT02955966\u003c/span\u003e\u003cspan address=\"https://ichgcp.net/es/clinical-trials-registry/NCT02955966\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e; PETIFI PROJECT29, Clinical trials.gov identifier NCT05688592 [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMore than half of the clinicians that answered the survey would take into account the results of the \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT to make changes in treatment or order new diagnostic tests. However, as validated by the answers of 45% of the respondents, the patient\u0026rsquo;s immunological status is likely to influence the duration of the glucose uptake, presumably reflecting the fungal activity [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Different duration of activity of fungal lesions has been observed in different types of hosts [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The natural history of the \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT imaging of IFI is still unknown, and the optimal uptake threshold to safely discontinue antifungal needs to be determined.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003e4. Other technical aspects of \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT uptake\u003c/h2\u003e \u003cp\u003eCancer lesions present typically a high glucose uptake in \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT. Historically, a SUV of 2.5 or higher was considered to be indicative of malignant tissue; however, there has been a wide range of SUVs reported for other diseases [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Uncertainty about the different \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT uptake by lesions of diverse etiology was reflected in the responses to the survey, with 50% believing that it would be possible to differentiate neoplasia from infection, or considering that different fungal species could have different glucose uptake intensities. On the contrary, a large majority believed that it is not possible to distinguish bacterial from fungal infection based on glucose uptake. Interestingly, several publications suggest that glucose uptake by fungal lesions is often above the 2.5 SUV threshold, and that it could vary depending on the fungal species [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Further studies on IFI characteristics in \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT will improve evaluation of Oncology and Hematology patients at risk for IFI.\u003c/p\u003e \u003cp\u003e \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT generates somewhat more radiation than CT since patients are receiving not only radiation from the CT component of the examination but also lingering radiation from the radiopharmaceutical, \u003csup\u003e18\u003c/sup\u003eF-FDG [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. In this sense, inconsistent answers from the survey indicate ignorance of this issue by the majority of the respondents. Only 23% indicated the correct option, that is, that \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT has a slightly higher exposure than HRCT, similar to the answers in the survey carried out among Australian practitioners [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Awareness of this only small increase in radiation exposure might help eliminate barriers for the use of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003e5. Experience of participants in the use of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT\u003c/h2\u003e \u003cp\u003eDespite the availability of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT among the respondents, slightly more than half used it regularly for infection management, but only 17% specifically for IFI management, compared to a widespread use in Oncology indications. This results are similar to those of a European survey on the treatment of invasive aspergillosis [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] and the Australian survey [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBarriers to the use of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT for IFI, in addition to the aforementioned access and funding difficulties, consist in unawareness of existing evidence in some aspects and insufficient evidence in others, reflected by the percentage of respondents who doubted about its added value as compared to conventional techniques or believed that it did not provide relevant information, and a great proportion who reported concerns about its cost-effectiveness in this indication. Additionally, the survey showed some concern of exposure to additional radiation.\u003c/p\u003e \u003cp\u003eEvidence regarding \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT usefulness for IFI management is based mainly in retrospective single center studies. Although \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT has long been used in patients at high risk for IFI, and its results in monitoring the response to antifungals are promising, there are still many areas of uncertainty (Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Prospective multicenter studies that compare head to head \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT to conventional imaging in the same patient are needed, especially regarding natural history of IFI from \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT perspective, follow-up timing and criteria to safely end antifungal therapy.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAreas of uncertainty regarding usefulness of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT for IFI management to be addressed by future research\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArea\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEvidence gap/ Research question\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRequired investigations\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiagnosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eValue of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT for the differential diagnosis between colonization and infection in patients with positive cultures from non-sterile sites\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eProspective study that analyzes the results of performing \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT to assess active lesions in patients with fungal isolates and whether it determines modification of management\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eValue of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT for the differential diagnosis between bacterial and fungal infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMulticenter registry that compares the type of uptake of the different etiologies\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eValue of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT for the differential diagnosis between fungal species infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMulticenter registry that compares the type of uptake of the different fungal species\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eValue of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT for the differential diagnosis between cancer and fungal infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMulticenter registry that compares the type of uptake of the different etiologies\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStaging\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAdded value of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT performed at diagnosis to rule out or confirm dissemination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHead to head comparison with conventional techniques\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFollow-up\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNormal duration of glucose uptake in \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT in the case of a good outcome, and to what extent is it influenced by immunological status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSerial \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT at different time points in patients with different types of underlying immunocompromise and correlation with outcome\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOptimal timing of follow-up \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eProtocolized \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT at different time points of IFI follow-up\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOptimal glucose uptake threshold to stop antifungals\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCorrelation of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT SUV values with clinical parameters and fungal biomarkers\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrognosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT parameters such as TLG (total lesion glycolysis) and MV (metabolic volume) showed the ability to predict whether a patient will achieve a complete metabolic response.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eProspective study that analyzes patient\u0026acute;s outcome through these parameters.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEfficiency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDisagreement about the indication of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT for IFI as compared to conventional imaging\u003c/p\u003e \u003cp\u003eLack of reimbursement of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT in this indication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCost-effectiveness studies\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec23\" class=\"Section3\"\u003e \u003ch2\u003eLimitations of the survey\u003c/h2\u003e \u003cp\u003eOnly 10.4% of those to whom the survey was sent responded and, in 68.9% of the questions, the response rate was not 100%, in line with other surveys [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. However, the characteristics of the respondents correspond to the target population of physicians managing patients with IFI, so that we can consider that the results are generalizable to clinicians working in hospitals of similar characteristics. The majority of the respondents come from southern European countries, though there was a considerable representation of a variety of other mainly western countries.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eAlthough many clinicians consider that \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT could be better than conventional techniques for IFI management, there remain many areas of uncertainty to be resolved regarding its role in this indication. Unawareness of existing evidence, and lack of good quality evidence in other areas, hamper its generalized use. The present survey unveils the need to generate evidence to establish a protocolized use of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT that helps clinicians in their day-to-day decision making to improve IFI management in a cost-effective way.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePositron emission tomography/computed tomography with \u003csup\u003e18\u003c/sup\u003eF-fluorodeoxyglucose\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFN\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003efebrile neutropenia\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIFI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einvasive fungal infection\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHSCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehematopoietic stem cell transplantation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGEMICOMED\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGrupo de Estudio de Micolog\u0026iacute;a M\u0026eacute;dica dentro de la Sociedad Espa\u0026ntilde;ola de Enfermedades Infecciosas y Microbiolog\u0026iacute;a Cl\u0026iacute;nica\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGESITRA-IC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGrupo de Estudio de Infecci\u0026oacute;n en el Trasplante y el Hu\u0026eacute;sped Inmunocomprometido de la Sociedad Espa\u0026ntilde;ola de Enfermedades Infecciosas y Microbiolog\u0026iacute;a Cl\u0026iacute;nica\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGIM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGrupo de Infect\u0026oacute;logos de Madrid\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eESGICH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEuropean Society of Clinical Microbiology and Infectious Diseases. Study Group for Infections in Compromised Hosts\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEFISG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEuropean Society of Clinical Microbiology and Infectious Diseases. Fungal Infection Study Group\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEANM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEuropean Association of Nuclear Medicine\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSITA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSociet\u0026agrave; Italiana di Terapia Antinfettiva\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eICU\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIntensive Care Unit\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFUO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003efever of unknown origin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHRCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehigh-resolution computed tomography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFN\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eFebrile neutropenia\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003ePATIENT AND PUBLIC INVOLVEMENT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eETHICAL ASPECTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study has been approved by the Ethical Research Committee of the Puerta de Hierro-Majadahonda Hospital as an opinion survey (EXE-01/24).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePOTENTIAL CONFLICTS OF INTEREST\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eROLE OF FUNDING SOURCE\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAndrea Guti\u0026eacute;rrez Villanueva is contracted by the Fundaci\u0026oacute;n para la Investigaci\u0026oacute;n Biom\u0026eacute;dica del Hospital Universitario Puerta de Hierro-Majadahonda and Fondo de Investigaci\u0026oacute;n Sanitaria (FIS) CM22/00248.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eACKNOWLEDGMENTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank all the survey respondents for taking their time to answer the questions. Special thanks to Ana Alastruey, Maddalena Giannella, Antonio Vena, Jon Salmanton, Maricela Valerio, Rafael Duarte, Eleni Magira and Miguel Salavert for their dedicated help to diffuse the survey.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAnkrah AO, Creemers-Schild D, de Keizer B, Klein HC, Dierckx R, Kwee TC, et al. The Added Value of [(18)F]FDG PET/CT in the Management of Invasive Fungal Infections. Diagnostics (Basel). 2021;11(1). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/diagnostics11010137\u003c/span\u003e\u003cspan address=\"10.3390/diagnostics11010137\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDouglas AP, Thursky KA, Worth LJ, Drummond E, Hogg A, Hicks RJ, et al. 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Radiat Prot Dosimetry. 2010;139(1\u0026ndash;3):208\u0026ndash;13. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/rpd/ncq026\u003c/span\u003e\u003cspan address=\"10.1093/rpd/ncq026\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"mycopathologia","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"myco","sideBox":"Learn more about [Mycopathologia](https://www.springer.com/journal/11046)","snPcode":"11046","submissionUrl":"https://submission.nature.com/new-submission/11046/3","title":"Mycopathologia","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"18F-FDG PET-CT, survey, febrile neutropenia, immunocompromised, invasive fungal infection, invasive fungal disease","lastPublishedDoi":"10.21203/rs.3.rs-4242318/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4242318/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRecent data support \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT for the management of infections in immunocompromised patients, including invasive fungal infection (IFI). However, its role is not well established in clinical practice.\u003c/p\u003e\n\u003cp\u003eWe performed an international survey to evaluate the knowledge of physicians about the usefulness of \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT in IFI, in order to define areas of uncertainty.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAn online survey was distributed to infectious diseases working groups in December 2023-January 2024. It included questions regarding access to \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT, knowledge on its usefulness for IFI and experience of the respondents. A descriptive analysis was performed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e180 respondents answered; 60.5% were Infectious Diseases specialists mainly from Spain (52.8%) and Italy (23.3%). 84.4% had access to \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT at their own center.\u003c/p\u003e\n\u003cp\u003e85.6% considered that \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT could be better than conventional tests for IFI. In the context of IFI risk, 81.1% would consider performing \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT to study fever without a source and around 50% to evaluate silent lesions and assess response, including distinguishing residual from active lesions.\u003c/p\u003e\n\u003cp\u003eBased on the results of the follow-up \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT, 56.7% would adjust antifungal therapy duration. 60% would consider a change in the diagnostic or therapeutic strategy in case of increased uptake or new lesions.\u003c/p\u003e\n\u003cp\u003eUncovering occult lesions (52%) and diagnosing/excluding endocarditis (52.7%) were the situations in which \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT was considered to have the most added value.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAlthough the majority considered that \u003csup\u003e18\u003c/sup\u003eF-FDG PET-CT may be useful for IFI, many areas of uncertainty remain: timing and indication in which it adds most value, duration of uptake, the threshold for discontinuing treatment or the influence of immune status. There is a need for protocolized research to improve IFI management.\u003c/p\u003e","manuscriptTitle":"What Do We Know About the Usefulness of 18f-fdg Pet-ct for the Management of Invasive Fungal Infection? An International Survey.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-29 13:25:49","doi":"10.21203/rs.3.rs-4242318/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2024-04-20T03:03:04+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-04-19T23:10:18+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"Mycopathologia","date":"2024-04-19T22:57:01+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-04-11T03:36:29+00:00","index":"","fulltext":""},{"type":"submitted","content":"Mycopathologia","date":"2024-04-09T09:38:51+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"mycopathologia","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"myco","sideBox":"Learn more about [Mycopathologia](https://www.springer.com/journal/11046)","snPcode":"11046","submissionUrl":"https://submission.nature.com/new-submission/11046/3","title":"Mycopathologia","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"75f39a51-4fd5-412b-b13f-370b31762494","owner":[],"postedDate":"April 29th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-09-23T16:03:20+00:00","versionOfRecord":{"articleIdentity":"rs-4242318","link":"https://doi.org/10.1007/s11046-024-00881-y","journal":{"identity":"mycopathologia","isVorOnly":false,"title":"Mycopathologia"},"publishedOn":"2024-09-16 15:57:41","publishedOnDateReadable":"September 16th, 2024"},"versionCreatedAt":"2024-04-29 13:25:49","video":"","vorDoi":"10.1007/s11046-024-00881-y","vorDoiUrl":"https://doi.org/10.1007/s11046-024-00881-y","workflowStages":[]},"version":"v1","identity":"rs-4242318","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4242318","identity":"rs-4242318","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}