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Patient 10 with a Candida abscess in the right thyroid lobe, already present on the first (left) 18F-FDG PET/CT scan and increased on a second scan (right)
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Between 30 and 50% of febrile neutropenic episodes are accounted for by infection. C-reactive protein (CRP) is a nonspecific parameter for infection and inflammation but might be employed as a trigger for diagnosis. The aim of the study was to evaluate whether (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT can be used to detec...
Citations
... The CT component was non-contrast enhanced. All patients complied with a previous fasting period of at least six hours (12)(13)(14)(15)(16)(17)(18) h in cases of suspected endocarditis; in this case a dietary modification protocol was also applied). Ideally, they should maintain blood glucose levels lower than 180 mg/dL. ...
... Original articles Seven original articles that studied the usefulness of 18 F-FDG PET-CT in FN were found through the systematic search, five of them prospective and two retrospective [14][15][16][17][18][19][20]. The characteristics of the original articles that evaluated 18 F-FDG-PET-CT's usefulness for FN management are summarized in Table 3. ...
... Studies that do not compare conventional tests and 18 F-FDG PET-CT in the same patient Three articles evaluated the contribution of 18 F-FDG PET-CT in the diagnosis of infection without doing a head to head comparison with conventional tests in the same patient. These studies either performed conventional tests and 18 F-FDG PET-CT in different patients [17] or performed only 18 F-FDG PET-CT [16,18]. A total of 92 patients with FN were evaluated in these studies. ...
Febrile neutropenia (FN) is a complication of hematologic malignancy therapy. An early diagnosis would allow optimization of antimicrobials. The 18F-FDG-PET-CT may be useful; however, its role is not well established. We analyzed retrospectively patients with hematological malignancies who underwent 18F-FDG-PET-CT as part of FN management in our university hospital and compared with conventional imaging. In addition, we performed a systematic review of the literature assessing the usefulness of 18F-FDG-PET-CT in FN. A total of 24 cases of FN underwent 18F-FDG-PET-CT. In addition, 92% had conventional CT. In 5/24 episodes (21%), the fever was of infectious etiology: two were bacterial, two were fungal, and one was parasitic. When compared with conventional imaging, 18F-FDG-PET-CT had an added value in 20 cases (83%): it diagnosed a new site of infection in 4 patients (17%), excluded infection in 16 (67%), and helped modify antimicrobials in 16 (67%). Antimicrobials could be discontinued in 10 (41.6%). We identified seven publications of low quality and one randomized trial. Our results support those of the literature. The available data suggest that 18F-FDG-PET-CT is useful in the management of FN, especially to diagnose fungal infections and rationalize antimicrobials. This review points out the low level of evidence and indicates the gaps in knowledge.
... 10 ¹⁸Ffluorodeoxyglucose ([¹⁸F]FDG)PETCT is a promi sing investigation with improved sensitivity and specificity for identifying the causes of neutropenic fever compared with conventional approaches in small retro spective and nonrandomised prospective studies. 5,[11][12][13][14] Potential benefits included the ability to detect infection in dense tissues, such as the liver and spleen, and [¹⁸F]FDGPETCT also shows promise for localising invasive fungal disease and detecting its dissemination. [15][16][17] We postulated that the use of [¹⁸F]FDGPETCT could positively affect decision making in persistent and recurrent neutropenic fever by miti gating unnecessary antimicrobial escalation, with more rational use of empirical antibacterial and antifungal therapy and thus facilitate anti microbial stewardship. ...
Background
Management of neutropenic fever in high-risk haematology patients is challenging; there are often few localising clinical features, and diagnostic tests have poor sensitivity and specificity. We aimed to compare how [¹⁸F]flurodeoxyglucose ([¹⁸F]FDG)-PET-CT scans and conventional CT scans affected the guidance of antimicrobial management and the outcomes of patients with persistent or recurrent neutropenic fever.
Methods
We did a multicentre, open-label, phase 3, randomised, controlled trial in two tertiary referral hospitals in Australia. We recruited adults aged 18 years or older who were receiving conditioning chemotherapy for haematopoietic stem-cell transplantation or chemotherapy for acute leukaemia and had persistent (>72 h) or recurrent (new fever beyond 72 h of initial onset interspersed with >48 h defervescence) neutropenic fever. Exclusion criteria were pregnancy, allergy to iodinated contrast, or estimated glomerular filtration rate of less than 30 mL/min. Patients were randomly assigned by computer-generated randomisation chart (1:1) to [¹⁸F]FDG-PET-CT or conventional CT. Masking was not possible because of the nature of the investigation. Scans were done within 3 days of random assignment. The primary endpoint was a composite of starting, stopping, or changing the spectrum (broadening or narrowing) of antimicrobial therapy—referred to here as antimicrobial rationalisation—within 96 h of the assigned scan, analysed per protocol. This trial is registered with clinicaltrials.gov, NCT03429387, and is complete.
Findings
Between Jan 8, 2018, and July 23, 2020, we assessed 316 patients for eligibility. 169 patients were excluded and 147 patients were randomly assigned to either [¹⁸F]FDG-PET-CT (n=73) or CT (n=74). Nine patients did not receive a scan per protocol, and two participants in each group were excluded for repeat entry into the study. 65 patients received [¹⁸F]FDG-PET-CT (38 [58%] male; 53 [82%] White) and 69 patients received CT (50 [72%] male; 58 [84%] White) per protocol. Median follow up was 6 months (IQR 6–6). Antimicrobial rationalisation occurred in 53 (82%) of 65 patients in the [¹⁸F]FDG-PET-CT group and 45 (65%) of 69 patients in the CT group (OR 2·36, 95% CI 1·06–5·24; p=0·033). The most frequent component of antimicrobial rationalisation was narrowing spectrum of therapy, in 28 (43%) of 65 patients in the [¹⁸F]FDG-PET-CT group compared with 17 (25%) of 69 patients in the CT group (OR 2·31, 95% CI 1·11–4·83; p=0·024).
Interpretation
[¹⁸F]FDG-PET-CT was associated with more frequent antimicrobial rationalisation than conventional CT. [¹⁸F]FDG-PET-CT can support decision making regarding antimicrobial cessation or de-escalation and should be considered in the management of patients with haematological diseases and persistent or recurrent high-risk neutropenic fever after chemotherapy or transplant conditioning.
Funding
National Health and Medical Research Council Centre of Research Excellence (APP1116876), Melbourne Health foundation, Gilead Research Fellowship grants supported this study.
... Stanzani and colleagues reported that improved radiologic assessment using CT pulmonary angiography, which can distinguish angioinvasive fungal disease from more common bacterial pneumonia or other non-angioinvasive processes in the lung, supported reduction in empiric antifungal use among high-risk hematology populations with European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG)-defined possible aspergillosis [51]. Similarly, fluorodeoxyglucose positron emission tomography/CT may detect occult or undiagnosed disseminated IFD in more than one-third of patients and detect resolution of the infection sooner than conventional CT, possibly supporting earlier discontinuation of antifungal therapy [52][53][54][55]. ...
In recent years, the global public health community has increasingly recognized the importance of antimicrobial stewardship (AMS) in the fight to improve outcomes, decrease costs, and curb increases in antimicrobial resistance around the world. However, the subject of antifungal stewardship (AFS) has received less attention. While the principles of AMS guidelines likely apply to stewarding of antifungal agents, there are additional considerations unique to AFS and the complex field of fungal infections that require specific recommendations. In this article, we review the literature on AMS best practices and discuss AFS through the lens of the global core elements of AMS. We offer recommendations for best practices in AFS based on a synthesis of this evidence by an interdisciplinary expert panel of members of the Mycoses Study Group Education and Research Consortium. We also discuss research directions in this rapidly evolving field. AFS is an emerging and important component of AMS, yet requires special considerations in certain areas such as expertise, education, interventions to optimize utilization, therapeutic drug monitoring, and data analysis and reporting.
... FDG PET/CT is a functional imaging technique that allows whole-body scanning that is of particular value when attempting to identify clinically occult and disseminated infections. Small studies have shown promising results indicating that FDG PET/CT has higher sensitivity in the identification of IFI than conventional CT [13,17,19], and demonstrates benefit in identifying areas of clinically occult infection and dissemination [13,[18][19][20][21][22]. Although the presence of active malignancy can be a confounding factor in differentiating infective foci from tumour involvement, the pattern of abnormality and correlative CT findings can generally allow assignment of the relative likelihoods of each process [23]. ...
... FDG PET/CT is a functional imaging technique that allows whole-body scanning that is of particular value when attempting to identify clinically occult and disseminated infections. Small studies have shown promising results indicating that FDG PET/CT has higher sensitivity in the identification of IFI than conventional CT [13,17,19], and demonstrates benefit in identifying areas of clinically occult infection and dissemination [13,[18][19][20][21][22]. Although the presence of active malignancy can be a confounding factor in differentiating infective foci from tumour involvement, the pattern of abnormality and correlative CT findings can generally allow assignment of the relative likelihoods of each process [23]. ...
Purpose:
Invasive fungal infections (IFIs) are common in immunocompromised patients. While early diagnosis can reduce otherwise high morbidity and mortality, conventional CT has suboptimal sensitivity and specificity. Small studies have suggested that the use of FDG PET/CT may improve the ability to detect IFI. The objective of this study was to describe the proven and probable IFIs detected on FDG PET/CT at our centre and compare the performance with that of CT for localization of infection, dissemination and response to therapy.
Methods:
FDG PET/CT reports for adults investigated at Peter MacCallum Cancer Centre were searched using keywords suggestive of fungal infection. Chart review was performed to describe the risk factors, type and location of IFIs, indication for FDG PET/CT, and comparison with CT for the detection of infection, and its dissemination and response to treatment.
Results:
Between 2007 and 2017, 45 patients had 48 proven/probable IFIs diagnosed prior to or following FDG PET/CT. Overall 96% had a known malignancy with 78% being haematological. FDG PET/CT located clinically occult infection or dissemination to another organ in 40% and 38% of IFI patients, respectively. Of 40 patients who had both FDG PET/CT and CT, sites of IFI dissemination were detected in 35% and 5%, respectively (p < 0.001). Of 18 patents who had both FDG PET/CT and CT follow-up imaging, there were discordant findings between the two imaging modalities in 11 (61%), in whom normalization of FDG avidity of a lesion suggested resolution of active infection despite a residual lesion on CT.
Conclusion:
FDG PET/CT was able to localize clinically occult infection and dissemination and was particularly helpful in demonstrating response to antifungal therapy.
... The authors confirmed that the presence of hypermetabolic central lymph nodes had 100% specificity for focal etiology of fever, even in viremic patients, and lack of increased FDG uptake in the central lymph nodes in FUO patients had 100% negative predictive value for focal disease. A few studies have demonstrated the potential for FDG-PET in neutropenic patients with FUO, revealing a high negative predictive value for ruling out foci of inflammation [23,24]. ...
... 3 Additionally, they can be falsely negative when patients are unable to mount a sufficient response to infection as is often the case in immunosuppressed or immunodeficient patients. 4,5 While antibiotics are critical in the case of a true infection, they are not useful for the management of sterile inflammation or other infection mimics and may in fact be harmful leading to side effects, risk of generating antibiotic-resistant strains, and disruption of the normal microbiome. 6 In this era of increasing antibiotic resistance, especially with health care-associated infections, treatment with broad spectrum antibiotics contributes to the public health emergency of antibiotic resistance. ...
Many methods to diagnose bacterial infections rely on imaging. These techniques include computed tomography (CT) and magnetic resonance imaging (MRI) for structural information, and positron emission tomography (PET) for metabolic data. However, frequently there is significant overlap in the imaging appearance of infectious and non-infectious entities using these tools. To address this concern, recent approaches have targeted bacteria-specific metabolic pathways. For example, radiolabelled sugars derived from sorbitol and maltose have been investigated as PET radiotracers, since these are efficiently incorporated into bacteria but are poor substrates for mammalian cells. We have previously shown that para-aminobenzoic acid (PABA) is an excellent candidate for development as a bacteria-specific imaging tracer as it is rapidly accumulated by a wide range of pathogenic bacteria, including metabolically quiescent bacteria and clinical strains, but not by mammalian cells. Therefore, in this study we developed an efficient radiosynthesis for [11C]PABA, investigated its accumulation into Escherichia coli and Staphylococcus aureus laboratory strains in vitro, and shown that it can distinguish between infection and sterile inflammation in a murine model of acute bacterial infection.
... Fluorodeoxyglucose-positron emission tomography (FDG-PET), in combination with CT, is increasingly recognised as beneficial in the identification and management of infection in the adult cancer population. 2 In a prospective study of 20 patients with prolonged febrile neutropenia (FN), FDG-PET/CT identified eight additional sites of infection and significantly altered management in 75%, compared to conventional evaluation. 2 Other studies in the immunocompromised adult population confirm the beneficial contribution of FDG-PET/CT towards management, including a positive effect on antimicrobial usage, with cessation or rationalisation of broad-spectrum empiric agents. 3,4 Comparatively, literature regarding the use of FDG-PET and infection in immunocompromised children is limited. A retrospective study investigating FDG-PET/CT in 31 children with pyrexia of unknown origin (PUO) included 12 with immunosuppression, where FDG-PET/CT correctly identified the source of fever in seven (88%). 5 Another retrospective study of 69 children with PUO, albeit not immunocompromised, found FDG-PET helpful in reaching final diagnosis in 45% of patients. ...
... The clinical impact of the FDG-PET/CT on patient management was assessed using previously described methodology. [2][3][4] The impact of the FDG-PET/CT was deemed 'high' if any of the following criteria were met: 1 Led to additional investigations or procedures (including referral to other specialist teams) resulting in diagnosis. 2 Detected inflammation suggestive of infection not identified by conventional imaging or microbiological investigations. ...
... This is in keeping with adult studies demonstrating that FDG-PET/CT has increased ability to identify occult infection or inflammation. [2][3][4] In addition, the capacity of FDG-PET/CT to diagnose infection or inflammation does not appear to be impaired by neutropenia, as FDG-PET/CT was still positive in many of the patients with profound neutropenia. ...
Aim:
Fever in immunocompromised children presents significant challenges. We aimed to determine the clinical impact of fluorodeoxyglucose-positron emission tomography (FDG-PET) in combination with computed tomography (CT) in children with malignancy or following haematopoietic stem cell transplantation with prolonged or recurrent fever.
Methods:
Immunocompromised children who underwent FDG-PET/CT for investigation of prolonged or recurrent fever were identified from hospital databases. The clinical impact of the FDG-PET/CT was considered 'high' if it contributed to any of the following: diagnosis of a new site infection/inflammation, change to antimicrobials or chemotherapy, or additional investigations or specialist consult contributing to final diagnosis.
Results:
Fourteen patients underwent an FDG-PET/CT for prolonged or recurrent fever. Median age was 11 years and 46% had diagnosis of acute lymphoblastic leukaemia. The median absolute neutrophil count on the day of FDG-PET/CT was 0.47 cells/μL. The clinical impact of FDG-PET/CT was 'high' in 11 (79%) patients, contributing to rationalisation of antimicrobials in three, and cessation of antimicrobials in five. Compared to conventional imaging, FDG PET/CT identified seven additional sites of clinically significant infection/inflammation in seven patients. Of the 10 patients who had a cause of fever identified, FDG-PET/CT contributed to the final diagnosis in six (60%).
Conclusion:
This study has identified potential utility for FDG-PET/CT in immunocompromised children with prolonged or recurrent fever. Further prospective studies are needed to compare FDG-PET/CT versus conventional imaging, to identify the optimal timing of FDG-PET/CT and to study the role of subsequent scans to monitor response to therapy.
... Nasal congestion or signs and symptoms of sinusitis should give reason for a CT scan of paranasal sinuses (BIII) [74]. First data on PET-CT indicate a potential use for early identification of the source of fever/infection, particularly abdominal foci [75][76][77][78]. Despite these positive reports, an explicit recommendation for its routine use cannot be given due to the lack of systematic studies. ...
Fever may be the only clinical symptom at the onset of infection in neutropenic cancer patients undergoing myelosuppressive chemotherapy. A prompt and evidence-based diagnostic and therapeutic approach is mandatory. A systematic search of current literature was conducted, including only full papers and excluding allogeneic hematopoietic stem cell transplant recipients. Recommendations for diagnosis and therapy were developed by an expert panel and approved after plenary discussion by the AGIHO. Randomized clinical trials were mainly available for therapeutic decisions, and new diagnostic procedures have been introduced into clinical practice in the past decade. Stratification into a high-risk versus low-risk patient population is recommended. In high-risk patients, initial empirical antimicrobial therapy should be active against pathogens most commonly involved in microbiologically documented and most threatening infections, including Pseudomonas aeruginosa, but excluding coagulase-negative staphylococci. In patients whose expected duration of neutropenia is more than 7 days and who do not respond to first-line antibacterial treatment, specifically in the absence of mold-active antifungal prophylaxis, further therapy should be directed also against fungi, in particular Aspergillus species. With regard to antimicrobial stewardship, treatment duration after defervescence in persistently neutropenic patients must be critically reconsidered and the choice of anti-infective agents adjusted to local epidemiology. This guideline updates recommendations for diagnosis and empirical therapy of fever of unknown origin in adult neutropenic cancer patients in light of the challenges of antimicrobial stewardship.
Electronic supplementary material
The online version of this article (doi:10.1007/s00277-017-3098-3) contains supplementary material, which is available to authorized users.
... 18F-fluorodeoxyglucose PET (18F-FDG PET-CT) may be helpful in ruling out undetected infection [10]. Beyond case reports, PET-CT was not yet explored in larger cohort studies including hematologic IPA patients. ...
Purpose of review:
The diagnosis of invasive aspergillosis in hematologic patients is a complex composite of clinical preconditions and features, imaging findings, biomarker combinations from appropriate clinical samples and microbiological and/or histological findings.
Recent findings:
Recent developments in the evolving landscape of diagnostic tests for invasive aspergillosis in adult hematology patients are highlighted.
Summary:
Novel approaches and tools are currently under development. Focusing optimized diagnostic performance, in particular the combination of biomarkers from appropriate clinical samples, improved diagnostic performance distinctly.
... Teóricamente la disminución en el número de neutrófilos metabólicamente activados podría disminuir la sensibilidad del PET/CT, sin embargo la activación de macrófagos y también de las células del tejido conectivo adyacentes a un foco inflamatorio explicarían porque pueden encontrarse focos de aumento de metabolismo en este grupo 20 . Entre las causas en las que el PET/CT puede aportar información se encuentran los focos de tromboflebitis séptica asociados a catéter, los focos de captación pulmonar, especialmente en el contexto de infecciones fúngicas y también la mayor captación del tracto GI debido a mucositis, la que por sí sola puede explicar la causa de fiebre cuando es severa, pero que también puede asociarse a bacteriemias por flora comensal 20,22 . ...
La Tomografía por emisión de positrones/tomografía computada (PET/CT) se ha vuelto fundamental para la evaluación oncológica. En los últimos años se ha hecho evidente su utilidad para evaluar otras patologías inflamatorias no neoplásicas, las cuales pueden presentar aumento del metabolismo medible. El PET/CT tiene la ventaja de poder detectar enfermedades incluso cuando no tienen un correlato en las imágenes morfológicas, permitiendo además localizar de manera precisa estas alteraciones. Entre estas patologías se encuentran el estudio de fiebre de origen desconocido, enfermedades inflamatorias, enfermedades del tejido conectivo, vasculitis y también en el seguimiento y diagnóstico de algunas patologías infecciosas. Se realizará una revisión en la literatura de la utilidad del PET/CT en estas patologías complementada con casos clínicos.
