Importance of Blood Glucose Management Before 18F-FDG PET/CT in 322 Patients with Bacteremia of Unknown Origin.

We investigated the effects of blood glucose levels on the performance of 18F-FDG PET/CT for detecting an infection focus in patients with bacteremia. Methods: A total of 322 consecutive patients with bacteremia who underwent 18F-FDG PET/CT between 2010 and 2021 were included. Logistic regression analysis was performed to evaluate the association between finding a true-positive infection focus on 18F-FDG PET/CT and blood glucose level, type of diabetes, and use of hypoglycemic medication. C-reactive protein, leukocyte count, duration of antibiotic treatment, and type of isolated bacteria were considered as well. Results: Blood glucose level (odds ratio, 0.76 per unit increase; P = <0.001) was significantly and independently associated with 18F-FDG PET/CT outcome. In patients with a blood glucose level between 3.0 and 7.9 mmol/L (54-142 mg/dL), the true-positive detection rate of 18F-FDG PET/CT varied between 61% and 65%, whereas in patients with a blood glucose level between 8.0 and 10.9 mmol/L (144-196 mg/dL), the true-positive detection rate decreased to 30%-38%. In patients with a blood glucose level greater than 11.0 mmol/L (200 mg/dL), the true-positive detection rate was 17%. In addition to C-reactive protein (odds ratio, 1.004 per point increase; P = 0.009), no other variables were independently associated with 18F-FDG PET/CT outcome. Conclusion: In patients with moderate to severe hyperglycemia, 18F-FDG PET/CT was much less likely to identify the focus of infection than in normoglycemic patients. Although current guidelines recommend postponing 18F-FDG PET/CT only in cases of severe hyperglycemia with glucose levels greater than 11 mmol/L (200 mg/dL), a lower blood glucose threshold seems to be more appropriate in patients with bacteremia of unknown origin and other infectious diseases.

Limitations and Pitfalls of FDG-PET/CT in Infection and Inflammation.

White blood cells activated by either a pathogen or as part of a systemic inflammatory disease are characterized by high energy consumption and are therefore taking up the glucose analogue PET tracer FDG avidly. It is therefore not surprising that a steadily growing body of research and clinical reports now supports the use of FDG PET/CT to diagnose a wide range of patients with non-oncological diseases. However, using FDG PET/CT in patients with infectious or inflammatory diseases has some limitations and potential pitfalls that are not necessarily as pronounced in oncology FDG PET/CT. Some of these limitations are of a general nature and related to the laborious acquisition of PET images in patients that are often acutely ill, whereas others are more disease-specific and related to the particular metabolism in some of the organs most commonly affected by infections or inflammatory disease. Both inflammatory and infectious diseases are characterized by a more diffuse and less pathognomonic pattern of FDG uptake than oncology FDG PET/CT and the affected organs also typically have some physiological FDG uptake. In addition, patients referred to PET/CT with suspected infection or inflammation are rarely treatment naïve and may have received varying doses of antibiotics, corticosteroids or other immune-modulating drugs at the time of their examination. Combined, this results in a higher rate of false positive FDG findings and also in some cases a lower sensitivity to detect active disease. In this review, we therefore discuss the limitations and pitfalls of FDG PET/CT to diagnose infections and inflammation taking these issues into consideration. Our review encompasses the most commonly encountered inflammatory and infectious diseases in head and neck, in the cardiovascular system, in the abdominal organs and in the musculoskeletal system. Finally, new developments in the field of PET/CT that may help overcome some of these limitations are briefly highlighted.

FDG-PET/CT in intensive care patients with bloodstream infection.

BACKGROUND: 2-Deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) is an advanced imaging technique that can be used to examine the whole body for an infection focus in a single examination in patients with bloodstream infection (BSI) of unknown origin. However, literature on the use of this technique in intensive care patients is scarce. The purpose of this study was to evaluate the diagnostic yield of FDG-PET/CT in intensive care patients with BSI. METHODS: In this retrospective cohort study, all intensive care patients from our Dutch university medical center who had culture-proven BSI between 2010 and 2020 and underwent FDG-PET/CT to find the focus of infection were included. Diagnostic performance was calculated and logistic regression analysis was performed to evaluate the association between FDG-PET/CT outcome and C-reactive protein level (CRP), leukocyte count, duration of antibiotic treatment, duration of ICU stay, quality of FDG-PET/CT, and dependency on mechanical ventilation. In addition, the impact of FDG-PET/CT on clinical treatment was evaluated. RESULTS: 30 intensive care patients with BSI were included. In 21 patients, an infection focus was found on FDG-PET/CT which led to changes in clinical management in 14 patients. FDG-PET/CT achieved a sensitivity of 90.9% and specificity of 87.5% for identifying the focus of infection. Poor quality of the FDG-PET images significantly decreased the likelihood of finding an infection focus as compared to reasonable or good image quality (OR 0.16, P = 0.034). No other variables were significantly associated with FDG-PET/CT outcome. No adverse events during the FDG-PET/CT procedure were reported. CONCLUSION: FDG-PET/CT has a high diagnostic yield for detecting the infection focus in patients with BSI admitted to intensive care. Poor PET image quality was significantly associated with a decreased likelihood of finding the infection focus in patients with BSI. This could be improved by adequate dietary preparation and cessation of intravenous glucose and glucose-regulating drugs. Recent advances in PET/CT technology enable higher image quality with shorter imaging time and may contribute to routinely performing FDG-PET/CT in intensive care patients with BSI of unknown origin.

PET/CT Imaging for Personalized Management of Infectious Diseases.

Positron emission tomography combined with computed tomography (PET/CT) is a nuclear imaging technique which is increasingly being used in infectious diseases. Because infection foci often consume more glucose than surrounding tissue, most infections can be diagnosed with PET/CT using 2-deoxy-2-[18F]fluoro-D-glucose (FDG), an analogue of glucose labeled with Fluorine-18. In this review, we discuss common infectious diseases in which FDG-PET/CT is currently applied including bloodstream infection of unknown origin, infective endocarditis, vascular graft infection, spondylodiscitis, and cyst infections. Next, we highlight the latest developments within the field of PET/CT, including total body PET/CT, use of novel PET radiotracers, and potential future applications of PET/CT that will likely lead to increased capabilities for patient-tailored treatment of infectious diseases.

Clinical implications of increased uptake in bone marrow and spleen on FDG-PET in patients with bacteremia.

PURPOSE: To investigate which clinical factors and laboratory values are associated with high FDG uptake in the bone marrow and spleen on 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) in patients with bacteremia. METHODS: One hundred forty-five consecutive retrospective patients with bacteremia who underwent FDG-PET/CT between 2010 and 2017 were included. Mean standard uptake values (SUVmean) of FDG in bone marrow, liver, and spleen were measured. Bone marrow-to-liver SUV ratios (BLR) and spleen-to-liver SUV ratios (SLR) were calculated. Linear regression analyses were performed to examine the association of BLR and SLR with age, gender, hemoglobin, leukocyte count, platelets, glucose level, C-reactive protein (CRP), microorganism, days of antibiotic treatment before FDG-PET/CT, infection focus, use of immunosuppressive drugs, duration of hospital stay (after FDG-PET/CT), ICU admission, and mortality. RESULTS: C-reactive protein (p = 0.006), a cardiovascular or musculoskeletal focus of infection (p = 0.000 for both), and bacteremia caused by Gram-negative bacteria (p = 0.002) were independently and positively associated with BLR, while age (p = 0.000) and glucose level before FDG-PET/CT (p = 0.004) were independently and negatively associated with BLR. For SLR, CRP (p = 0.001) and a cardiovascular focus of infection (p = 0.020) were independently and positively associated with SLR, while age (p = 0.002) and glucose level before FDG-PET/CT (p = 0.016) were independently and negatively associated with SLR. CONCLUSION: High FDG uptake in the bone marrow is associated with a higher inflammatory response and younger age in patients with bacteremia. In patients with high FDG uptake in the bone marrow, a cardiovascular or musculoskeletal focus of infection is more likely than other foci, and the infection is more often caused by Gram-negative species. High splenic FDG uptake is associated with a higher inflammatory response as well, and a cardiovascular focus of infection is also more likely in case of high splenic FDG uptake.

Role of FDG-PET/CT in children with fever of unknown origin.

PURPOSE: To determine the role of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET)/computed tomography (CT) in children with fever of unknown origin (FUO). METHODS: This retrospective single-center study included 110 children (0-18 years) with FUO who underwent FDG-PET/CT between 2010 and 2019. The diagnostic value of FDG-PET/CT for identifying cause of fever was calculated, treatment modifications after FDG-PET/CT were assessed, and logistic regression analyses were performed to identify clinical and biochemical factors associated with FDG-PET/CT outcome. RESULTS: In 53 out of 110 patients (48%), FDG-PET/CT identified a (true positive) cause of fever. Endocarditis (11%), systemic juvenile idiopathic arthritis (5%), and inflammatory bowel disorder (5%) were the most common causes of FUO. In 42 patients (38%), no cause of fever was found on FDG-PET/CT. In 58 out of 110 patients (53%), treatment modifications were made after FDG-PET/CT. FDG-PET/CT achieved a sensitivity of 85.5%, specificity of 79.2%, positive predictive value of 84.1%, and negative predictive value of 80.9%. On multivariate logistic regression, C-reactive protein was positively associated with finding a true positive focus of fever on FDG-PET/CT (OR = 1.01 (95% CI 1.00-1.02) per mg/L increase in CRP), while leukocyte count was negatively associated with finding a true positive focus of fever (OR = 0.91 (95% CI 0.85-0.97) per 109 leukocytes/L increase). CONCLUSION: FDG-PET/CT is a valuable diagnostic tool in the evaluation of children with FUO, since it may detect a true underlying cause in almost half (48%) of all cases where none was found otherwise. It allows full-body evaluation in patients without disease-specific symptoms on one examination. CRP and leukocyte count were significantly associated with FDG-PET/CT results, which may contribute to a priori assessment on the outcome of FDG-PET/CT. Future research could be aimed at evaluating more patient-specific factors to prospectively estimate the added value of FDG-PET/CT in children with FUO.

FDG-PET/CT for Detecting an Infection Focus in Patients With Bloodstream Infection: Factors Affecting Diagnostic Yield.

PURPOSE: To investigate the diagnostic performance of F-fluoro-2-deoxy-D-glucose (FDG) PET/ CT for the detection of an infection focus in patients with a bloodstream infection (BSI) and to identify factors influencing the diagnostic yield of FDG-PET/CT. METHODS: This retrospective single-center study included 185 consecutive patients with a BSI who underwent an FDG-PET/CT scan for the detection of an infection focus between 2010 and 2017. The final diagnosis at hospital discharge was used as reference standard. Diagnostic performance of FDG-PET/CT for the detection of an infection focus was assessed, and logistic regression analyses were performed to identify factors associated with FDG-PET/CT yield. RESULTS: An infection focus was identified on FDG-PET/CT in 120 (64.8%) of 185 patients. FDG-PET/CT achieved a sensitivity of 80.2%, specificity of 79.6%, positive predictive value of 90.8%, and a negative predictive value of 61.4% for detecting an infection focus in patients with a BSI. Blood cultures positive for enterococci (odds ratio, 0.14; P = 0.019) and days of antibiotic treatment before FDG-PET/CT (odds ratio, 0.94 per day increase; P = 0.014) were statistically significant independent predictors of a lower odds of detecting an infection focus on FDG-PET/CT. In patients who received antibiotics for less than 7 days before FDG-PET/CT, an infection focus was found in 71% (56/79). In patients who received antibiotics for 8 to 14 days before FDG-PET/CT, an infection focus was found in 52% (22/42). After 15 to 21 days of antibiotic treatment, an infection focus was found in 61% (8/13), and for 22 days or more, this declined to 38% (5/13). CONCLUSIONS: FDG-PET/CT is a useful method for detecting an infection focus in patients with BSI. However, longer duration of antibiotic treatment before FDG-PET/CT and bacteremia with enterococci reduce the diagnostic yield of FDG-PET/CT. These factors should be taken into account when considering an FDG-PET/CT scan for this indication.

18F-FDG PET/CT in Autosomal Dominant Polycystic Kidney Disease Patients with Suspected Cyst Infection.

The objective of this study was to determine the value of 18F-FDG PET/CT for diagnosing renal or hepatic cyst infection in patients with autosomal dominant polycystic kidney disease (ADPKD). Methods: This retrospective, single-center study included all patients who had ADPKD and underwent 18F-FDG PET/CT because of suspected cyst infection between 2010 and 2017. Results: Thirty 18F-FDG PET/CT scans of 30 individual patients were included; 19 of them had positive results for cyst infection. According to a previously established clinical and biochemical reference standard, 18F-FDG PET/CT achieved a sensitivity of 88.9%, a specificity of 75.0%, a positive predictive value of 84.2%, and a negative predictive value of 81.8% for the diagnosis of cyst infection. In 5 cases, 18F-FDG PET/CT suggested that the symptoms could be explained by a different pathologic process, including pneumonia (n = 1), generalized peritonitis (n = 1), pancreatitis (n = 1), colitis (n = 1), and cholangitis (n = 1). The total duration of the hospital stay and the duration between the 18F-FDG PET/CT scan and hospital discharge for patients with 18F-FDG PET/CT scan results that were positive for cyst infection were significantly longer than those for patients with negative scan results (P = 0.005 and P = 0.009, respectively). Creatinine levels were significantly higher in patients with 18F-FDG PET/CT scan results that were positive for cyst infection than in patients with negative scan results (P = 0.015). Other comparisons of clinical parameters (age, sex, presence of fever [>38.5°C] for more than 3 d, abdominal pain, history of solid-organ transplantation and nephrectomy, and immune status), laboratory values (C-reactive protein level, leukocyte count, and estimated glomerular filtration rate), and microbiologic test results (blood and urine cultures) were not significantly different (P = 0.13-1.00) in patients with positive and negative 18F-FDG PET/CT scan results. Conclusion:18F-FDG PET/CT is a useful imaging modality for the evaluation of patients with ADPKD and suspected cyst infection.

FDG-PET/CT as a New Method for Diagnosis and Whole-Body Evaluation of Lemierre Syndrome.

Lemierre syndrome is a rare disease that is defined by a pharyngeal infection, complicated by septicemia and internal jugular vein thrombosis followed by septic emboli. Because of its rarity, a delay in diagnosis is not uncommon. However, given the mortality rate of approximately 2%, prompt diagnosis and detection of septic emboli are essential to initiate prompt treatment, preventing organ damage and ongoing sepsis. We present 3 cases that demonstrate the value of FDG-PET/CT as a possible alternative or adjunct to conventional imaging methods for diagnosis and whole-body evaluation of Lemierre syndrome.