Fidel J. Vos

A prospective multi-centre study of the value of FDG-PET as part of a structured diagnostic protocol in patients with fever of unknown origin.

PurposeSince 18F-fluorodeoxyglucose (FDG) accumulates in neoplastic cells and in activated inflammatory cells, positron emission tomography (PET) with FDG could be valuable in diagnosing patients with fever of unknown origin (FUO). The aim of this study was to validate the use of FDG-PET as part of a structured diagnostic protocol in the general patient population with FUO.MethodsFrom December 2003 to July 2005, 70 patients with FUO were recruited from one university hospital (n=38) and five community hospitals (n=32). A structured diagnostic protocol including FDG-PET was used. A dedicated, full-ring PET scanner was used for data acquisition. FDG-PET scans were interpreted by two staff members of the department of nuclear medicine without further clinical information. The final clinical diagnosis was used for comparison with the FDG-PET results.ResultsOf all scans, 33% were clinically helpful. The contribution of FDG-PET to the final diagnosis did not differ significantly between patients diagnosed in the university hospital and patients diagnosed in the community hospitals. FDG-PET contributed significantly more often to the final diagnosis in patients with continuous fever than in patients with periodic fever. FDG-PET was not helpful in any of the patients with normal erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP).ConclusionFDG-PET is a valuable imaging technique as part of a diagnostic protocol in the general patient population with FUO and a raised ESR or CRP.

18F-FDG PET/CT for Detection of Metastatic Infection in Gram-Positive Bacteremia

The timely detection of metastatic infectious foci in gram-positive bacteremia is crucial, because these foci often require prolonged antibiotic treatment or drainage. The diagnosis of metastatic infectious foci is difficult because localizing symptoms are often absent. We investigated whether 18F-FDG PET/CT was able to detect such foci and whether detection influenced clinical outcome. Methods: One hundred fifteen nonneutropenic patients with gram-positive bacteremia were prospectively included. Patients with positive blood cultures growing Staphylococcus aureus, Streptococcus species, or Enterococcus species were eligible when a risk factor for developing metastatic infectious foci was present. 18F-FDG PET/CT was performed within 2 wk after the first positive blood culture. Abnormal 18F-FDG uptake had to be confirmed by radiologic, microbiologic, or pathologic studies. Results were compared with a matched historical control group of 230 patients in whom no 18F-FDG PET/CT was performed. Results: Significantly more patients were diagnosed with metastatic foci in the study group (67.8% vs. 35.7%). Of the imaging investigations performed, 18F-FDG PET/CT was the first to delineate infectious foci in 35 patients (30%). In the remaining 70%, either symptoms on physical examination or other imaging techniques first revealed infectious foci. The sensitivity, specificity, negative predictive value, and positive predictive value of 18F-FDG PET/CT were 100%, 87%, 100%, and 89%, respectively. Relapse rates decreased from 7.4% to 2.6% among study patients (P = 0.09) and from 8.9% to 1.4% in patients with S. aureus (P = 0.04). Overall mortality after 6 mo decreased from 32.2% to 19.1% in the 18F-FDG PET/CT group (P = 0.014). Conclusion: In the diagnostic work-up of high-risk patients with gram-positive bacteremia, 18F-FDG PET/CT is a valuable technique that results in lower mortality rates. In patients with S. aureus bacteremia, relapse rates decreased significantly after the addition of 18F-FDG PET/CT.

Randomized Trial of Longer-Term Therapy for Symptoms Attributed to Lyme Disease

BACKGROUND The treatment of persistent symptoms attributed to Lyme disease remains controversial. We assessed whether longer-term antibiotic treatment of persistent symptoms attributed to Lyme disease leads to better outcomes than does shorter-term treatment. METHODS In a randomized, double-blind, placebo-controlled trial conducted in Europe, we assigned patients with persistent symptoms attributed to Lyme disease--either related temporally to proven Lyme disease or accompanied by a positive IgG or IgM immunoblot assay for Borrelia burgdorferi--to receive a 12-week oral course of doxycycline, clarithromycin plus hydroxychloroquine, or placebo. All study groups received open-label intravenous ceftriaxone for 2 weeks before initiating the randomized regimen. The primary outcome measure was health-related quality of life, as assessed by the physical-component summary score of the RAND-36 Health Status Inventory (RAND SF-36) (range, 15 to 61, with higher scores indicating better quality of life), at the end of the treatment period at week 14, after the 2-week course of ceftriaxone and the 12-week course of the randomized study drug or placebo had been completed. RESULTS Of the 281 patients who underwent randomization, 280 were included in the modified intention-to-treat analysis (86 patients in the doxycycline group, 96 in the clarithromycin-hydroxychloroquine group, and 98 in the placebo group). The SF-36 physical-component summary score did not differ significantly among the three study groups at the end of the treatment period, with mean scores of 35.0 (95% confidence interval [CI], 33.5 to 36.5) in the doxycycline group, 35.6 (95% CI, 34.2 to 37.1) in the clarithromycin-hydroxychloroquine group, and 34.8 (95% CI, 33.4 to 36.2) in the placebo group (P=0.69; a difference of 0.2 [95% CI, -2.4 to 2.8] in the doxycycline group vs. the placebo group and a difference of 0.9 [95% CI, -1.6 to 3.3] in the clarithromycin-hydroxychloroquine group vs. the placebo group); the score also did not differ significantly among the groups at subsequent study visits (P=0.35). In all study groups, the SF-36 physical-component summary score increased significantly from baseline to the end of the treatment period (P<0.001). The rates of adverse events were similar among the study groups. Four serious adverse events thought to be related to drug use occurred during the 2-week open-label ceftriaxone phase, and no serious drug-related adverse event occurred during the 12-week randomized phase. CONCLUSIONS In patients with persistent symptoms attributed to Lyme disease, longer-term antibiotic treatment did not have additional beneficial effects on health-related quality of life beyond those with shorter-term treatment. (Funded by the Netherlands Organization for Health Research and Development ZonMw; PLEASE ClinicalTrials.gov number, NCT01207739.).

Cost-Effectiveness of Routine 18F-FDG PET/CT in High-Risk Patients with Gram-Positive Bacteremia

Gram-positive bacteremia has a high morbidity and mortality rate of approximately 30%. Delayed diagnosis of clinically silent metastatic infectious foci is an important indicator for a complicated outcome. 18F-FDG PET/CT allows detection of focal infection, resulting in lower relapse rates and mortality. Here, we present a cost-effectiveness analysis associated with introduction of 18F-FDG PET/CT for patients with gram-positive bacteremia. Methods: A cost-effectiveness analysis in a prospective 18F-FDG PET/CT group (n = 115) and matched control group (n = 230) was performed alongside a clinical study, the results of which were previously published. Mortality at 6 mo was considered the final effect outcome and was used in the denominator of the incremental cost-effectiveness ratio. Results: Mortality in the 18F-FDG PET/CT group was 19%, compared with 32% in the control group (P < 0.01). Incremental costs of 18F-FDG PET/CT were

Metastatic infectious disease and clinical outcome in Staphylococcus aureus and Streptococcus species bacteremia

9,454 (95% confidence interval [CI],

Detection of pacemaker and lead infection with FDG-PET.

3,963–

The Use of FDG-PET/CT in Patients With Febrile Neutropenia

14,947), mainly because of admission (mean,

Nuclear medicine imaging of infection in cancer patients (with emphasis on FDG-PET)

6,631; 95% CI,

Clinical Impact of Preincubation of Blood Cultures at 37°C

1,449–

The clinical impact of preincubation of blood cultures at 37°C

11,814). Additional costs were related to echocardiography (P < 0.01), not to 18F-FDG PET/CT (P = 0.8). The mean incremental costs of the 18F-FDG PET/CT strategy estimated by stratification for endocarditis were