We present a 35-year-old male with a previous diagnosis of systemic lupus erythematosus and lupus nephritis. Four years ago, he developed severe aortic regurgitation secondary to a bicuspid aortic valve, which required Bentall–De Bono surgery that included the placement of a woven Dacron tube graft of 28 mm in the ascending aorta plus a biological 26 mm INC-type locally manufactured aortic valve replacement. One month before admission, he began with swelling of the lower extremities and dyspnoea; a few days later, fever and diaphoresis were added. One week before his admission, he had three episodes of syncope, the last one accompanied by Stoke–Adams syndrome, which is why he came to our emergency department. On arrival, he was found to have a temperature of 99.8°F (37.7°C) and a heart rate of 40 b.p.m. Physical examination revealed an intense Grade III/IV holosystolic murmur in the aortic area. In laboratory studies, 17.3 × 109/L leucocytes (normal range < 9.79 × 109/L), 14.6 × 109/L neutrophils (normal range < 6.48 × 109/L), 31 mg/L C-reactive protein (normal range < 5 mg/L), 8.180 µg/mL D-dimer (normal range < 0.24 µg/mL), 2449 pg/mL N-terminal (NT)-prohormone BNP (normal range = 0 pg/mL), and 40.7 ng/L high-sensitivity T troponin (normal range < 14) were found. The initial electrocardiogram showed a sinus rhythm with a complete right bundle branch block and a first-degree atrioventricular block (). Due to symptoms and biochemical findings, he was admitted to the coronary care unit to rule out prosthetic valve dysfunction and possible IE. Two days later, he developed a third-degree atrioventricular block requiring a temporary pacemaker, resulting in a notable reduction of symptoms without impact on fever or inflammatory biomarkers. Seven days later, a permanent pacemaker was placed. Meanwhile, TTE was performed, showing an aortic valve prosthesis with an increased velocity gradient (maximum velocity gradient of 4 m/s and a median gradient of 37 mmHg) with a mild central regurgitation flow without paravalvular leaks. No evidence of an aortic root abscess or vegetations (; see, and ). The left ventricular ejection fraction (LVEF) was preserved (68%). The mitral and tricuspid valves had mild insufficiencies. A complimentary TEE was obtained, which did not find suggestive images of IE (see, ). Continuing the approach for IE, CTA was performed without evidence of perivalvular complications, but an infarction on the right kidney was found, which was considered a probable embolic phenomenon (). 99mTc-Ubiquicidin scintigraphy was performed without evidence of abnormal uptake (). The patient continued having feverish episodes, and B. licheniformis was found in two of the four serial blood cultures; an evaluation by the infectious disease department led to the decision to start empiric antibiotic treatment with IV vancomycin within 48 h from admission. Until that moment, the modified DC categorized the patient as ‘possible IE’ with four minor criteria (positive blood culture but not meeting major criteria, fever, presence of embolic phenomena, and a predisposing condition). However, no imaging study could evidence the infection (TTE, TEE, CTA, or 99mTc-ubiquicidin scintigraphy); therefore, following the 2015 ESC guideline recommendation, it was decided to complement with 18F-FDG-PET/CT, a non-invasive nuclear imaging technique, as part of the diagnostic protocol. The patient had adequate preparation 24 h before the study with a low-carbohydrate, high-fat, and protein diet, avoiding IV glucose solutions, and prolonged 15-h fasting. Since the patient had different probable sites of infection (Bentall–De Bono surgery, a valve prosthesis, and a pacemaker), a whole-body PET study was acquired according to the protocol for a patient with a fever of unknown origin. Images were reconstructed with and without attenuation correction. An additional dedicated cerebral bed was acquired, looking for septic emboli. The 18F-FDG images showed abnormally intense heterogeneous uptake in the prosthetic aortic annulus with focal uptake around valve sutures and periprosthetic extension to the ascending aorta graft with maximum standardized uptake value (SUVmax) of 8.2 (). The pattern was persistent on non–attenuation-corrected (NAC) images, ruling out overcorrection artefacts. Non-enchanted CT images showed a poorly delimited perivalvular soft tissue lesion. With these findings, and according to the 2015 ESC guidelines, we considered 18F-FDG-PET/CT a major criterion of the modified DC for IE diagnosis, letting us reclassify the patient towards a ‘definitive IE’ diagnosis due to B. licheniformis. After antimicrobial susceptibility testing, the organism proved susceptible to cephalothin, gentamicin, clindamycin, vancomycin, and trimethoprim–sulfamethoxazole. Based on susceptibilities, IV antibiotic therapy was adjusted with IV trimethoprim–sulfamethoxazole. The case was discussed, and it was concluded that surgical treatment should not be performed due to the high surgical risk and the fact that the isolated pathogen responsible for the IE had a slow growth rate and there was no evidence of vegetation or perivalvular compromise; additionally, the fever and inflammatory biomarkers had decreased. Likewise, the patient’s symptoms improved significantly after the cardiac peacemaker was implanted, which suggested that clinical decompensation at presentation was secondary to a degree of atrioventricular block. With that evidence, it was decided to continue with IV antibiotics over 4 weeks. After remission of fever, decreased inflammatory response, and negative control blood cultures, the patient was discharged in good clinical condition with the indication to continue on antibiotics for two more weeks. Two months later, a follow-up TTE was performed. The patient was in good clinical condition, and the imaging showed improvement in increased velocity gradient through the aortic valve prosthesis (maximum velocity gradient 1.9 m/s, median gradient 8 mmHg), which confirms the response to conservative treatment (; see, ).