From the Research
The current Australian guidelines for managing fever of unknown origin (FUO) in suspected sepsis recommend immediate empiric broad-spectrum antibiotic therapy after appropriate cultures are obtained, without delaying treatment for diagnostic procedures. First-line empiric therapy typically includes a combination of an antipseudomonal beta-lactam (such as piperacillin-tazobactam 4.5g IV every 6 hours, meropenem 1g IV every 8 hours, or cefepime 2g IV every 8 hours) plus an aminoglycoside for synergy in severe cases. For patients with risk factors for resistant organisms, vancomycin 15-20mg/kg IV every 8-12 hours should be added. Fluid resuscitation with crystalloids (20-30mL/kg) is recommended alongside vasopressors if needed to maintain mean arterial pressure above 65mmHg. The guidelines emphasize early source control when possible and daily reassessment of antimicrobial therapy with de-escalation based on culture results, typically within 48-72 hours. Antibiotic duration should be individualized but generally ranges from 7-10 days depending on clinical response, source control, and pathogen identified. These recommendations aim to balance rapid intervention to prevent septic shock progression while avoiding antibiotic overuse that contributes to resistance, as supported by the most recent study on FUO 1.
Some key points to consider in the management of FUO include:
- The importance of a comprehensive history and physical examination to guide the initial evaluation, as emphasized in 2 and 3.
- The use of diagnostic tests such as blood cultures, lactate dehydrogenase, creatine kinase, rheumatoid factor, and antinuclear antibodies, as well as imaging studies like 18F fluorodeoxyglucose positron emission tomography plus computed tomography, to help guide the clinician toward tissue biopsy, as discussed in 2 and 4.
- The need for restraint in performing invasive procedures in patients with FUO in whom no cause of fever has been determined during diagnostic work-up, as recommended in 4.
- The high proportion of infectious diseases, particularly tuberculosis, as a cause of FUO, as found in the study by 1.
Overall, the management of FUO requires a careful and systematic approach, taking into account the patient's clinical presentation, laboratory results, and imaging studies, as well as the potential risks and benefits of different diagnostic and therapeutic strategies, as supported by the evidence from 5, 2, 3, 1, and 4.