Diagnostic Approach to Prolonged Fever

Initial Laboratory Evaluation

A comprehensive diagnostic workup for patients with prolonged fever should include complete blood count with differential, inflammatory markers, liver function tests, urinalysis, and blood cultures as first-line laboratory investigations, as recommended by the Centers for Disease Control and Prevention 1, 2
The American College of Physicians suggests that white blood cell count may be normal in up to 75% of patients with prolonged fever, but is still essential for evaluation 1
The presence of leukocytosis or left shift warrants careful assessment for bacterial infection, according to the Infectious Diseases Society of America 2, 3
The European Society of Clinical Microbiology and Infectious Diseases recommends that C-reactive protein and erythrocyte sedimentation rate should be measured in all patients with prolonged fever 4, 5
Procalcitonin levels can help discriminate bacterial infection from other inflammatory processes causing fever, as suggested by the Society of Critical Care Medicine 5

Blood cultures should be obtained if bacteremia is suspected, especially in critically ill patients, as recommended by the Infectious Diseases Society of America 2, 5
Serologic testing for specific antibodies should be performed for suspected infectious causes like Q fever, according to the Centers for Disease Control and Prevention 7, 8
Molecular diagnostic tests, such as polymerase chain reaction testing, may be useful in detecting specific pathogens when indicated, as suggested by the European Society of Clinical Microbiology and Infectious Diseases 7, 8

The American Academy of Pediatrics recommends that evaluation for Kawasaki disease should be considered in children with prolonged fever and compatible clinical criteria 4, 6
The American Geriatrics Society suggests that normal WBC count does not rule out infection in elderly patients, and that the combination of fever, leukocytosis, and bandemia has high specificity for bacterial infection in this population 3
The Infectious Diseases Society of America recommends that more extensive workup may be required for immunocompromised patients, including testing for opportunistic infections 9