What is the appropriate treatment approach for a patient with a new onset of fever?

Approach to New Onset Fever

For a patient with new onset fever, begin with a systematic clinical assessment to identify the source, obtain appropriate cultures before initiating antimicrobials, and reserve empiric antibiotics for patients with high probability of bacterial infection or signs of sepsis. 1

Temperature Measurement

• Use central temperature monitoring methods (pulmonary artery catheter thermistors, bladder catheters, or esophageal balloon thermistors) when these devices are already in place or when accurate temperature measurement is critical to diagnosis and management 1, 2
• For patients without central monitoring devices, use oral or rectal temperatures rather than less reliable methods such as axillary, tympanic membrane, temporal artery thermometers, or chemical dot thermometers 1
• Fever is defined as core body temperature >38.3°C (101°F) 3

Initial Diagnostic Workup

Imaging Studies

• Obtain a chest radiograph for all patients who develop fever during ICU stay 1
• For patients with recent thoracic, abdominal, or pelvic surgery, perform CT imaging (in collaboration with surgical service) if initial workup does not identify an etiology 1
• For patients with fever and abnormal chest radiograph, perform thoracic bedside ultrasound when expertise is available to identify pleural effusions and parenchymal or interstitial lung pathology 1
• Do not routinely perform abdominal ultrasound in patients without abdominal signs, symptoms, liver function abnormalities, or recent abdominal surgery 1
• Perform formal bedside diagnostic ultrasound of the abdomen in patients with fever and recent abdominal surgery, abdominal symptoms, or suspicion of abdominal source (abnormal physical examination, elevated transaminases, alkaline phosphatase, or bilirubin) 1

Blood Cultures

• Collect at least two sets of blood cultures (ideally 60 mL total blood volume) one after the other from different anatomical sites without time interval between them 1
• Draw three to four blood cultures within the first 24 hours of fever onset, making every effort to obtain cultures before initiating antimicrobial therapy 1
• For patients with central venous catheters, simultaneously collect central venous catheter and peripherally drawn blood cultures to calculate differential time to positivity 1
• Sample at least two lumens when central venous catheter cultures are indicated 1
• Use 2% chlorhexidine gluconate in 70% isopropyl alcohol for skin antisepsis (requires 30 seconds drying time), or tincture of iodine as equally effective alternative 1

Respiratory Testing

• For patients with suspected pneumonia or new upper respiratory symptoms (cough), test for viral pathogens using viral nucleic acid amplification test panels 1
• Test for SARS-CoV-2 by PCR based on levels of community transmission 1
• Do not routinely perform blood testing for viral pathogens (herpesviruses, adenovirus) in immunocompetent ICU patients 1

Urinary Tract Evaluation

• For febrile ICU patients with pyuria and suspected urinary tract infection, replace the urinary catheter and obtain urine cultures from the newly placed catheter 1

Biomarker Testing

For low to intermediate probability of bacterial infection:

• Measure procalcitonin (PCT) or C-reactive protein (CRP) in addition to bedside clinical evaluation to help rule out bacterial infection 1

For high probability of bacterial infection:

• Do not measure PCT or CRP to rule out bacterial infection, as these tests are not useful when bacterial infection is highly likely 1

Antipyretic Therapy

• Avoid routine use of antipyretic medications for the specific purpose of reducing temperature in critically ill patients with fever 1
• For patients who value comfort by reducing temperature, use antipyretics over nonpharmacologic methods 1
• Fever is an evolved defense mechanism that augments immune cell performance and induces stress on pathogens; blocking fever may be harmful in patients with infections 4

Antimicrobial Therapy Decisions

When to Initiate Empiric Antibiotics

• Initiate immediate empiric antibiotics within 1 hour if sepsis is suspected, before culture results are available 2
• Direct broad-spectrum coverage against likely pathogens based on suspected source, risk for multidrug-resistant organisms, and local susceptibility patterns 2
• Implement source control measures (removing infected catheters, draining abscesses, surgical intervention) as indicated 2

When to Withhold Empiric Antibiotics

• Avoid empiric antimicrobial therapy in patients with low probability of bacterial infection, as inappropriate antibiotic use selects resistant bacterial strains 3
• Empiric antimicrobial therapy has not been shown effective for fever of unknown origin and should be avoided except in neutropenic, immunocompromised, or critically ill patients 5

Critical Pitfalls to Avoid

• Do not delay antibiotics in septic patients, as this increases mortality; when clinical distinction between infectious and non-infectious fever is unclear, err on the side of initiating empiric therapy 2, 3
• Consider non-infectious causes including drug fever, withdrawal syndromes, blood transfusion reactions, deep venous thrombosis, aspiration, and other inflammatory states 2, 3
• Avoid relying on unreliable temperature methods (axillary, tympanic) for critical clinical decisions 2
• Do not overlook atypical presentations, as elderly and immunocompromised patients may have severe infections without fever 2
• Distinguish fever from hyperthermia (temperatures >106°F), as antipyretics are ineffective for hyperthermia 3
• Temperatures between 102°F-106°F are more likely infectious, while temperatures <102°F or >106°F suggest non-infectious causes 3

Special Populations

Neutropenic Patients with Fever

• Hospitalize and initiate empiric antibacterial therapy with vancomycin plus antipseudomonal antibiotics (cefepime, carbapenem, or piperacillin-tazobactam) 1
• For persistent or recurrent fever in neutropenic patients, add empiric antifungal therapy as yeasts and molds remain primary causes 1
• Treatment duration for most bacterial skin and soft tissue infections should be 7-14 days 1