What is the initial treatment protocol for a patient presenting to the emergency room (ER) or outpatient (OP) department with fever?

Treatment Protocol for Fever in ER/OP Setting

Immediate Triage and Risk Stratification

All febrile patients presenting to the ER or outpatient department require immediate temperature confirmation (≥38.0°C/100.4°F) using rectal measurement in neonates/young children or oral measurement in cooperative older patients and adults, followed by age-based risk stratification to determine disposition and empirical treatment needs. 1

Age-Specific Initial Assessment

Neonates and Infants (≤90 days)

• All febrile infants aged 29-90 days require lumbar puncture immediately, as no adequate predictors exist to safely exclude bacterial meningitis 1
• Infants <28 days are at highest risk (13% serious bacterial infection rate) and require full sepsis workup: blood culture, urine culture via catheterization/suprapubic aspiration, lumbar puncture, and chest radiograph 1
• Initiate empirical antibiotics immediately after cultures if bacterial meningitis is suspected, as 71% of bacterial meningitis cases have positive blood cultures 1
• Most common pathogens are E. coli (43.7%) and Group B Streptococcus; cover Listeria monocytogenes empirically 1

Children (2 months to 2 years)

• Evaluate well-appearing febrile children for urinary tract infection based on clinical predictors 1
• Obtain urine testing via catheterization or suprapubic aspiration (not bag collection) 1
• Perform chest radiograph only if specific respiratory findings are present 1
• Only 58% of children with bacteremia or bacterial meningitis appear clinically ill, so maintain high index of suspicion 1

Adults Without Travel History

• Perform chest radiograph as initial imaging 1
• Obtain blood cultures only if septic shock is present or results will change management 1
• For post-surgical patients with fever and abdominal symptoms or abnormal liver function tests, obtain formal bedside diagnostic ultrasound 1
• Pursue CT imaging for post-surgical patients or those with abdominal/pelvic symptoms when initial workup is non-diagnostic 1

Travel History: Mandatory Screening

Malaria testing must be performed immediately in all patients with fever who have visited any tropical or subtropical country within the past year, as this is the most important potentially fatal cause of tropical fever. 2

Essential Travel History Components

Document on all laboratory request forms 2:

• Exact locations visited and dates of travel
• Timing of symptom onset relative to travel dates
• Risk activities (animal exposure, freshwater swimming, sexual contacts, insect bites)
• Immunization history and malaria prophylaxis use
• Associated symptoms (respiratory, gastrointestinal, neurological, rash)

Mandatory Initial Investigations for Returned Travelers

• Perform both thick blood film and rapid diagnostic test (RDT) simultaneously for initial malaria workup 2
• If initial tests are negative but clinical suspicion remains, repeat testing: three thick films/RDTs over 72 hours are required to confidently exclude malaria 2
• Obtain two sets of blood cultures before starting any antibiotics 2
• Complete blood count with differential, renal and liver function tests, urinalysis 2
• Consider serum save for serology, EDTA sample for PCR, chest X-ray, liver ultrasound as clinically indicated 2

Geographic-Specific Empirical Treatment

Sub-Saharan Africa Exposure

• Highest priority: P. falciparum malaria (most cases present within 1 month but can occur up to 6 months) 2
• Also consider: typhoid, rickettsial infections, viral hemorrhagic fevers 2
• Start empirical antibiotics immediately without waiting for culture results when suspected meningococcemia or typhoid with negative malaria tests 2

South/Southeast Asia Exposure

• Highest incidence: typhoid/enteric fever 3, 2
• Also common: dengue, scrub typhus, malaria 3, 2
• For suspected enteric fever, ceftriaxone is first-line empirical choice if patient clinically unstable 2
• If clinically stable, ciprofloxacin remains alternative (2-week treatment duration) 2

Middle East/North Africa Exposure

• Consider enteric fever, brucellosis 3, 2
• Ceftriaxone empirically if clinically unstable; ciprofloxacin if stable from this region 3, 2

Neutropenic Fever Protocol

Empirical antibiotic therapy should be administered promptly to all neutropenic patients at the onset of fever, as progression of infection can be rapid and early bacterial infections cannot be reliably distinguished from noninfected patients at presentation. 3

Initial Evaluation

• Obtain two sets of blood cultures immediately (one from central venous catheter lumen if present, one from peripheral vein) 3
• Complete blood count, renal and hepatic function tests, chest radiograph 3
• Examine for focal signs: periodontium, pharynx, lower esophagus, lung, perineum/anus, eye fundus, skin (including catheter sites) 3

Empirical Antibiotic Selection

Cefepime 2 g IV every 8 hours is FDA-approved for empiric monotherapy in febrile neutropenic patients, administered for 7 days or until resolution of neutropenia. 4

• Monotherapy with cefepime or carbapenem is appropriate for most patients 3
• Insufficient data exist to support monotherapy in high-risk patients (recent bone marrow transplantation, hypotension at presentation, underlying hematologic malignancy, severe or prolonged neutropenia)—these patients require combination therapy 4
• Do not add vancomycin empirically for persistent fever alone 3
• If vancomycin was added empirically at outset, stop it if blood cultures have incubated for 48 hours and demonstrated no pathogenic gram-positive organisms 3

Monitoring and Reassessment

• Median time to defervescence in patients with hematologic malignancies is 5 days; for solid tumor patients it is 2 days 3
• Persistent fever alone in a patient whose condition is otherwise stable is rarely an indication to alter the antibiotic regimen 3
• Reassess after 2-4 days: specific antimicrobial additions or changes should be guided by clinical change or culture results rather than fever pattern alone 3
• In patients whose fever resolves but who remain neutropenic for more than 7 days, re-evaluate the need for continued antimicrobial therapy frequently 4

Antipyretic Therapy

Paracetamol 1,000 mg represents the first choice for symptomatic treatment of fever in the ED, with the combination paracetamol 500 mg/ibuprofen 150 mg as an alternative, particularly for bacterial fever. 5

Specific Indications for Antipyretic Treatment

• Fever should be treated in cardiorespiratory patients, neurosurgical patients, and those in whom temperature exceeds 40°C (104°F) 6
• Avoid routine antipyretic use in otherwise healthy children; minimize use and administer selectively with caution 7

Efficacy Data

• Both paracetamol 1,000 mg and paracetamol/ibuprofen 500/150 mg achieve 1-degree temperature reduction and 1-point symptom reduction in approximately 37-42% of patients at 1 hour 5
• At 2 hours, both regimens achieve ≥2-point symptom reduction in approximately 90-92% of patients 5
• Paracetamol/ibuprofen combination is more effective than paracetamol alone in patients with bacterial fever at 1 hour (48.6% vs 33.6%) 5

Non-Pharmacological Measures

• Encourage fluid intake and unwrap/remove excess clothing 7
• Do not use tepid sponging routinely, as it causes discomfort without overall beneficial effect 7

COVID-19 Considerations

For patients with fever plus respiratory symptoms or relevant exposure history, perform RT-PCR nasopharyngeal swab and baseline chest imaging (CT preferred, chest X-ray or lung ultrasound if CT unavailable). 1

Diagnostic Criteria

Suspect COVID-19 if 1:

• Fever with respiratory symptoms and travel/residence in area with local transmission within 14 days, OR
• Acute respiratory illness with confirmed COVID-19 contact within 14 days, OR
• Severe respiratory infection requiring hospitalization without alternative explanation

Characteristic Laboratory Findings

• Leucopenia, lymphopenia 1
• Elevated AST, inflammatory markers (CRP, ESR), LDH 1
• Elevated D-dimer and fibrinogen 1

Critical Pitfalls to Avoid

• Never assume any location is "low-risk" for tropical diseases—even Mediterranean and Middle Eastern countries can harbor serious infections 2, 8
• Do not delay malaria testing or empirical antibiotics in unstable patients while pursuing diagnosis 2
• Do not add vancomycin empirically for persistent fever alone in neutropenic patients 3
• Do not use tepid sponging for fever management 7
• Avoid combining nephrotoxic drugs (cisplatin, amphotericin B, cyclosporine, vancomycin, aminoglycosides) when possible 3

Mandatory Consultation Triggers

Immediate infectious disease/tropical medicine consultation is indicated for: 2

• Suspected viral hemorrhagic fever
• Positive malaria films requiring confirmation and species-specific treatment
• Critically ill patients with tropical exposure
• Undiagnosed fever after initial workup in returned travelers