What are the causes and treatment options for fever with chills?

Causes and Treatment of Fever with Chills

Immediate Action: Obtain Blood Cultures Before Any Antibiotics

The single most critical step is obtaining blood cultures within 30-90 minutes of presentation, before administering any antibiotics, as bacteria are rapidly cleared from the bloodstream and diagnostic yield drops significantly after antibiotic administration 1, 2.

Primary Causes of Fever with Chills

Infectious Causes (Most Common)

• Bacteremia/Sepsis: The most frequent and important cause, with chills or rigors indicating high-grade bacteremia requiring urgent evaluation 1, 3
• Pneumonia with secondary bacterial infection: Occurs in approximately 40% of viral respiratory tract infections requiring hospitalization 2
• Urinary tract infections: Particularly pyelonephritis with ascending infection 1
• Intra-abdominal infections: Including cholangitis (Charcot's triad: fever, jaundice, right upper quadrant pain) and peritonitis 1
• Malaria: Classic presentation with fever, chills, fatigue developing on day seven in travelers from endemic areas (likelihood ratio 5.1) 2
• Meningitis: When accompanied by altered mental status or meningismus 1

Non-Infectious Causes

• Drug fever: A cytokine-mediated response that mimics infectious fever 4, 5
• Malignancy: Particularly lymphomas and leukemias 6
• Inflammatory conditions: Including vasculitis and connective tissue diseases 4
• Venous thromboembolism: Can present with fever and chills 6

Risk Stratification: Who Needs Immediate Treatment?

High-Risk Features Requiring Immediate Antibiotics (Within 1 Hour)

• Hemodynamic instability or septic shock: Mortality increases 10% for every hour of antibiotic delay in cirrhotic patients 1
• Immunocompromised state: Neutropenia, chemotherapy, transplant recipients 1, 4
• Signs of organ dysfunction: Altered mental status, acute kidney injury, hypoxemia (SpO2 <92%) 1, 2
• Suspected meningitis: Altered mental status with meningismus 1
• Suspected cholangitis: Fever, jaundice, right upper quadrant pain 1
• Age ≥50 years with fever and chills: 55% likelihood of serious bacterial infection 1

Lower-Risk Patients Where Observation Is Reasonable

• Stable, immunocompetent patients without signs of sepsis or organ dysfunction can complete diagnostic workup and be observed for 1-2 hours before initiating antibiotics, provided blood cultures have been obtained and close monitoring is in place 1

Complete Diagnostic Workup (Obtain Within 30-90 Minutes)

• Blood cultures (two sets from separate sites, never from central lines due to contamination risk) 1, 2
• Complete blood count with differential (looking for leukocytosis, left shift, thrombocytopenia) 1, 2
• Comprehensive metabolic panel (checking for acute kidney injury, hypoalbuminemia) 1, 2
• Lactate level (serial measurements if sepsis suspected) 1, 2
• Urinalysis and urine culture 1, 2
• Chest radiography 7
• If travel history to endemic areas: Thick and thin blood films (Giemsa stained) for malaria, which remains the gold standard 2

Empiric Antibiotic Selection Strategy

For Community-Acquired Infections (Mild Severity)

• Amoxicillin, azithromycin, or fluoroquinolones for suspected community-acquired pneumonia 7

For Severe Infections Requiring Hospitalization

• Anti-pseudomonal monotherapy (ceftazidime or carbapenem) or combination therapy based on local resistance patterns, covering both resistant Gram-positive cocci and Gram-negative bacilli 7, 1, 4

For Neutropenic Fever

• Vancomycin plus anti-pseudomonal antibiotics (ceftazidime or carbapenem) 1, 4
• Add empiric antifungal therapy (amphotericin B) if fever persists after 5 days of antibiotics 7, 4

For Travelers from Endemic Areas

• Intravenous ceftriaxone as first-line for suspected enteric fever (typhoid) from Asia 1
• Doxycycline empirically if high clinical suspicion for rickettsial infection (African tick bite fever, Mediterranean spotted fever) 1

Symptomatic Treatment

Antipyretic Therapy

• Ibuprofen 200 mg orally when temperature exceeds 38.5°C, repeated every 4-6 hours (maximum 4 times in 24 hours) 7
• Temperature below 38°C is acceptable and may be beneficial for antiviral treatment 7
• Consider prophylactic acetaminophen to reduce severity of rigors and chills 1

Supportive Care for Hemodynamic Instability

• Immediate fluid resuscitation with 250-500 mL crystalloid boluses for hypotensive patients 1, 2
• Continuous monitoring: vital signs, pulse oximetry, strict intake/output, serial lactate measurements 1, 2

Red Flags Requiring Immediate Hospitalization

• Oxygen saturation <92% 1, 2
• Evidence of organ dysfunction (altered mental status, acute kidney injury) 1, 2
• Severe thrombocytopenia 1, 2
• Persistent hypotension despite fluid resuscitation 1, 2
• Confusion, seizures, or reduced Glasgow Coma Scale 1, 2
• Parasitemia >1% if malaria confirmed 2

Critical Pitfalls to Avoid

• Never delay blood cultures until after antibiotic administration—this is the most common error that significantly reduces diagnostic yield 1, 2
• Do not assume "toxic appearance" or high fever predicts bacterial infection—these are unreliable indicators 1
• Avoid obtaining blood cultures from central venous catheters—contamination rates are significantly higher 1
• Do not miss atypical presentations in elderly or cirrhotic patients—they may lack fever or localizing symptoms despite serious infection 1
• Avoid empiric antimicrobial therapy in fever of unknown origin—it has not been shown to be effective except in neutropenic, immunocompromised, or critically ill patients 6

Reassessment Strategy for Persistent Fever

If fever persists after 3-5 days of appropriate antibiotic therapy 7:

• Review all previous culture results and perform meticulous physical examination 7
• Repeat blood cultures and culture specific sites of infection 7
• Obtain chest radiography and consider ultrasonography or high-resolution CT for suspected pneumonitis, sinusitis, or cecitis 7
• Consider adding vancomycin if not already included and criteria for resistant organisms are met 7
• Consider adding antifungal therapy (amphotericin B) if fever persists beyond 5 days without identified source 7