What are the possible differential diagnoses for a 25-year-old man presenting with six days of high‑grade fever, hypotension (mean arterial pressure <65 mm Hg) and leukocytosis (white‑blood‑cell count 18,400 cells/µL)?

Differential Diagnosis: Septic Shock with Suspected Bacterial Infection

This 25-year-old male with 6 days of high-grade fever, hypotension (MAP <65 mmHg), and leukocytosis (WBC 18,400/µL) most likely has septic shock from a bacterial infection, and requires immediate blood cultures, broad-spectrum antibiotics within 1 hour, aggressive fluid resuscitation with 30 mL/kg crystalloid, and vasopressor support with norepinephrine to maintain MAP ≥65 mmHg. 1, 2

Primary Diagnosis: Septic Shock

This patient meets diagnostic criteria for septic shock based on:

• Persistent hypotension (MAP <65 mmHg) indicating hemodynamic compromise 1, 3
• Leukocytosis (18,400/µL; normal is <12,000/µL) indicating inflammatory response 2
• Prolonged fever (6 days) suggesting ongoing infection 1, 2

The combination of these findings indicates severe sepsis with organ dysfunction and tissue hypoperfusion. 2, 3

Most Likely Infectious Sources to Investigate

Bacterial Infections (Most Common)

Pneumonia/Respiratory tract infection - Most common source in young adults with septic shock 1

• Obtain chest X-ray or CT imaging immediately 1
• Look for cough, dyspnea, chest pain, abnormal lung sounds 2

Intra-abdominal infection (appendicitis, cholecystitis, peritonitis) 1

• Perform abdominal ultrasound or CT scan 1
• Examine for abdominal pain, tenderness, guarding, absent bowel sounds 2

Urinary tract infection/pyelonephritis 1

• Obtain urinalysis and urine culture 1
• Check for dysuria, flank pain, costovertebral angle tenderness 2

Bloodstream infection (bacteremia from any source, including catheter-related) 1

• Obtain at least 2 sets of blood cultures (aerobic and anaerobic) before antibiotics 1
• Draw one percutaneously and one through vascular access devices if present 1

Meningitis/CNS infection 1

• Assess for severe headache, altered mental status, meningeal signs (nuchal rigidity, photophobia, Kernig/Brudzinski signs) 1
• Perform lumbar puncture if no contraindications (elevated intracranial pressure, coagulopathy) 1

Soft tissue/skin infections (necrotizing fasciitis, cellulitis, abscess) 1

• Examine for decubitus ulcers, perineal/perianal abscesses, retained foreign bodies 1
• Look for erythema, warmth, swelling, crepitus 2

Less Common but Important Considerations

Endocarditis 1

• Obtain blood cultures (multiple sets) 1
• Perform echocardiography if murmur present or high suspicion 1

Tuberculosis (especially if endemic area or risk factors) 1, 4

• Consider in prolonged fever without obvious source 4
• Obtain sputum cultures, chest imaging 4

Fungal infections (invasive candidiasis) - particularly if immunocompromised 1

• Consider 1,3-β-D-glucan assay, mannan/anti-mannan antibodies 1

Non-Infectious Differential Diagnoses (Less Likely Given Presentation)

Drug-related fever 4

• Review medication history for recent additions 4
• However, this typically does NOT cause hypotension or leukocytosis of this magnitude 2

Autoimmune/rheumatologic conditions (vasculitis, adult-onset Still's disease) 4

• Less likely with acute presentation and hypotension 4
• Would expect different laboratory pattern (often normal or low WBC) 2

Malignancy (lymphoma, leukemia) 4

• Unlikely to present with acute hypotension 4
• Would typically have other hematologic abnormalities 2

Immediate Diagnostic Workup (Within 1 Hour)

Laboratory tests: 1, 2

• Blood cultures (at least 2 sets) before antibiotics 1
• Serum lactate level (elevated >1 mmol/L indicates tissue hypoperfusion) 1, 2
• Complete metabolic panel (creatinine, bilirubin for organ dysfunction) 2
• Coagulation studies (INR, aPTT, platelets) 2
• Procalcitonin and C-reactive protein (elevated >2 SD above normal supports bacterial infection) 1, 2

Imaging studies: 1

• Chest X-ray (pneumonia, effusion) 1
• Abdominal ultrasound or CT if abdominal source suspected 1
• Bedside ultrasound to avoid transport risks 1

Cultures from all potential sources: 1

• Urine culture 1
• Sputum culture if respiratory symptoms 1
• Wound cultures if skin/soft tissue infection 1

Critical Pitfalls to Avoid

Do NOT delay antibiotics - Each hour of delay decreases survival by 7.6% 1

• Administer broad-spectrum IV antibiotics within 1 hour of recognizing septic shock 1, 2

Do NOT wait for culture results - Obtain cultures quickly but never delay antibiotics >45 minutes 1

Do NOT under-resuscitate with fluids - Give full 30 mL/kg crystalloid bolus in first 3 hours 1, 2

Do NOT delay vasopressors - If MAP remains <65 mmHg after initial fluid bolus, start norepinephrine immediately 1, 3

Do NOT overlook occult sources - Examine for hidden infections (perineal abscess, retained tampon, otitis media, decubitus ulcers) 1