What is the appropriate diagnostic workup and treatment plan for a geriatric patient with fever of unknown origin, presenting with altered mental status, and multiple comorbidities, including diabetes mellitus type 2 (DM-2), hypertension, and systolic dysfunction, currently on prednisone (corticosteroid) for temporal arteritis?

Fever of Unknown Origin in a Geriatric Long-Term Care Resident with Multiple Comorbidities

Immediate Clinical Assessment

This 40-year-old patient from long-term care presenting with fever (101.5°F), altered mental status, tachypnea (RR=28), and hypoxemia (88% on room air) most likely has pneumonia and requires urgent evaluation for sepsis, with tachypnea >25 breaths/min being 90% sensitive and 95% specific for pneumonia in this population. 1

Critical Risk Factors Present

This patient has multiple high-risk features that dramatically increase infection susceptibility and complicate diagnosis:

• Immunosuppression: Prednisone 20 mg daily for temporal arteritis significantly impairs immune response and may mask typical inflammatory signs 1
• Diabetes mellitus: Predisposes to skin infections and urinary tract infections 1
• Neurogenic bladder: 39-fold increased risk of bacteremia if indwelling catheter present 1
• Altered mental status and developmental delay: Increases aspiration pneumonia risk 1
• Systolic dysfunction (EF 30%): Limits physiologic reserve and increases mortality risk 2

Presentation Analysis

Atypical Geriatric Sepsis Presentation

The combination of altered mental status, tachypnea, and fever without localizing symptoms is classic for sepsis in geriatric patients, who often present atypically with functional decline rather than classical inflammatory signs. 2

Key atypical features in this case:

• New altered mental status: Most common presentation of sepsis in geriatrics, present in 77% of episodes of functional decline 2
• Tachypnea (RR=28): Exceeds the critical threshold of >25 breaths/min, which has 90% sensitivity and 95% specificity for pneumonia in long-term care residents 1
• Hypoxemia (88% on room air): Suggests respiratory pathology, meeting criteria for arterial hypoxemia (PaO₂/FiO₂ <300) 2
• Fever 101.5°F (38.6°C): Meets diagnostic criteria for infection in long-term care residents (≥100°F/37.8°C) 1

Differential Diagnosis Priority

Primary considerations based on clinical presentation and risk factors:

1. Aspiration pneumonia (highest probability given altered mental status, tachypnea, hypoxemia, developmental delay) 1
2. Healthcare-associated pneumonia (from long-term care facility) 1
3. Urosepsis (neurogenic bladder, diabetes, potential catheter) 1
4. Skin/soft tissue infection (diabetes, immobility, pressure ulcers) 1
5. Temporal arteritis flare (already on prednisone, can present with fever) 3, 4
6. Diabetic ketoacidosis (infection trigger, insulin-dependent DM-2) 1

Diagnostic Workup

Immediate Focused Physical Examination

Perform systematic evaluation targeting the most common infection sources in long-term care residents: 1

• Respiratory rate: Already documented at 28 (critical finding) 1
• Mental status: Document Glasgow Coma Scale, assess for delirium vs. baseline 1, 2
• Hydration status: Assess skin turgor, mucous membranes, capillary refill 1, 2
• Skin examination: Turn patient to examine sacral area, perineum, perirectal area for pressure ulcers or cellulitis 1
• Chest examination: Auscultate for rales, rhonchi, decreased breath sounds 1
• Cardiovascular: Assess for new murmur (endocarditis), signs of heart failure decompensation 1
• Abdomen: Palpate for tenderness, assess bowel sounds (ileus is sepsis sign) 2
• Indwelling devices: Check for urinary catheter, feeding tubes, IV lines 1

Mandatory Initial Laboratory Tests

Order the following first-line tests before initiating antibiotics: 5

• Complete blood count with differential: Assess for leukocytosis, left shift, thrombocytopenia (<100 × 10³/μL suggests sepsis) 2, 5
• Comprehensive metabolic panel: Evaluate for acute kidney injury (creatinine increase >0.5 mg/dL), hyperglycemia, electrolyte abnormalities 2
• Inflammatory markers: C-reactive protein or procalcitonin (>2 SD above normal suggests sepsis) 2, 5
• Lactate: Hyperlactatemia (>1 mmol/L) indicates sepsis 2
• Urinalysis with culture: High-yield given neurogenic bladder and diabetes 1
• Blood cultures: Obtain at least 3 sets before antibiotics 5
• Arterial blood gas: Assess oxygenation, acid-base status given hypoxemia 2
• Chest radiograph: Essential given tachypnea and hypoxemia 1
• Hemoglobin A1c and fingerstick glucose: Assess diabetic control 1

Additional Targeted Testing

• Sputum culture: If patient can produce specimen 1
• Liver function tests: Hyperbilirubinemia (>4 mg/dL) suggests sepsis-related organ dysfunction 2
• ESR: If temporal arteritis flare suspected (typically 14-149 mm/hr, mean 97) 3
• ECG and troponin: Given cardiac history and sepsis risk 2

Advanced Imaging Considerations

Do NOT pursue PET-CT or extensive FUO workup at this stage - this patient has clear localizing signs (tachypnea, hypoxemia, altered mental status) and does not meet FUO criteria (fever >3 weeks without diagnosis). 5, 6 PET-CT is reserved for true FUO after initial workup is unrevealing. 5

Treatment Plan

Immediate Management (First Hour)

Initiate sepsis bundle immediately - this patient meets sepsis criteria with organ dysfunction (altered mental status, hypoxemia, tachypnea): 2

1. Supplemental oxygen: Target SpO₂ ≥94% 2
2. IV access and fluid resuscitation: Crystalloid bolus if hypotensive (SBP <90 mmHg or MAP <70 mmHg) 2
3. Blood cultures × 3 sets: Before antibiotics 5
4. Empiric broad-spectrum antibiotics within 1 hour:
   • For aspiration pneumonia/healthcare-associated pneumonia: Piperacillin-tazobactam 4.5g IV q6h OR ceftriaxone 2g IV daily PLUS metronidazole 500mg IV q8h PLUS vancomycin (dose by renal function) to cover MRSA 1
   • Adjust based on local antibiogram and patient's previous cultures from long-term care facility 1

Critical Medication Adjustments

Address the prednisone issue immediately:

• Continue prednisone 20 mg daily - do NOT abruptly discontinue due to adrenal suppression risk 3
• Consider stress-dose steroids if patient becomes hemodynamically unstable 2
• Avoid empiric high-dose steroids - they increase hospital-acquired infection risk, hyperglycemia, GI bleeding, and delirium without improving mortality 5

Diabetes management:

• Hold metformin (risk of lactic acidosis in sepsis) 1
• Continue basal insulin (Levemir) but adjust dose based on glucose monitoring 1
• Use insulin infusion if DKA develops 1

Heart failure management:

• Continue Coreg but monitor for hypotension 2
• Adjust Lasix based on volume status - may need to hold if hypotensive 2

Monitoring Requirements

• Continuous pulse oximetry 2
• Hourly vital signs initially 2
• Urine output monitoring: Oliguria (<0.5 mL/kg/h for ≥2 hours) indicates acute kidney injury 2
• Serial lactate measurements: Should clear with appropriate treatment 2
• Fingerstick glucose q4-6h: Prednisone and infection increase hyperglycemia risk 1

Preventative Measures for Long-Term Care Residents

Infection Prevention Strategies

Implement the following to reduce future infection risk: 1

• Pneumonia prevention:

  • Elevate head of bed 30-45 degrees during feeding 1
  • Oral hygiene protocols 1
  • Swallowing evaluation if recurrent aspiration 1
  • Pneumococcal and annual influenza vaccination 1

• UTI prevention:

  • Remove indwelling catheter if present (39-fold bacteremia risk) 1
  • Implement scheduled toileting program for neurogenic bladder 1
  • Adequate hydration 1

• Skin infection prevention:

  • Pressure ulcer prevention protocol with turning schedule 1
  • Optimize diabetes control (target A1c <8% in frail elderly) 1
  • Daily skin inspection 1

Long-Term Care Facility Communication

Establish clear protocols with facility: 1

• Temperature monitoring criteria: Single reading ≥100°F (37.8°C) or repeated oral temps ≥99°F (37.2°C) warrant evaluation 1
• Early recognition of atypical presentations: functional decline, falls, incontinence, decreased mobility 2
• Rapid notification protocols for certified nursing assistants to alert advanced practice providers 1
• Antibiotic stewardship to reduce resistance 1

Geriatric-Specific Considerations

Temporal Arteritis Context

This patient's underlying temporal arteritis on prednisone creates diagnostic complexity: 3, 4

• Temporal arteritis itself can cause fever (common in 38.2% initially misdiagnosed as FUO) 3
• However, acute presentation with tachypnea and hypoxemia suggests superimposed infection rather than vasculitis flare 3
• If infection workup negative and fever persists >3 weeks, consider temporal arteritis flare with ESR and temporal artery evaluation 3, 4

Prognosis and Goals of Care

Discuss goals of care early given multiple comorbidities and poor physiologic reserve: 7

• Elderly patients with FUO and multiple comorbidities have limited reserve and are vulnerable to irreversible functional deterioration 7
• However, FUO in elderly is often associated with treatable conditions, justifying intensive evaluation 7
• If true FUO develops (fever >3 weeks without diagnosis), up to 75% resolve spontaneously with good prognosis 6, 8

Common Pitfalls to Avoid

1. Do NOT delay antibiotics waiting for culture results in septic patients - mortality increases with each hour of delay 2
2. Do NOT attribute all symptoms to baseline dementia - altered mental status is sepsis until proven otherwise 2
3. Do NOT pursue extensive FUO workup prematurely - this patient has localizing signs requiring immediate treatment 5
4. Do NOT stop prednisone abruptly - risk of adrenal crisis 3
5. Do NOT use empiric steroids for fever without diagnosis - increases infection risk and masks findings 5
6. Do NOT overlook aspiration risk in developmentally delayed patients with altered mental status 1