What is the recommended approach for an infectious workup?

Infectious Workup Approach

For patients requiring an infectious workup, immediately obtain at least two sets of blood cultures from different anatomical sites (ideally 60 mL total blood volume) before initiating antibiotics, along with chest radiography and inflammatory markers (CRP, ESR), then proceed with site-specific cultures and advanced imaging based on clinical presentation. 1, 2, 3

Initial Laboratory Evaluation

Essential First-Line Tests

• Complete blood count with differential to identify leukopenia, thrombocytopenia, or anemia that may indicate specific infectious etiologies 1, 4, 2
• Inflammatory markers: C-reactive protein and erythrocyte sedimentation rate provide baseline inflammatory status 4, 2, 3
• Blood cultures: Minimum of two sets from different anatomical sites before any antibiotic administration 2, 3, 5
  • Optimal volume is 60 mL total blood (approximately 10 mL per bottle) 3, 6
  • For patients with central venous catheters, obtain simultaneous central and peripheral cultures to calculate differential time to positivity 3
  • In critically ill or unstable patients, obtain 3 blood cultures over 1-2 hours then start empiric therapy 2
  • In non-acutely ill patients, consider withholding antibiotics for ≥48 hours to obtain additional blood cultures 2

Site-Specific Microbiological Sampling

• Respiratory specimens: Sputum culture and sensitivity, nasal swab if indicated 1
• Urine culture and sensitivity for suspected urinary source 1
• Bronchoalveolar lavage (BAL) if pulmonary infiltrates detected on imaging, performed at segmental bronchus supplying area of radiographic abnormality 1
  • BAL samples must reach microbiology laboratory within 4 hours of sampling 1
  • Follow standardized protocol for bronchoscopy and BAL 1
  • Avoid transbronchial biopsies in neutropenic and thrombocytopenic patients 1

Initial Imaging Studies

Standard Imaging

• Chest radiography is mandatory as part of initial diagnostic approach 4, 2, 3
• Pulse oximetry for any suspected pulmonary involvement 1

Advanced Imaging Indications

• CT chest with IV contrast for suspected pulmonary source, particularly in surgical ICU patients (identifies source in 72% of cases) 3
• CT abdomen/pelvis with IV contrast for abdominal symptoms, abnormal liver tests, or recent abdominal surgery (81.82% positive predictive value for septic foci) 3
• For postoperative patients: CT imaging of operative area if fever occurs several days postoperatively without identified alternative cause 2, 3
• Avoid routine abdominal ultrasound in patients without abdominal signs, symptoms, or liver function abnormalities 3

Advanced Diagnostic Workup When Initial Evaluation Unrevealing

[18F]FDG PET/CT

• Highly recommended when initial workup is non-diagnostic, with diagnostic yield of 56% and sensitivity of 84-86% 4, 2, 3
• Critical timing: Perform ideally within 3 days of starting oral glucocorticoid therapy to avoid false negatives 4, 2, 3
• Prognostic value: Negative PET/CT predicts favorable outcome through spontaneous remission 2, 3
• Consider myocardial suppression preparation when cardiac etiology is suspected 4

Specialized Microbiological Testing

• For diarrhea with or without acute abdomen: Specific test for Clostridioides difficile and its toxin 1
• For suspected viral encephalitis: CSF for HSV 1 and 2 NAAT, enterovirus NAAT, or other virus-specific testing 1
• For suspected fungal infection: Aspergillus galactomannan in blood (threshold 0.5) or BAL samples (cutoff ≥1.0) 1
• For Pneumocystis pneumonia: Quantitative P. jirovecii PCR with >1450 copies/ml is diagnostic; negative β-D-glucan makes diagnosis highly unlikely 1

Empiric Antimicrobial Therapy Considerations

Timing of Initiation

• Critically ill patients with sepsis/septic shock: Start broad-spectrum antibiotics immediately after obtaining blood cultures 1, 5
• Neutropenic patients (ANC <500 cells/mm³): Immediate broad-spectrum antibiotics with antipseudomonal activity 2, 3
• Urgent antimicrobial therapy should not be postponed by awaiting bronchoscopy and BAL results 1

Empiric Regimen Selection Based On

• Local epidemiology and resistance patterns 1, 5
• Individual patient risk factors for MDR bacteria 1, 5
• Clinical severity and infection source 1
• Previous antimicrobial exposure and documented colonization with MDR bacteria 5

Special Population Considerations

Immunocompromised Patients

• Diagnosis must be multidisciplinary with high clinical suspicion 1
• Clinical signs may not be reliable; the greater the immunocompromise, the less reliable the signs 1
• Laboratory tests may not accurately reflect severity of clinical condition 1
• Consider HIV-specific infections (abdominal tuberculosis, Mycobacterium avium complex) in HIV-positive patients 1

Febrile Neutropenic Patients

• Thoracic CT scan must be available within 24 hours of clinical indication 1
• When infiltrates detected, bronchoscopy and BAL should be arranged within 24 hours 1
• Avoid sinus CT routinely in prolonged febrile neutropenia without localizing symptoms 3

Febrile Infants ≤90 Days

• Higher risk of invasive bacterial infection requiring urinalysis, inflammatory markers, blood culture 2
• Consider lumbar puncture based on risk stratification 2

Common Pitfalls to Avoid

• Do not diagnose "fever of unknown origin" prematurely—it requires fever >38.3°C for at least 3 weeks with no diagnosis despite thorough evaluation 4, 3
• Avoid high-dose steroids without specific indication as they increase risk of hospital-acquired infection, hyperglycemia, GI bleeding, and delirium 3
• Do not use NSAIDs routinely as they impair renal and coagulation function and increase stress ulcer risk 3
• Enterococci from blood culture, coagulase-negative staphylococci, Corynebacterium spp., and Candida from sputum/tracheal aspirates do not represent causative pathogens for lung infiltrates 1

Antimicrobial Stewardship

• Reassess appropriateness and need for antimicrobial treatment daily 1
• De-escalate from broad-spectrum to narrow-spectrum once culture and susceptibility results available 1, 5
• Duration of therapy: 4-5 days for intra-abdominal infections with adequate source control; 5-7 days for bloodstream infections; 8 days for ventilator-associated pneumonia 1
• Optimize antibiotic dosing to achieve pharmacokinetic-pharmacodynamic targets, with loading doses in sepsis/septic shock 1