What tests should be included in a comprehensive infectious workup?

Comprehensive Infectious Disease Workup

A comprehensive infectious workup should include blood cultures, complete blood count with differential, urinalysis with culture when indicated, and targeted molecular diagnostic tests based on clinical presentation and suspected pathogens.

Initial Laboratory Evaluation

• Complete blood count (CBC) with differential should be performed for all patients with suspected infection within 12-24 hours of symptom onset, with particular attention to white blood cell count and presence of left shift (WBC ≥14,000 cells/mm³ or band neutrophils ≥16%) 1
• Blood chemistry panel including renal and liver function tests should be obtained to assess organ function and potential complications of infection 1
• C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are useful inflammatory markers for suspected infections 1
• HIV testing should be performed on all patients with suspected infectious syndromes, particularly encephalitis, regardless of perceived risk factors 1

Microbiological Testing

Blood Cultures

• Blood cultures remain the gold standard for diagnosing bloodstream infections and should be collected before initiating antimicrobial therapy 2
• At least two sets of blood cultures from different venipuncture sites are recommended for optimal sensitivity 1
• Blood cultures may have limited yield in certain settings such as long-term care facilities but are essential in patients with suspected bacteremia 1

Molecular Diagnostic Methods

• Nucleic acid amplification tests (NAATs) provide faster results than conventional cultures and can detect pathogens in patients who have received prior antimicrobial therapy 3
• Multiplex PCR panels for bloodstream infections can identify common bacterial and fungal pathogens and certain resistance genes within hours rather than days 4
• PCR-based testing should complement rather than replace conventional cultures, as cultures remain necessary for complete antimicrobial susceptibility testing 3

Respiratory Infections

• For respiratory symptoms, appropriate specimens include sputum cultures, nasopharyngeal swabs, or bronchial lavage depending on the clinical context 1
• Molecular testing for respiratory viruses (including influenza, RSV, and SARS-CoV-2) should be considered based on clinical presentation and epidemiology 1

Central Nervous System Infections

• Cerebrospinal fluid (CSF) analysis should include cell count, protein, glucose, Gram stain, culture, and targeted molecular testing 1
• CSF PCR testing for HSV-1, HSV-2, VZV, and enteroviruses should be performed in all cases of suspected viral encephalitis 1
• Additional CSF testing for EBV, CMV, HHV-6, and arboviruses should be guided by clinical presentation and epidemiological factors 1

Urinary Tract Infections

• Urinalysis and urine cultures should be reserved for symptomatic patients with suspected UTI, not performed routinely in asymptomatic individuals 1
• Clean-catch midstream specimens are preferred; catheterization may be necessary for proper collection in some patients 1
• Microscopic examination for pyuria (≥10 WBCs/high-power field) or positive leukocyte esterase/nitrite on dipstick should precede culture 1

Special Considerations

Viral Diagnostic Testing

• Serological testing (IgM and IgG) for viral pathogens should be performed on paired acute and convalescent serum samples 1
• For suspected EBV infection, testing should include heterophile antibody (monospot) and specific antibodies to viral capsid antigen (VCA) and Epstein-Barr nuclear antigen (EBNA) 1
• For CMV infection, both serological testing and quantitative viral load by NAAT may be necessary, particularly in immunocompromised hosts 1

Immunocompromised Patients

• More extensive testing is warranted in immunocompromised patients, including broader molecular panels and fungal diagnostics 1
• Quantitative viral load testing (e.g., CMV, EBV) is particularly important in transplant recipients and HIV-infected individuals 1

Spine and Joint Infections

• Imaging studies (MRI preferred) should complement laboratory testing for suspected spine infections 1
• Joint aspirates should be sent for cell count, crystal analysis, Gram stain, culture, and in some cases molecular testing 1

Common Pitfalls to Avoid

• Collecting specimens after initiating antimicrobial therapy, which reduces culture sensitivity 2
• Relying solely on molecular methods without obtaining cultures for antimicrobial susceptibility testing 3
• Ordering tests without clear clinical indications, which increases costs and may lead to false positive results 1
• Failing to consider epidemiological factors and travel history when selecting diagnostic tests 1
• Not communicating relevant clinical information to the microbiology laboratory, which may affect test selection and interpretation 1