In a patient with normal procalcitonin, elevated C‑reactive protein, elevated white blood cell count, and increased serum creatinine, what is the likely cause and how should I manage it?

Normal Procalcitonin with Elevated CRP, WBC, and Creatinine: Likely Non-Bacterial Inflammatory Process

This laboratory pattern strongly suggests a non-bacterial inflammatory condition rather than bacterial sepsis, and you should focus your diagnostic workup on inflammatory diseases, acute kidney injury from non-infectious causes, or viral/atypical infections rather than immediately initiating broad-spectrum antibiotics. 1, 2

Understanding the Laboratory Pattern

The dissociation between normal procalcitonin and elevated inflammatory markers is diagnostically significant:

• Procalcitonin <0.25 ng/mL has a 96-98.6% negative predictive value for bacterial infections, particularly gram-negative infections, making bacterial sepsis highly unlikely 2
• CRP elevation without PCT elevation suggests non-bacterial inflammation such as autoimmune disease, viral infection, malignancy, or inflammatory conditions 1, 3
• The elevated creatinine may represent acute kidney injury from the underlying inflammatory process rather than septic acute kidney injury 4, 5

Most Likely Diagnostic Categories

Non-Bacterial Infections

• Viral infections (including COVID-19, influenza, other respiratory viruses) elevate CRP and WBC without significant PCT elevation 6, 7
• Atypical pathogens (mycoplasma, chlamydia) can produce this pattern 6

Inflammatory/Autoimmune Conditions

• CRP levels of 50-100 mg/L suggest inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, or vasculitis 1
• Polymyalgia rheumatica, systemic lupus erythematosus, or other connective tissue diseases should be considered 1

Acute Kidney Injury (Non-Septic)

• CRP is independently associated with renal function abnormalities in non-diabetic populations, suggesting inflammatory kidney injury 5
• The elevated creatinine may be primary (acute interstitial nephritis, glomerulonephritis) rather than secondary to sepsis 4

Malignancy

• CRP 50-100 mg/L can indicate solid tumors, lymphoma, or multiple myeloma, particularly with constitutional symptoms 1

Critical Management Algorithm

Step 1: Assess for Bacterial Infection Despite Normal PCT

• Check for shock, hypotension, tachycardia >90/min, altered mental status, or organ dysfunction 6
• If hemodynamically unstable or signs of severe sepsis present, initiate empirical antibiotics immediately without waiting for further workup, as PCT sensitivity ranges only 38-91% 2, 7
• If clinically stable, bacterial infection is unlikely and antibiotics can be safely withheld while pursuing alternative diagnoses 2

Step 2: Targeted Diagnostic Workup

For the elevated creatinine:

• Obtain urinalysis with microscopy looking for dysmorphic RBCs (glomerulonephritis), WBC casts (pyelonephritis/interstitial nephritis), or proteinuria 4
• Calculate fractional excretion of sodium to differentiate prerenal from intrinsic kidney injury
• Review medication list for nephrotoxic agents causing acute interstitial nephritis 4

For the inflammatory markers:

• Obtain blood cultures, respiratory viral panel, and urinary antigens before any antibiotic consideration 7
• Measure ESR, ANA, ANCA, complement levels, and rheumatoid factor if autoimmune disease suspected 1
• Consider age-appropriate cancer screening if CRP >50 mg/L with constitutional symptoms 1

Step 3: Serial Monitoring

• Repeat PCT in 12-24 hours if clinical status changes or new fever develops, as PCT rises within 2-3 hours of bacterial infection onset 2, 8
• Repeat CRP after 24-48 hours, as CRP peaks later than PCT in infectious processes 8, 9
• Monitor creatinine daily to assess trajectory of kidney injury 4

Common Pitfalls to Avoid

• Do not rely on CRP alone to guide antibiotic decisions in this scenario, as CRP lacks specificity for bacterial infection and will be elevated from the underlying inflammatory process 2, 3
• Do not assume normal PCT completely excludes infection in immunocompromised patients, those with localized infections, or early presentation (<6 hours) 2
• Do not overlook drug-induced causes: drug hypersensitivity reactions can elevate both PCT and CRP while causing acute interstitial nephritis 2
• Shock states (cardiogenic, hemorrhagic) can elevate PCT independent of infection, so consider hemodynamic causes if patient is hypotensive 2

When to Reconsider Bacterial Infection

Initiate antibiotics if any of the following develop:

• PCT rises above 0.5 ng/mL on repeat testing 2, 8
• Clinical deterioration with new fever >38.3°C, hypotension, or organ dysfunction 6
• Positive blood, urine, or respiratory cultures 7
• Imaging reveals abscess, pneumonia with consolidation, or other bacterial source 6, 1