Localized Infection? HBP Testing Knows It First

Since procalcitonin (PCT) was first proposed in 1993 as a biomarker for bacterial infections, it has become one of the key indicators in the clinical diagnosis of severe bacterial infections due to its unique advantages. However, its application as a diagnostic marker has remained somewhat controversial due to the inherent limitations of its biological characteristics.

The Expert Consensus on Emergency Clinical Application of Procalcitonin (2012) pointed out that not all patients with bacterial pneumonia exhibit elevated PCT levels. In fact, around 50% of bacterial pneumonia patients have PCT levels < 0.5 ng/mL, and 28% have levels < 0.1 ng/mL. Therefore, normal or mildly elevated PCT levels cannot rule out bacterial pneumonia.

Similarly, the Expert Consensus on Clinical Application of PCT in Pediatric Lower Respiratory Tract Infections (2022 Edition) also emphasizes that normal serum PCT levels do not exclude bacterial infection. In cases of localized bacterial infections, or in patients with neutropenia or severe malnutrition, PCT levels may remain low even when infection is present.

Both expert consensuses highlight the critical point: a normal PCT result does not definitively exclude bacterial infection, with localized infections being one of the primary reasons.

What Is a Localized Infection?

Infections can be categorized into localized and systemic infections.

Localized infection refers to the invasion of a specific tissue or organ by pathogens. Examples include:

1. Skin infections (e.g., boils, cellulitis), typically presenting with localized redness, swelling, or pus;

2. Wound infections, characterized by pain, discharge, or odor around the wound;

3. Oral and ENT infections such as pulpitis, tonsillitis, otitis media, sinusitis, and parotitis;

4. Respiratory infections like pneumonia, bacterial bronchitis, or lung abscess;

5. Gastrointestinal infections, such as appendicitis, cholecystitis, cholangitis, and peritonitis;

6. Urinary and reproductive tract infections, including cystitis, urethritis, and pelvic inflammatory disease.

   
   

The term “localized” is relative—if a localized infection is not promptly identified and properly treated, it may progress to bacteremia or spread to other organs, ultimately leading to severe systemic infections such as sepsis.

Thus, identifying the specific site and pathogen in the early stages of infection is crucial for selecting the appropriate antibiotics. Physicians typically rely on clinical symptoms, physical signs, and laboratory tests for diagnosis.

If PCT Falls Short in Diagnosing Localized Infections, Is There an Alternative?

The answer is yes—and that alternative is Heparin-Binding Protein (HBP).HBP shows strong potential to fill the diagnostic gap where PCT underperforms, especially in detecting early-stage localized bacterial infections.

HBP vs. PCT: A New Frontier in Localized Bacterial Infection Diagnosis

HBP (Heparin-Binding Protein) is one of the earliest proteins released following neutrophil activation, typically showing a significant increase within 1–2 hours after infection. Upon bacterial invasion, neutrophils rapidly recognize pathogens, become activated, and degranulate. HBP, a key component stored in granules, is massively released into the local microenvironment at the infection site. This ultra-early, source-specific release pattern enables HBP to trigger strong infection signals even before clinical symptoms become evident and before other biomarkers (including PCT) begin to rise.

PCT (Procalcitonin), in contrast, is synthesized and released by extrathyroidal tissues in response to bacterial endotoxins or inflammatory cytokines (e.g., TNF-α, IL-6). Its elevation typically requires a stronger systemic inflammatory response, with significant increases often occurring 6–12 hours or more post-infection. In early-stage or localized infections, PCT response can be delayed or minimal.

Advantage of HBP: Ultra-Early Warning Signal

HBP’s ability to act as a highly sensitive early-warning biomarker enables clinicians to initiate timely antimicrobial treatment and intervention during the critical early window—before the infection spreads or worsens—thereby significantly improving outcomes and reducing the risk of progression to severe illness.

HBP Indicates Localized Infection More Precisely

• HBP release is directly linked to the activation and recruitment of neutrophils at the infection site.

• In localized bacterial infections, HBP concentrations significantly increase at the infection site and surrounding vascular endothelium.

• While HBP also rises in severe infections, its levels in local tissues are much higher than in circulating blood, and the elevation directly reflects local inflammation intensity.

In comparison:

• PCT is highly sensitive to systemic inflammatory responses, especially bacterial, but lacks tissue specificity.

• Elevated PCT levels may occur in non-infectious systemic conditions such as major trauma, surgery, burns, cardiogenic shock, active autoimmune diseases, severe viral infections (e.g., H1N1), and certain cancers (e.g., medullary thyroid carcinoma, small-cell lung cancer).

• This limits PCT’s specificity in differentiating infection from non-infectious causes, particularly for localizing the infection site.

Key Advantage of HBP in Clinical Settings

When assessing patients with suspected localized bacterial infections (e.g., post-operative fever, community-acquired pneumonia, complicated UTIs), elevated HBP levels offer more specific evidence of bacterial presence and severity, reducing false positives due to non-infectious inflammation. Its local concentration profile supports more accurate localization and extent of infection.

Complementary Roles: HBP and PCT Are Not Rivals, But Allies

• PCT remains important in diagnosing systemic bacterial infections, assessing severity, and monitoring treatment response. It generally has higher specificity than CRP for distinguishing bacterial from viral infections.

• HBP, however, excels in early detection, localization of infection, assessing vascular leakage risk, and ultra-early treatment monitoring.

Ideal Strategy: Combined HBP + PCT Detection

1. HBP↑ / PCT→ or slightly↑→ Highly suggests early/localized bacterial infection. Prompt search for the focus and initiate treatment.

2. Both HBP↑ & PCT↑→ Indicates severe infection with systemic inflammation; possible organ dysfunction or risk of septic shock.

3. HBP↓ rapidly during monitoring→ Suggests effective treatment and good prognosis, even if PCT declines more slowly.

4. HBP remains high or rebounds→ Strongly indicates treatment failure or complications (e.g., undrained abscess); immediate intervention needed.

Clinical Significance and Challenges of HBP

HBP has been well-documented by numerous clinical studies as a novel, early, and specific biomarker for localized bacterial infections. Its advantages are particularly notable in emergency, ICU, and post-operative infection monitoringsettings.

However, broader clinical application still faces challenges such as:

• Standardization (assay methods, cut-off values),

• Cost considerations, and

• Awareness and adoption by clinicians.

Outlook

With continued research and technological advancements, HBP is expected to become a key tool in the precise management of localized bacterial infections. Together with traditional markers like PCT, it will contribute to a more complete and efficient biomarker system for infection diagnosis and management.