What are the causes of elevated temperatures with positive Procalcitonin (PCT)?

From the Guidelines

Elevated temperatures with a positive procalcitonin (PCT) level typically indicate bacterial infection, particularly sepsis or severe systemic infection. Procalcitonin is a biomarker that rises significantly during bacterial infections but remains relatively low in viral infections or non-infectious inflammatory conditions. Common causes include:

• Pneumonia
• Urinary tract infections
• Intra-abdominal infections like appendicitis or diverticulitis
• Meningitis
• Bloodstream infections Severe bacterial infections trigger the release of procalcitonin from various tissues throughout the body in response to bacterial endotoxins and inflammatory cytokines. The combination of fever and elevated PCT warrants prompt antibiotic therapy, with empiric broad-spectrum antibiotics like piperacillin-tazobactam, ceftriaxone plus azithromycin, or meropenem depending on the suspected source and severity. Blood cultures should be obtained before starting antibiotics when possible. PCT levels can also help monitor treatment response, with decreasing levels suggesting effective therapy. Non-infectious causes of elevated PCT include major trauma, burns, surgery, cardiogenic shock, and some autoimmune conditions, though these typically cause less dramatic PCT elevations than bacterial sepsis 1.

According to the study by Teepe et al 1, the only predictor for lower respiratory tract infection was discolored sputum, and adding CRP level > 30 mg/L increased the area under the ROC curve. For bacterial pneumonia, comorbidity, fever, and crackles at auscultation had diagnostic value, and when CRP level > 30 mg/L was added, the area under the ROC curve improved. However, procalcitonin levels did not add diagnostic value.

In contrast, the study by van Vugt 1 found that the measurement of procalcitonin concentrations added no relevant additional diagnostic information over symptoms and signs. The proportions of pneumonia in the low-, intermediate-, and high-risk groups were 0.7%, 3.8%, and 18.2%, respectively. The addition of continuous procalcitonin to the symptoms and signs model nonsignificantly increased the area under the curve.

The most recent and highest quality study 1 suggests that procalcitonin levels do not add significant diagnostic value in determining the cause of elevated temperatures, and CRP levels and clinical symptoms are more useful in diagnosing bacterial infections. Therefore, in patients with elevated temperatures and positive procalcitonin levels, it is essential to consider other diagnostic factors, such as CRP levels, clinical symptoms, and blood cultures, to guide antibiotic therapy and management.

From the Research

Causes for Elevated Temperatures and Positive Procalcitonin

• Elevated temperatures and positive procalcitonin can be caused by bacterial infections, as procalcitonin is a biomarker used to diagnose bacterial infections and monitor treatment 2, 3.
• Prolonged use of piperacillin/tazobactam, a widely used anti-infective agent, can lead to adverse drug reactions, including fever and elevated levels of procalcitonin, C-reactive protein, and other laboratory abnormalities 4.
• In some cases, the use of piperacillin/tazobactam can lead to reversible laboratory abnormalities, which can mislead clinical assessments and lead to unnecessary diagnostic tests and therapeutic interventions 4.
• The clinical situation, including the pretest probability for bacterial infection, acuity, and severity of presentation, should be considered when interpreting procalcitonin test results 2.
• Procalcitonin-guided antibiotic stewardship can help reduce antibiotic exposure and associated side effects, and improve patient outcomes 2, 3.

Laboratory Abnormalities Associated with Piperacillin/Tazobactam

• Elevated levels of procalcitonin, C-reactive protein, transaminases, myocardial enzymes, and D-dimer have been reported in patients receiving prolonged treatment with piperacillin/tazobactam 4.
• These laboratory abnormalities can be reversible, and stopping piperacillin/tazobactam can lead to a return to normal test results within a short period of time 4.
• Clinicians should be vigilant for these adverse effects in patients undergoing extended piperacillin/tazobactam treatment, as early recognition can prevent unnecessary diagnostic tests and therapeutic interventions 4.

Clinical Use of Procalcitonin

• Procalcitonin can be used to differentiate bacterial from non-bacterial infections and inflammation states, particularly in respiratory illness 2.
• Procalcitonin-guided antibiotic stewardship can help reduce antibiotic exposure and associated side effects, and improve patient outcomes 2, 3.
• The use of procalcitonin in clinical practice should be based on careful patient assessment, evidence-based clinical algorithms, and continuous notification and regular feedback from all antibiotic stewardship stakeholders 2.