Procalcitonin-guided diagnosis and antibiotic stewardship revisited

Abstract

Several controlled clinical studies have evaluated the potential of the infection biomarker procalcitonin (PCT) to improve the diagnostic work-up of patients with bacterial infections and its influence on decisions regarding antibiotic therapy. Most research has focused on lower respiratory tract infections and critically ill sepsis patients. A clinical utility for PCT has also been found for patients with urinary tract infections, postoperative infections, meningitis, and patients with acute heart failure with possible superinfection (i.e., pneumonia). In these indications, PCT levels measured on hospital admission were found to substantially reduce the initiation of antibiotic treatment in low-risk situations (i.e., bronchitis, chronic obstructive pulmonary disease exacerbation). For more severe infections (i.e., pneumonia, sepsis), antibiotic stewardship by monitoring of PCT kinetics resulted in shorter antibiotic treatment durations with early cessation of therapy. Importantly, these strategies appear to be safe without increasing the risk for mortality, recurrent infections, or treatment failures. PCT kinetics also proved to have prognostic value correlating with disease severity (i.e., pancreatitis, abdominal infection) and resolution of illness (i.e., sepsis). Although promising findings have been published in these different types of infections, there are a number of limitations regarding PCT, including suboptimal sensitivity and/or specificity, which makes a careful interpretation of PCT in the clinical context mandatory. This narrative review aims to update clinicians on the strengths and limitations of PCT for patient management, focusing on research conducted within the last 4 years.

Procalcitonin Monitoring as a Guide for Antimicrobial Therapy: A Review of Current Literature

“…If the initial PCT level is below the threshold for antibiotic discontinuation, a repeat measurement is recommended within 6–24 hours to account for patients with a later PCT peak . Note that PCT levels should always be assessed in conjunction with clinical assessments and other laboratory parameters; PCT levels alone should not be used to guide antimicrobial therapy decisions …”

Biomarker-guided antibiotic therapy—strengths and limitations

“…Evidence is strong regarding the association of biomarker-guided strategies with a reduction in antibiotic exposure without adverse clinical outcomes. In order to empower such evidence and to deeply understand its potential effect on mortality it is essential in future RCTs to expand patients' selection criteria to better reflect reality (52): clinicians have to deal with patients of increasing complexity (particularly in ICU setting) with a variety of likely infection foci-some of them not included in the available studies (25). Moreover, the true value of biomarkers in reducing antibiotic exposure must be tested against the best available evidence, which clearly evolves to shorter antibiotic courses, and not against a longer (more than 7-8 days) standard care strategy.…”

“…Early observational studies defined PCT cut-off ranges according to which bacterial aetiology for infection was very unlikely (<0.1 ng/mL), unlikely (0.1-0.25 ng/mL), likely (0.25-0.5 ng/mL) and very likely (>0.5 ng/mL); antibiotics were discourage when PCT <0.25 ng/mL and encouraged whenever PCT >0.25 ng/mL (24). Optimal PCT cut-offs have been established for different clinical settings and/ or types of infection; some showed safety and efficacy in randomized-controlled trial (RCT) while others were only tested in observational studies (25)(26)(27). PCT cut-off ranges and some overruling criteria have been included in algorithms to help decide on the initiation and duration of antibiotic therapy and have been validated and subsequently applied in different RCTs, with slight differences between studies.…”

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“…Por ello puede utilizarse en el seguimiento de las infecciones bacterianas, reduciendo el usode antibióticos así como costos del tratamiento y hospitalización. PCT es el biomarcador más estudiado (8)(9)(10) demostrando sensibilidad y especificidad aceptables para infecciones bacterianas .…”