What is the role of procalcitonin (PCT) and C-reactive protein (CRP) levels in the evaluation for community-acquired pneumonia (CAP)?

Updated: Oct 31, 2019
  • Author: Stephanie L Baer, MD; Chief Editor: Michael Stuart Bronze, MD  more...
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Answer

Answer

C-reactive protein (CRP) and procalcitonin are inflammatory biomarkers that have been extensively studied in recent years as possible adjuncts for the diagnosis and management of pneumonia.

CRP is widely available and is relatively inexpensive, although, as a nonspecific acute-phase reactant, it has limited ability to differentiate between causes of inflammation.

Procalcitonin (PCT) is a calcitonin preceptor peptide that is released in response to microbial endotoxins and pro-inflammatory cytokines triggered with bacterial infection (interleukin-1beta, tumor necrosis factor alpha, and interleukin 6), while being down-regulated by interferon gamma, a cytokine released in response to viral infections. [11] Thus, there has been significant interest in whether procalcitonin may be able to help quickly determine a bacterial etiology of infection. PCT has shown promise in diagnosing bacterial versus nonbacterial infection, predicting CAP severity and prognosis, and guiding duration of antibiotic therapy in pneumonia. However, at this point, significant controversy remains regarding the practical utility of procalcitonin in clinical practice. Various factors contribute to the dispute, including limitations of the test itself (eg, PCT may not be systemically released in localized infections such as empyema), insufficient availability or delay in results of the PCT assay at many treating facilities, conflicting results among studies, and lack of consistent established cutpoints to guide management decisions. Further prospective studies are needed to help clarify these and other issues, such as cost-effectiveness.

Several studies to date have demonstrated PCT levels alone or in combination with CRP may help predict mortality in CAP. [13] The time from symptom onset influences both CRP and PCT levels at the time of CAP diagnosis, [53] which may need to be considered when determining how to apply PCT values to prognostic and/or management decisions.

A 2018 meta-analysis of patient data from 26 randomized controlled trials assessed the safety of procalcitonin-guided antibiotic decisions (relating to either initiating or continuing antibiotics) in patients with acute respiratory infections. [54] Among the 6,708 patients whose data were included, 30-day all-cause mortality rates were significantly lower (adjusted odds ratio [aOR], 0.83 [95% CI, 0.70-0.99]) in patients who were randomized to the PCT-guided treatment arm compared to controls, as was duration of antibiotic exposure (5.7 vs 8.1 days; P < 0.001) and frequency of adverse effects due to antibiotic therapy (16% vs 22%, aOR, 0.68 [95% CI, 0.57-0.82]). However, there was not a statistically significant difference in rate of treatment failure between the PCT-guided and control groups (aOR, 0.9 [95% CI, 0.80-1.010]). This meta-analysis included a heterogenous group of respiratory tract diagnoses, including acute exacerbations of COPD and bronchitis, in addition to CAP, hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP). Although CAP represented the most number of primary diagnoses, it comprised less than half of the cases. No significant difference in all-cause 30-day mortality rate was detected when the analysis was restricted to patients with a diagnosis of CAP (aOR, 0.82 [95% CI, 0.66-1.03]), although treatment failure (aOR, 0.78 [95% CI, 0.66-0.93] and antibiotic side effects (aOR, 0.62 [95% CI, 0.48-0.8]) were significantly less common in the PCT-guided group, yet length of ICU stay was longer (aOR, 1.45 [95% CI, 0.15-2.75]). One limitation of this meta-analysis was that adherence to the PCT algorithm varied greatly among the studies, ranging from 44%-100%. The PCT thresholds used to help guide antibiotic therapy also varied among the studies, potentially affecting applicability to clinical practice.

The 2016 IDSA/ATS guidelines on HAP/VAP recommended against the addition of either PCT or CRP to clinical criteria alone when deciding whether to initiate antibiotics, although they did provide a weak recommendation for the use of PCT levels plus clinical criteria to help guide discontinuation of antibiotics in patients with VAP. [55] A consensus statement addressing appropriate use of PCT is expected to be an important component of the next iteration of the IDSA/ATS CAP guidelines.


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