Per the 2019 clinical practice guidelines of the American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) for the diagnosis and treatment of adults with community-acquired pneumonia (CAP), empiric antibiotic therapy should be initiated if CAP is clinically suspected and radiographically confirmed, independent of serum procalcitonin levels. Studies have suggested that procalcitonin levels may be used to distinguish the etiology of respiratory infection, specifically that procalcitonin levels of ≥ 0.25 µg/L indicate a high likelihood of bacterial pneumonia, while procalcitonin levels ≤ 0.1 µg/L indicate a high likelihood of viral infection. However, a recent study of hospitalized CAP patients failed to identify a procalcitonin threshold that allows for determination between bacterial and viral pathogens. Furthermore, the reported sensitivity of procalcitonin in determining bacterial infection ranges from 38% to 91%, reinforcing the fact that procalcitonin levels alone should not be used to justify withholding antibiotics from patients with CAP. Further studies in patients with radiographically confirmed pneumonia are warranted to elucidate the validity and safety of using procalcitonin levels in the guidance of antibiotic therapy in patients with pneumonia. [1]
The IDSA guidelines state that in patients with CAP and a positive influenza test, no biomarkers (such as a low procalcitonin level), and early clinical stability, early antibiotic discontinuation at 48 to 72 hours can be considered. Studies have shown a procalcitonin-guided pathway and serial procalcitonin (PCT) measurement can reduce the duration of antibiotic therapy in CAP, but these cases average in a length of treatment greater than standards of practices in the U.S. Serial procalcitonin measurement is likely to be useful primarily in settings where the average length of stay for patients with CAP exceeds normal practice (e.g., 5–7 days). However, procalcitonin levels may not be elevated in concurrent viral and antibacterial infection or with important pathogens such as Legionella and Mycoplasma. [1]
Procalcitonin (PCT) has been broadly investigated for the identification and management of bacterial infections, as its levels typically rise in presence of these infections. Causative infectious pathogens generate an inflammatory response resulting in release of pro-inflammatory and anti-inflammatory cytokines, including PCT. A higher level of PCT is released due to gram negative bacterial infections compared to gram positive, due to the distinct pathways of activation of the inflammatory cascades. Prompt identification of such infections would allow for more proactive antibiotic treatment. However, utilization of PCT for bacterial infections, despite its high specificity, is complicated due to certain circumstances that may result in increased PCT levels. Still, evidence supports the use of PCT to achieve antibiotic stewardship for treatment of community acquired pneumonia, which multiplies early in cases of infection. Based on data derived from numerous trials, PCT levels > 0.25 ng/mL are indicative of high likelihood of bacterial respiratory infection. Use of PCT to initiate antibiotic treatment has been found to result in lower risk of mortality, lower antibiotic use, and lower risk for antibiotic-related side effects. Bacterial co-infections are common in patients with influenza pneumonia, ranging from 20% to 30%, frequently resulting in worse outcomes, yet studies specific to the use of PCT for identification of bacterial respiratory co-infection in patients with influenza pneumonia are limited. [2]
A 2014 prospective cohort study and individual patient data meta-analysis evaluated the diagnostic utility of PCT in critically ill patients with pneumonia during the 2009 H1N1 influenza pandemic. The prospective cohort component involved 46 intensive care unit (ICU) admissions with pneumonia at a tertiary care hospital in Cologne, Germany, during the 2009 and 2010 influenza seasons. PCT and clinical characteristics were assessed within 24 hours of ICU admission. Additionally, data from five previously published studies were systematically reviewed and included in a meta-analysis, resulting in a pooled cohort of 161 patients with confirmed H1N1 influenza or bacterial pneumonia, or both. PCT levels were significantly elevated in patients with bacterial pneumonia (median 6.2 mcg/L, interquartile range [IQR] 0.9–20) compared to those with isolated H1N1 pneumonia (median: 0.56 mcg/L, IQR 0.18 to 3.33; p<0.0001). The area under for PCT in detecting bacterial pneumonia was 0.72 (95% confidence interval [CI] 0.64 to 0.80), increasing to 0.76 (95% CI 0.68 to 0.85) when patients with hospital-acquired pneumonia and immune-compromising disorders were excluded. At a 0.5 mcg/L PCT cutoff, the sensitivity and negative predictive value for bacterial pneumonia were 80.5% (95% CI 69.9 to 88.7) and 73.2% (95% CI 59.7 to 84.2), respectively, improving to 85.5% (95% CI 73.3 to 93.5) and 82.2% (95% CI 68.0 to 92.0) in patients with community-acquired pneumonia and no immune suppression. Although PCT demonstrated reasonable accuracy in distinguishing bacteria from viral pneumonia, the authors cautioned against its use as a sole marker for guiding antibiotic therapy in critically ill patients. [3]
A 2013 systematic review and meta-analysis evaluated the diagnostic accuracy of PCT in identifying secondary bacterial infections among patients with influenza pneumonia. The analysis included six studies from Korea, France, Italy, and Australia, involving a total of 416 patients, of whom 137 had confirmed bacterial coinfections. The findings indicated that PCT has a sensitivity of 0.84 (95% CI 0.75 to 0.90) and a specificity of 0.64 (95% CI 0.58 to 0.69), with an area under the summary receiver operating characteristic (ROC) curve of 0.68 (95% CI 0.64 to 0.72). The positive likelihood ratio of 2.31 (95% CI 1.93 to 2.78) was deemed insufficient for PCT to serve as a rule-in test, while the negative likelihood ratio of 0.26 (95% CI 0.17 to 0.40) suggested utility as a rule-out test. Subgroup analysis demonstrated improved diagnostic performance among intensive care unit (ICU) patients, with a sensitivity of 0.91 (95% CI 0.82 to 0.97) and a lower negative likelihood ratio of 0.14 (95% CI 0.06 to 0.31). The findings suggest that while PCT cannot be used as a standalone rule-in test for bacterial pneumonia in influenza patients, its strong rule-out capability, particularly in ICU settings, may help guide clinical decision-making and antimicrobial stewardship strategies. [4]