You are moonlighting in your local emergency department one afternoon when you
encounter a relatively healthy 54-year-old non-smoking female whose only medical
history is hypertension. She is complaining of five days of fevers, chills, subjective
shortness of breath, and a cough productive of yellow/green sputum. She denies
recent sick contacts. She reports her temperature has been as high as 102.2 degrees
Fahrenheit (39 degrees Celsius).
On physical exam the patient is hemodynamically stable with an oxygen saturation
of 93% on room air. She has scattered wheezes on lung auscultation with no
fremitus or egophany. She noted mild improvement after an albuterol and atrovent
treatment, with improvement in wheezing. Chest X-ray reveals some streaky
opacities in the right lung base that are likely due to atelectasis. Labs reveal a white
blood cell count of 12.5, but are otherwise normal.
At this point you suspect the patient has bronchitis (which you know is a viral
illness), but you still have some concern that the patient may be developing
pneumonia. You consider whether or not to treat her with antibiotics and wish you
had a lab test to help you out (knowing that the white blood cell count is
nonspecific). You remember reading something about using procalcitonin to
differentiate viral from bacterial lower respiratory infections. After your shift, you
decide to search the literature and see just how useful procalcitonin really is…
Population: Adult patients with suspected lower respiratory tract infection (pneumonia, bronchitis, COPD, asthma
Intervention: Porcalcitonin measurement
Comparison: Usual care
Outcome: Decreased rates of unnecessary antibiotic administration, mortality, repeat emergency department visits, failed outpatient therapy.
PubMed was searched using the terms “procalcitonin AND respiratory” with results
limited to clinical trials and meta-analyses (https://tinyurl.com/ybfd4t6t). This
resulted in 117 citations from which the following four articles were chosen.
Article 1: Schuetz, P, Christ-Crain M, Thomann R, et al; ProHOSP Study Group. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA. 2009
Article 2: Schuetz P, Wirz Y, Sager R, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev. 2017 Oct 12;10:CD007498.
Article 3: Huang DT, Yealy DM, Filbin MR, et al: ProACT Investigators. Procalcitonin-Guided Use of Antibiotics for Lower Respiratory Tract Infection. N. Engl J Med. 2018 Jul 19;379(3): 236-249
Article 4: Walsh EE, Swinburne AJ, Becker KL, et al. Can serum procalcitonin levels help interpret indeterminate chest radiographs in patients hospitalized with acute respiratory illness? J Hosp Med. 2013 Feb;8(2): 61-7
The CDC estimates that 1 in 3 antibiotics prescribed in the US is unnecessary. For
respiratory infections, the problem may be even worse, with some studies
suggesting rates of inappropriate antibiotic prescription as high as 45%. The
overprescribing of antibiotics has become a worldwide concern, resulting in rising
rates of antibiotic resistance, increasing rates of Clostridium difficile infections, and
high rates of antibiotic adverse drug events. Mechanisms to reduce the unnecessary
prescribing of antibiotics have therefore become paramount. Procalcitonin has been
proposed as a potential indicator of bacterial infection, and hence may be useful in
guiding antibiotic therapy in patients with respiratory infections.
Some studies on procalcitonin in respiratory tract infections have shown promising
results. One prospective, randomized controlled trial conducted in Switzerland
(Schuetz 2009) found a decrease in antibiotic prescription rates among patients
with procalcitonin-guided therapy compared to guideline-based therapy (overall
rates reduced by 12.2%, 95% CI 8.1 to 16.3%) with a modest reduction in adverse
outcomes (-3.5%, 95% CI -7.6 to 0.4%). Similar results were found in a recent
Cochrane review and meta-analysis of data from 2017 (Schuetz 2017), with a mean
reduction in antibiotic exposure of 2.43 days (95% CI 2.15 to 2.71) with no
difference in treatment failure rates. Interestingly, the pooled data also
demonstrated a reduction in mortality among patients with procalcitonin-guided
therapy of 1.4%, with an odds ratio of 0.83 (95% CI 0.70 to 0.99). Unfortunately,
both the Swiss study and the Cochrane review were spearheaded by the same
investigator, who is a paid consultant for BRAHMs, the company that makes the
procalcitonin assay. This high degree of industry sponsorship is concerning, with a
high risk of resulting bias in favor of procalcitonin.
One prospective, randomized controlled trial from the US looked at prescribing rates
with procalcitonin-guided therapy (Huang 2018). Unlike the Swiss study, this one
found no difference in antibiotic prescribing rates or antibiotic exposure (mean
number of days 4.2 vs. 4.3). While this study was different, in that procalcitonin was
only used to guide the initial prescribing of antibiotics where in the Swiss study it was used to guide discontinuation as well, these results may be due to a lack of
Overall, this data is somewhat conflicting. There are several studies with similar
results to the Swiss study, but there is a great deal of industry bias in these as well.
While it is nearly certain that antibiotics are overprescribed in patients with
respiratory infection, and while measures need to be undertaken to reduce
prescription rates among such patients, it is unclear if procalcitonin is actually
helpful in this regard.