Will Procalcitonin Become An Indispensable Diagnostic Tool To Guide Antibiotics Use in Respiratory Infections? A Step Closer Towards The Reality

From the results of a multicenter, randomized controlled trial reported in the September 9 issue of the Journal of the American Medical Association (JAMA), it seems probable that Procalcitonin (PCT) measurements may reduce rates of antibiotic use for lower respiratory tract infections (LRTIs).

Although procalcitonin is not routinely used in clinical practice in Malaysia, certainly as more and more data are available in the future, it may become an important diagnostic and prognostic adjunct.

Inappropriate antibiotic prescribing for lower respiratory tract infection (LRTI) is widespread and can promote bacterial resistance while increasing costs and incidence of drug-related adverse effects.

In that study, Schuetz P et al. from the ProHOSP Study Group, evaluated whether the use of a serum procalcitonin (PCT)-based algorithm could safely reduce antibiotic administration for LRTI (defined as community-acquired pneumonia, exacerbation of chronic obstructive pulmonary disease, or acute bronchitis).

The algorithm encouraged or discouraged antibiotic use according to different PCT cutoff values. They randomized 1359 consecutive adult patients who presented to six tertiary care hospital emergency departments in Switzerland with LRTI diagnosed by clinical and laboratory criteria to receive antibiotic administration according to the algorithm or standard guidelines.

The primary outcome of that study, i.e., incidence of adverse outcomes within 30 days (a composite of death, intensive care unit admission, disease-specific complications, and recurrent infection requiring antibiotics) did not differ significantly between the algorithm and standard guidelines groups (15.4% and 18.9%).

But the good news is that the mean duration of antibiotic exposure and the incidence of antibiotic-associated adverse effects were significantly lower in the algorithm group than in the standard guidelines group (5.7 vs. 8.7 days, respectively, and 19.8% vs. 28.1%, respectively).

Although LRTIs are responsible for more disease and death in the U.S. than any other infection, to date, clinical markers are inaccurate for distinguishing between bacterial and viral infection.

Procalcitonin is released in response to bacterial infection, correlates with severity of LRTI, and is rarely elevated in viral infections. (Note: PCT levels are usually low in viral infections, chronic inflammatory disorders or autoimmune processes whereas the PCT levels in sepsis are generally greater than 1-2 ng/mL and often reach values between 10 and 100 ng/mL, or considerably higher in individual cases, thus enabling the diagnostic differentiation between these various clinical conditions and a severe sepsis)

PCT has the greatest sensitivity (85%) and specificity (91%) for differentiating patients with SIRS from those with sepsis, when compared with IL-2, IL-6, IL-8, CRP and TNF-alpha (Click here to download a copy of the article).

Besides being highly specific increase in response to severe systemic bacterial infections and sepsis, another major advantage of Procalcitonin (PCT) compared to other parameters is its early rise in response to the infections. Thus, in septic conditions increased PCT levels can be observed 3-6 hours after infectious challenge.

This study demonstrates that a clinical decision rule based on PCT levels can appropriately diminish antibiotic use and help tailor duration of therapy without compromising patient safety.

Reference:
Schuetz P et al. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: The ProHOSP randomized controlled trial. JAMA 2009 Sep 9; 302:1059.

Other references:
1. Christ-Crain M, Stolz D, Bingisser R; et al. Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. Am J Respir Crit Care Med. 2006;174(1):84-93. Click here to download in pdf.

2. Nobre V, Harbarth S, Graf JD; et al. Use of procalcitonin to shorten antibiotic treatment duration in septic patients. Am J Respir Crit Care Med. 2008;177(5):498-505. Click here to download in pdf.