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1、Serum Procalcitonin Levels It Is All About Confidence Albrich and colleagues1 successfully orchestrated an observational, multinational, multicenter, prospective study of the influence of serum procalcitonin (PCT) levels on the care of patients with lower respiratory tract infections (LRTIs). Specif
2、ically, does access to PCT levels plus the use of an interpretative advice algorithm influence the duration of antibiotic therapy? The comparison was between patients whose physicians were compliant with the algorithm vs patients whose physicians were noncompliant. Noncompliance was defined as failu
3、re to follow the algorithm by either initiation of antibiotic therapy or failure to discontinue therapy despite low PCT levels in the absence of predefined criteria that allowed the algorithm to be overruled. In short, the algorithm advice was overruled and managed based on clinical judgment. The pr
4、imary end point was duration of antibiotic therapy. Of 1208 patients who received at least 1 dose of an antibiotic, the mean duration of therapy was 5.9 days when the algorithm was followed and 7.4 days (P.001) when physicians did not comply with the algorithm. The shorter duration stood the test of
5、 multivariable analyses looking for confounders; of course, some important confounder may have been missed. Of interest, algorithm compliance was substantively better in those centers that had participated in earlier PCT studies. I suggest that algorithm compliance, or lack thereof, is a direct refl
6、ection of the confidence level of physicians in the interpretation of the meaning of serum PCT levels. The study by Albrich et al1 is the latest of several studies of patients with LRTIs and PCT treatment guidance. In most studies, compliance with the PCT algorithm shortened the duration of antibiot
7、ic therapy.2,3Nonetheless, a healthy skepticism persists. Critics worry about the specificity of an increase in PCT levels for bacterial as opposed to viral infection. Physicians wonder what happens to serum PCT levels if there is dual infection, eg, pneumonia due to Streptococcus pneumoniaeconcomit
8、ant with influenza tracheobronchitis. Why dose the serum PCT level increase in patients after aortocoronary bypass surgery or in patients with cardiogenic shock? In short, does the serum PCT level help the clinician beyond the usual markers of activation of an innate immune response, ie, erythrocyte
9、 sedimentation rate (ESR), C-reactive protein (CRP), and white blood cell and differential counts? With the caveat that we need a lot more information, the emerging data suggest that PCT levels add value. Like ESR and CRP, PCT is part of the early phases of an innate immune response. A virtue of PCT
10、 levels is that they increase within 4 to 6 hours of initiation of bacterial infection or intravenous endotoxin, while increases in CRP level and ESR require 24 or more hours.4,5Serum PCT levels do not increase substantively after uncomplicated viral respiratory tract infections (RTIs). The mechanis
11、m is believed to be viral-induced increases in -interferon, which in turn represses PCT gene reanscription.6 Retrospective studies of children with RTIs indicate little to no increase in serum PCT levels in response to viral or mycoplasma infection.7Note also that serum PCT levels increased in patie
12、nts with bacterial meningitis but did not increase in patients with viral meningitis.8Clearly, there is an urgent need to use the powerful modern tools of molecular diagnostics in patients of all ages with RTIs to establish a more definite microbial etiology (perhaps mixed pathogen etiology) of the
13、RTI and correlate the results with serum PCT levels. Confidence in PCT levels would also be enhanced if the basic biology was better understood. In vitro, PCT synthesis is stimulated by bacterial lipopolysaccharide (endotoxin), tumor necrosis factor, and interleukin 1.4-6 Of interest, the magnitude
14、of PCT production was greater in patients with bacteremia due to gram-negative bacteria as opposed to bacteremia with gram-positive bacteria.9 This observation is pertinent to clinical low intestinal perfusion states that are associated with elevations in serum PCT levels. Bacterial endotoxin is det
15、ectable in human serum during and after aortocoronary bypass surgery.10Bacterial endotoxin is detectable in human serum in profound cardiogenic shock, some general surgery patients, patients with severe pancreatitis, and other patients with poor perfusion of the mucosa of the intestinal tract.4,10 T
16、he supposition is that the gut bacteria “ translocate ”into the submucosa and then to the bloodstream with concomitant elevation of PCT levels as a market of activation of an innate immune response. Understanding the science will increase confidence. However, for serum PCT levels to influence patient care, the clinician needs the PCT result at point of care. Similar to white blood cell count, it is strongly suggested that, if offered, serum PCT levels should be available at all times with resul
