Biomarkers in the diagnosis and monitoring of infections

From a recent free full text review:

In a large retrospective study of 1006 patients, an ESR of 100 mm/hour or more had low sensitivity of 0.36 among patients with infection, 0.25 among those with malignant neoplasms, and 0.21 among patients with noninfectious inflammatory disorders. However, specificity was high...

C-reactive protein has some advantages over ESR because it seems to be a better measure of an acute-phase response and is also more sensitive than ESR to subtle changes in the acute-phase response [1]. It is primarily produced by the liver in response to cytokines...

With mild to moderate stimulus, such as uncomplicated skin infection, cystitis, or bronchitis, it can rise to 50–100 mg/L within 6 hours [8]. Low levels of elevated CRP, with values between 2 mg/L and 10 mg/L, may be seen with “metabolic inflammatory” states such as smoking, uremia, cardiac ischemia, and other low level noninfectious inflammatory conditions...

Procalcitonin is the peptide prehormone of calcitonin that, under normal conditions, is secreted by the C-cells of the thyroid gland in response to hypercalcemia or as a result of medullary carcinoma of thyroid. In systemic inflammatory conditions and, in particular, bacterial infections, PCT secretion is stimulated by various cytokines such as IL-1, IL-6, and tumor necrosis factor-alpha. In viral infections, the PCT production is downgraded...

Osteoarticular Infections

The likelihood of diabetic foot osteomyelitis increases with ESR value of more than 70 mm/h [19]. In another prospective study, the sensitivity and specificity of CRP for the diagnosis of osteomyelitis at a level of more than 14 mg/L was 0.85 and 0.83; the sensitivity and specificity of ESR at a level more than 67 mm/hour was 0.84 and 0.75; and the sensitivity and specificity of PCT at a level more than 0.30 ng/mL was 0.81 and 0.71...

The authors recommended that ESR be used for the follow-up of patients with osteomyelitis [20].

Concerning sepsis, the review notes:

In a meta-analysis..the authors concluded that PCT is a helpful biomarker for early diagnosis of sepsis.. The cutoff for PCT concentrations differed between 0.5 ng/mL and 2.0 ng/mL, with a median of 1.1 ng/mL. The pooled sensitivity and specificity of serum PCT levels in the early diagnosis of sepsis was noted to be 0.77 (95% CI, 0.72–0.81) and 0.79 (95% CI, 0.74–0.84), respectively [29]...

Another meta-analysis examining patients with bacteremia concluded that low PCT levels can be used to rule out the presence of bacteremia [32]...

Concerning pneumonia:

Procalcitonin levels can be useful in early identification of bacterial pneumonia, guide antibiotic management, and help stratify patients with a higher risk.. In a randomized trial involving 302 consecutive patients, PCT guidance substantially reduced antibiotic use in lower respiratory tract infections without compromising outcomes from withholding antibiotics. In the PCT group, antibiotic treatment was based on serum PCT concentrations as follows: strongly discouraged, less than 0.1 µg/L; discouraged, less than 0.25 µg/L; encouraged, greater than 0.25 µg/L; strongly encouraged, greater than 0.5 µg/L [36]. A Cochrane database review of more than 14 trials also concluded that the use of PCT to guide initiation and duration of antibiotic treatment in patients with pneumonia was not associated with higher mortality rates or treatment failure...

There is also at least moderate evidence that PCT guidance to discontinue antibiotic therapy does not increase morbidity..and that PCT guidance does not increase mortality, hospital length of stay, or ICU admission rates in patients diagnosed with pneumonia in an inpatient...

This is of interest given PCT's ability to distinguish between viral and bacterial infection and recent surprising findings pointing to a high frequency of viral infections as etiology of community acquired pneumonia.

A meta-analysis involving both adult and pediatric studies reported that the serum concentrations of CRP had a sensitivity that ranged from 0.69 to 0.99 and a specificity that ranged from 0.28 to 0.99. The authors concluded that CRP may have a good NPV, but the overall usefulness in diagnosing meningitis remained uncertain.

The use of biomarkers is an emerging hot topic in infectious disease. As we have seen before with D dimer and BNP/pro-BNP there will be some misuse with the hope that further study and dissemination of information will refine our approach.