Abstract
Biomarkers of infection, namely C-reactive protein and procalcitonin (PCT), are potentially useful in the diagnosis of infection as well as in the assessment of its response to antibiotic therapy. C-reactive protein variations overtime appears to have a good performance for the diagnosis of infection. Procalcitonin shows a better correlation with clinical severity. In addition, to overcome the worldwide problem of antibiotic overuse as well as misuse, biomarker guidance of antibiotic stewardship represents a promising new approach. In several randomized, controlled trials, including adult critically ill patients, PCT guidance was repeatedly associated with a decrease in the duration of antibiotic therapy. However, these trials present several limitations, namely high rate of patients’ exclusion, high rate of algorithm overruling, long duration of antibiotic therapy in the control group, disregard the effect of renal failure on PCT level, and above all a possible higher mortality and higher late organ failure in the PCT arm. In addition, some infections (e.g., endocarditis) as well as frequent nosocomial bacteria (e.g., Pseudomonas aeruginosa) are not suitable to be assessed by PCT algorithms. Therefore, the true value of PCT-guided algorithm of antibiotic stewardship in assisting the clinical decision-making process at the bedside remains uncertain. Future studies should take into account the issues identified in the present review.
Highlights
During the past three decades, the incidence of sepsis has been consistently rising, surpassing that of cardiac failure and has an annual mortality rate above acute myocardial infarction [1,2]
The PneumA trial [15] was a prospective, randomized, controlled trial (RCT) in 51 French intensive care units (ICU) designed to assess whether 8 days was as effective as 15 days of adequate antibiotic therapy in microbiologically documented late-onset ventilator-associated pneumonia (VAP) (N = 402)
12 available an active discontinuation policy could safely decrease the duration of antibiotic therapy to 6 days (p = 0.001). Both groups presented similar hospital mortality and ICU and hospital length of stay (LOS) (p = 0.357, p = 0.798, p = 0.865, respectively). These findings suggest that shorter courses of antibiotic therapy, 6–8 days, in VAP can be safely achieved without the use of biomarkers
Summary
During the past three decades, the incidence of sepsis has been consistently rising, surpassing that of cardiac failure and has an annual mortality rate above acute myocardial infarction [1,2]. Can biomarkers be used to guide antibiotic therapy in severe sepsis? Because the inflammatory cascade plays a central role in host-pathogen interaction and in infection control mechanisms, these mediators have been assessed as surrogate markers of infection, both in diagnosis and in monitoring response [11]. Do we need biomarkers to guide/reduce antibiotic therapy in severe sepsis, namely in VAP? The PneumA trial [15] was a prospective, randomized, controlled trial (RCT) in 51 French intensive care units (ICU) designed to assess whether 8 days was as effective as 15 days of adequate antibiotic therapy in microbiologically documented late-onset VAP (N = 402). The second study was a single-center, prospective RCT designed to evaluate the effectiveness and safety of a discontinuation policy on the duration of antibiotic therapy of VAP (N = 290) [16].
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