Procalcitonin (PCT)-guided antibiotic stewardship: an international experts consensus on optimized clinical use.

Background Procalcitonin (PCT)-guided antibiotic stewardship (ABS) has been shown to reduce antibiotics (ABxs), with lower side-effects and an improvement in clinical outcomes. The aim of this experts workshop was to derive a PCT algorithm ABS for easier implementation into clinical routine across different clinical settings. Methods Clinical evidence and practical experience with PCT-guided ABS was analyzed and discussed, with a focus on optimal PCT use in the clinical context and increased adherence to PCT protocols. Using a Delphi process, the experts group reached consensus on different PCT algorithms based on clinical severity of the patient and probability of bacterial infection. Results The group agreed that there is strong evidence that PCT-guided ABS supports individual decisions on initiation and duration of ABx treatment in patients with acute respiratory infections and sepsis from any source, thereby reducing overall ABx exposure and associated side effects, and improving clinical outcomes. To simplify practical application, the expert group refined the established PCT algorithms by incorporating severity of illness and probability of bacterial infection and reducing the fixed cut-offs to only one for mild to moderate and one for severe disease (0.25 µg/L and 0.5 µg/L, respectively). Further, guidance on interpretation of PCT results to initiate, withhold or discontinue ABx treatment was included. Conclusions A combination of clinical patient assessment with PCT levels in well-defined ABS algorithms, in context with continuous education and regular feedback to all ABS stakeholders, has the potential to improve the diagnostic and therapeutic management of patients suspected of bacterial infection, thereby improving ABS effectiveness.

C1-esterase inhibitor infusion increases survival rates for patients with sepsis*.

OBJECTIVES: Systemic inflammatory response variability displays differing degrees of organ damage and differing outcomes of sepsis. C1-esterase inhibitor, an endogenous acute-phase protein, regulates various inflammatory and anti-inflammatory pathways, including the kallikrein-kinin system and leukocyte activity. This study assesses the influence of high-dose C1-esterase inhibitor administration on systemic inflammatory response and survival in patients with sepsis. DESIGN: Open-label randomized controlled study. SETTING: Surgical and medical intensive care units of nine university and city hospitals. PATIENTS: : Sixty-one patients with sepsis. INTERVENTIONS: Patients were randomized to receive either 12,000 U of C1-esterase inhibitor infusions in addition to conventional treatment or conventional treatment only (n = 41 C1-esterase inhibitor, 20 controls). Blood samples for measurement of C1-esterase inhibitor, complement components C3 and C4, and C-reactive protein concentrations were drawn on days 1, 3, 5, 7, 10, and 28. MEASUREMENTS AND MAIN RESULTS: Quartile analysis of C1-esterase inhibitor activity in sepsis subjects revealed that the lowest quartile subgroup had similar activity levels (0.7-1.2 U/L), when compared to healthy volunteers (p > .05). These normal-level C1-esterase inhibitor sepsis patients nevertheless displayed increased C-reactive protein (p = .04) production and higher likelihoods of a more severe sepsis (p = .001). Overall, infusion of C1-esterase inhibitor increased C1-esterase inhibitor (p < .005 vs. control on days 2, 3, and 5) functional activity, resulted in higher C3 levels (p < .05 vs. control on days 2 and 3), followed by decreased C-reactive protein (p < .05 vs. control on days 3 and 10). Simultaneously, C1-esterase inhibitor infusion in sepsis patients was associated with reduced all-cause mortality (12% vs. 45% in control, p = .008) as well as sepsis-related mortality (8% vs. 45% in control, p = .001) assessed over 28 days. The highest absolute reduction risk of 70% was achieved in sepsis patients with Simplified Acute Physiology Score II scores >27. CONCLUSION: In the present study, patients in the lowest quartile of C1-esterase inhibitor activity in combination with high C-reactive protein demonstrated a higher risk of developing severe sepsis. In general, high-dose C1-esterase inhibitor infusion down-regulated the systemic inflammatory response and was associated with improved survival rates in sepsis patients, which could have important treatment and survival implications for individuals with C1-esterase inhibitor functional deficiency.

Prospective surveillance for surgical site infection in St. Petersburg, Russian Federation.

OBJECTIVE: To assess the risk-adjusted incidence and predictors of surgical site infections (SSIs). DESIGN: Prospective, multicenter, observational cohort study. SETTING: Seven surgical departments at 3 urban academic hospitals in St. Petersburg, Russian Federation. PATIENTS: All patients had surgery performed between January 15 and May 12, 2000. A total of 1,453 surgical procedures were followed up. Medical records were unavailable for less than 3% of all patients; patients were not excluded for any other reason. The mean patient age was 49.3 years, 61% were female, and 34% had an American Society of Anesthesiologists physical status classification (hereafter, "ASA classification") of at least 3. Surgery for 45% of the patients was emergent. RESULTS: In all, 138 patients (9.5%) developed SSI, for a rate that was approximately 3.5 times the risk-stratified rates in the United States. Male sex (odds ratio [OR], 1.54), ASA classifications of 3 (OR, 3.7) or 4 (OR, 5.0), longer duration of surgery (OR, 2.2), and wound classes of 3 (OR, 5.5) or 4 (OR, 14.3) were associated with increased SSI risk in multivariate analysis. Endoscopic surgery was associated with a lower risk of SSI (OR, 0.23). Antibiotic prophylaxis was used in 0%-33% of operations, and 69% of uninfected patients received antibiotics after the operation. CONCLUSIONS: The SSI rates are significantly higher than previously reported. Although this finding may be attributable to inadequate antibiotic prophylaxis, local infection control and surgical practices may also be contributors. Use of antibiotic prophylaxis should be encouraged and the effect of local practices further investigated. Active SSI surveillance should be expanded to other parts of the Russian Federation.