Integrating infection and sepsis management through holistic early warning systems and heuristic approaches: a concept proposal.

This is a first attempt to integrate the three pillars of infection management: the infection prevention and control (IPC), and surveillance (IPCS), antimicrobial stewardship (AMS), and rapid identification and management of sepsis (RIMS). The new 'Sepsis-3' definition extrapolates the diagnosis of sepsis from our previously slightly naïve concept of a stepwise evolving pattern. In doing so, however, we have placed the transition from infection toward sepsis in the domain of uncertainty and time-dependency. This now demands that clinical judgment be used in the risk stratification of patients with infection, and that pragmatic local solutions be used to prompt clinicians to evaluate formally for sepsis. We feel it is necessary to stimulate the development of a new generation of concepts and models aiming at embracing uncertainty. We see the opportunity for a heuristic approach focusing on the relevant clinical predictors at hand allowing to navigate the uncertainty of infection diagnosis under time constraints. The diverse and situated clinical approaches eventually emerging need to focus on the understanding of infection as the unbalanced interactions of host, pathogen, and environment. In order extend such approach throughout the patient journey we propose a holistic early warning system underpinned by the risk-based categories of hazards and vulnerabilities iteratively fostered by the information gathered by the infection prevention control and surveillance, clinical microbiology, and clinical chemistry services.

Early osteopontin levels predict mortality in patients with septic shock.

BACKGROUND: Inflammatory biomarkers could be useful to stratify the risk of sepsis adverse outcome and potentially improving the clinical management. Here, we investigated the prognostic role of the inflammatory molecule osteopontin (OPN) in patients with severe sepsis with and without septic shock. MATERIAL AND METHODS: This is a sub-analysis of 957 patients with sepsis/septic shock from the Albumin Italian Outcome Sepsis (ALBIOS) study. Alongside demographic, clinical, and laboratory data, we assessed plasmatic values of OPN at day 1, 2 and 7 after enrolment. The primary outcome was the predictive role of OPN values at day 1on death for any cause at 28 days after enrolment. RESULTS: Plasma OPN values at day 1 were higher in patients with septic shock and correlated with the severity of multi-organ dysfunction. Once categorized for 28-day mortality, survivors were characterized by lower OPN levels at each time point and statistically significant drop overtime (p<0.001 for all). Similarly, OPN reduction during the first 7 days was associated with reduced hospitalization and mortality overtime. Multivariate logistic and Cox regression models confirmed plasma OPN at day 1 as predictor of both 28- and 90-day mortality and infection resolution as well, independently of demographic, clinical and therapeutic variables. However, this prognostic value was limited to septic shock patients. CONCLUSIONS: In patients with septic shock, OPN plasma levels at day 1 predict a poor clinical outcome. These results provide the rationale for future pathophysiological studies aimed at clarifying the mechanisms triggered by OPN in septic shock (ALBIOS ClinicalTrials.gov Identifier: NCT00707122).

Biological meshes for abdominal hernia: Lack of evidence-based recommendations for clinical use.

BACKGROUND: In the clinical literature on abdominal hernia repair, no sound criteria have been established to support the use of biological meshes as opposed to synthetic ones. Furthermore, the information on biological meshes is quite scarce, and so their place in therapy has not yet been defined. METHODS: The treatment of primary and incisional ventral hernia was the target intervention evaluated in our analysis. Our study consisted of the following phases: a) Identification of the biologic meshes available on the market; b) Literature search focused on efficacy and safety of these meshes; c) Analysis of the findings derived from the literature search. The information collected this way was reviewed narratively, and presented according to standard meta-analysis. The main end-points of our analysis included infection of surgical wound at 1 month and recurrence at 12 months. RESULTS: Our clinical literature comprised 11 trials that evaluated 5 biological meshes: Permacol (706 patients), Strattice (324 patients), Surgisis (44 patients), Tutomesh (38 patients) and Xenmatrix (22 patients). These studies generally showed a poor methodological quality. Surgical wound infection showed a wide between-study variability (95%CI: from 12.0% to 22.9%). Also the 12-month relapse rate demonstrated a wide 95%CI (from 5.0% to 19.9%). A significantly lower rate of recurrence at 12 months was found for Permacol compared with Strattice (rate difference: -14.2%; 95%CI: -22.1% to -6.2%). DISCUSSION: Our analysis provided an overview of 5 biological meshes currently available on the market. The different types of meshes showed a marked statistical variability in the clinical outcomes. Hence, nearly all comparisons between different meshes in the two clinical end-points did not reach statistical significance. One exception was represented by the finding that cross-linked meshes had a significantly lower recurrence rate at 12 months than non-cross-linked meshes.

[The interplay of diagnostic and antimicrobial stewardship for the management of septic patients: the Tuscan model.] / L'integrazione tra stewardship diagnostica e antimicrobica nella gestione del paziente settico in Toscana.

Antimicrobial resistance is a global threat caused by the rapid spread of multiresistant microorganisms. Antimicrobial stewardship (AS) is a coordinated intervention designed to improve the appropriate use of antimicrobials by promoting the selection of the optimal drug regimen, dose, duration of therapy and route of administration. AS programs have proved effective in reducing antimicrobial resistance, inappropriate antimicrobial use and in improving patient outcomes. Recently developed rapid diagnostic technologies in microbiology (RDTM) allows a faster and etiological diagnosis of infection and a reduction in the use of unnecessary empirical therapies. This may result in important advancement in time-critical care pathways for septic patients. Nevertheless, RDTM are costly and if not rationally positioned may consume resources and hinder the efficacy of AS programs. In this regard, Tuscany Region is engaged in designing, through a systemic approach, an effective high-quality clinical microbiological service grid. In order to develop a sustainable and equitable model for integrating diagnostic and antimicrobial stewardship we conducted a survey in the regional network of 14 microbiological laboratories. The results shows that in order to develop a sustainable service we need to improve the communication at the interface between laboratories and care unit, harmonize the time windows for processing samples and to devise a robust score for stratifying patient with suspected sepsis.

Non-inferiority of colistin compared with standard care for the treatment of ventilator-associated pneumonia.

This study examined the literature on the treatment of ventilator-associated pneumonia (VAP) using colistin or standard care (SC). Based on this clinical material, a meta-analysis was conducted and a non-inferiority test was performed. Studies were selected for inclusion based on the following criteria: (a) patients with VAP; (b) experimental arm based on intravenous or aerosolized colistin; and (c) control arm based on SC. The meta-analysis employed a fixed-effect model, and the endpoint was the rate of clinical response. No pre-specified non-inferiority threshold for the upper boundary of the 95% confidence interval was adopted; instead, the intention was to perform a retrospective evaluation of whether the threshold suggested by the results was acceptable on clinical grounds. In total, eight controlled studies were included. The pooled risk ratio was 1.019 for colistin compared with SC (95% confidence interval 0.895-1.16); this result corresponds to a non-significant 1.9% increase in cure rate with colistin compared with SC (range +16% to -10.5%). Heterogeneity was minimal (0%). The post-hoc non-inferiority threshold for colistin compared with SC was -10.5% in terms of relative cure rate (pooled risk ratio = 0.895). This margin was considered to be acceptable on clinical grounds. This analysis found that colistin can play a role in the treatment of VAP, particularly when given as a combination of aerosolized and intravenous drug.

Adverse events in cardiac surgery, a mixed methods retrospective study in an Italian teaching hospital.

RATIONALE, AIMS, AND OBJECTIVES: Adverse events (AEs) are a major concern in surgery, but the evidence in cardiac surgery is limited, especially on the contributory factors. According to the data of the National Outcomes Program, a unit was selected to conduct a mixed methods investigation into the incidence, type, and cause of AE, given its mortality rate that was double the national average on coronary artery bypass grafting, valve reparation, and replacement. METHODS: A retrospective investigation on the performance of a cardiac surgery, combining the routinely collected data on process and outcome measures with a 2-stage structured review of 280 medical records performed by 3 expert clinicians, with the support of a methodologist. RESULTS: At least one risk had been verified in 137 of 280 cases (48.9%, 95% CI, 43.1-54.8). The total number of AE was 42, with an incidence of 15% (95% CI, 10.8-20.2) and a preventability of 80.9% (95% CI, 69.1-92.8). In 11.9% of AE, the consequence is death, disability in 40.5%, and extended hospital stay in 69% of the cases. Adverse events are associated with problems in care management at the ward (89/137, 64.9%, 95% CI, 56.9-72.9), followed by surgical complications (46/137, 33.6%, 95% CI, 25.7-41.5) and infection/sepsis (32/137, 23.4%, 95% CI, 16.3-30.4). An active error was made by the health care workers in 31 of 42 cases with AE, either during the decision making or during the execution of an action. A total of 36 AEs were due to deficiencies attributed to organizational factors and 31 were linked to poor teamwork. CONCLUSIONS: The mixed methods approach demonstrated how a deep understanding of AE and poor performance may emerge thanks to the combination of routinely available data and experts' evaluations. The main limitation of this study is its focus on the cardiac surgery rather than on the entire process of care. The evaluation could have been integrated with on-site observations and the analysis of reported incidents.