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The massive consumption of antibiotics in the ICU is responsible for substantial ecological side effects that promote the dissemination of multidrug-resistant bacteria (MDRB) in this environment. Strikingly, up to half of ICU patients receiving empirical antibiotic therapy have no definitively confirmed infection, while de-escalation and shortened treatment duration are insufficiently considered in those with documented sepsis, highlighting the potential benefit of implementing antibiotic stewardship programs (ASP) and other quality improvement initiatives. The objective of this narrative review is to summarize the available evidence, emerging options, and unsolved controversies for the optimization of antibiotic therapy in the ICU. Published data notably support the need for better identification of patients at risk of MDRB infection, more accurate diagnostic tools enabling a rule-in/rule-out approach for bacterial sepsis, an individualized reasoning for the selection of single-drug or combination empirical regimen, the use of adequate dosing and administration schemes to ensure the attainment of pharmacokinetics/pharmacodynamics targets, concomitant source control when appropriate, and a systematic reappraisal of initial therapy in an attempt to minimize collateral damage on commensal ecosystems through de-escalation and treatment-shortening whenever conceivable. This narrative review also aims at compiling arguments for the elaboration of actionable ASP in the ICU, including improved patient outcomes and a reduction in antibiotic-related selection pressure that may help to control the dissemination of MDRB in this healthcare setting.

Purpose: To test whether the polymyxin B hemoperfusion (PMX HP) fiber column reduces mortality and organ failure in peritonitis-induced septic shock (SS) from abdominal infections., Method: Prospective, multicenter, randomized controlled trial in 18 French intensive care units from October 2010 to March 2013, enrolling 243 patients with SS within 12 h after emergency surgery for peritonitis related to organ perforation. The PMX HP group received conventional therapy plus two sessions of PMX HP. Primary outcome was mortality on day 28; secondary outcomes were mortality on day 90 and a reduction in the severity of organ failures based on Sequential Organ Failure Assessment (SOFA) scores., Primary Outcome: day 28 mortality in the PMX HP group (n = 119) was 27.7 versus 19.5% in the conventional group (n = 113), p = 0.14 (OR 1.5872, 95% CI 0.8583-2.935). Secondary endpoints: mortality rate at day 90 was 33.6% in PMX-HP versus 24% in conventional groups, p = 0.10 (OR 1.6128, 95% CI 0.9067-2.8685); reduction in SOFA score from day 0 to day 7 was -5 (-11 to 6) in PMX-HP versus -5 (-11 to 9), p = 0.78. Comparable results were observed in the predefined subgroups (presence of comorbidity; adequacy of surgery, <2 sessions of hemoperfusion) and for SOFA reduction from day 0 to day 3., Conclusion: This multicenter randomized controlled study demonstrated a non-significant increase in mortality and no improvement in organ failure with PMX HP treatment compared to conventional treatment of peritonitis-induced SS.

Background: In the intensive care unit (ICU), the outcomes of patients with acute mesenteric ischemia (AMI) are poorly documented. This study aimed to determine the risk factors for death in ICU patients with AMI., Methods: A retrospective, observational, non-interventional, multicenter study was conducted in 43 ICUs of 38 public institutions in France. From January 2008 to December 2013, all adult patients with a diagnosis of AMI during their hospitalization in ICU were included in a database. The diagnosis was confirmed by at least one of three procedures (computed tomography scan, gastrointestinal endoscopy, or upon surgery). To determine factors associated with ICU death, we established a logistic regression model. Recursive partitioning analysis was applied to construct a decision tree regarding risk factors and their interactions most critical to determining outcomes., Results: The death rate of the 780 included patients was 58 %. Being older, having a higher sequential organ failure assessment (SOFA) severity score at diagnosis, and a plasma lactate concentration over 2.7 mmol/l at diagnosis were independent risk factors of ICU mortality. In contrast, having a prior history of peripheral vascular disease or an initial surgical treatment were independent protective factors against ICU mortality. Using age and SOFA severity score, we established an ICU mortality score at diagnosis based on the cutoffs provided by recursive partitioning analysis. Probability of survival was statistically different (p < 0.001) between patients with a score from 0 to 2 and those with a score of 3 and 4., Conclusion: Acute mesenteric ischemia in ICU patients was associated with a 58 % ICU death rate. Age and SOFA severity score at diagnosis were risk factors for mortality. Plasma lactate concentration over 2.7 mmol/l was also an independent risk factor, but values in the normal range did not exclude the diagnosis of AMI.

Objective: To examine the effect of intratracheal heparin instillation on Legionella pneumophila-related acute lung injury (ALI) and systemic dissemination., Design: Prospective, controlled experimental study., Setting: University research laboratory., Interventions: A/J mice received 5 microg of sulfated heparin intratracheally co-instilled with 10(6) or 10(8) colony-forming units (CFU) of a virulent isolate of L. pneumophila., Measurements and Results: ALI was assessed in control groups (PBS and PBS-heparin) and on days 1, 2 and 3 post-infection, in terms of the lung wet-to-dry (W/D) weight ratios and of lung endothelial permeability to radio-labeled albumin (Perm-I(125)). Lung bacterial loads were measured and systemic spread was assessed by blood and target organ culture. The alveolar inflammatory response was evaluated by measuring the cytokine levels (TNF-alpha, IFN-gamma, IL-6 and IL-12p70) in bronchoalveolar lavage fluids (BALF). Co-instilled heparin improved mouse survival after the 10(8) CFU challenge (p < 0.01). On day 2, heparin co-instillation significantly reduced the W/D ratio and Perm-I(125) (p < 0.01 and p < 0.001 respectively), improved lung bacterial clearance (p < 0.001), prevented systemic dissemination (blood, liver, spleen, kidneys and brain cultures, all p < 0.05) and significantly increased IFN-gamma and IL-12p70 levels in BALF (p < 0.05)., Conclusions: Heparin co-instillation during intratracheal L. pneumophila challenge has a protective effect on the alveolar-capillary barrier and prevents bacterial dissemination. These results tend to confirm the competitive inhibition by heparin of L. pneumophila attachment to lung epithelium in vivo, and point to the possible involvement of a heparan-sulfate adhesin in L. pneumophila binding to pneumocytes.

Objective: To study the prognostic impact of the appropriateness of initial antimicrobial therapy in patients suffering from ventilator-associated pneumonia (VAP)., Design and Setting: Observational cohort from January 1994 to December 2001 in one intensive care unit (ICU) from an university-affiliated, urban teaching hospital., Patients: All 132 consecutive patients exhibiting bacteriologically documented VAP during ICU stay., Measurements and Results: Initial antimicrobial treatment was deemed appropriate when the period from initial VAP diagnosis and subsequent administration of antibiotics was within 24 h and all causative pathogens were in vitro susceptible to at least one of the antibiotics of the regimen. Such a treatment was present in 106 episodes. Fifty-eight patients died. In bivariate analysis an appropriate initial antimicrobial therapy was associated with a significantly lower mortality rate (40% vs. 62%). In multivariate analysis the three independent factors present upon VAP onset and associated with death were pulmonary involvement of more than a single lobe on chest radiograph, platelet count less than 150000/mm(3), and Simplified Acute Physiology Score II higher than 37. Appropriate antimicrobial therapy was associated with a nonsignificant trend toward a lower mortality., Conclusions: In our cohort the mortality rate was lower in patients suffering from VAP when the initial antimicrobial therapy was appropriate. However, such a factor did not appear as an independent prognostic factor.