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Emerging resistance to antibiotics shows no signs of decline. At the same time, few new antibacterials are being discovered. There is a worldwide recognition regarding the danger of this situation. The urgency of the situation and the conviction that practices should change led the Société de Réanimation de Langue Française (SRLF) and the Société Française d'Anesthésie et de Réanimation (SFAR) to set up a panel of experts from various disciplines. These experts met for the first time at the end of 2012 and have since met regularly to issue the following 67 recommendations, according to the rigorous GRADE methodology. Five fields were explored: i) the link between the resistance of bacteria and the use of antibiotics in intensive care; ii) which microbiological data and how to use them to reduce antibiotic consumption; iii) how should antibiotic therapy be chosen to limit consumption of antibiotics; iv) how can antibiotic administration be optimized; v) review and duration of antibiotic treatments. In each institution, the appropriation of these recommendations should arouse multidisciplinary discussions resulting in better knowledge of local epidemiology, rate of antibiotic use, and finally protocols for improving the stewardship of antibiotics. These efforts should contribute to limit the emergence of resistant bacteria.

Objective: High volume hemofiltration (HVHF) has shown potential benefits in septic animals and a few reports suggested a hemodynamic improvement in humans. However, randomized studies are still lacking. Our goal was to evaluate the hemodynamic effects of HVHF in septic shock patients with acute renal failure (ARF)., Design and Setting: Prospective randomized study in an intensive care unit (ICU)., Patients: Twenty patients with septic shock and ARF., Interventions: Patients were randomized to either high volume hemofiltration [HVHF 65 ml/(kg h)] or low volume hemofiltration [LVHF 35 ml/(kg h). Vasopressor dose was adjusted to reach a mean arterial pressure (MAP) > 65 mmHg., Measurements and Results: We performed six hourly measurements of MAP, norepinephrine dose, PaO(2)/FiO(2) and lactate, and four daily urine output and logistic organ dysfunction (LOD) score. Baseline characteristics of the two groups were comparable on randomization. Mean norepinephrine dose decreased more rapidly after 24 h of HVHF treatment compared to LVHF treatment (P = 0.004) whereas lactate and PaO(2)/FiO(2) did not differ between the two treatment groups. During the 4-day follow-up, urine output was slightly increased in the HVHF group (P = 0.059) but the LOD score evolution was not different. Duration of mechanical ventilation, renal replacement therapy and ICU length of stay were also comparable. Survival on day 28 was not affected., Conclusion: HVHF decreased vasopressor requirement and tended to increase urine output in septic shock patients with renal failure. However, a larger trial is required to confirm our results and perhaps to show a benefit in survival.

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.

Objectives: Procalcitonin (PCT) kinetics is a good prognosis marker in infectious diseases, but few studies of community-acquired pneumonia (CAP) have been performed in intensive care units (ICU). We analyzed the relationship between PCT kinetics and outcome in ICU patients with severe CAP., Design and Setting: Prospective observational study in a 16-bed university hospital ICU., Patients: 100 critically ill patients with community-acquired pneumonia., Measurements and Results: Median PCT was 5.2 ng/ml on day 1 and 2.9 ng/ml on day 3. It increased from day 1 to day 3 in nonsurvivors but decreased in survivors. In multivariate analysis four variables were associated with death: invasive ventilation (odds ratio 10-), multilobar involvement (5.6-), LOD score (6.9-), and PCT increase from day 1 to day 3 (4.5-). In intubated patients with a PCT level below 0.95 ng/ml on day 3 the survival rate was 95%., Conclusion: Increased PCT from day 1 to day 3 in severe CAP is a poor prognosis factor. A PCT level less than 0.95 ng/ml on day 3 in intubated patients is associated with a favorable outcome.

Objective: To describe risk factors of severe pneumococcal community-acquired pneumonia and to study variables influencing outcome., Design: Retrospective (1987-1992) and prospective (1993-1995) study., Setting: Three participating ICUs from primary care hospitals., Patients: Five hundred and five patients (mean age: 63 +/- 17 years) with severe community-acquired pneumonia (CAP). Three groups of patients were defined: pneumococcal CAP (group 1), CAP with microbial diagnosis other than Streptococcus pneumoniae (group 2), CAP from group 2 and CAP without microbial diagnosis (group 3)., Measurements and Results: Admission data and data on the disease's course were recorded. The mean Simplified Acute Physiologic Score (SAPS) was 12.5 +/- 5.4. On admission 288 (57 %) patients were mechanically ventilated (mv) and 82 (16.2 %) required inotropic support. A microbial diagnosis was established for 309 (61.2%) patients. S. pneumoniae was isolated in 137 (27.1%) patients. Severe pneumococcal CAP was independently associated with male sex (p = 0.01), lack of antibiotics use before admission (p = 0.0001), non-aspiration pneumonia (p = 0.01) and septic shock (p = 0.0001). The overall mortality rate was 27.5 % (29.2 % in group 1). In patients with severe pneumococcal CAP, multivariate analysis showed that leukopenia less than 3,500/mm3 (p = 0.0004), age over 65 years (p = 0.01), septic shock (p = 0.01), sepsis related complications (p = 0.0001), ICU complications (p = 0.001) and inadequacy of antimicrobial therapy (p = 0.002) worsened the prognosis., Conclusions: Few features facilitate the identification of pneumococcal CAP on ICU admission. The prognosis is mostly related to severity of illness (leukopenia, septic shock) while comorbidities do not seem to influence outcome. Sepsis-related disorders, ICU complications and adequate antimicrobial chemotherapy are the major variables affecting the outcome during an ICU stay.

Objective: To determine predictors of intensive care unit (ICU) mortality in patients with community-acquired pneumonia (CAP), to develop a pneumonia-specific prognostic index, and to evaluate this index prospectively., Design: Combined retrospective and prospective clinical study over two periods: January 1987-December 1992 and January 1993-December 1994., Setting: Four medical ICUs in the north of France., Patients: Derivation cohort: 335 patients admitted to one ICU were retrospectively studied to determine prognosis factors and to develop a pneumonia-specific prognostic index. Validation cohort: 125 consecutive patients, admitted to four ICUs, were prospectively enrolled to evaluate this index., Results: In the derivation cohort, 16 predictors of mortality were identified and assigned a value directly proportional to their magnitude in the mortality model: aspiration pneumonia (-0.37), grading of sepsis > or = 11 (-0.2), antimicrobial combination (-0.01), Glasgow score > 12+mechanical ventilation (MV) (+0.09), serum creatinine > or = 15 mg/l (+0.22), chest involvement shown by X-ray > or = 3 lobes (+0.28), shock (+0.29), bacteremia (+0.29), initial MV (+0.29), underlying ultimately or rapidly fatal illness (+0.31), Simplified Acute Physiology Score > or = 12 (+0.49), neutrophil count < or = 3500/ mm3 (+0.52), acute organ system failure score > or = 2 (+0.64), delayed MV (+0.67), immunosuppression (+1.38), and ineffective initial antimicrobial therapy (+1.5). An index was obtained by adding each patient's points. According to a receiver operating characteristic curve, the cut-off value of this index was 2.5. In the validation cohort, an index of > or = 2.5 could predict death with a positive predictive value of 0.92, sensitivity 0.61, and specificity 0.98., Conclusion: This index, which performs well in classifying patients at high-risk of death, may help physicians in initial patient care (appropriateness of the initial antimicrobial therapy) and guide future clinical research (analysis and design of therapeutic trials).

Objectives: To characterize the epidemiology and to determine the prognosis factors in severe community-acquired pneumonia among patients admitted to an intensive care unit., Design: Retrospective clinical study., Setting: Intensive Care and Infectious Diseases Unit of a municipal general hospital of Lille University Medical School., Patients: 299 consecutive patients exhibiting severe community-acquired pneumonia., Measurements and Results: On admission to ICU, 149 patients required mechanical ventilation for acute respiratory failure and 44 exhibited septic shock. Pulmonary involvement was bilateral in 71 patients. There were 260 organisms isolated from 197 patients (65.9%), the most frequent being Streptococcus pneumoniae (n = 80), Staphylococcus spp. (n = 57) and Gram-negative bacilli (n = 81). Overall mortality was 28.5% (85 patients). According to univariate analysis, mortality was associated with age over 60 years, anticipated death within 5 years, immunosuppression, shock, mechanical ventilation, bilateral pulmonary involvement, bacteremia, neutrophil count < 3500/mm3, total serum protein level < 45 g/l, serum creatinine > 15 mg/l, non-aspiration pneumonia, ineffective initial therapy and complications. Multivariate analysis selected only 5 factors significantly associated with prognosis: anticipated death within 5 years, shock, bacteremia, non-pneumonia-related complications and ineffective initial therapy., Conclusion: The effectiveness of the initial therapy appears to be the most significant prognosis factor and, as the one and only related to the initial medical intervention, suggests a need for permanent optimization of our antimicrobial strategies.

Objective: To study the pharmacokinetics of vancomycin in three patients with acute renal failure related to multi-organ failure during continuous venovenous hemodiafiltration (CVVHD)., Design: Prospective exploratory, open-labelled study., Setting: Critical Care Unit in a University Medical Centre., Patients: 3 patients exhibiting hemodynamic instability and oligo-anuric acute renal failure requiring extra-renal epuration were included in this study., Intervention: Every patient received 7.5 mg/kg IV vancomycin over 1 h for a documented or suspected nosocomial staphylococcal infection. Serum and dialysate outlets samples were collected before infusion and 1, 3, 6, 12, 18, 24 after the end of infusion., Measurements and Results: Mean age was 58.7 years (range 41-79) and mean SAPS 15.7 (9-23). The mean peak concentrations were 27.3 mg/l (range 15.6-45.6) one hour after the end of infusion. The average remaining vancomycin concentration 24 h after the onset of infusion was 3.6 mg/l (range 2.6-4.5). The mean terminal disposition rate constant and elimination half-life were 0.05 h-1 and 13.9 h respectively. Mean total body clearance was 38.9 +/- 4.3 ml/min and dialysate outlet (DO) clearance 4.2 +/- 1.3 ml/min. The mean volume of distribution was 47.4 +/- 6.4 l., Conclusion: CVVHD is effective for vancomycin elimination. In these patients, the elimination half-life is almost constant, involving a following injection of vancomycin 12 h later to achieve effective concentrations.