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The aim of this study was to investigate the relationship between nasal and rectal Staphylococcus aureus carriage in intensive care unit (ICU) patients and the occurrence of ICU-acquired infections related to S. aureus carriage. Three hundred and ninety-five patients admitted in ICU were screened for S. aureus nasal and rectal carriages and followed to record S. aureus infections during their stay. S. aureus strains were genotyped by arbitrarily primed PCR, spa-typing, microarray and whole genome sequencing. At ICU admission, 112 of 363 (30.9%) patients carried S. aureus including 61 (16.8%) exclusive nasal carriers, 40 (11.0%) combined nasal and rectal carriers and 11 (3.0%) exclusive rectal carriers. The 152 S. aureus isolates from nasal and rectal swabs belonged to 19 clonal complexes (CCs). Patients colonized in both nose and rectum harboured different strains in at least 40% of cases according to arbitrarily primed PCR data. Nasal carriers of CC5 S. aureus had an increased risk of rectal carriage (RR = 1.85, P

Rationale: Acute kidney injury (AKI) is associated with a poor outcome. Although pulmonary embolism (PE) may promote AKI through renal congestion and/or hemodynamic instability, its frequency and influence on outcome in patients with acute PE have been poorly studied. Methods: The frequency of AKI (defined according to the “Kidney Disease: Improving Global Outcomes” definition) at baseline and its influence on the 30-day mortality was evaluated in patients with acute PE from the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry. We used multivariate analysis to assess whether the presence of AKI influenced the risk for 30-day death. Results: The study included 21,131 patients, of whom 6222 (29.5%) had AKI at baseline: 4385 patients (21%) in stage 1, 1385 (6.5%) in stage 2 and 452 (2%) in stage 3. The proportion of patients with high-risk PE in those with no AKI, AKI stage 1, AKI stage 2 or AKI stage 3 was: 2.8%, 5.3%, 8.8% and 12%, respectively (p < 0.001). After 30 days, 1236 patients (5.9%) died. Overall mortality was 4% in patients with no AKI, 8.4% in AKI stage 1, 14% in AKI stage 2 and 17% in AKI stage 3 (all p < 0.001). AKI was independently associated with an increased risk of all-cause death at 30 days (odds ratio = 1.25; 95%CI: 1.02–1.54). Conclusions: One in every 3–4 patients with acute PE had AKI at baseline. The presence of AKI independently predicted 30-day mortality. This study suggests that AKI may deserve to be evaluated as a prognostic factor in patients with acute PE.

As a therapy or a support to other therapies, despite being largely beneficial to patients in general, transfusion it is not devoid of some risks. In a moderate number of cases, patients may manifest adverse reactions, otherwise referred to as transfusion-associated hazards (TAHs). The latest French 2016 haemovigilance report indicates that 93% of TAHs are minor (grade 1), 5.5% are moderate (grade 2) and 1.6% are severe (grade 3), with only five deaths (grade 4) being attributed to transfusion with relative certainty (imputability of level [or grade] 1 to 3). Health-care providers need to be well aware of the benefits and potential risks (to best evaluate and discuss the benefit-risk ratio), how to prevent TAHs, the overall costs and the availability of alternative therapeutic options. In high-income countries, most blood establishments (BEs) and hospital blood banks (HBBs) have developed tools for reporting and analysing at least severe transfusion reactions. With nearly two decades of haemovigilance, transfusion reaction databases should be quite informative, though there are four main caveats that prevent it from being fully efficient: (ai) reporting is mainly declarative and is thus barely exhaustive even in countries where it is mandatory by law; (aii) it is often difficult to differentiate between the different complications related to transfusion, diseases, comorbidities and other types of therapies in patients suffering from debilitating conditions; (aiii) there is a lack of consistency in the definitions used to describe and report some transfusion reactions, their severity and their likelihood of being related to transfusion; and (aiv) it is difficult to assess the imputability of a particular BC given to a patient who has previously received many BCs over a relatively short period of time. When compiling all available information published so far, it appears that TAHs can be analysed using different approaches: (bi) their pathophysiological nature; (bii) their severity; (biii) the onset scheme; (biv) a quality assessment (preventable or non-preventable); (bv) their impact on ongoing therapy. Moreover, TAHs can be reported either in a non-integrative or in an integrative way; in the latter case, presentation may also differ when issued by a blood establishment or a treating ward. At some point, a recapitulative document would be useful to gain a better understanding of TAHs in order to decrease their occurrence and severity and allow decision makers to determine action plans: this is what this review attempts to make. This review attempts to merge the different aspects, with a focus on the hospital side, i.e., how the most frequent TAHs can be avoided or mitigated.

Beyond their hemostatic functions, platelets alter their inflammatory response according to the bacterial stimulus. Staphylococcus aureus is associated with exacerbated inflammation and thrombocytopenia, which is associated with poor prognosis during sepsis. Acetylsalicylic acid and statins prevent platelet aggregation and decrease the mortality rate during sepsis. Therefore, we assessed whether these two molecules could reduce in vitro platelet activation and the inflammatory response to S. aureus. Platelets were exposed to clinical strains of S. aureus in the presence or absence of acetylsalicylic acid or fluvastatin. Platelet activation, aggregation, and release of soluble sCD62P, sCD40 Ligand, RANTES and GROα were assessed. Platelet cell death was evaluated by analyzing the mitochondrial membrane potential, phosphatidylserine exposure, platelet microparticle release and caspase-3 activation. All S. aureus strains induced platelet activation but not aggregation and decreased the platelet count, the expression of cell death markers and the release of RANTES and GROα. Acetylsalicylic acid but not fluvastatin limited platelet activation and inflammatory factor release and restored the platelet count by protecting platelets from Staphylococcus-induced expression of cell death markers. This study demonstrates that acetylsalicylic acid limits S. aureus-induced effects on platelets by reducing cell death, revealing new strategies to reduce the platelet contribution to bacteremia-associated inflammation.

Assessment of hospital survival with respect to acute kidney injury duration. A total of 447 patients were included in this study, including 283 patients (63.3%) with an acute kidney injury at admission (175 and 108 patients with persistent and transient acute kidney injury, respectively). Patients with persistent acute kidney injury more frequently had stage 3 acute kidney injury (42.9% vs 30.6%; p = 0.04). Hospital survival was 76.2% (n = 125) in patients without acute kidney injury, 70.4% (n = 76) in patients with transient acute kidney injury, and 61.1% (n = 107) in patients with persistent acute kidney injury. After adjustment for confounding factors, the factors associated with lower hospital survival were the need for vasopressors (odds ratio, 0.65; 95% CI, 0.43-0.98) and the presence of persistent acute kidney injury (odds ratio, 0.58; 95% CI, 0.36-0.95). When included in the final model, stage 3 acute kidney injury was independently associated with a lower hospital survival (odds ratio, 0.83; 95% CI, 0.70-0.98), and persistent acute kidney injury was no longer associated with outcome. CONCLUSION: Two thirds of the critically ill patients with acute kidney injury have persistent acute kidney injury. Although mortality increased progressively with the duration of acute kidney injury, we found no independent association between this duration and patient outcome when the acute kidney injury severity is taken into account. Our results suggest that the classical "prerenal acute kidney injury" and "acute tubular necrosis" paradigm might be of limited interest from a pathophysiological or prognostic point of view.

International audience; BACKGROUND: Increasing evidence suggests that dysnatraemia at ICU admission may predict mortality. Little information is available, however, on the potential effect of dysnatraemia correction.Patients and MethodsObservational multicentre cohort study in patients admitted between 2005 and 2012 to 18 French ICUs. Hyponatraemia and hypernatraemia were defined as serum sodium concentration < 135 and > 145 mmoL/L, respectively. We assessed the influence on day-28 mortality of dysnatraemia correction by day 3 and of the dysnatraemia correction rate. RESULTS: Of 7067 included patients, 1830 (25.9%) had hyponatraemia and 634 (9.0%) hypernatraemia at ICU admission (day 1). By day 3, hyponatraemia had been corrected in 1019 (1019/1830, 55.7%) and hypernatraemia in 393 (393/634, 62.0%) patients. After adjustment for confounders, persistent hyponatraemia or hypernatraemia on day 3 was independently associated with higher day-28 mortality (odds ratio [OR], 1.31; 95% confidence interval [95%CI], 1.06-1.61; and OR, 1.86; 95%CI, 1.37-2.54; respectively). Hyponatraemia corrected by day 3, hypernatraemia corrected by day 3, and ICU-acquired hyponatraemia were not associated with day-28 mortality. Median correction rate from days 1 to 3 was 2.58 mmoL/L per day (IQR, 0.67-4.55). Higher natraemia correction rate was associated with lower crude and adjusted day-28 mortality rates (OR per mmoL/L per day, 0.97; 95%CI, 0.94-1.00; p = 0.04; and OR per mmoL/L per day, 0.93; 95%CI, 0.90-0.97; p = 0.0003, respectively). CONCLUSION: Our results indicate that dysnatraemia correction is independently associated with survival, with the effect being greater with faster correction rates of up to 12 mmoL/L/day.

To assess renal resistive index variations in response to fluid challenge.Prospective cohort study.Three ICUs in French teaching hospitals.Consecutive patients receiving mechanical ventilation and requiring a fluid challenge.Resistive index measurement before and after fluid challenge.Renal Doppler was used to measure resistive index and esophageal Doppler to monitor aortic blood flow. Of the 35 included patients, 17 (49%) met our definition for fluid challenge responsiveness, that is, had at least a 10% increase in aortic blood flow. After fluid challenge, mean arterial pressure increased from 73 mm Hg (interquartile range 68-79) to 80 mm Hg (75-86; p0.0001) and stroke volume from 50 mL (30-77) to 55 mL (39-84; p0.0001). Stroke volume changes after fluid challenge were +28.6% (+18.8% to +38.8%) in fluid challenge responders and +3.1% (-1.6% to 7.4%) in fluid challenge nonresponders. Renal resistive index was unchanged after fluid challenge in both nonresponders (0.72 [0.67-0.75] before and 0.71 [0.67-0.75] after fluid challenge; p = 0.62) and responders (0.70 [0.65-0.75] before and 0.72 [0.68-0.74] after fluid challenge; p = 0.11). Stroke volume showed no correlations with resistive index changes after fluid challenge in the overall population (r² = 0.04, p = 0.25), in fluid challenge responders (r² = -0.02, p = 0.61), or in fluid challenge nonresponders (r² = 0.08, p = 0.27). Stroke volume did not correlate with resistive index changes after fluid challenge in the subgroups without acute kidney injury (AKIN definition), with transient acute kidney injury, or with persistent acute kidney injury.Systemic hemodynamic changes induced by fluid challenge do not translate into resistive index variations in patients without acute kidney injury, with transient acute kidney injury, or with persistent acute kidney injury.

Platelets are currently acknowledged as cells of innate immunity and inflammation and play a complex role in sepsis. We examined whether different types of LPS have different effects on the release of soluble signaling/effective molecules from platelets. We used platelet-rich plasma from healthy volunteers and LPS from two strains of gram-negative bacteria with disparate LPS structures. We combined LPS-stimulated platelet supernatants with reporter cells and measured the PBMC cytokine secretion profiles. Upon stimulation of platelets with both Escherichia coli O111 and Salmonella minnesota LPS, the platelet LPS::TLR4 interaction activated pathways to trigger the production of a large number of molecules. The different platelet supernatants caused differential PBMC secretion of IL-6, TNFα, and IL-8. Our data demonstrate that platelets have the capacity to sense external signals differentially through a single type of pathogen recognition receptor and adjust the innate immune response appropriately for pathogens exhibiting different types of 'danger' signals.

International audience; IMPORTANCE: Experimental evidence suggests that cyclosporine prevents postcardiac arrest syndrome by attenuating the systemic ischemia reperfusion response. OBJECTIVE: To determine whether early administration of cyclosporine at the time of resuscitation in patients with out-of-hospital cardiac arrest (OHCA) would prevent multiple organ failure. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, single-blind, randomized clinical trial was conducted from June 22, 2010, to March 13, 2013 (Cyclosporine A in Out-of-Hospital Cardiac Arrest Resuscitation [CYRUS]). Sixteen intensive care units in 7 university-affiliated hospitals and 9 general hospitals in France participated. A total of 6758 patients who experienced nonshockable OHCA (ie, asystole or pulseless electrical activity) were assessed for eligibility. Analyses were performed according to the intention-to-treat analysis. INTERVENTIONS: Patients received an intravenous bolus injection of cyclosporine, 2.5 mg/kg, at the onset of advanced cardiovascular life support (cyclosporine group) or no additional intervention (control group). MAIN OUTCOMES AND MEASURES: The primary end point was the Sequential Organ Failure Assessment (SOFA) score, assessed 24 hours after hospital admission, which ranges from 0 to 24 (with higher scores indicating more severe organ failure). Secondary end points included survival at 24 hours, hospital discharge, and favorable neurologic outcome at discharge. RESULTS: Of the 6758 patients screened, 794 were included in intention-to-treat analysis (cyclosporine, 400; control, 394). The median (interquartile range [IQR]) ages were 63.0 (54.0-71.8) years for the cyclosporine group and 66.0 (57.0-74.0) years for the control group. The cohorts included 293 men (73.3%) in the treatment group and 288 men (73.1%) in the control group. At 24 hours after hospital admission, the SOFA score was not significantly different between the cyclosporine (median, 10.0; IQR, 7.0-13.0) and the control (median, 11.0; IQR, 7.0-15.0) groups. Survival was not significantly different between the 98 (24.5%) cyclosporine vs 101 (25.6%) control patients at hospital admission (adjusted odds ratio [aOR], 0.94; 95% CI, 0.66-1.34), at 24 hours for 67 (16.8%) vs 62 (15.7%) patients (aOR, 1.08; 95% CI, 0.71-1.63), and at hospital discharge for 10 (2.5%) vs 5 (1.3%) patients (aOR, 2.00; 95% CI, 0.61-6.52). Favorable neurologic outcome at discharge was comparable between the cyclosporine and control groups: 7 (1.8%) vs 5 (1.3%) patients (aOR, 1.39; 95% CI, 0.39-4.91). CONCLUSION AND RELEVANCE: In patients presenting with nonshockable cardiac rhythm after OHCA, cyclosporine does not prevent early multiple organ failure. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01595958; EudraCT Identifier: 2009-015725-37.

Objectives We sought to assess the incidence of acetaminophen-induced hypotension. Our secondary objectives were to describe systemic hemodynamic changes and factors associated with this complication. Design Prospective observational study. Setting Three ICUs. Patients Adult patients requiring IV acetaminophen infusion. Arterial pressure was monitored via an arterial catheter for 3 hours. Hypotension was defined as a decrease in the mean arterial pressure of greater than or equal to 15% compared with the baseline. Results Overall, 160 patients were included in this study. Eighty-three patients (51.9%) experienced acetaminophen-induced hypotension according to our definition. In patients with acetaminophen-induced hypotension, the nadir mean arterial pressure was 64 mm Hg (95% CI, 54-74). Hypotension was observed 30 minutes (95% CI, 15-71) after acetaminophen infusion. Changes in mean arterial pressure were closely correlated with decreases in the diastolic arterial pressure (r = 0.92) and to a lesser extent with changes in the pulse pressure (r = 0.18) and heart rate (r = 0.09). Changes in the body temperature were not correlated with changes in mean arterial pressure (r = 0.0002; p = 0.85). None of the patients' baseline characteristics (shock, use of angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers, lactates, renal replacement therapy, chronic heart disease, and indication for acetaminophen infusion) or clinically relevant characteristics (baseline severity according to Logistic Organ Dysfunction score, need for vasopressors, use of antihypertensive agents, need for mechanical ventilation, or changes in the body temperature) were independently associated with acetaminophen-induced hypotension. Among patients with acetaminophen-induced hypotension, 29 (34.9%) required therapeutic intervention. Conclusions Half of the patients who received IV injections of acetaminophen developed hypotension, and up to one third of the observed episodes necessitated therapeutic intervention. Adequately powered randomized studies are needed to confirm our findings, provide an accurate estimation of the consequences of acetaminophen-induced hypotension, and assess the pathophysiologic mechanisms involved.

Meprobamate poisoning are serious and sometimes fatal. Faced with a potential stop of marketing, we conducted a multicenter retrospective study to assess the severity criteria presented by patients admitted to the ICU for severe meprobamate poisoning, whether with alone form or in combination with aceprometazine. One hundred fourty-six patients have been enrolled between January 2005 and June 2011: 38 had a single meprobamate poisoning, 104 to meprobamate and aceprometazine and 4 to both forms. At admission, 88% of patients exhibited coma (Glasgow ≤ 7) and half of them a systolic blood pressure ≤90 mmHg. Mortality rate was 3%. Our results did not find any significant between-group difference, either in regard of clinical or biological severity criteria. These data argue for a cessation of marketing of all meprobamate-based specialities. Language: fr

We calculated the incidence of nosocomial infection in 2 intensive care units (ICUs) on the basis of prevalence data recorded from 1997 through 2002 and compared these estimates to cumulative incidences measured in the 2 ICUs during the same period to investigate the feasibility and the reliability of converting prevalence data to incidence estimates. Decreases in the calculated and measured incidences over time in the ICUs were found to be statistically significantly related.

Doppler-based renal resistive index (RI) might help in distinguishing transient from persistent acute kidney injury (AKI). The main objective of these systematic review and meta-analysis was to investigate the diagnostic performance of RI in predicting short-term reversibility of AKI.A systematic review of the literature was performed. Relevant studies were identified in Pubmed and Cochrane databases covering the years 1985 to 2013 and reviewed independently by 3 authors. Renal transplant recipients were excluded from this analysis. The summary estimates were computed using a random-effects model based on the DerSimonian and Lair meta-analytic method.Among the 154 unique articles identified, 9 studies were included. Of the 176 patients in these studies with elevated RI or pulsatility index, 146 (83%) had a persistent AKI vs 44 (16%) of the 273 patients with normal values. Elevated RI or pulsatility index was associated with an increased risk of persistent AKI (odds ratio, 29.85; 95% confidence interval [CI], 8.73-102.16; P.00001) with significant heterogeneity (I(2) = 75.0%, P.0001). The pooled sensitivity and specificity were 0.83 (95% CI, 0.77-0.88) and 0.84 (95% CI, 0.79-0.88). The summary positive and negative likelihood ratios were 4.9 (95% CI, 2.44-9.87) and 0.21 (95% CI, 0.11-0.41).These results suggest that an elevated RI may be a predictor of persistent AKI in critically ill patients. Further studies are warranted, however, to clarify the exact test performance given the marked heterogeneity among the included studies.

Donati and colleagues [1] evaluated the benefits of fresh, leukodepleted (LD) versus non-leukodepleted (nLD) erythrocyte transfusions on the microcirculation in sepsis patients. Oxygenation appeared equal in both groups. Differences between the two kinds of blood cells are presented in Table 1. In the reported study, there is a difference between the age of erythrocytes in the two groups (1.5 to 3 days for nLD versus 3.5 to 5 days for LD erythrocytes; a U test indicates P

We investigated the effects of either intravenous (IV) or intrabronchial (IB) treatment with transforming growth factor beta1 (TGF-beta1) during bacterial pneumonia in rats. Immediately following IB Escherichia coli inoculation (T0), animals (n=270) were randomized to receive a single treatment with human recombinant TGF-beta1 either via IV or IB, or via both IV and IB routes, or to receive placebo (human serum albumin, HSA) only. Blood and lung analysis was done at 6 and 168 h after E. coli inoculation. Other animals (n=40) were administered IV TGF-beta1 or HSA at T0 and 6, 12 and 24 h after E. coli inoculation to investigate the effects of multiple treatments also on survival rates alone. All animals received ceftriaxone daily. Route of administration did not influence TGF-beta1 (p=ns for the effect of TGF-beta1 comparing IV vs IB routes) and we averaged over this variable in analysis. The relative risk of death (mean +/- sem) was not altered by either single treatments administered at T0 (-0.18 +/- 0.25, p=0.47) or multiple treatments (0.40 +/- 0.50, p=0.66) of TGF-beta1. Single treatment with TGF-beta1 first decreased and then increased vascular leukocytes at 6 and 168 h, respectively, but increased alveolar leukocytes at both time points (p=0.02 comparing the differing effects of TGF-beta1 on vascular and alveolar leukocytes at 6 and 168 h). Although TGF-beta1 decreased blood and lung bacteria counts at 6 and 168 h, it also increased serum tumor necrosis factor levels and lung injury scores at these time points (p

To investigate the prognostic factors in acute respiratory distress syndrome (ARDS) patients focusing on the use of prone positioning (PP).Retrospective study conducted in an intensive care unit of a university hospital.All consecutive mechanically ventilated ARDS patients surviving on day 7 after the diagnosis of ARDS.The study included all ARDS patients who survived more than 7 days after ARDS diagnosis between January 1995 and December 2002. Demographic and respiratory variables were collected on day 1, and the management of ARDS was analyzed during the first 7 days ( n=125). We performed a univariate analysis and a stepwise logistic regression analysis comparing survivors and nonsurvivors on day 28 and at 2 and 6 months.Mortality rates on day 28 and at 2 and 6 months were 21.6%, 32%, and 44% respectively. A SAPS II score less than 49, McCabe score, and the use of PP introduced in the first 7 days of ARDS management appeared to be independently correlated with a decrease in mortality.The SAPS II score, the McCabe score, and use of PP are independently correlated with the outcome in ARDS patients.

International audience; BACKGROUND AND OBJECTIVES: Increasing experimental evidence suggests that acute respiratory distress syndrome (ARDS) may promote AKI. The primary objective of this study was to assess ARDS as a risk factor for AKI in critically ill patients.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was an observational study on a prospective database fed by 18 intensive care units (ICUs). Patients with ICU stays >24 hours were enrolled over a 14-year period. ARDS was defined using the Berlin criteria and AKI was defined using the Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease criteria. Patients with AKI before ARDS onset were excluded.RESULTS: This study enrolled 8029 patients, including 1879 patients with ARDS. AKI occurred in 31.3% of patients and was more common in patients with ARDS (44.3% versus 27.4% in patients without ARDS; P

International audience; OBJECTIVES: Providing appropriate training of procedural skills to residents while ensuring patient safety through trainee supervision is a difficult and constant challenge. We sought to determine how effective and safe procedural skill acquisition is in French ICUs and to identify failure and complication risk factors. DESIGN: Multicenter prospective observational study. Invasive procedures performed by residents were recorded during two consecutive semesters. SETTING: Eighty-four residents. SUBJECTS: Eighty-four residents. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Number of invasive procedures performed, failure and complication rates, supervision, and assistance provided. Five thousand six hundred seventeen procedures were prospectively studied: 1,007 tracheal intubations, 1,272 arterial and 2,586 central venous catheter insertions, 457 fiberoptic bronchoscopies, and 295 chest tube insertions. During the semesters, residents performed a median of 10 intubations, 14 arterial catheter insertions, and 26 central venous catheter insertions. Complication rates were low, similar to those in the literature: 8.6% desaturation and 7.4% esophageal placement during intubation; 0.4% and 2.3% pneumothorax with jugular and subclavian central venous catheter insertions, respectively. We identified risk factors for failure and complications. Higher rates of failure and complications for intubation were associated with residents with no or little previous experience (p < 0.001); failure of internal jugular vein catheterization was associated with left-side insertion (p = 0.005) and absence of mechanical ventilation (p = 0.007). Supervision and assistance were more frequent at the beginning of the semester and for intubation and chest tube insertion. Finally, residents had less access to fiberoptic bronchoscopy and chest tube insertion. CONCLUSION: Procedural skills acquisition by residents in the ICU appears feasible and safe with complication rates comparable to what has previously been reported. We identified specific procedures and situations associated with higher failure and complication rates that could require proactive training. Questions still remain regarding minimal numbers of procedures to attain competence and how best to provide procedural training.

Introduction: The purpose of this study was to assess the value of a serum assay for ceftazidime (CAZ) in patients in the intensive care unit (ICU) of the Saint-Etienne University Teaching Hospital and in other ICUs in the region to optimize therapy. Material and Methods: Between November 1, 2005, and February 29, 2008, for patients hospitalized in ICUs not on dialysis and undergoing continuous CAZ infusion, serum assay of the antibiotic was performed 36 to 48 hours after the start of treatment using a single serum sample. The target serum CAZ concentration was 40 ± 10 mg/L with a concentration/minimum inhibitory concentration ratio of 5 or greater × minimum inhibitory concentration of CAZ when a strain was isolated. Results: Serum CAZ concentration was determined in 92 patients (28 females, 64 males) receiving CAZ by continuous infusion. The mean age was 66 years (range, 19-89 years) and the mean weight was 73 kg (range, 33-122 kg). The CAZ dose was between 1 g and 6 g/24 hours. The mean serum CAZ concentration was 46.9 mg/L (range, 7.4-162.3 mg/L). Serum CAZ concentrations were as follows: 30 to 50 mg/L in 35.9% of patients, less than 30 mg/L in 36.9%, and greater than 50 mg/L in 27.2%. Infection was documented in 51 patients, with 42 strains of Pseudomonas aeruginosa being detected. The serum concentration/minimum inhibitory concentration ratio was 5 or greater for 84.3%. Antibiotic dosage was adjusted based on the CAZ assay results. Conclusion: Our study suggests that CAZ measurement is needed in ICUs to achieve adequate CAZ concentrations to avoid treatment toxicity and to achieve efficacy as rapidly as possible, particularly in strains having limited susceptibility to antibiotics.

Objective: To examine the incidence and the bacteriological and clinical significance of endotoxaemia in ICU patients with severe sepsis or septic shock. Design: Prospective review. Setting: A 15-bed general ICU in a university hospital. Patients: One hundred sixteen patients hospitalised in our ICU fulfilling Bone's criteria for severe sepsis or septic shock and with an available early endotoxin assay (chromogenic limulus assay). Interventions: None. Measurements and results: The clinical characteristics of the population were: age 63.6 ± 11.4 years; SAPS II: 45.4 ± 15.6; mechanical ventilation: 72.4 %; septic shock: 51.7 % (n = 60); bacteraemia: 28.4 % (n = 33); gram-negative bacteria (GNB) infection 47.4 % (n = 55); ICU mortality: 39.6 % (n = 46). Detectable endotoxin occurred in 61 patients (51.2 %; mean level: 310 ± 810 pg/ml). There was no relationship between detectable endotoxin and severity of infection at the moment of the assay. Endotoxaemia was associated with a higher incidence of bacteraemia (39.3 % vs 16.3 %; p = 0.01). There was a trend (p = 0.09) towards an association between positive endotoxin and gram-negative bacteraemia or GNB infection but this was non-significant. This relationship became significant only in the case of bacteraemia associated with GNB infection irrespective of the site of infection. Conclusion: Early detection of endotoxaemia appeared to be associated with GNB infection only in cases of bacteraemic GNB infection. Early endotoxaemia correlated neither to occurrence of organ dysfunction nor mortality in patients with severe sepsis or septic shock. This study suggests that the use of endotoxaemia as a diagnostic or a prognostic marker in daily practice remains difficult.

It was shown in children that serum procalcitonin was the best marker to use to differentiate bacterial from viral meningitis. To evaluate procalcitonin in the diagnosis of acute bacterial and viral meningitis, we conducted a prospective study including adult patients who were suspected of having meningitis and who were admitted to an emergency department. Cerebrospinal fluid (CSF) and serum levels of procalcitonin were measured in 105 consecutive patients. The diagnosis of meningitis was based on clinical findings, gram staining, culture, and chemical analysis of CSF. Twenty-three patients had bacterial meningitis, 57 had viral meningitis, and 25 did not have meningitis. Bacteriologic and chemical analysis of CSF did not allow correct differentiation of viral from bacterial meningitis. On the other hand, a serum procalcitonin level >0.2 ng/mL had a sensitivity and specificity of up to 100% in the diagnosis of bacterial meningitis. Serum procalcitonin levels seem to be the best marker in differentiating between bacterial and viral meningitis in adults.

Objective To determine the efficacy and safety of using natural platelet-activating factor receptor antagonist (PAFra), BN 52021, to treat patients with severe Gram-negative bacterial sepsis. Design A prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial. Setting Fifty-nine academic medical center intensive care units in Europe. Patients Six hundred nine patients with severe sepsis, suspected to be related to Gram-negative bacterial infection, who received PAFra or placebo. Interventions Patients were randomized to receive either a dose of PAFra (120 mg iv) every 12 hrs over a 4-day period or placebo over a 4-day period. Measurements and Main Results The patients were well matched at study entry for severity of illness and for risk factors known to influence the outcome of sepsis. Among all randomized patients, the 28-day, all-cause mortality rate was 49% (152/308) in the placebo group, and 47% (140/300) in the PAFra group (p = .50). When analyzed on the basis of the previously defined target population, the 28-day, all-cause mortality rate was 50% (115/232) in the placebo group and 44% (94/212) in the PAFra group, yielding a 12% reduction in mortality rate (p = .29). In patients with documented infection involving other organisms, there was no difference between treated and placebo groups. When the outcomes of organ dysfunctions were examined in the overall population and in the documented Gram-negative bacterial infection population, the number of patients who resolved hepatic dysfunction tended to be higher in the treated group than in the placebo group (p = .06). The number of adverse events reported were not different between the two groups. Conclusions A 4-day administration of the studied PAFra (BN 52021) failed to demonstrate a statistically significant reduction in the mortality rate of patients with severe sepsis suspected to be related to Gram-negative bacterial infection. If PAFra treatment has any therapeutic activity in severe Gram-negative bacterial sepsis, the incremental benefits are small and will be difficult to demonstrate in a patient population as defined by this clinical trial. (Crit Care Med 1998; 26:1963-1971)

Resume La serotherapie anti-infectieuse avait ete progressivement abandonnee ces dernieres annees, avecl'apparition d'antibiotiques efficaces mais aussi en raison de sa mauvaise tolerance et de sa faible efficacite, en dehors d'indications limitees, essentiellement en prevention. Le developpement d'anticorps monoclonaux humanises, l'apparition de bacteries multiresistantes, l'absence d'agents anti-infectieux efficaces notamment dans certaines infections virales, la mortalite toujours elevee du choc septique et de l'infection, malgre les antibiotiques les plus modernes, chez les immunodeprimes, de plus en plus severes et nombreux, ont fait reconsiderer l'interet des immunoglobulines aussi bien en preventif qu'en curatif, en monotherapie et/ou en association avec les antimicrobiens, dans certains infections.

Freeman, Bradley D., Zenaide Quezado, Fabrice Zeni, Charles Natanson, Robert L. Danner, Steven Banks, Marcello Quezado, Yvonne Fitz, John Bacher, and Peter Q. Eichacker. rG-CSF reduces endotoxemia and improves survival during E. coli pneumonia. J. Appl. Physiol. 83(5): 1467–1475, 1997.—We investigated the effects of recombinant granulocyte colony-stimulating factor (rG-CSF) during canine bacterial pneumonia. Beagles with chronic tracheostomies received daily subcutaneous rG-CSF (5 μg/kg body wt) or placebo for 14 days, beginning 9 days before intrabronchial inoculation with E. coli. Animals received antibiotics and fluid support; a subset received humidified oxygen (fractional inspired O20.40). Compared with controls, rG-CSF increased circulating neutrophil counts (57.4 vs. 11.0 × 103/mm3, day 1 after infection; P = 0.0001), decreased plasma endotoxin (7.5 vs. 1.1 EU/ml at 8 h; P< 0.01) and serum tumor necrosis factor-α (3,402 vs. 729 pg/ml at 2 h; P = 0.01) levels, and prolonged survival (relative risk of death = 0.45, 95% confidence interval 0.21–0.97; P = 0.038). Also, rG-CSF attenuated sepsis-associated myocardial dysfunction ( P < 0.001). rG-CSF had no effect on pulmonary function or on blood and lung bacteria counts (all P = not significant). Other animals challenged with endotoxin (4 mg/kg iv) after similar treatment with rG-CSF had lower serum endotoxin levels (7.62 vs. 5.81 log EU/ml at 6 h; P < 0.01) and less cardiovascular dysfunction ( P < 0.05 to < 0.002) but similar tumor necrosis factor-α levels ( P = not significant) compared with controls. Thus prophylactic rG-CSF sufficient to increase circulating neutrophils during bacterial pneumonia may improve cardiovascular function and survival by mechanisms that in part enhance the clearance of bacterial toxins but do not improve lung function.

International audience; INTRODUCTION: Urinary indices have limited effectiveness in separating transient acute kidney injury (AKI) from persistent AKI in ICU patients. Their time-course may vary with the mechanism of AKI. The primary objective of this study was to evaluate the diagnostic value of changes over time of the usual urinary indices in separating transient AKI from persistent AKI. METHODS: An observational prospective multicenter study was performed in six ICUs involving 244 consecutive patients, including 97 without AKI, 54 with transient AKI, and 93 with persistent AKI. Urinary sodium, urea and creatinine were measured at ICU admission (H0) and on 6-hour urine samples during the first 24 ICU hours (H6, H12, H18, and H24). Transient AKI was defined as AKI with a cause for renal hypoperfusion and reversal within 3 days. RESULTS: Significant increases from H0 to H24 were noted in fractional excretion of urea (median, 31% (22 to 41%) and 39% (29 to 48%) at H24, P < 0.0001), urinary urea/plasma urea ratio (15 (7 to 28) and 20 (9 to 40), P < 0.0001), and urinary creatinine/plasma creatinine ratio (50 (24 to 101) and 57 (29 to 104), P = 0.01). Fractional excretion of sodium did not change significantly during the first 24 hours in the ICU (P = 0.13). Neither urinary index values at ICU admission nor changes in urinary indices between H0 and H24 performed sufficiently well to recommend their use in clinical setting (area under the receiver-operating characteristic curve ≤0.65). CONCLUSION: Although urinary indices at H24 performed slightly better than those at H0 in differentiating transient AKI from persistent AKI, they remain insufficiently reliable to be clinically relevant.

Introduction Differentiating between sterile inflammation and bacterial infection in critically ill patients with fever and other signs of the systemic inflammatory response syndrome (SIRS) remains a clinical challenge. The objective of our study was to mine an existing genome-wide expression database for the discovery of candidate diagnostic biomarkers to predict the presence of bacterial infection in critically ill children. Methods Genome-wide expression data were compared between patients with SIRS having negative bacterial cultures (n = 21) and patients with sepsis having positive bacterial cultures (n = 60). Differentially expressed genes were subjected to a leave-one-out cross-validation (LOOCV) procedure to predict SIRS or sepsis classes. Serum concentrations of interleukin-27 (IL-27) and procalcitonin (PCT) were compared between 101 patients with SIRS and 130 patients with sepsis. All data represent the first 24 hours of meeting criteria for either SIRS or sepsis. Results Two hundred twenty one gene probes were differentially regulated between patients with SIRS and patients with sepsis. The LOOCV procedure correctly predicted 86% of the SIRS and sepsis classes, and Epstein-Barr virus-induced gene 3 (EBI3) had the highest predictive strength. Computer-assisted image analyses of gene-expression mosaics were able to predict infection with a specificity of 90% and a positive predictive value of 94%. Because EBI3 is a subunit of the heterodimeric cytokine, IL-27, we tested the ability of serum IL-27 protein concentrations to predict infection. At a cut-point value of ≥5 ng/ml, serum IL-27 protein concentrations predicted infection with a specificity and a positive predictive value of >90%, and the overall performance of IL-27 was generally better than that of PCT. A decision tree combining IL-27 and PCT improved overall predictive capacity compared with that of either biomarker alone. Conclusions Genome-wide expression analysis has provided the foundation for the identification of IL-27 as a novel candidate diagnostic biomarker for predicting bacterial infection in critically ill children. Additional studies will be required to test further the diagnostic performance of IL-27. The microarray data reported in this article have been deposited in the Gene Expression Omnibus under accession number GSE4607.

Resume Introduction L’actinomycose est une infection bacterienne subaigue ou chronique qui atteint le sujet aussi bien immunocompetent qu’immunodeprime. Les lesions cervico-faciales et thoraco-abdominales sont les plus frequentes. Les localisations cerebrales sont exceptionnelles mais de pronostic severe. Observation Une femme de 56 ans, immunocompetente, etait hospitalisee pour un tableau infectieux non documente avec troubles du comportement et desorientation temporo-spatiale. Une aggravation progressive des signes neurologiques conduisait au coma avec necessite de ventilation mecanique. La neuro-imagerie montrait des abces cerebraux multiples dont la biopsie stereotaxique neurochirurgicale permettait le diagnostic anatomo-pathologique d’actinomycose. Un traitement adapte par bi-antibiotherapie et sans exerese chirurgicale permettait une evolution clinique favorable. Commentaires En l’absence de documentation microbiologique, l’examen histologique permet le diagnostic d’actinomycose cerebrale. Une double antibiotherapie adaptee peut permettre la guerison sans sequelle, meme en presence d’abces cerebraux multiples.

Meprobamate poisoning are serious and sometimes fatal. Faced with a potential stop of marketing, we conducted a multicenter retrospective study to assess the severity criteria presented by patients admitted to the ICU for severe meprobamate poisoning, whether with alone form or in combination with aceprometazine. One hundred fourty-six patients have been enrolled between January 2005 and June 2011: 38 had a single meprobamate poisoning, 104 to meprobamate and aceprometazine and 4 to both forms. At admission, 88% of patients exhibited coma (Glasgow ≤ 7) and half of them a systolic blood pressure ≤ 90 mmHg. Mortality rate was 3%. Our results did not find any significant between-group difference, either in regard of clinical or biological severity criteria. These data argue for a cessation of marketing of all meprobamate-based specialities.

International audience; INTRODUCTION: Several factors, including diuretic use and sepsis, interfere with the fractional excretion of sodium, which is used to distinguish transient from persistent acute kidney injury (AKI). These factors do not affect the fractional excretion of urea (FeUrea). However, there are conflicting data on the diagnostic accuracy of FeUrea. METHODS: We conducted an observational, prospective, multicenter study at three ICUs in university hospitals. Unselected patients, except those with obstructive AKI, were admitted to the participating ICUs during a six-month period. Transient AKI was defined as AKI caused by renal hypoperfusion and reversal within three days. The results are reported as medians (interquartile ranges). RESULTS: A total of 203 patients were included. According to our definitions, 67 had no AKI, 54 had transient AKI and 82 had persistent AKI. FeUrea was 39% (28 to 40) in the no-AKI group, 41% (29 to 54) in the transient AKI group and 32% (22 to 51) in the persistent AKI group (P = 0.12). FeUrea was of little help in distinguishing transient AKI from persistent AKI, with the area under the receiver operating characteristic curve being 0.59 (95% confidence interval, 0.49 to 0.70; P = 0.06). Sensitivity was 63% and specificity was 54% with a cutoff of 35%. In the subgroup of patients receiving diuretics, the results were similar. CONCLUSIONS: FeUrea may be of little help in distinguishing transient AKI from persistent AKI in critically ill patients, including those receiving diuretic therapy. Additional studies are needed to evaluate alternative markers or strategies to differentiate transient from persistent AKI.

We prospectively measured the concentrations of immunoreactive tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), and interleukin-6 (IL-6) in the serum and ascitic fluid of 14 alcoholic cirrhotic patients with spontaneous bacterial peritonitis (SBP) and 16 alcoholic cirrhotic patients with sterile ascitic fluid. TNF-alpha levels in ascitic fluid were significantly higher for the patients with SBP: 399.57 +/- 129.23 pg/mL vs. 35.76 +/- 5.57 pg/mL (P < .001). IL-6 levels in ascitic fluid were also significantly higher for the patients with SBP: 170,713 +/- 57,109 ng/mL vs. 5,414 +/- 973 ng/mL (P < .001). By contrast, serum levels of TNF-alpha and IL-6 were just slightly more elevated than normal values. The concentration of IL-1 in the ascitic fluid of all patients was elevated, but there was no difference between patients with SBP or sterile ascites in this respect. In the patients with SBP, levels of TNF-alpha and IL-6 in ascitic fluid decreased during the first 48 hours of antibiotic treatment. Our results suggest that measurements of TNF-alpha and IL-6 in ascitic fluid may become useful markers both for the diagnosis of SBP and for monitoring the treatment of cirrhotic patients.

Lymphoma cell proliferation in the blood vessels of parenchymal organs may result in vessel obstruction and ischaemia. We report the case of a patient who had intravascular lymphoma with predominant pulmonary involvement. A 38-year-old man was referred to the intensive care unit for acute respiratory failure and prolonged fever. Appropriate investigations failed to demonstrate any bacterial, viral, parasitic, or mycobacterial infection. Chest computed tomography ruled out proximal or sub-segmental pulmonary embolism, but the ventilation/perfusion lung scan indicated a high probability of pulmonary embolism. Examination of a skin biopsy established the diagnosis of intravascular lymphoma. Intravascular lymphoma is a rare disease characterised by exclusive or predominant growth of neoplastic cells within the lumina of small blood vessels. Lung involvement is common but rarely at the forefront of the clinical picture. In the case described here, immediate chemotherapy combined with adequate supportive care ensured a full recovery.

Acute kidney injury (AKI) in cancer patients is a dreadful complication that causes substantial morbidity and mortality. Moreover, AKI may preclude optimal cancer treatment by requiring a decrease in chemotherapy dosage or by contraindicating potentially curative treatment. The pathways leading to AKI in cancer patients are common to the development of ARF in other conditions. However, AKI may also develop because of etiologies arising from cancer treatment, such as nephrotoxic chemotherapy agents, or the disease itself, including post-renal obstruction, compression or infiltration, and metabolic or immunological mechanisms.

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To assess the potential role of procalcitonin and tumor necrosis factor-alpha, interleukin-6 and interleukin-8, in the prognosis of patients with sepsis.Prospective study.The emergency unit of a teaching hospital.We included 131 patients with sepsis: 15 (12%) with septic shock, 20 (15%) with severe sepsis and 96 (73%) with sepsis.Out of the 131 patients, 112 (85.5%) survived and 19 (14.5%) died. These two groups of patients differed with regard to simplified acute physiology score II, severity of infectious disease and underlying disease, bacteremia and type of microorganisms. The mean serum levels of tumor necrosis factor, interleukin-6, interleukin-8, procalcitonin and lactates at study entry were higher in nonsurvivors than in survivors. Multivariate regression analysis showed the most significant of these variables to be serum procalcitonin level (P=0.0007), simplified acute physiology score II (P=0.03) and serum lactate level (P=0.03). Using a model incorporating these three variables, with a cut-off value corresponding to a 15% probability of predicting mortality, death could be correctly predicted in 99.5% of cases and survival in 95%. This cut-off value allowed us to maximize the prediction of death. When serum procalcitonin levels were not taken into account, the best model included simplified acute physiology score II and serum lactate and interleukin-6 levels, but the rate of correct prediction of death then dropped to 84%.Stepwise multivariate logistic regression analysis showed serum procalcitonin level to be a valuable marker of sepsis severity, compared with the 15 other clinical, biochemical and bacteriologic variables tested.

Objectives The objective of our study was to define the characteristics of patients admitted to the emergency department (ED) presenting with a methicillin-resistant Staphylococcus aureus (MRSA) infection. Patients and Methods The study included all patients admitted to the ED between January 2003 and December 2004 in whom a staphylococcal infection was documented. The risk factors associated with carriage of MRSA, the diagnosis made in the ED, and the treatment administered were established from the patients' medical files. The sites from which the bacteria were isolated, the spectrum of resistance of the staphylococci to different antibiotics, and the presence or absence of the gene coding for Panton-Valentin leukocidin for certain S aureus isolates were determined from the reports issued by the bacteriologic department. Two groups of patients were compared: those with an infection caused by MRSA and those with an infection due to methicillin-susceptible S aureus (MSSA). Results A total of 238 patients were included, 93 presenting with an infection caused by MRSA and 145 an infection due to MSSA. The patients harboring MRSA had a higher median age than those carrying MSSA (74 vs 61 years, P = .0001), experienced a greater loss of autonomy (according to the Knauss index), and had more comorbidity factors. Nine patients, younger than 40 years, presented with an infection due to MRSA in the absence of any comorbidity factor or any factor associated with carriage of these bacteria. Seven patients in the MRSA group were tested for Panton-Valentine leukocidin genes, and a positive result was obtained in 2 of them. Regardless of whether the infection was caused by MRSA or by MSSA, the bacteria were most frequently isolated from a cutaneous site, in 40% and 65% of the patients, respectively. Irrespective of the group, 28% of the patients presented with bacteremia. The spectrum of resistance of these MRSA strains suggested a hospital rather than community origin. The initial antibiotic therapy was rarely appropriate in the case of an infection due to MRSA. Conclusion Infections caused by MRSA accounted for a high proportion of the staphylococcal infections diagnosed in the ED, necessitating a rational approach to the prescription of antibiotics for infections of this type.

There is mounting evidence showing the value of low-dose corticosteroids in patients with septic shock requiring vasopressor therapy. It remains unclear whether adrenal function tests should be carried out systematically to guide the decision on glucocorticoid therapy.The retrospective study was conducted in 52 patients in three university hospital ICUs. We included consecutive patients with catecholamine-dependent septic shock who had not received ketoconazole, glucocorticoids, or etomidate in the 24 h before the ACTH test, and who had survived to day 3 after the shock onset. All patients had a 250-microg ACTH test before systematic glucocorticoid therapy was started. Various definitions of relative adrenal insufficiency were used (based on cortisol basal level and/or change in cortisol level after ACTH stimulation). We defined hemodynamic improvement as a 50% reduction in the vasoactive agent dose in the 3 days following the initiation of glucocorticoid treatment. The relationship between the hemodynamic improvement and the results of the adrenal function tests was analyzed.Hemodynamic improvement occurred in 29 patients (55.8%). Baseline characteristics, sites of infection, types of micro-organisms and antibiotic management did not differ between patients with and those without hemodynamic improvement. Relative adrenal insufficiency whatever the definition was not associated with hemodynamic improvement.In catecholamine-dependent septic shock patients managed with systematic glucocorticoid therapy the results of ACTH stimulation do not predict hemodynamic improvement.

Inferior vena cava thrombosis is a major complication after filter placement. The thrombus can propagate through the filter leading to a high risk of pulmonary embolism. We report such a case in a patient with a Gunther filter, successfully treated with urokinase, and we discuss the efficacy and the safety of thrombolytic therapy in such situations.

Objective: To investigate the respective contribution of endogenous and exogenous transmission of Pseudomonas aeruginosa in the colonization of lungs in the mechanically ventilated patient, to estimate the role of P. aeruginosa colonization in the occurrence of severe infections, and to extrapolate appropriate control measures for the prevention of P. aeruginosa ventilator-associated pneumonia. Design: Prospective study of the presence of P. aeruginosa (in stomach fluid, throat specimens, stool, and sputum) on admission, twice a week throughout the patient's stay, and in their environment. O-serotyping, pulsed-field gel electrophoresis, and arbitrarily-primed polymerase chain reaction were used to characterize the strains. Setting: The two intensive care units (ICUs 1 and 2) of a university hospital. Patients: During a 6-month period, 59 patients were included (21 in ICU 1 and 38 in ICU 2). Results: P. aeruginosa was isolated in 26 patients, including ten pneumonia cases and seven colonizations on admission. The incidence of acquired colonization was statistically different between the two ICUs: 5.5 and 20.5 per 1000 days of mechanical ventilation, in ICUs 1 and 2, respectively. Endogenous acquisition was the main origin of P. aeruginosa colonization (21 of 26 patients) and the upper respiratory tract was the main bacterial reservoir in broncho-pulmonary colonization and infection. However, during the 6-month period of the study, a multidrug-resistant strain of P. aeruginosa O:11, isolated in the sink of the room of 12 patients, was found responsible for two colonizations (1 digestive, 1 throat/lungs) and one pneumonia. As a whole, from 26 cases of colonization/infection with P. aeruginosa, 5 were related to an exogenous contamination (environmental reservoir in 4 patients and cross-contamination in one patient). Conclusions: These results emphasize the need for applying various infection control measures to prevent colonization of patients with P. aeruginosa, including strategies to limit the potential of sinks from acting as a source or reservoir for this bacterium.

Objective: To assess the potential role of procalcitonin and pro-inflammatory cytokines, TNF-α, and IL-6, in the diagnosis of spontaneous bacterial peritonitis (SBP). Design: Prospective study. Setting: The emergency unit of a teaching hospital. Patients: We included 21 patients with SBP and 40 patients with sterile ascitic fluid. Interventions: None. Measurements and main results: For the diagnosis of SBP, the best markers were serum levels of procalcitonin with a cut-off value of 0.75 ng/ml, a sensitivity of 95 %, a specificity of 98 %, and ascitic fluid levels of IL-6 with a cut-off value of 5000 ng/ml, a sensitivity of 100 %, and a specificity of 88 %. C-reactive protein and serum polymorphonuclear count have low sensitivity/specificity at 62/92 % and 57/90 %, respectively. From 21 patients with SBP, ascitic fluid to serum ratio of TNF-α and IL-6 was greater than to 2 in all cases with a mean at 6.2 ± 6.5 and 34 ± 31, respectively. By contrast, this ratio for procalcitonin was less than 1 in all cases with a mean at 0.31 ± 0.25. We found no correlation between procalcitonin levels and cytokine levels in either ascitic fluid or serum. Conclusions: Serum procalcitonin level may become a useful marker for the diagnosis of SBP in cirrhotic patients. The low ratio of ascitic fluid to serum procalcitonin supports the hypothesis that procalcitonin is not produced intraperitoneally.

The use of bicarbonates in the treatment of severe diabetic ketoacidosis remains controversial, especially regarding the benefit/risk ratio. The aim of this study was to assess the efficacy of bicarbonate therapy during severe diabetic ketoacidosis (pH7.10).Retrospective study.The emergency unit of a teaching hospital.The records of 39 patients consecutively admitted for severe diabetic ketoacidosis were analyzed (pH7.10). The patients were divided into two groups: group 1 (n = 24; patients with bicarbonate treatment) and group 2 (n = 15; patients without bicarbonate treatment).None.We compared two groups of patients presenting with severe diabetic ketoacidosis (pH values between 6.83 and 7.08) treated with or without bicarbonate. A group of 24 patients received 120+/-40 mmol sodium bicarbonate. The two groups were similar at admission with regard to clinical and biological parameters. No difference could be demonstrated between the two groups concerning the clinical parameters or the normalization time of biochemical parameters. If the number of patients with hypokalemia was comparable between the two groups, the potassium supply was significantly more important in group 1 compared with group 2 (366+/-74 mmol/L vs. 188+/-109 mmol/L, respectively; p.001).Data from the literature and this study are not in favor of the use of bicarbonate in the treatment of diabetic ketoacidosis with pH values between 6.90 and 7.10.

We investigated whether inhibiting an endothelial adhesion molecule [intracellular adhesion molecule 1 (ICAM-1)] would alter outcome and lung injury in a similar fashion to inhibition of a leukocyte adhesion molecule (integrin CD11b) in a rat model of gram-negative pneumonia. Inhibition of ICAM-1 with monoclonal antibody (MAb) 1A29 (1 mg/kg sc or 0.2 or 2 mg/kg iv, q 12 h × 3) or of CD11b with MAb 1B6 (1 mg/kg sc, q 12 h × 3) were compared against similarly administered placebo proteins in rats challenged with intrabronchial Escherichia coli. After challenge, all animals were treated with antibiotics. ICAM-1 MAb (6 mg/kg, iv, total dose) increased mortality vs. control ( P = 0.03). CD11b MAb (3 mg/kg, sc, total dose) did not significantly ( P = 0.16) increase mortality rates, but this was not in a range of probability to exclude a harmful effect. All other doses of MAb had no significant effect on survival rates. ICAM-1 and CD11b MAbs had significantly different effects on the time course of lung injury, circulating white cells and lymphocytes, and lung lavage white cells and neutrophils ( P = 0.04–0.003). CD11b MAb decreased, whereas ICAM-1 MAb increased these measures compared with control from 6 to 12 h after E. coli. However, from 144 to 168 h after E. coli both MAbs increased these measures compared with control rats but to a greater level with CD11b MAb. Thus both ICAM-1 and CD11b appear to be necessary for survival during E. coli pneumonia. Although these adhesion molecules may participate differently in early lung injury, with CD11b increasing and ICAM-1 decreasing inflammation and injury, both are important for the resolution of later injury. During gram-negative pneumonia the protective roles of ICAM-1 and CD11b may make their therapeutic inhibition difficult.

To investigate the effect of blocking nitric oxide production on cardiovascular function and survival in canine septic shock treated with or without a conventional vasopressor.Randomized, controlled trial.An animal research laboratory at the National Institutes of Health.Sixty purpose-bred beagles.Fibrin clots containing Escherichia coli were surgically placed into the peritoneal cavity. N(omega)-monomethyl-L-arginine (L-NMMA) 10 mg/kg followed by 0.5, 1.0, or 4.0 mg/kg/hr), epinephrine (1 microg/kg/min), both, or neither were infused for 24 hrs beginning 6 hrs after the onset of infection. All animals received fluid and antibiotic therapy.Serum nitric oxide metabolites, nitrite and nitrate, increased with infection (p = .024) and decreased with L-NMMA (p = .004, all doses combined). Myocardial nitric oxide synthase activity was ranked as follows: nonsurvivorssurvivorsnoninfected controls (p.01). Other tissues examined showed the same pattern. L-NMMA produced sustained increases in systemic vascular resistance index and mean arterial pressure 9 and 24 hrs after the onset of infection (por = .04). Left ventricular ejection fraction was depressed by septic shock (p = .01) and further decreased by L-NMMA (p = .02). However, control and L-NMMA cardiac index values were similar (p.4), perhaps because L-NMMA increased pulmonary artery occlusion pressure (p = .02). From 9 to 24 hrs, epinephrine, in the absence or presence of L-NMMA, blunted recovery of cardiac index (p.02) and had a diminishing vasopressor effect (p = .05). Neither L-NMMA nor epinephrine, individually or combined, significantly altered survival rates at the doses investigated (por = .69).The tested doses showed that nitric oxide production was inhibited by L-NMMA in canine septic shock, but mortality and myocardial depression were unaffected. These results suggest that if L-NMMA has a beneficial effect on survival rates in septic shock, it is small.

To determine whether a continuous intravenous infusion of pentoxifylline, a methylxanthine derivative, alters the serum cytokine concentrations and/or hemodynamic measurements in patients with septic shock.A prospective, randomized, double-blind, placebo-controlled study.Medical intensive care unit in a university hospital.Sixteen patients with septic shock.Patients were randomly assigned to receive either pentoxifylline (1 mg/kg) followed by an infusion of 1.5 mg/kg/hr for 24 hrs (n = 8), or placebo (n = 8).Tumor necrosis factor (TNF) and interleukin (IL)-6 concentrations were measured by radioimmunoassays; IL-8 concentrations by an enzyme-linked immunosorbent assay (ELISA) and pentoxifylline concentrations by high-performance liquid chromatography at 0, 3, 6, 12, 18, 24 and 48 hrs after study entry. Pulmonary artery catheter-derived hemodynamics were measured at 0, 0.75, 3, 6, 12, 18, and 24 hrs. In pentoxifylline-treated patients, at 24 hrs, serum concentrations of TNF were significantly lower compared with controls (12 +/- 2 vs. 42 +/- 12 pg/mL, respectively, p = .04). Serum concentrations of IL-6 and IL-8 did not differ between the two treatment groups. There were also no significant differences in any hemodynamic and oxygenation measurements comparing the two treatment groups. Pentoxifylline concentrations were 1,544 +/- 241 ng/mL after the initial dose, and 5,776 +/- 1,781 ng/mL at the end of the 24-hr infusion. Five patients in the pentoxifylline group and four patients in the placebo group died.Pentoxifylline is able to decrease serum TNF but not IL-6 or IL-8 serum concentrations during septic shock. Pentoxifylline was well tolerated by all eight patients with no adverse effect. Further studies are needed to determine if pentoxifylline's ability to lower circulating TNF concentration without altering hemodynamics will improve outcome in septic shock.

Forty-two strains of Acinetobacter baumannii were isolated from 15 patients hospitalized in a French intensive care unit. An epidemiological study based on the typing of these isolates was carried out using biotyping, antibiotyping, and ribotyping to recognize the transmission of multiresistant strains by transfer of a patient from one hospital to another. Fifteen strains from the outbreak (1 strain for each patient), five Acinetobacter baumannii strains isolated before the outbreak in Bellevue Hospital (St. Etienne), and five strains isolated in Cochin Hospital (Paris) were included. The three methods gave a good correlation: the epidemic strains had the same antibiotic resistance pattern, the same biotype, and the same ribotypes obtained with three different endonucleases.

The purpose of this study was to evaluate adult first seizures in an emergency department by analyzing etiologic and epidemiological data and studying the usefulness of biological screening, electroencephalogram (EEG), and cerebral computed tomography (CT) scan. This was a retrospective study of a 3-year period during which 247 patients were admitted to an emergency department for a first generalized seizure. A CT scan had been performed in 247 patients and an EEG in 209. Etiologies were found to be (1) unknown, (2) alcohol abuse, (3) stroke, and (4) tumor. Early recurrence rate was 18.5%. EEG was of low interest in emergency. The rate of cerebral focal lesions on CT scan was significantly lower when both examination results and EEG were normal. The rate of metabolic abnormalities was 4.9%. It was concluded that (1) a short hospitalization is advisable because of recurrences, (2) recurrence rate does not increase significantly in patients with focal cerebral lesion, (3) metabolic screening is necessary, and (4) CT scan will be an outpatient procedure for most patients.

A previously healthy 42-year-old man developed, after a neglected tonsillitis, a severe Fusobacterium necrophorum septicemia with disseminated intravascular coagulation. Peripheral, painful, cyanotic and gangrenous lesions appeared on toes, external ears and nose tip. The patient survived. Consumption coagulopathy associated with tonsillitis should suggest F. necrophorum infection. Growth of these bacteria in blood cultures is slow and confirmation of the infection may thus be delayed.

Introduction In seriously infected patients with acute renal failure and who require continuous renal replacement therapy, data on continuous infusion of ceftazidime are lacking. Here we analyzed the pharmacokinetics of ceftazidime administered by continuous infusion in critically ill patients during continuous venovenous haemodiafiltration (CVVHDF) in order to identify the optimal dosage in this setting.