Implementation of French Recommendations for the Prevention and the Treatment of Hospital-acquired Pneumonia: A Cluster-randomized Trial.

BACKGROUND: We determined whether an audit on the adherence to guidelines for hospital-acquired pneumonia (HAP) can improve the outcomes of patients in intensive care units (ICUs). METHODS: This study was conducted at 35 ICUs in 30 hospitals. We included consecutive, adult patients hospitalized in ICUs for 3 days or more. After a 3-month baseline period followed by the dissemination of recommendations, an audit on the compliance to recommendations (audit period) was followed by a 3-month cluster-randomized trial. We randomly assigned ICUs to either receive audit and feedback (intervention group) or participate in a national registry (control group). The primary outcome was the duration of ICU stay. RESULTS: Among 1856 patients enrolled, 602, 669, and 585 were recruited in the baseline, audit, and intervention periods, respectively. The composite measures of compliance were 47% (interquartile range [IQR], 38-56%) in the intervention group and 42% (IQR, 25-53%) in the control group (P = .001). As compared to the baseline period, the ICU lengths of stay were reduced by 3.2 days in the intervention period (P = .07) and by 2.8 days in the control period (P = .02). The durations of ICU stay were 7 days (IQR, 5-14 days) in the control group and 9 days (IQR, 5-20 days) in the intervention group (P = .10). After adjustment for unbalanced baseline characteristics, the hazard ratio for being discharged alive from the ICU in the control group was 1.17 (95% confidence interval, .69-2.01; P = .10). CONCLUSIONS: The publication of French guidelines for HAP was associated with a reduction of the ICU length of stay. However, the realization of an audit to improve their application did not further improve outcomes. CLINICAL TRIALS REGISTRATION: NCT03348579.

Decreased duration of intravenous cephalosporins in intensive care unit patients with selective digestive decontamination: a retrospective before-and-after study.

Selective digestive decontamination (SDD) reduces the rate of infection and improves the outcomes of patients admitted to an intensive care unit (ICU). A risk associated with its use is the development of multi-drug-resistant organisms. We hypothesized that a 1-day reduction in systemic antimicrobial exposure in the SDD regimen would not affect the outcomes of our patients. In this before-and-after study design, 199 patients and 248 patients were included in a 3-day SDD group and a 2-day SDD group, respectively. The rates of hospital-acquired pneumonia and ICU infections were similar in both groups. The rates of bloodstream infection and bacteriuria were significantly lower in the 2-day SDD group than in the 3-day SDD group. Compared with the patients in the 3-day group, the patients in the 2-day SDD group received fewer antibiotics and less exposure to mechanical ventilation, and they used fewer ICU resources. The rates of ICU mortality and 28-day mortality were similar in both groups. The incidence of multi-drug-resistant organisms was similar in both groups. Within the limitations inherent to our study design, reducing the exposure of prophylactic systemic antibiotics in the SDD setting from 3 days to 2 days was not associated with impaired outcomes. Future randomized controlled trials should be conducted to test this hypothesis and investigate the effects on the development of multi-drug resistant organisms.

Sex-Mediated Response to the Beta-Blocker Landiolol in Sepsis: An Experimental, Randomized Study.

OBJECTIVES: To investigate any gender effect of the beta-1 adrenergic blocker, landiolol, on cardiac performance and energy metabolism in septic rats, and to explore the expression of genes and proteins involved in this process. DESIGN: Randomized animal study. SETTING: University research laboratory. SUBJECTS: Male and female Wistar rats. INTERVENTIONS: One hour after cecal ligation and puncture, male and female rats were randomly allocated to the following groups: sham male, cecal ligation and puncture male, cecal ligation and puncture + landiolol male, sham female, cecal ligation and puncture female, and cecal ligation and puncture + landiolol female. Cardiac MRI was carried out 18 hours after cecal ligation and puncture to assess in vivo cardiac function. Ex vivo cardiac function measurement and P magnetic resonance spectroscopy were subsequently performed using an isovolumic isolated heart preparation. Finally, we assessed cardiac gene and protein expression. MEASUREMENTS AND MAIN RESULTS: In males, landiolol increased indexed stroke volume by reversing the indexed end-diastolic volume reduction without affecting left ventricle ejection fraction. In females, landiolol did not increase indexed stroke volume and indexed end-diastolic volume but decreased left ventricle ejection fraction. Landiolol had no effect on ex vivo cardiac function and on high-energy phosphate compounds. The effect of landiolol on the gene expression of natriuretic peptide receptor 3 and on protein expression of phosphorylated-AKT:AKT ratio and endothelial nitric oxide synthase was different in males and females. CONCLUSIONS: Landiolol improved the in vivo cardiac performance of septic male rats while deleterious effects were reported in females. Expression of natriuretic peptide receptor 3, phosphorylated-AKT:AKT, and endothelial nitric oxide synthase are signaling pathways to investigate to better understand the sex differences in sepsis.

Female hormones prevent sepsis-induced cardiac dysfunction: an experimental randomized study.

Although epidemiologic research has demonstrated significant differences in incidence and outcomes of sepsis according to sex, their underlying biological mechanisms are poorly understood. Here, we studied the influence of hormonal status by comparing in vivo cardiac performances measured by MRI in non-ovariectomized and ovariectomized septic female rats. Control and ovariectomized rats were randomly allocated to the following groups: sham, sepsis and sepsis plus landiolol. Sepsis was induced by caecum ligation and punction (CLP). Landiolol, a short-acting selective ß1-adrenergic blocker improving the in vivo cardiac performance of septic male rats was perfused continuously after sepsis induction. Cardiac MRI was carried out 18 h after induction of sepsis to assess in vivo cardiac function. Capillary permeability was evaluated by Evans Blue administration and measurement of its tissue extravasation. Variation in myocardial gene and protein expression was also assessed by qPCR and western-blot in the left ventricular tissue. Sepsis reduced indexed stroke volume, cardiac index and indexed end-diastolic volume compared to sham group in ovariectomized females whereas it had no effect in control females. This was associated with an overexpression of JAK2 expression and STAT3 phosphorylation on Ser727 site, and an inhibition of the adrenergic pathways in OVR females. Landiolol increased the indexed stroke volume by reversing the indexed end-diastolic volume reduction after sepsis in ovariectomized females, while it decreased indexed stroke volume and cardiac index in control. This was supported by an overexpression of genes involved in calcium influx in OVR females while an inactivation of the ß-adrenergic and a calcium efflux pathway was observed in control females. Sepsis decreased in vivo cardiac performances in ovariectomized females but not in control females, presumably associated with a more pronounced inflammation, inhibition of the adrenergic pathway and calcium efflux defects. Administration of landiolol prevents this cardiac dysfunction in ovariectomized females with a probable activation of calcium influx, while it has deleterious effects in control females in which calcium efflux pathways were down-regulated.

Beta-lactam allergy labeling in intensive care units: An observational, retrospective study.

ABSTRACT: This retrospective study aimed to describe the association between the "ß-lactam allergy" labeling (BLAL) and the outcomes of a cohort of intensive care unit (ICU) patients.Retrospective cohort study.Seven ICU of the Aix Marseille University Hospitals from Marseille in France.We collected the uses of the label "ß-lactam allergy" in the electronic medical files of patients aged 18 years or more who required more than 48 hours in the ICU with mechanical ventilation and/or vasopressors admitted to 7 ICUs of a single institution.We retrospectively compared the patients with this labeling (BLAL group) with those without this labeling (control group).The primary outcome was the duration of ICU stay. Among the 7146 patients included in the analysis, 440 and 6706 patients were classified in the BLAL group and the control group, respectively. The prevalence of BLAL was 6.2%. In univariate and multivariate analyses, BLAL was weakly or not associated with the duration of ICU and hospital stays (respectively, 6 [3-14] vs 6 [3-14] days, standardized beta -0.09, P = .046; and 18 [10-29] vs 15 [8-28] days, standardized beta -0.09, P = .344). In multivariate analysis, the ICU and 28-day mortality rates were both lower in the BLAL group than in the control group (aOR 0.79 95% CI [0.64-0.98] P = .032 and 0.79 [0.63-0.99] P = .042). Antibiotic use differed between the 2 groups, but the outcomes were similar in the subgroups of septic patients in the BLAL group and the control group.In our cohort, the labeling of a ß-lactam allergy was not associated with prolonged ICU and hospital stays. An association was found between the labeling of a ß-lactam allergy and lower ICU and 28-day mortality rates.Trial registration: Retrospectively registered.

Vasopressors to treat refractory septic shock.

Norepinephrine is the first line vasopressor used in patients with septic shock. However, norepinephrine doses above 1 µg/kg/min are associated with mortality rates of over 80%, suggesting a need to implement adjunctive strategies prior to reaching this dosage. The present study therefore sought to review the existing and emergent vasopressor agents for patients with refractory septic shock. This paper summarizes the use of vasoactive drugs that may be considered in the context of refractory shock. The clinical application of present and future therapies and the related outcome are discussed. A review of the available literature indicated that vasopressin may be a good first option in patients with refractory septic shock, but evidence remains somewhat sparse. Although the use of vasopressin in these circumstances is likely preferable to the use of terlipressin, a pro-drug with an extended half-life, the use of selepressin, a pure V1 agonist, should be further assessed in future studies. Angiotensin II is another emerging option that uses a different signaling pathway. However, nitric oxide synthase inhibitors and methylene blue do not appear to be appropriate in the management of patients with refractory septic shock. In conclusion, the use of different adjunctive agents in combination with the use of norepinephrine may be useful in patients with refractory septic shock, but care must be taken to avoid excessive vasoconstriction.

Incidental Finding of Thrombus by Ultrasonography in a Trauma Patient with an Intravascular Cooling Device.

In patients with traumatic brain injury, coagulation disorders may both cause bleeding and thrombosis. The addition of risk factors, including invasive devices, probably increases the risk of complications. The benefit of using intravascular cooling device should be balanced by the risk to generate thrombosis. The use of routine ultrasound was associated with an incidental diagnosis of thrombus, accelerating the onset of curative anticoagulation.

Efficacy and safety of antimicrobial de-escalation as a clinical strategy.

INTRODUCTION: De-escalation is a widely recommended strategy in regard to guidelines, with an associated adherence to guidelines being around 50%. This review discusses data supporting de-escalation and possible obstacles for its implementation. Areas covered: Although it does not have a consensual definition, de-escalation consists of reducing the spectrum of empirical antimicrobial treatment based on the microbiological findings. Many observational studies have suggested that this strategy is likely safe and efficient for treating various types of infection. However, randomized controlled trials published as of now have not shown any improvement on the outcomes. Regarding the adverse effects of de-escalation on ecological pressure and multidrug resistance emergence, the data are contradictory. The implementation of new techniques, such as rapid diagnosis, can help guide clinicians. Expert opinion: De-escalation should be included as part of a large antibiotic stewardship program to balance the risk and benefit of each administration, and each physician prescribing antibiotics should be challenged for the quality of her/his prescription on a daily basis. In the future, one of our duties will involve determining whether a delay of antimicrobial treatment - making it possible to improve diagnostic performance and obtain the first laboratory results - is either safe or unsafe for our patients.

Effect of landiolol on sex-related transcriptomic changes in the myocardium during sepsis.

OBJECTIVES: The aims of this study are to better understand phenotypic differences between male and female rats during sepsis, to characterise the contribution of the beta1-adrenergic blocker landiolol to septic cardiomyopathy and to determine why landiolol induces divergent effects in males and females. METHODS: The myocardial transcriptional profiles in male and female Wistar rats were assessed after the induction of sepsis by cecal ligation and puncture and addition of landiolol. RESULTS: Our results showed major differences in the biological processes activated during sepsis in male and female rats. In particular, a significant decrease in processes related to cell organisation, contractile function, ionic transport and phosphoinositide-3-kinase/AKT (PI3K/AKT) signalling was observed only in males. The transcript of ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3 (SERCA3) was sex-differently regulated. In males, landiolol reversed several signalling pathways dysregulated during sepsis. The expression level of genes encoding tubulin alpha 8 (TUBA8) and myosin heavy chain 7B (MYH7) contractile proteins, phosphatase 2 catalytic subunit alpha (PPP2CA), G protein-coupled receptor kinase 5 (GRK5) and A-kinase anchoring protein 6 (AKAP6) returned to their basal levels. In contrast, in females, landiolol had limited effects. CONCLUSION: In males, landiolol reversed the expression of many genes that were deregulated in sepsis. Conversely, sepsis-induced deregulation of gene expression was less pronounced in females than in males, and was maintained in the landiolol-treated females. These findings highlight important sex-related differences and confirm previous observations on the important benefit of landiolol intake on cardiac function in male rats.

Integrating extended focused assessment with sonography for trauma (eFAST) in the initial assessment of severe trauma: Impact on the management of 756 patients.

BACKGROUND: Before total body computed tomography scan, an initial rapid imaging assessment should be conducted in the trauma bay. It generally includes a chest x-ray, pelvic x-ray, and an extended focused ultrasonography assessment for trauma. This initial imaging assessment has been poorly described since the increase in the use of ultrasound. Therefore, our study aimed to evaluate the diagnostic accuracy and therapeutic impact of this initial imaging work-up in severe trauma patients. A secondary aim was to assess the therapeutic impact of a chest x-ray according to the lung ultrasonography findings. METHODS: Patients with severe trauma who were admitted directly to our level 1 trauma center were consecutively included in this retrospective single center study. The diagnostic accuracy, therapeutic impact, and appropriate decision rate were calculated according to the initial assessment results of the whole body computed tomography scan and surgery reports. RESULTS: Among the 1315 trauma patients admitted, 756 were included in this research. Lung ultrasound showed a higher diagnostic accuracy for haemothorax and pneumothorax cases than the chest x-ray. Sensitivity and specificity of the abdominal ultrasound to detect intraperitoneal effusion were 70% and 96%, respectively. The initial assessment had a therapeutic impact in 76 (10%) of the patients, including 16 (2%) immediate laparotomies and 58 (7%) chest tube insertions. The pelvic x-ray had no therapeutic impact, and when the lung ultrasound was normal, the chest x-ray had a therapeutic impact of only 0.13%. Combining the chest x-ray and lung ultrasound allowed adequate management of all the pneumothorax and haemothorax cases. Only one of the 756 patients had initial management that was judged as inappropriate. This patient had a missed pelvic disjunction with active retroperitoneal bleeding, and underwent an inappropriate immediate laparotomy. CONCLUSIONS: In our cohort, the initial imaging assessment allowed appropriate decisions in 755 of 756 patients, with a global therapeutic impact of 10%. The pelvic x-ray had a minimal therapeutic impact, and in the patients with normal lung ultrasounds, the chest x-ray marginally affected the management of our patients. The potential consequences of abandoning systematic chest and pelvic x-rays should be investigated in future randomized prospective studies.