Empirical Antibiotic Therapy for Gram-Negative Bacilli Ventilator-Associated Pneumonia: Observational Study and Pharmacodynamic Assessment.

Background: Strong evidence suggests a correlation between pharmacodynamics (PD) index and antibiotic efficacy while dose adjustment should be considered in critically ill patients due to modified pharmacokinetic (PK) parameters and/or higher minimum inhibitory concentrations (MICs). This study aimed to assess pharmacodynamic (PD) target attainment considering both antibiotics serum concentrations and measured MICs in these patients. Method: A multicentric prospective open-label trial conducted in 11 French ICUs involved patients with Gram-negative bacilli (GNB) ventilator-associated pneumonia (VAP) confirmed by quantitative cultures. Results: We included 117 patients. Causative GNBs were P. aeruginosa (40%), Enterobacter spp. (23%), E. coli (20%), and Klebsiella spp. (16%). Hence, 117 (100%) patients received ß-lactams, 65 (58%) aminoglycosides, and two (1.5%) fluoroquinolones. For ß-lactams, 83% of the patients achieved a Cmin/MIC > 1 and 70% had a Cmin/MIC > 4. In the case of high creatinine clearance (CrCL > 100 mL/min/1.73 m2), 70.4% of the patients achieved a Cmin/MIC ratio > 1 versus 91% otherwise (p = 0.041), and 52% achieved a Cmin/MIC ratio > 4 versus 81% (p = 0.018). For aminoglycosides, 94% of the patients had a Cmax/MIC ratio > 8. Neither ß-lactams nor aminoglycosides PK/PD parameters were associated clinical outcomes, but our data suggest a correlation between ß-lactams Cmin/MIC and microbiological success. Conclusion: In our ICU patients treated for GNB VAP, using recommended antibiotic dosage led in most cases to PK/PD targets attainment for aminoglycosides and ß-lactams. High creatinine clearance should encourage clinicians to focus on PK/PD issues.

Potential Impact of Rapid Multiplex PCR on Antimicrobial Therapy Guidance for Ventilated Hospital-Acquired Pneumonia in Critically Ill Patients, A Prospective Observational Clinical and Economic Study.

Objectives: To investigate the potential impact of the syndromic multiplex FilmArray® Pneumonia plus Panel (FAPP) on the antimicrobial treatment guidance of patients with ventilated hospital-acquired pneumonia (VHAP). Methods: Respiratory fluids from 100 adult patients with VHAP, receiving invasive mechanical ventilation in three intensive care units from one French university hospital, were tested prospectively using FAPP. Conventional cultures were performed in parallel as routine practice. Clinicians were left blinded to the FAPP results. Antimicrobial therapies based on FAPP results were simulated by independent blinded experts according to a predefined algorithm and compared to 1) those prescribed in practice according to local guidelines (real-life), and 2) those that complied with the international ERS/ESICM/ESCMID/ALAT recommendations. The primary endpoint was the number of days of broad-spectrum antimicrobial therapy. Secondary endpoints were the rates of microbiological treatment failure and cost-effectiveness ratio. Results: The predicted median duration of broad-spectrum antibiotics was 0 [0-1.25] day in the FAPP-based simulation, versus 2 [0-6] days in real-life (p<0.0001) and 2 [2-3.25] days in the recommendations-based simulation (p<0.0001). Treatment failure was predicted in 3% of cases with FAPP results versus observed in 11% in real-life (p=0.08) and 6% with recommendations-based simulation (p=0.37). The incremental cost-effectiveness ratio was 1 121 € [-7021; 6794] to avoid one day of non-optimized antimicrobial therapy. Conclusions: Our results suggest that using FAPP in patients with VHAP has the potential to reduce the use of broad-spectrum antimicrobial therapy without increasing the risk of microbial treatment failure.

Cost-effectiveness of point-of-care viscoelastic haemostatic assays in the management of bleeding during cardiac surgery: protocol for a prospective multicentre pragmatic study with stepped-wedge cluster randomised controlled design and 1-year follow-up (the IMOTEC study).

INTRODUCTION: During cardiac surgery-associated bleeding, the early detection of coagulopathy is crucial. However, owing to time constraints or lack of suitable laboratory tests, transfusion of haemostatic products is often inappropriately triggered, either too late (exposing to prolonged bleeding and thus to avoidable administration of blood products) or blindly to the coagulation status (exposing to unnecessary haemostatic products administration in patients with no coagulopathy). Undue exposition to transfusion risks and additional healthcare costs may arise. With the perspective of secondary care-related costs, the IMOTEC study (Intérêt MédicO-économique de la Thrombo-Elastographie, dans le management transfusionnel des hémorragies péri-opératoires de chirurgies Cardiaques sous circulation extracorporelle) aims at assessing the cost-effectiveness of a point-of-care viscoelastic haemostatic assay (VHA: RoTem or TEG)-guided management of bleeding. Among several outcome measures, particular emphasis will be put on quality of life with a 1-year follow-up. METHODS AND ANALYSIS: This is a multicentre, prospective, pragmatic study with stepped-wedge cluster randomised controlled design. Over a 36-month period (24 months of enrolment and 12 months of follow-up), 1000 adult patients undergoing cardiac surgery with cardiopulmonary bypass will be included if a periprocedural significant bleeding occurs. The primary outcome is the cost-effectiveness of a VHA-guided algorithm over a 1-year follow-up, including patients' quality of life. Secondary outcomes are the cost-effectiveness of the VHA-guided algorithm with regard to the rate of surgical reexploration and 1-year mortality, its cost per-patient, its effectiveness with regard to haemorrhagic, infectious, renal, neurological, cardiac, circulatory, thrombotic, embolic complications, transfusion requirements, mechanical ventilation free-days, duration of intensive care unit and in-hospital stay and mortality. ETHICS AND DISSEMINATION: The study was registered at Clinicaltrials.gov and was approved by the Committee for the Protection of Persons of Nantes University Hospital, The French Advisory Board on Medical Research Data Processing and the French Personal Data Protection Authority. A publication of the results in a peer-reviewed journal is planned. TRIAL REGISTRATION NUMBER: NCT02972684; Pre-results.

Point-of-care ultrasound in intensive care units: assessment of 1073 procedures in a multicentric, prospective, observational study.

OBJECTIVE: To describe current use and diagnostic and therapeutic impacts of point-of-care ultrasound (POCUS) in the intensive care unit (ICU). BACKGROUND: POCUS is of growing importance in the ICU. Several guidelines recommend its use for procedural guidance and diagnostic assessment. Nevertheless, its current use and clinical impact remain unknown. METHODS: Prospective multicentric study in 142 ICUs in France, Belgium, and Switzerland. All the POCUS procedures performed during a 24-h period were prospectively analyzed. Data regarding patient condition and the POCUS procedures were collected. Factors associated with diagnostic and therapeutic impacts were identified. RESULTS: Among 1954 patients hospitalized during the study period, 1073 (55%) POCUS/day were performed in 709 (36%) patients. POCUS served for diagnostic assessment in 932 (87%) cases and procedural guidance in 141 (13%) cases. Transthoracic echocardiography, lung ultrasound, and transcranial Doppler accounted for 51, 17, and 16% of procedures, respectively. Diagnostic and therapeutic impacts of diagnostic POCUS examinations were 84 and 69%, respectively. Ultrasound guidance was used in 54 and 15% of cases for central venous line and arterial catheter placement, respectively. Hemodynamic instability, emergency conditions, transthoracic echocardiography, and ultrasounds performed by certified intensivists themselves were independent factors affecting diagnostic or therapeutic impacts. CONCLUSIONS: With regard to guidelines, POCUS utilization for procedural guidance remains insufficient. In contrast, POCUS for diagnostic assessment is of extensive use. Its impact on both diagnosis and treatment of ICU patients seems critical. This study identified factors associated with an improved clinical value of POCUS.