Relative faecal abundance to predict extended-spectrum β-lactamase-producing Enterobacterales related ventilator‑associated pneumonia

Abstract Background Antimicrobial stewardship (AMS) for ventilator-associated pneumonia (VAP) in carriers of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) presents significant challenges. The abundance of ESBL-E rectal carriage has emerged as a potentially valuable tool for predicting ESBL-E-related VAP. Methods This single-center, retrospective study was conducted between October 2019 and April 2023 in the medical ICU of a university hospital. The relative abundance of ESBL-E rectal carriage (RAC) was calculated as the ratio of ESBL-E counts to the total number of aerotolerant bacteria. The aim was to evaluate the predictive value of RAC for diagnosing ESBL-E-related VAP in patients with confirmed VAP who were ESBL-E carriers. Results During the study period, 478 patients with ESBL-E carriage were admitted to the ICU, of whom 231 (48%) required mechanical ventilation. Eighty-three patients (17%) developed a total of 131 confirmed VAP episodes, of which 62 episodes (47%) were ESBL-E-related VAP. The median interval between the last rectal screening and VAP occurrence was 4 [3–7] days. RAC was not associated with ESBL-E-related VAP in the entire cohort (p = 0.39). Similar findings were observed in several sensitivity analyses, including the following subsets: recent and high-quality screening (interval between screening and VAP ≤ 7 days and bacterial load on rectal swab > 104 CFU/mL, p = 0.21); first VAP episodes only (p = 0.41); cases involving Escherichia coli exclusively (p = 0.08) or other ESBL-E strains (p = 0.29); and VAP associated with Gram-negative bacteria (p = 0.26) or Enterobacterales (p = 0.34). However, in a multivariable model, rectal colonization with non-Escherichia coli ESBL strains was independently associated with ESBL-E-related VAP (adjusted odds ratio [aOR] 1.213 [95% CI 1.005–1.463], p = 0.045). Conclusion RAC was not associated with confirmed VAP in ESBL-E carriers. Further studies are needed to explore effective strategies for improving AMS in ESBL-E carriers with suspected VAP

High flow nasal cannula and low level continuous positive airway pressure have different physiological effects during de novo acute hypoxemic respiratory failure

Abstract Background Large tidal volumes during de novo acute hypoxemic respiratory failure (AHRF) may promote patient self-inflicted lung injury. Tidal volume assessment under high flow nasal cannula (HFNC) is not routinely feasible at the bedside. Our objective was to determine whether tidal volume during low-level continuous positive airway pressure (CPAP) could predict tidal volume during HFNC and to compare the physiological effects of HFNC and low-level CPAP. Methods Prospective, single-center study including 29 de novo AHRF patients treated with HFNC (50 to 60 L.min− 1). Patients were monitored using electrical impedance tomography during HFNC then CPAP at 4 cmH2O. Tidal volume during HFNC was calculated based on tidal impedance variation. The ability of tidal volume under low-level CPAP to predict tidal volume under HFNC was explored using Bland-Altman analysis. CPAP and HFNC were compared in terms of tidal volume, minute ventilation, respiratory comfort, dyspnea, oxygenation, ventilation distribution, end-expiratory lung volume, thoraco-abdominal asynchrony and recruitment. Results Under HFNC, patients had a tidal volume of 6.6 (5.9–8.7) mL.kg− 1 PBW. 20 (69%) patients exhibited a tidal volume between 4 and 8 mL.kg− 1 PBW, while in 5 (17%) patients it exceeded 9 mL.kg− 1 PBW. Tidal volume under CPAP was higher (9.4 (8.3–11) mL.kg− 1 PBW, p  11.5 mL.kg− 1 PBW ) tidal volume under low-level CPAP predicted a larger (> 9 mL.kg− 1 PBW ) tidal volume under HFNC with 80% sensitivity and 96% specificity. Low-level CPAP was associated with increased minute ventilation, end-expiratory lung volume, and oxygenation as compared to HFNC. It decreased signs of respiratory distress in the most severe patients but was associated with lower comfort compared to HFNC. Conclusion Among ICU patients with de novo AHRF, tidal volume under HFNC was mostly protective. Tidal volume during CPAP at 4 cmH2O did not predict tidal volume during HFNC. Such low-level CPAP was associated with increased tidal volume, minute ventilation, end-expiratory volume, and oxygenation. Trial registration ClinicalTrials.gov ID NCT03919331. Registration date: 2019-03-26

Performance and impact of rapid multiplex PCR on diagnosis and treatment of ventilated hospital-acquired pneumonia in patients with extended-spectrum β-lactamase-producing Enterobacterales rectal carriage

Abstract Background Antimicrobial stewardship (AMS) for ventilator-associated pneumonia (VAP) or ventilated hospital-acquired pneumonia (vHAP) in extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) carriers is challenging. BioFire® FilmArray® Pneumonia plus Panel (mPCR) can detect bacteria and antibiotic resistance genes, including bla CTX-M, the most common ESBL-encoding gene. Methods This monocentric, prospective study was conducted on a group of ESBL-E carriers from March 2020 to August 2022. The primary objective was to evaluate the concordance between the results of mPCR and conventional culture performed on respiratory samples of ESBL-E carriers to investigate suspected VAP/vHAP. The secondary objective was to appraise the impact of performing or not mPCR on initial antibiotic therapy adequacy in ESBL-E carriers with confirmed VAP/vHAP. Results Over the study period, 294 patients with ESBL-E carriage were admitted to the ICU, of who 168 (57%) were mechanically ventilated. (i) Diagnostic performance of mPCR was evaluated in suspected 41 episodes of VAP/vHAP: bla CTX-M gene was detected in 15/41 (37%) episodes, where 9/15 (60%) were confirmed ESBL-E-induced pneumonia. The culture and bla CTX-M were concordant in 35/41 (85%) episodes, and in all episodes where bla CTX-M was negative (n = 26), the culture never detected ESBL-E. (ii) The impact of mPCR on initial antibiotic therapy adequacy was assessed in 95 episodes of confirmed VAP/vHAP (22 episodes were tested with mPCR and 73 without); 47 (49%) episodes were ESBL-E-induced, and 24 (25%) were carbapenem-resistant bacteria-induced. The use of mPCR was significantly associated with higher prescription of adequate empirical antibiotic therapy in the multivariable logistic regression (adjusted odds ratio (aOR) (95% CI) of 7.5 (2.1–35.9), p = 0.004), propensity-weighting (aOR of 5.9 (1.6–22.1), p = 0.008), and matching-cohort models (aOR of 5.8 (1.5–22.1), p = 0.01). Conclusion mPCR bla CTX-M showed an excellent diagnostic value to rule out the diagnosis of ESBL-E related pneumonia in ESBL-E carriers with suspected VAP/vHAP. In addition, in patients with confirmed VAP/vHAP, a mPCR-based antibiotic therapy was associated with an increased prescription of adequate empirical antibiotic therapy. Performing mPCR on respiratory samples seems to be a promising tool in ESBL-E carriers with suspected vHAP/VAP. However, if mPCR is used in very low pre-test clinical probability of pneumonia, due to the high sensitivity and the rate of overdiagnosed pneumonia, the risk of overconsumption of carbapenem may prevail. Further studies are warranted

Restrictive use of Restraints and Delirium Duration in the Intensive Care Unit (R2D2-ICU): protocol for a French multicentre parallel-group open-label randomised controlled trial

Introduction Physical restraint (PR) is prescribed in patients receiving invasive mechanical ventilation in the intensive care unit (ICU) to avoid unplanned removal of medical devices. However, it is associated with an increased risk of delirium. We hypothesise that a restrictive use of PR, as compared with a systematic use, could reduce the duration of delirium in ICU patients receiving invasive mechanical ventilation.Methods and analysis The Restrictive use of Restraints and Delirium Duration in ICU (R2D2-ICU) study is a national multicentric, parallel-group, randomised (1:1) open-label, controlled, superiority trial, which will be conducted in 10 ICUs. A total of 422 adult patients requiring invasive mechanical ventilation for an expected duration of at least 48 hours and eligible for prescription of PR will be randomly allocated within 6 hours from intubation to either the restrictive PR use group or the systematic PR use group, until day 14, ICU discharge or death, whichever comes first. In both groups, PR will consist of the use of wrist straps. The primary endpoint will be delirium or coma-free days, defined as the number of days spent alive in the ICU without coma or delirium within the first 14 days after randomisation. Delirium will be assessed using the Confusion Assessment Method-ICU twice daily. Key secondary endpoints will encompass agitation episodes, opioid, propofol, benzodiazepine and antipsychotic drug exposure during the 14-day intervention period, along with a core outcome set of measures evaluated 90 days postrandomisation.Ethics and dissemination The R2D2-ICU study has been approved by the Comité de Protection des Personnes (CPP) ILE DE FRANCE III—PARIS (CPP19.09.06.37521) on June 10th, 2019). Participant recruitment started on 25 January 2021. Results will be published in international peer-reviewed medical journals and presented at conferences.Trial registration number NCT04273360

Effects of Standard-Dose Prophylactic, High-Dose Prophylactic, and Therapeutic Anticoagulation in Patients With Hypoxemic COVID-19 Pneumonia The ANTICOVID Randomized Clinical Trial

International audienceIMPORTANCE Given the high risk of thrombosis and anticoagulation-related bleeding in patients with hypoxemic COVID-19 pneumonia, identifying the lowest effective dose of anticoagulation therapy for these patients is imperative. OBJECTIVES To determine whether therapeutic anticoagulation (TA) or high-dose prophylactic anticoagulation (HD-PA) decreases mortality and/or disease duration compared with standard-dose prophylactic anticoagulation (SD-PA), and whether TA outperforms HD-PA; and to compare the net clinical outcomes among the 3 strategies. DESIGN, SETTINGS, AND PARTICIPANTS The ANTICOVID randomized clinical open-label trial included patients with hypoxemic COVID-19 pneumonia requiring supplemental oxygen and having no initial thrombosis on chest computer tomography with pulmonary angiogram at 23 health centers in France from April 14 to December 13, 2021. Of 339 patients randomized, 334 were included in the primary analysis-114 patients in the SD-PA group, 110 in the HD-PA, and 110 in the TA. At randomization, 90% of the patients were in the intensive care unit. Data analyses were performed from April 13, 2022, to January 3, 2023. INTERVENTIONS Patients were randomly assigned (1:1:1) to receive either SD-PA, HD-PA, or TA with low-molecular-weight or unfractionated heparin for 14 days. MAIN OUTCOMES AND MEASURES A hierarchical criterion of all-cause mortality followed by time to clinical improvement at day 28. Main secondary outcome was net clinical outcome at day 28 (composite of thrombosis, major bleeding, and all-cause death). RESULTS Among the study population of 334 individuals (mean [SD] age, 58.3 [13.0] years; 226 [67.7%] men and 108 [32.3%] women), use of HD-PA and SD-PA had similar probabilities of favorable outcome (47.3% [95%CI, 39.9% to 54.8%] vs 52.7%[95%CI, 45.2%to 60.1%]; P = .48), as did TA compared with SD-PA (50.9% [95%CI, 43.4%to 58.3%] vs 49.1% [95%CI, 41.7%to 56.6%]; P = .82) and TA compared with HD-PA (53.5%[95%CI 45.8% to 60.9%] vs 46.5% [95%CI, 39.1% to 54.2%]; P = .37). Net clinical outcome was met in 29.8% of patients receiving SD-PA (20.2%thrombosis, 2.6%bleeding, 14.0% death), 16.4% receiving HD-PA (5.5%thrombosis, 3.6%bleeding, 11.8%death), and 20.0% receiving TA (5.5% thrombosis, 3.6% bleeding, 12.7%death). Moreover, HD-PA and TA use significantly reduced thrombosis compared with SD-PA (absolute difference, -14.7 [95%CI -6.2 to -23.2] and -14.7 [95%CI -6.2 to -23.2], respectively). Use of HD-PA significantly reduced net clinical outcome compared with SD-PA (absolute difference, -13.5; 95%CI -2.6 to -24.3). CONCLUSIONS AND RELEVANCE This randomized clinical trial found that compared with SD-PA, neither HD-PAnor TAuse improved the primary hierarchical outcome of all-cause mortality or time to clinical improvement in patients with hypoxemicCOVID-19 pneumonia; however, HD-PA resulted in significantly better net clinical outcome by decreasing the risk of de novo thrombosis