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Objective To analyse the biliary pharmacokinetics/pharmacodynamics (PK/PD) of continuous infusion (CI) meropenem-vaborbactam (MEM-VBM) in a case series of orthotopic liver transplant (OLT) recipients being treated for Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) related biliary tract infections (BTIs) or as preemptive therapy of KPC-Kp rectal colonization. Methods Critical OLT recipients receiving CI MEM-VBM (2 g/2 g q8h over 8 h) because of KPC-Kp related BTIs or as preemptive therapy of KPC-Kp rectal colonization, having Kehr's tube positioned and undergoing simultaneous therapeutic drug monitoring of MEM and VBM in plasma and bile were retrospectively assessed. Bile-to-plasma ratio of free steady-state concentrations (f Css) of MEM and VBM was used for assessing biliary penetration. Optimal joint MEM-VBM PK/PD target attainment was defined as MEM f Css/MIC ratio >4 coupled with VBM free area under time–concentration curve (f AUC)/threshold concentration (CT) ratio >24. Results Overall, four critical OLT recipients were included. Median bile-to-plasma ratio was 0.32 for MEM (range 0.21–0.79) and 0.40 for VBM (range 0.20–0.77). Biliary MEM-VBM joint PK/PD target attainment was optimal in 3/4 OLT recipients and quasi-optimal in the other one. Conclusions The 1:1 proportion between MEM and VBM concentrations was maintained unchanged in the bile, allowing us to assume that the efficacy of MEM-VBM may be appropriate even in the treatment of BTIs. CI administration was an effective strategy for attaining aggressive biliary joint PK/PD targets against pathogens with an MIC up to 2 mg/L. [ABSTRACT FROM AUTHOR]

Background: Prone positioning (PP) has been used to improve oxygenation in patients affected by the SARS-CoV-2 disease (COVID-19). Several mechanisms, including lung recruitment and better lung ventilation/perfusion matching, make a relevant rational for using PP. However, not all patients maintain the oxygenation improvement after returning to supine position. Nevertheless, no evidence exists that a sustained oxygenation response after PP is associated to outcome in mechanically ventilated COVID-19 patients. We analyzed data from 191 patients affected by COVID-19-related acute respiratory distress syndrome undergoing PP for clinical reasons. Clinical history, severity scores and respiratory mechanics were analyzed. Patients were classified as responders (≥ median PaO2/FiO2 variation) or non-responders (< median PaO2/FiO2 variation) based on the PaO2/FiO2 percentage change between pre-proning and 1 to 3 h after re-supination in the first prone positioning session. Differences among the groups in physiological variables, complication rates and outcome were evaluated. A competing risk regression analysis was conducted to evaluate if PaO2/FiO2 response after the first pronation cycle was associated to liberation from mechanical ventilation. Results: The median PaO2/FiO2 variation after the first PP cycle was 49 [19–100%] and no differences were found in demographics, comorbidities, ventilatory treatment and PaO2/FiO2 before PP between responders (96/191) and non-responders (95/191). Despite no differences in ICU length of stay, non-responders had a higher rate of tracheostomy (70.5% vs 47.9, P = 0.008) and mortality (53.7% vs 33.3%, P = 0.006), as compared to responders. Moreover, oxygenation response after the first PP was independently associated to liberation from mechanical ventilation at 28 days and was increasingly higher being higher the oxygenation response to PP. Conclusions: Sustained oxygenation improvement after first PP session is independently associated to improved survival and reduced duration of mechanical ventilation in critically ill COVID-19 patients. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

Background: To assess the impact of attaining aggressive beta-lactam pharmacokinetic/pharmacodynamic (PK/PD) targets on clinical efficacy in critical orthotopic liver transplant (OLT) recipients with documented early Gram-negative infections., Methods: OLT recipients admitted to the post-transplant ICU between June 2021 and May 2024 having documented Gram-negative infections treated with targeted therapy continuous infusion (CI) beta-lactams, and undergoing therapeutic drug monitoring (TDM)-guided beta-lactam dosing adjustment in the first 72 hours were prospectively enrolled. Free steady-state concentrations (fCss) of beta-lactams (BL) and/or of beta-lactamase inhibitors (BLI) were calculated, and aggressive PK/PD target attainment was measured. Multivariate logistic regression analyses were performed for testing independent variables associated with 30-day resistance occurrence., Results: Fifty critical OLT recipients were treated with CI beta-lactam in mono- (n=34) or in combination (n=16) therapy for documented Gram-negative infections (46% hospital-acquired/ventilator-associated pneumonia). Combination therapy was selected more frequently for treating intraabdominal infections (P=0.03) and was associated with lower attainment of aggressive PK/PD target (P=0.03). No significant difference in clinical/microbiological outcome emerged between mono- and combination therapy. Four patients (8.0%) developed 30-day resistance occurrence. At multivariate analysis, failure in attaining an aggressive beta-lactam PK/PD target emerged as the only independent predictor of 30-day resistance development (OR 14.33; 95% CI 1.46-140.53; P=0.02)., Conclusions: Attaining an aggressive PK/PD target of CI beta-lactams in critical OLT recipients treated for documented Gram-negative infections could represent an effective strategy for minimizing the risk of 30-day resistance occurrence to the selected beta-lactam., (© The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Postoperative pulmonary complications (PPCs) significantly contribute to postoperative morbidity and mortality. We conducted a study to determine the incidence of PPCs after major elective abdominal surgery and their association with early and 1-year mortality in patient without pre-existing respiratory disease., Methods: We conducted a multicenter observational prospective clinical study in 40 Italian centers. 1542 patients undergoing elective major abdominal surgery were recruited in a time period of 14 days and clinically managed according to local protocol. The primary outcome was to determine the incidence of PPCs. Further, we aimed to identify independent predictors for PPCs and examine the association between PPCs and mortality., Results: PPCs occurred in 12.6% (95% CI 11.1-14.4%) of patients with significant differences among general (18.3%, 95% CI 15.7-21.0%), gynecological (3.7%, 95% CI 2.1-6.0%) and urological surgery (9.0%, 95% CI 6.0-12.8%). PPCs development was associated with known pre- and intraoperative risk factors. Patients who developed PPCs had longer length of hospital stay, higher risk of 30-days hospital readmission, and increased in-hospital and one-year mortality (OR 3.078, 95% CI 1.825-5.191; P<0.001)., Conclusions: The incidence of PPCs in patients without pre-existing respiratory disease undergoing elective abdominal surgery is high and associated with worse clinical outcome at one year after surgery. General surgery is associated with higher incidence of PPCs and mortality compared to gynecological and urological surgery.

This review aims at evaluating the existing evidence regarding post reperfusion syndrome, providing a description of the pathophysiologic mechanisms involved and possible management and preventive strategies. A PubMed search was conducted using the MeSH database, "Reperfusion" AND "liver transplantation" were the combined MeSH headings; EMBASE and the Cochrane library were also searched using the same terms. 52 relevant studies and one ongoing trial were found. The concept of post reperfusion syndrome has evolved through years to a multisystemic disorder. The implications of the main organ, recipient and procedure related factors in the genesis of this complex syndrome are discussed in the text as the novel pharmacologic and technical approaches to reduce its incidence. However the available evidence about risk factors, physiopathology and preventive measures is still confusing, the presence of two main definitions and the numerosity of possible confounding factors greatly complicates the interpretation of the studies.

Aim: To evaluate the currently available evidence on thoracic epidural anesthesia effects on splanchnic macro and microcirculation, in physiologic and pathologic conditions., Methods: A PubMed search was conducted using the MeSH database. Anesthesia, Epidural was always the first MeSH heading and was combined by boolean operator AND with the following headings: Circulation, Splanchnic; Intestines; Pancreas and Pancreatitis; Liver Function Tests. EMBASE, Cochrane library, ClinicalTrials.gov and clinicaltrialsregister.eu were also searched using the same terms., Results: Twenty-seven relevant studies and four ongoing trials were found. The data regarding the effects of epidural anesthesia on splanchnic perfusion are conflicting. The studies focusing on regional macro-hemodynamics in healthy animals and humans undergoing elective surgery, demonstrated no influence or worsening of regional perfusion in patients receiving thoracic epidural anesthesia (TEA). On the other hand most of the studies focusing on micro-hemodynamics, especially in pathologic low flow conditions, suggested that TEA could foster microcirculation., Conclusion: The available studies in this field are heterogeneous and the results conflicting, thus it is difficult to draw decisive conclusions. However there is increasing evidence deriving from animal studies, that thoracic epidural blockade could have an important role in modifying tissue microperfusion and protecting microcirculatory weak units from ischemic damage, regardless of the effects on macro-hemodynamics.