How does plastic compare with alternative materials in the packaging sector? A systematic review of LCA studies.

In the recent years, packaging made of conventional plastics has been increasingly replaced by materials believed to be more sustainable. However, perceived sustainability must align with scientific assessments, such as life cycle assessments (LCAs). This review analysed 53 peer-reviewed studies published in the time range 2019-2023, aiming at understanding the state of the art in LCA about the environmental impacts of packaging by focusing on the comparison between plastics and alternative materials. The literature showed that consumer perceptions often differ from LCA findings and revealed that, frequently, conventional plastics are not the least environmentally friendly choice. Bioplastics typically show benefits only in the climate change and the fossil resource depletion impact categories. The heavy weight of glass turns out to affect its environmental performances with respect to the light plastics, with reuse being an essential strategy to lower the burdens. The comparison between plastics and metals is more balanced, leaning more towards plastics for food packaging. Similarly, article resulted often preferable than plastics. Finally, for the other materials (i.e. wood and textiles), the picture is variable. To be competitive with plastics, the alternative materials require improvements like the optimisation of their production processes, their reuse and enhanced end-of-life options. At the same time, recycled polymers could boost the eco-performance of virgin plastics.

Low-molecular-weight heparin for the prevention of clinical worsening in severe non-critically ill COVID-19 patients: a joint analysis of two randomized controlled trials.

Coronavirus disease 2019 (COVID-19) carries a high risk of vascular thrombosis. However, whether a specific anticoagulation intensity strategy may prevent clinical worsening in severe COVID-19 patients is still debated. We conducted a joint analysis of two randomized controlled trials, COVID-19 HD (NCT044082359) and EMOS-COVID (NCT04646655), to assess the efficacy and safety of two anticoagulant regimens in hospitalized severe COVID-19 patients. Subjects with COVID-19-associated respiratory compromise and/or coagulopathy were randomly assigned to low (4000 IU qd) or high (70 IU Kg-1 every 12 h) enoxaparin dose. The primary efficacy endpoint was clinical worsening within 30 days, defined as the occurrence of at least one of the following events, whichever came first: in-hospital death, evidence of arterial or venous thromboembolism, acute myocardial infarction, need for either continuous positive airway pressure (CPAP) or non-invasive ventilation (NIV) in patients receiving standard oxygen therapy or none at randomization, and need for mechanical ventilation in any patient. The safety endpoint was major bleeding. We estimated the relative risk (RR) and its 95% confidence interval (CI) for the outcomes. Among 283 patients included in the study (144 in the low-dose and 139 in the high-dose group), 118 (41.7%) were on NIV or CPAP at randomization. 23/139 (16.5%) patients in the high-dose group reached the primary endpoint compared to 33/144 (22.9%) in the low-dose group (RR 0.72, 95% CI 0.45-1.17). No major bleeding was observed. No significant differences were found in the clinical worsening of hospitalized COVID-19 patients treated with high versus low doses of enoxaparin.

A Machine Learning Approach to Predict Weight Change in ART-Experienced People Living With HIV.

INTRODUCTION: The objective of the study was to develop machine learning (ML) models that predict the percentage weight change in each interval of time in antiretroviral therapy-experienced people living with HIV. METHODS: This was an observational study that comprised consecutive people living with HIV attending Modena HIV Metabolic Clinic with at least 2 visits. Data were partitioned in an 80/20 training/test set to generate 10 progressively parsimonious predictive ML models. Weight gain was defined as any weight change >5%, at the next visit. SHapley Additive exPlanations values were used to quantify the positive or negative impact of any single variable included in each model on the predicted weight changes. RESULTS: A total of 3,321 patients generated 18,322 observations. At the last observation, the median age was 50 years and 69% patients were male. Model 1 (the only 1 including body composition assessed with dual-energy x-ray absorptiometry) had an accuracy greater than 90%. This model could predict weight at the next visit with an error of <5%. CONCLUSIONS: ML models with the inclusion of body composition and metabolic and endocrinological variables had an excellent performance. The parsimonious models available in standard clinical evaluation are insufficient to obtain reliable prediction, but are good enough to predict who will not experience weight gain.

Quality of life and intrinsic capacity in patients with post-acute COVID-19 syndrome is in relation to frailty and resilience phenotypes.

The objective of this study was to characterize frailty and resilience in people evaluated for Post-Acute COVID-19 Syndrome (PACS), in relation to quality of life (QoL) and Intrinsic Capacity (IC). This cross-sectional, observational, study included consecutive people previously hospitalized for severe COVID-19 pneumonia attending Modena (Italy) PACS Clinic from July 2020 to April 2021. Four frailty-resilience phenotypes were built: "fit/resilient", "fit/non-resilient", "frail/resilient" and "frail/non-resilient". Frailty and resilience were defined according to frailty phenotype and Connor Davidson resilience scale (CD-RISC-25) respectively. Study outcomes were: QoL assessed by means of Symptoms Short form health survey (SF-36) and health-related quality of life (EQ-5D-5L) and IC by means of a dedicated questionnaire. Their predictors including frailty-resilience phenotypes were explored in logistic regressions. 232 patients were evaluated, median age was 58.0 years. PACS was diagnosed in 173 (74.6%) patients. Scarce resilience was documented in 114 (49.1%) and frailty in 72 (31.0%) individuals. Predictors for SF-36 score < 61.60 were the phenotypes "frail/non-resilient" (OR = 4.69, CI 2.08-10.55), "fit/non-resilient" (OR = 2.79, CI 1.00-7.73). Predictors for EQ-5D-5L < 89.7% were the phenotypes "frail/non-resilient" (OR = 5.93, CI 2.64-13.33) and "frail/resilient" (OR = 5.66, CI 1.93-16.54). Predictors of impaired IC (below the mean score value) were "frail/non-resilient" (OR = 7.39, CI 3.20-17.07), and "fit/non-resilient" (OR = 4.34, CI 2.16-8.71) phenotypes. Resilience and frailty phenotypes may have a different impact on wellness and QoL and may be evaluated in people with PACS to identify vulnerable individuals that require suitable interventions.

Epidemiology and Prevention of Early Infections by Multi-Drug-Resistant Organisms in Adults Undergoing Liver Transplant: A Narrative Review.

Invasive bacterial infections are a leading cause of morbidity and mortality after liver transplant (LT), especially during the first months after LT, and infections due to multi-drug-resistant organisms (MDRO) are increasing in this setting. Most of the infections in patients in intensive care unit arise from the endogenous microflora and, for this reason, pre-LT MDRO rectal colonization is a risk factor for developing MDRO infections in the post-LT. Moreover, the transplanted liver may carry an increased risk of MDRO infections due to organ transportation and preservation, to donor intensive care unit stay and previous antibiotic exposure. To date, little evidence is available about how MDRO pre-LT colonization in donors and recipients should address LT preventive and antibiotic prophylactic strategies, in order to reduce MDRO infections in the post-LT period. The present review provided an extensive overview of the recent literature on these topics, with the aim to offer a comprehensive insight about the epidemiology of MDRO colonization and infections in adult LT recipients, donor-derived MDRO infections, possible surveillance, and prophylactic strategies to reduce post-LT MDRO infections.

Persistent SARS-CoV-2 infection with multiple clinical relapses in two patients with follicular lymphoma treated with bendamustine and obinutuzumab or rituximab.

PURPOSE: People with hematologic malignancies have a significantly higher risk of developing severe and protracted forms of SARS-CoV-2 infection compared to immunocompetent patients, regardless of vaccination status. RESULTS: We describe two cases of prolonged SARS-CoV-2 infection with multiple relapses of COVID-19 pneumonia in patients with follicular lymphoma treated with bendamustine and obinutuzumab or rituximab. The aim is to highlight the complexity of SARS-CoV-2 infection in this fragile group of patients and the necessity of evidence-based strategies to treat them properly. CONCLUSIONS: Patients with hematological malignancies treated with bendamustine and anti-CD20 antibodies had a significant risk of prolonged and relapsing course of COVID-19. Specific preventive and therapeutic strategies should be developed for this group of patients.

Pneumocystis jirovecii pneumonia in patients with decompensated cirrhosis: a case series.

OBJECTIVES: Pneumocystis jirovecii pneumonia (PCP) incidence is increasing in people without HIV. Decompensated liver cirrhosis is not currently considered a risk factor for PCP. The aim of this paper is to describe a case series of patients with decompensated liver cirrhosis and PCP. METHODS: All consecutive patients hospitalized with decompensated cirrhosis and microbiology-confirmed PCP at Policlinico Modena University Hospital from January 1, 2016 to December 31, 2021 were included in our series. RESULTS: Eight patients were included. All patients had advanced-stage liver disease with a model for end-stage liver disease score above 15 (6/8 above 20). Four were on an active orthotopic liver transplant waiting list at the time of PCP diagnosis. Five patients did not have any traditional risk factor for PCP, whereas the other three were on glucocorticoid treatment for acute-on-chronic liver failure. All patients were treated with cotrimoxazole, except two who died before the diagnosis. Five patients died (62.5%), four of them within 30 days from PCP diagnosis. Of the remaining three, one patient underwent liver transplantation. CONCLUSION: Although further studies are needed, liver cirrhosis can be an independent risk factor for PCP in patients with decompensated cirrhosis that is mainly due to severe alcoholic hepatitis and who are on corticosteroids therapy, and primary prophylaxis for PCP should be considered.

External Validity of a Randomized Controlled Trial on Duration of Antibiotics for the Treatment of Gram-Negative Bacteremia.

INTRODUCTION: Reports regarding the external validity of randomized controlled trials (RCTs) are scarce. We aimed to assess the population external validity of an investigator-initiated RCT on the duration of antibiotics for the treatment of Gram-negative bacteremia by comparing patients included in the RCT to patients that were not included in the trial. METHODS: Hospitalized patients with Gram-negative bacteremia were recruited into an RCT and randomized to receive 7 or 14 days of covering antibiotic therapy in Israel and Italy from 2013 to 2017. In a concomitant observational study, RCT participants were compared with patients who fulfilled the inclusion criteria but were not included in the trial due to participation in other trials, discharge before approached by researchers, refusal to participate, or unwillingness of the treating physician to allow participants' recruitment. RESULTS: Six hundred and four RCT patients were compared with 613 nonincluded patients. Almost 50% of nonincluded patients (288/613) were dependent on others for activities of daily living at baseline compared to 37.7% of RCT participants (228/604). Dementia was nearly 2-fold more frequent in nonincluded patients than those included (5.9% [36/613] versus 3.6% [22/604], p = 0.07). Patients who were not included in the RCT were more likely to acquire their infection in the hospital (53.3% [327/613] versus 29.1% [176/604], p < 0.001). The primary composite outcome of mortality, clinical failure, readmissions, or extended hospitalization at 90 days occurred in 353 of 613 nonincluded patients (57.6%) compared to 299 of 604 RCT participants (49.6%), p = 0.005. However, on multivariate analysis noninclusion in the RCT was not an independent risk factor for clinical failure and mortality. CONCLUSIONS: RCTs, even with broad eligibility criteria, do not represent the whole spectrum of patients and leave out a population with more severe illness for whom the evidence is lacking.

Modifications of Chest CT Body Composition Parameters at Three and Six Months after Severe COVID-19 Pneumonia: A Retrospective Cohort Study.

We aimed to describe body composition changes up to 6-7 months after severe COVID-19 and to evaluate their association with COVID-19 inflammatory burden, described by the integral of the C-reactive protein (CRP) curve. The pectoral muscle area (PMA) and density (PMD), liver-to-spleen (L/S) ratio, and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, and IMAT) were measured at baseline (T0), 2-3 months (T1), and 6-7 months (T2) follow-up CT scans of severe COVID-19 pneumonia survivors. Among the 208 included patients (mean age 65.6 ± 11 years, 31.3% females), decreases in PMA [mean (95%CI) -1.11 (-1.72; -0.51) cm2] and in body fat areas were observed [-3.13 (-10.79; +4.52) cm2 for TAT], larger from T0 to T1 than from T1 to T2. PMD increased only from T1 to T2 [+3.07 (+2.08; +4.06) HU]. Mean decreases were more evident for VAT [-3.55 (-4.94; -2.17) cm2] and steatosis [L/S ratio increase +0.17 (+0.13; +0.20)] than for TAT. In multivariable models adjusted by age, sex, and baseline TAT, increasing the CRP interval was associated with greater PMA reductions, smaller PMD increases, and greater VAT and steatosis decreases, but it was not associated with TAT decreases. In conclusion, muscle loss and fat loss (more apparent in visceral compartments) continue until 6-7 months after COVID-19. The inflammatory burden is associated with skeletal muscle loss and visceral/liver fat loss.

Relationship between weight gain and insulin resistance in people living with HIV switching to integrase strand transfer inhibitors-based regimens.

OBJECTIVE: The primary objective was to explore weight and BMI changes in people with HIV (PWH) undergoing integrase strand transfer inhibitors (INSTI)-based regimens (vs. non-INSTI) in a large cohort and in the subsets of individuals without diabetes and insulin resistance (IR) at the time of switch to INSTI. The secondary objective was to identify risk factors for IR and cut-off of weight or BMI increase associated with IR in PWH switching to INSTI. DESIGN: A longitudinal matched-cohort study including PWH attending Modena HIV Metabolic Clinic, Italy. METHODS: PWH were divided into two groups: non-INSTI and INSTI-switch. The effect of switching to INSTI on weight and BMI change was tested through a linear mixed model. A mediation analysis explored the mediation effect of weight and BMI change in the association between the switch to INSTI and IR. RESULTS: We analyzed 2437 PWH (1025 INSTI-switch, 1412 non-INSTI), in 54 826 weight assessments. Trends for weight increase were significantly higher in early-INSTI-switch (vs. early-non-INSTI), but no difference was observed in the late period after the switch. In the subset of 634 PWH without IR, switching to INSTI (vs. non-INSTI) was associated with a lower risk of IR (hazard ratio = 0.70, 95% confidence interval: 0.51, 0.98). A weight increase by 1% reduced the total protective effect of INSTI by 21.1% over 1 year of follow-up, which identifies a 5% weight increase as a clinically meaningful weight gain definition. CONCLUSION: A cut-off of 5% weight gain from the time of INSTI-switch is associated with IR, which may be a clinically meaningful endpoint that could be used in clinical and research settings.

Intravenous methylprednisolone pulses in hospitalised patients with severe COVID-19 pneumonia: a double-blind, randomised, placebo-controlled trial.

RATIONALE: Pulse glucocorticoid therapy is used in hyperinflammation related to coronavirus disease 2019 (COVID-19). We evaluated the efficacy and safety of pulse intravenous methylprednisolone in addition to standard treatment in COVID-19 pneumonia. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, 304 hospitalised patients with COVID-19 pneumonia were randomised to receive 1 g of methylprednisolone intravenously for three consecutive days or placebo in addition to standard dexamethasone. The primary outcome was the duration of patient hospitalisation, calculated as the time interval between randomisation and hospital discharge without the need for supplementary oxygen. The key secondary outcomes were survival free from invasive ventilation with orotracheal intubation and overall survival. RESULTS: Overall, 112 (75.4%) out of 151 patients in the pulse methylprednisolone arm and 111 (75.2%) of 150 in the placebo arm were discharged from hospital without oxygen within 30 days from randomisation. Median time to discharge was similar in both groups (15 days, 95% CI 13.0-17.0 days and 16 days, 95% CI 13.8-18.2 days, respectively; hazard ratio (HR) 0.92, 95% CI 0.71-1.20; p=0.528). No significant differences between pulse methylprednisolone and placebo arms were observed in terms of admission to intensive care unit with orotracheal intubation or death (20.0% versus 16.1%; HR 1.26, 95% CI 0.74-2.16; p=0.176) or overall mortality (10.0% versus 12.2%; HR 0.83, 95% CI 0.42-1.64; p=0.584). Serious adverse events occurred with similar frequency in the two groups. CONCLUSIONS: Methylprenisolone pulse therapy added to dexamethasone was not of benefit in patients with COVID-19 pneumonia.

Inflammatory burden and persistent CT lung abnormalities in COVID-19 patients.

Inflammatory burden is associated with COVID-19 severity and outcomes. Residual computed tomography (CT) lung abnormalities have been reported after COVID-19. The aim was to evaluate the association between inflammatory burden during COVID-19 and residual lung CT abnormalities collected on follow-up CT scans performed 2-3 and 6-7 months after COVID-19, in severe COVID-19 pneumonia survivors. C-reactive protein (CRP) curves describing inflammatory burden during the clinical course were built, and CRP peaks, velocities of increase, and integrals were calculated. Other putative determinants were age, sex, mechanical ventilation, lowest PaO2/FiO2 ratio, D-dimer peak, and length of hospital stay (LOS). Of the 259 included patients (median age 65 years; 30.5% females), 202 (78%) and 100 (38.6%) had residual, predominantly non-fibrotic, abnormalities at 2-3 and 6-7 months, respectively. In age- and sex-adjusted models, best CRP predictors for residual abnormalities were CRP peak (odds ratio [OR] for one standard deviation [SD] increase = 1.79; 95% confidence interval [CI] = 1.23-2.62) at 2-3 months and CRP integral (OR for one SD increase = 2.24; 95%CI = 1.53-3.28) at 6-7 months. Hence, inflammation is associated with short- and medium-term lung damage in COVID-19. Other severity measures, including mechanical ventilation and LOS, but not D-dimer, were mediators of the relationship between CRP and residual abnormalities.

Metabolic-Associated Fatty Liver Disease Is Highly Prevalent in the Postacute COVID Syndrome.

BACKGROUND: A proposal has recently been advanced to change the traditional definition of nonalcoholic fatty liver disease to metabolic-associated fatty liver disease (MAFLD), to reflect the cluster of metabolic abnormalities that may be more closely associated with cardiovascular risk. Long coronavirus disease 2019 (COVID-19) is a smoldering inflammatory condition, characterized by several symptom clusters. This study aims to determine the prevalence of MAFLD in patients with postacute COVID syndrome (PACS) and its association with other PACS-cluster phenotypes. METHODS: We included 235 patients observed at a single university outpatient clinic. The diagnosis of PACS was based on ≥1 cluster of symptoms: respiratory, neurocognitive, musculoskeletal, psychological, sensory, and dermatological. The outcome was prevalence of MAFLD detected by transient elastography during the first postdischarge follow-up outpatient visit. The prevalence of MAFLD at the time of hospital admission was calculated retrospectively using the hepatic steatosis index. RESULTS: Of 235 patients, 162 (69%) were men (median age 61). The prevalence of MAFLD was 55.3% at follow-up and 37.3% on admission (P < .001). Insulin resistance (odds ratio [OR] = 1.5; 95% confidence interval [CI], 1.14-1.96), body mass index (OR = 1.14; 95% CI, 1.04-1.24), and the metabolic syndrome (OR = 2.54; 95% CI, 1.13-5.68) were independent predictors of MAFLD. The number of PACS clusters was inversely associated with MAFLD (OR = 0.86; 95% CI, .76-0.97). Thirty-one patients (13.2%) had MAFLD with no other associated PACS clusters. All correlations between MAFLD and other PACS clusters were weak. CONCLUSIONS: Metabolic-associated fatty liver disease was highly prevalent after hospital discharge and may represent a specific PACS-cluster phenotype, with potential long-term metabolic and cardiovascular health implications.

Predictive factors of clinical outcomes in patients with COVID-19 treated with tocilizumab: A monocentric retrospective analysis.

OBJECTIVE: The aim of this retrospective observational study is to analyse clinical, serological and radiological predictors of outcome in patients with COVID-19 pneumonia treated with tocilizumab, providing clinical guidance to its use in real-life. METHOD: This is a retrospective, monocentric observational cohort study. All consecutive patients hospitalized between February the 11th and April 14th 2020 for severe COVID-19 pneumonia at Reggio Emilia AUSL and treated with tocilizumab were enrolled. The patient's clinical status was recorded every day using the WHO ordinal scale for clinical improvement. Response to treatment was defined as an improvement of one point (from the status at the beginning of tocilizumab treatment) during the follow-up on this scale. Bivariate association of main patients' characteristics with outcomes was explored by descriptive statistics and Fisher or Kruskal Wallis tests (respectively for qualitative or quantitative variables). Each clinically significant predictor was checked by a loglikelihood ratio test (in univariate logistic models for each of the considered outcomes) against the null model. RESULTS: A total of 173 patients were included. Only hypertension, the use of angiotensin-converting enzyme inhibitors, PaO2/FiO2, respiratory rate and C-reactive protein were selected for the multivariate analysis. In the multivariable model, none of them was significantly associated with response. CONCLUSIONS: Evaluating a large number of clinical variables, our study did not find new predictors of outcome in COVID19 patients treated with tocilizumab. Further studies are needed to investigate the use of tocilizumab in COVID-19 and to better identify clinical phenotypes which could benefit from this treatment.

Evaluation of the anaerobic degradation of food waste collection bags made of paper or bioplastic.

The amount of compostable bioplastics collected with the food waste is constantly growing, particularly due to the bags used for collection. According to the Italian legislation, compostable bioplastics must be accepted by all biological treatment plants, including aerobic and anaerobic facilities. Anyway, the compostability standard requires only the assessment of the aerobic degradability, while it is generally not required to test the behaviour under anaerobic conditions. This aspect is evaluated in the paper, where the anaerobic degradability of bioplastic bags used for the food waste collection is assessed. First, Biochemical Methane Potential (BMP) tests were performed on four commercial types of bioplastic bags, including those designed only for the collection of food waste and the shoppers, that can be reused for the same purpose. Subsequently, an innovative approach for this kind of substrate was applied, subjecting two bags to semi-continuous co-digestion tests together with the food waste. Both tests were performed by comparing the behaviour of bioplastic bags with that of an alternative collection paper bag. Finally, tests to evaluate the influence of physical phenomena on the degradation of bioplastics were performed to better understand the results of biological tests. BMP tests indicated a good degradability (>71%) of bioplastic bags, while semi-continuous tests showed a much lower degradability (<27%), confirmed by the observation of the undigested bag pieces. On the contrary, the paper bag presents interesting characteristics, because its degradability in the semi-continuous tests (82%) resulted even higher than that observed in the BMP tests (74%). These results highlight an important difference between the bags mono-digestion by means of BMP tests and the semi-continuous co-digestion tests with food waste, which better simulate the full-scale operational conditions.

Tocilizumab or glucocorticoids treatment for patients with SARS-CoV-2 pneumonia: An observational study.

OBJECTIVE: To estimate the effect of tocilizumab or glucocorticoids in preventing death and intubation in patients hospitalized with SARS-CoV-2 pneumonia. METHODS: This was a retrospective cohort study enrolling all consecutive patients hospitalized at Reggio Emilia AUSL between February the 11th and April 14th 2020 for severe COVID-19 and treated with tocilizumab or glucocorticoids (at least 80 mg/day of methylprednisolone or equivalent for at least 3 days). The primary outcome was death within 30 days from the start of the considered therapies. The secondary outcome was a composite outcome of death and/or intubation. All patients have been followed-up until May 19th 2020, with a follow-up of at least 30 days for every patient. To reduce confounding due to potential non-comparability of the two groups, those receiving tocilizumab and those receiving glucocorticoids, a propensity score was calculated as the inverse probability weighting of receiving treatment conditional on the baseline covariates. RESULTS AND CONCLUSION: Therapy with tocilizumab alone was associated with a reduction of deaths (OR 0.49, 95% CI 0.21-1.17) and of the composite outcome death/intubation (OR 0.35, 95% CI 0.13-0.90) compared to glucocorticoids alone. Nevertheless, this result should be cautiously interpreted due to a potential prescription bias.

Tocilizumab or glucocorticoids treatment for patients with SARS-CoV-2 pneumonia: An observational study

Abstract Objective To estimate the effect of tocilizumab or glucocorticoids in preventing death and intubation in patients hospitalized with SARS-CoV-2 pneumonia. Methods This was a retrospective cohort study enrolling all consecutive patients hospitalized at Reggio Emilia AUSL between February the 11th and April 14th 2020 for severe COVID-19 and treated with tocilizumab or glucocorticoids (at least 80 mg/day of methylprednisolone or equivalent for at least 3 days). The primary outcome was death within 30 days from the start of the considered therapies. The secondary outcome was a composite outcome of death and/or intubation. All patients have been followed-up until May 19th 2020, with a follow-up of at least 30 days for every patient. To reduce confounding due to potential non-comparability of the two groups, those receiving tocilizumab and those receiving glucocorticoids, a propensity score was calculated as the inverse probability weighting of receiving treatment conditional on the baseline covariates. Results and conclusion Therapy with tocilizumab alone was associated with a reduction of deaths (OR 0.49, 95% CI 0.21-1.17) and of the composite outcome death/intubation (OR 0.35, 95% CI 0.13-0.90) compared to glucocorticoids alone. Nevertheless, this result should be cautiously interpreted due to a potential prescription bias.

Real-life experience with compassionate use of cefiderocol for difficult-to-treat resistant Pseudomonas aeruginosa (DTR-P) infections.

OBJECTIVES: To describe our real-life experience with cefiderocol in XDR and difficult-to-treat resistant Pseudomonas aeruginosa (DTR-P) infections without any other available treatment options. METHODS: We included patients with a proven infection due to an XDR/DTR-P, who had failed on previous regimens, and were treated with cefiderocol, following them prospectively to day 90 or until hospital discharge or death. RESULTS: Seventeen patients treated for >72 h with cefiderocol were included: 14 receiving combination regimens (82.4%) and 3 receiving monotherapy (17.6%). Fourteen patients were males (82%) with a median age of 64 years (IQR 58-73). Fifteen patients (88.2%) were admitted to the ICU and five had septic shock (29%). Seven cases (41.2%) were ventilator-associated pneumonia, of which 71% (5/7) occurred in COVID-19 patients. Four were complicated intrabdominal infections, one ecthyma gangrenosum, one nosocomial pneumonia and one empyema, one osteomyelitis, one primary bacteraemia, and one nosocomial external ventricular drainage meningitis. Clinical cure and microbiological cure rates were 70.6% and 76.5%, respectively. There were six deaths (35.3%) after a median of 8 days (IQR 3-10) from the end of treatment, but only two of them (11.7%) were associated with P. aeruginosa infection progression. CONCLUSIONS: Our experience collecting this large case series of DTR-P treated with cefiderocol may help clinicians consider this new option in this hard-to-manage setting. Our results are even more relevant in the current scenario of ceftolozane/tazobactam shortage. Importantly, this is the first study providing real-life data indicating adequate cefiderocol concentrations in CSF.

Risk factors for functional decline among survivors of Gram-negative bloodstream infection: A prospective cohort study.

OBJECTIVE: To identify risk factors for functional decline after hospitalization for Gram-negative bacteremia. PATIENTS AND METHODS: A prospective cohort study based on a randomized controlled trial conducted between January 1, 2013 and August 31, 2017 in Israel and Italy. Hospitalized patients with Gram-negative bacteremia who survived until day 90 and were not bedridden at baseline were included. The primary end point was functional decline at 90 days. RESULTS: Five hundred and nine patients were included. The median age of the cohort was 71 years (interquartile range [IQR], 60-80 years), 46.4% (236/509) were male and 352 of 509 (69%) patients were independent at baseline. Functional decline at 90 days occurred in 24.4% of patients (124/509). In multivariable analysis; older age (odds ratio [OR], 1.03; for an one-year increment, 95% confidence interval [CI] 1.01-1.05), functional dependence in instrumental activities of daily living at baseline (OR, 4.64; 95% CI 2.5-8.6), low Norton score (OR, 0.87; 95% CI 0.79-0.96) and underlying comorbidities: cancer (OR, 2.01; 95% CI 1.14-3.55) and chronic pulmonary disease (OR, 2.23 95% CI 1.12-4.42) and longer length of hospital stay (OR 1.09; for one-day increment, 95% CI 1.04-1.15) were associated with functional decline. Appropriate empirical antibiotic treatment was associated with lower rates of functional decline within 90 days (OR, 0.4; 95% CI 0.21-0.78). CONCLUSIONS: Patients surviving bloodstream infections have poor long term trajectories after clinical recovery and hospital discharge. This has vast implications for patients, their family members and health policy makers.