New perspectives in the antibiotic treatment of mechanically ventilated patients with infections from Gram-negatives

Introduction: Ventilator-associated pneumonia (VAP) is a common and potentially fatal complication of mechanical ventilation that is often caused by multidrug-resistant (MDR) Gram-negative bacteria (GNB). Despite the repurposing of older treatments and the novel antimicrobials, many resistance mechanisms cannot be confronted, and novel therapies are needed. Areas covered: We searched the literature for keywords regarding the treatment of GNB infections in mechanically ventilated patients. This narrative review presents new data on antibiotics and non-antibiotic approaches focusing on Phase 3 trials against clinically significant GNB that cause VAP. Expert opinion: Ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam stand out as new options for infections by Klebsiella pneumoniae carbapenemase-producing bacteria, whereas ceftolozane-tazobactam adds therapeutic flexibility in Pseudomonas aeruginosa infections with multiple resistance mechanisms. Ceftazidime-avibactam and ceftolozane-tazobactam have relevant literature. Aztreonam-avibactam holds promise for the treatment of infections by metallo-β-lactamase (MBL)-producing organisms. Recently approved cefiderocol possesses an extended antibacterial spectrum, including KPC- and MBL-producers. However, recently published data have toned down optimism about treating VAP caused by carbapenem-resistant Acinetobacter baumannii. For the latter, eravacycline may provide additional hope, pending pertinent data. Non-antibiotic treatments currently being considered as adjunct therapeutic approaches are welcome. Nevertheless, they will hopefully substitute current antimicrobials in the future. © 2020 Informa UK Limited, trading as Taylor & Francis Group

Early Occurrence of Adverse Events in Hospitalized Patients with COVID-19 and Beneficial Effect of Anticoagulation

Background/Aim: This study analyzed the characteristics of patients with COVID-19 with major events during the first days of hospitalization. Patients and Methods: This is a retrospective analysis of prospectively collected data from consecutive patients admitted to two hospitals in Athens, Greece. The characteristics of patients with COVID-19 who suffered the primary endpoint (venous thromboembolic events, intubation, and death) during the first days of hospitalization were analyzed. Results: Among 95 patients included in the analysis, 21 presented with major adverse events during a median follow-up of 13 days. More than 50% of these patients presented with a major event during the first 3 days. Anticoagulation treatment was inversely associated with the cumulative incidence of the primary endpoint [hazard ratio=0.16 (95% confidence interval=0.06-0.47)]. Patients with major events were older, with lower baseline SatO2, and higher number of Wells’ criteria and Charlson comorbidity index. Among these patients, those with hypertension were at higher risk for early occurrence of events (≤ first three days of hospitalization). Conclusion: Major adverse events may occur early in hospitalized patients with COVID-19 with a high-risk profile. Anticoagulation treatment appears to reduce this risk and thus prompt thromboprophylaxis should be employed in these patients. © 2022 International Institute of Anticancer Research. All rights reserved

Procalcitonin to reduce long-term infection-associated adverse events in sepsis a randomized trial

Rationale: Although early antimicrobial discontinuation guided by procalcitonin (PCT) has shown decreased antibiotic consumption in lower respiratory tract infections, the outcomes in long-term sepsis sequelae remain unclear. Objectives: To investigate if PCT guidance may reduce the incidence of long-term infection-associated adverse events in sepsis. Methods: In this multicenter trial, 266 patients with sepsis (by Sepsis-3 definitions) with lower respiratory tract infections, acute pyelonephritis, or primary bloodstream infection were randomized (1:1) to receive either PCT-guided discontinuation of antimicrobials or standard of care. The discontinuation criterion was >80% reduction in PCT levels or any PCT <0.5 mg/L at Day 5 or later. The primary outcome was the rate of infection-associated adverse events at Day 180, a composite of the incidence of any new infection by Clostridioides difficile or multidrug-resistant organisms, or any death attributed to baseline C. difficile or multidrug-resistant organism infection. Secondary outcomes included 28-day mortality, length of antibiotic therapy, and cost of hospitalization. Measurements and Main Results: The rate of infection-associated adverse events was 7.2% (95% confidence interval [CI], 3.8–13.1%; 9/125) versus 15.3% (95% CI, 10.1–22.4%; 20/131) (hazard ratio, 0.45; 95% CI, 0.20–0.98; P = 0.045); 28-day mortality 15.2% (95% CI, 10–22.5%; 19/125) versus 28.2% (95% CI, 21.2–36.5%; 37/131) (hazard ratio, 0.51; 95% CI, 0.29–0.89; P = 0.02); and median length of antibiotic therapy 5 (range, 5–7) versus 10 (range, 7–15) days (P, 0.001) in the PCT and standard-of-care arms, respectively. The cost of hospitalization was also reduced in the PCT arm. Conclusions: In sepsis, PCT guidance was effective in reducing infection-associated adverse events, 28-day mortality, and cost of hospitalization. Copyright © 2021 by the American Thoracic Society

Prone Positioning in Patients with COVID-19: Analysis of Multicenter Registry Data and Meta-analysis of Aggregate Data

Background/Aim: Evidence suggests a beneficial effect of prone positioning (PP) in COVID-19. Materials and Methods: Meta-analysis of individual (7 investigators’ groups) and aggregate data (PubMed/EMBASE) regarding the impact of PP on the ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PO2/FiO2) in patients with COVID-19. Results: Among 121 patients (mean age±SD 59.1±10.7 years, 55% males, 57% intubated) the mean post-versus pre- PP PO2/FiO2 difference was: (i) 50.4±64.3 mmHg, p<0.01, (ii) similar in awake (58.7±72.1 mmHg) versus intubated patients (44.1±57.5 mmHg, p=NS), (iii) inversely correlated with body mass index (r=–0.43, p<0.01). Meta-analysis of 23 studies (n=547, weighted age 58.3±4.1, 73% males, 59% intubated) showed a pooled PO2/FiO2 difference of 61.8 [95% confidence intervals=49.9-73.6] mmHg. Meta-regression analysis revealed no associations with baseline demographics, the time in PP before assessment, and the risk of bias of the studies. Conclusion: PP seems to improve oxygenation of patients with COVID-19. © 2022 International Institute of Anticancer Research. All rights reserved

HIV continuum of care: Bridging cross-sectional and longitudinal analyses

Objective: The aim of this study was to propose a unified continuum-of-care (CoC) analysis combining cross-sectional and longitudinal elements, incorporating time spent between stages. Design: The established 90-90-90 target follows a cross-sectional four-stage CoC analysis, lacking information on timing of diagnosis, antiretroviral therapy (ART) initiation, and viral suppression durability. Methods: Data were derived from the Athens Multicenter AIDS Cohort Study (AMACS). In the cross-sectional CoC, we added stratification of diagnosed people with HIV (PWH) by estimated time from infection to diagnosis; of those who ever initiated ART or achieved viral suppression by corresponding current status (in 2018); and cumulative incidence function (CIF) of ART initiation and viral suppression, treating loss-to-followup (LTFU) as competing event. Viral suppression was defined as viral load less than 500 copies/ml. Viral suppression durability was assessed by the CIF of viral load rebound. Findings: About 89.1% of PWH in 2018 were diagnosed (range of diagnoses: 1980 - 2018). Median time to diagnosis was 3.5 years (IQR: 1.1 - 7.0). Among diagnosed, 89.1% were ever treated, of whom 86.7% remained on ART. CIF of ART initiation and LTFU before ART initiation were 80.9 and 6.0% at 5 years since diagnosis, respectively. Among treated, 89.4% achieved viral suppression, of whom 87.4% were currently virally suppressed. The CIF of viral load rebound was 24.2% at 5 years since first viral suppression but substantially reduced in more recent years. Interpretation: The proposed analysis highlights time gaps in CoC not evident by the standard cross-sectional approach. Our analysis highlights the need for early diagnosis and identifies late presenters as a key population for interventions that could decrease gaps in the CoC. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved

Cardiovascular risk factors in HIV infected individuals: Comparison with general adult control population in Greece

Background Although combined antiretroviral therapy has substantially improved the prognosis of people living with HIV (PLHIV), mortality remains higher compared to the general population, mainly due to higher prevalence of non-HIV-related comorbidities, including cardiovascular diseases (CVD). We assessed the prevalence of CVD risk and its contributing factors in adult PLHIV versus general population controls in Greece. Settings Cross-sectional comparison of PLHIV (Athens-Multicenter-AIDS-Cohort-Study; AMACS) versus general population controls (National health examination survey; EMENO). Methods All HIV-infected adults with ≥1 measurement of interest (blood pressure, lipids, glucose, weight, height) between 2012-2014 and all EMENO participants (2014-2016) were included. Ten-year total CVD risk was estimated using the Framingham (FRS) or the Systematic Coronary Risk Evaluation (SCORE) equations. Results 5839 PLHIV (median age:41.6 years, 85.4% males) and 4820 controls (median age:48 years, 48.4% males) were included. Adjusting for age, sex and origin, PLHIV were more likely to be current smokers (adjusted OR:1.53 [95% CI:1.35-1.74]) and dyslipidemic (aOR:1.18; [1.04-1.34]), less likely to be obese (aOR:0.44 [0.38-0.52], with no differences in hypertension, diabetes or high (≥20%) FRS but with greater odds of high (≥5%) SCORE (aOR:1.55 [1.05-2.30]). Further adjustment for educational level, anti-HCV positivity and BMI showed higher prevalence of hypertension in PLHIV. Conclusions Despite the relative absence of obesity, PLHIV have higher prevalence of traditional CVD risk factors and higher risk of fatal CVD compared to general population. Regular screening and early management of CVD risk factors in PLHIV should be of high priority for CVD prevention. Copyright: © 2020 Touloumi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Cardiovascular risk factors in HIV infected individuals: Comparison with general adult control population in Greece

Background Although combined antiretroviral therapy has substantially improved the prognosis of people living with HIV (PLHIV), mortality remains higher compared to the general population, mainly due to higher prevalence of non-HIV-related comorbidities, including cardiovascular diseases (CVD). We assessed the prevalence of CVD risk and its contributing factors in adult PLHIV versus general population controls in Greece. Settings Cross-sectional comparison of PLHIV (Athens-Multicenter-AIDS-Cohort-Study; AMACS) versus general population controls (National health examination survey; EMENO). Methods All HIV-infected adults with ≥1 measurement of interest (blood pressure, lipids, glucose, weight, height) between 2012-2014 and all EMENO participants (2014-2016) were included. Ten-year total CVD risk was estimated using the Framingham (FRS) or the Systematic Coronary Risk Evaluation (SCORE) equations. Results 5839 PLHIV (median age:41.6 years, 85.4% males) and 4820 controls (median age:48 years, 48.4% males) were included. Adjusting for age, sex and origin, PLHIV were more likely to be current smokers (adjusted OR:1.53 [95% CI:1.35-1.74]) and dyslipidemic (aOR:1.18; [1.04-1.34]), less likely to be obese (aOR:0.44 [0.38-0.52], with no differences in hypertension, diabetes or high (≥20%) FRS but with greater odds of high (≥5%) SCORE (aOR:1.55 [1.05-2.30]). Further adjustment for educational level, anti-HCV positivity and BMI showed higher prevalence of hypertension in PLHIV. Conclusions Despite the relative absence of obesity, PLHIV have higher prevalence of traditional CVD risk factors and higher risk of fatal CVD compared to general population. Regular screening and early management of CVD risk factors in PLHIV should be of high priority for CVD prevention. Copyright: © 2020 Touloumi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Human immunodeficiency virus continuum of care in 11 european union countries at the end of 2016 overall and by key population: Have we made progress?

Background. High uptake of antiretroviral treatment (ART) is essential to reduce human immunodeficiency virus (HIV) transmission and related mortality; however, gaps in care exist. We aimed to construct the continuum of HIV care (CoC) in 2016 in 11 European Union (EU) countries, overall and by key population and sex. To estimate progress toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 target, we compared 2016 to 2013 estimates for the same countries, representing 73% of the population in the region. Methods. A CoC with the following 4 stages was constructed: number of people living with HIV (PLHIV); proportion of PLHIV diagnosed; proportion of those diagnosed who ever initiated ART; and proportion of those ever treated who achieved viral suppression at their last visit. Results. We estimated that 87% of PLHIV were diagnosed; 92% of those diagnosed had ever initiated ART; and 91% of those ever on ART, or 73% of all PLHIV, were virally suppressed. Corresponding figures for men having sex with men were: 86%, 93%, 93%, 74%; for people who inject drugs: 94%, 88%, 85%, 70%; and for heterosexuals: 86%, 92%, 91%, 72%. The proportion suppressed of all PLHIV ranged from 59% to 86% across countries. Conclusions. The EU is close to the 90-90-90 target and achieved the UNAIDS target of 73% of all PLHIV virally suppressed, significant progress since 2013 when 60% of all PLHIV were virally suppressed. Strengthening of testing programs and treatment support, along with prevention interventions, are needed to achieve HIV epidemic control. © The Author(s) 2020

Human immunodeficiency virus continuum of care in 11 european union countries at the end of 2016 overall and by key population: Have we made progress?

Background. High uptake of antiretroviral treatment (ART) is essential to reduce human immunodeficiency virus (HIV) transmission and related mortality; however, gaps in care exist. We aimed to construct the continuum of HIV care (CoC) in 2016 in 11 European Union (EU) countries, overall and by key population and sex. To estimate progress toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 target, we compared 2016 to 2013 estimates for the same countries, representing 73% of the population in the region. Methods. A CoC with the following 4 stages was constructed: number of people living with HIV (PLHIV); proportion of PLHIV diagnosed; proportion of those diagnosed who ever initiated ART; and proportion of those ever treated who achieved viral suppression at their last visit. Results. We estimated that 87% of PLHIV were diagnosed; 92% of those diagnosed had ever initiated ART; and 91% of those ever on ART, or 73% of all PLHIV, were virally suppressed. Corresponding figures for men having sex with men were: 86%, 93%, 93%, 74%; for people who inject drugs: 94%, 88%, 85%, 70%; and for heterosexuals: 86%, 92%, 91%, 72%. The proportion suppressed of all PLHIV ranged from 59% to 86% across countries. Conclusions. The EU is close to the 90-90-90 target and achieved the UNAIDS target of 73% of all PLHIV virally suppressed, significant progress since 2013 when 60% of all PLHIV were virally suppressed. Strengthening of testing programs and treatment support, along with prevention interventions, are needed to achieve HIV epidemic control