Search

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 μg/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

ObjectivesSubtypes A1 and B are the most prevalent HIV-1 clades in Greece. Subtype A1 epidemic is highly monophyletic and corresponds to transmissions that occurred locally. Our aim in this molecular epidemiology analysis was to investigate the role of early treatment in preventing new HIV-1 transmissions.MethodsOur analysis focused on 791 subtype A1 sequences from treatment-naïve individuals in Greece. Estimation of infection dates was performed by molecular clock calculations using Bayesian methods. We estimated the time interval between (1) the infection and sampling dates (linkage to care window), (2) the sampling dates and antiretroviral therapy (ART) initiation (treatment window), and (3) the infection dates and ART initiation (transmissibility window) for the study population. We also inferred the putative source of HIV infections between individuals of different groups divided according to the length of treatment, linkage to care or transmissibility window.ResultsA significant decline was detected for the treatment window during 2014–2015 versus the 2 previous years (p=0.0273), while the linkage to care interval remained unchanged during the study period. Inference of the putative source of HIV infections suggested that individuals with a recent diagnosis or narrow transmissibility window (time period between HIV infection and ART initiation) were not sources of HIV infections to other groups. Contrarily, a significant number of HIV infections originated from individuals with longer transmissibility window interval.ConclusionsOur findings showed that the treatment window is decreasing over time, presumably due to the updated treatment guidelines. Our study also demonstrates that people treated earlier after infection do not transmit at high rates, thus documenting the benefits of early ART initiation in preventing ongoing HIV-1 transmission.

Early increase of soluble urokinase plasminogen activator receptor (suPAR) serum levels is indicative of increased risk of progression of coronavirus disease 2019 (COVID-19) to respiratory failure. The SAVE-MORE double-blind, randomized controlled trial evaluated the efficacy and safety of anakinra, an IL-1α/β inhibitor, in 594 patients with COVID-19 at risk of progressing to respiratory failure as identified by plasma suPAR ≥6 ng ml−1, 85.9% (n = 510) of whom were receiving dexamethasone. At day 28, the adjusted proportional odds of having a worse clinical status (assessed by the 11-point World Health Organization Clinical Progression Scale (WHO-CPS)) with anakinra, as compared to placebo, was 0.36 (95% confidence interval 0.26–0.50). The median WHO-CPS decrease on day 28 from baseline in the placebo and anakinra groups was 3 and 4 points, respectively (odds ratio (OR) = 0.40, P, The SAVE-MORE phase 3 study demonstrates the efficacy of anakinra, an IL-1α/β inhibitor, in patients with COVID-19 and high serum levels of soluble plasminogen activator receptor.

Our aim was to investigate the dispersal patterns and parameters associated with local molecular transmission clusters (MTCs) of subtypes A1 and B in Greece (predominant HIV-1 subtypes). The analysis focused on 1751 (28.4%) and 2575 (41.8%) sequences of subtype A1 and B, respectively. Identification of MTCs was based on phylogenetic analysis. The analyses identified 38 MTCs including 2&ndash, 1518 subtype A1 sequences and 168 MTCs in the range of 2&ndash, 218 subtype B sequences. The proportion of sequences within MTCs was 93.8% (1642/1751) and 77.0% (1982/2575) for subtype A1 and B, respectively. Transmissions within MTCs for subtype A1 were associated with risk group (Men having Sex with Men vs. heterosexuals, OR = 5.34, p &lt, 0.001) and Greek origin (Greek vs. non-Greek origin, OR = 6.05, p &lt, 0.001) and for subtype B, they were associated with Greek origin (Greek vs. non-Greek origin, OR = 1.57, p = 0.019), younger age (OR = 0.96, p &lt, 0.001), and more recent sampling (time period: 2011&ndash, 2015 vs. 1999&ndash, 2005, OR = 3.83, p &lt, 0.001). Our findings about the patterns of across and within country dispersal as well as the parameters associated with transmission within MTCs provide a framework for the application of the study of molecular clusters for HIV prevention.

The aim of this study was to investigate the effect of the implementation of an antibiotic stewardship program (ASP) on antibiotic consumption in our 428-bed hospital. The Infection Control Committee implemented an ASP beginning in January 2016, aiming to reduce inappropriate antibiotic use through improved prescribing practices. The ASP included both pre-authorization and prospective audit and feedback strategies. We collected pharmacy and hospital data for the years 2015 (pre-intervention) and 2016 (post-intervention). Consumption data were expressed as daily defined doses (DDDs) per 100 patient-days (PD) and the significance of the differences between 2015 and 2016 was assessed by paired t-test. Antibiotic resistance rates for the most important hospital pathogens were monitored for 2015–2016. The ASP effectively reduced consumption of most antimicrobials; total antibiotic use decreased by 16.7% (from 104.3 in 2015 to 86.9 DDDs/100 patient-days in 2016, p

Objective Combined antiretroviral treatment (cART) results in profound immunologic improvement, but it is unclear whether CD4 cell counts return to levels similar to those of HIV-negative individuals. We explore long-term CD4 cell count evolution post-cART and its association with baseline levels, virologic suppression, pre-cART cumulative viremia and other factors. Design Data were derived from the AMACS. Included individuals were adults who started cART, at least 2003, while previously ART-naive. Methods Changes in CD4 cell counts were modeled through piecewise linear mixed models. Results A total of 3405 individuals were included. The majority was male (86.0%), homosexual (58.8%) with median (IQR) age at cART initiation 36 (31-44) years and a median (IQR) follow-up of 3.9 (2.0-6.9) years. Most persons (57%) starting cART with less than 200 cells/μl did not reach 600 cells/μl after 7 years of treatment. Those starting cART with 200-349 CD4 cells/μl could reach 600 cells/μl within less than 2 years of fully suppressive treatment. Probability of CD4 normalization (i.e. >800 cells/μl) after 7 years of suppressive treatment was 24 and 46% for those starting treatment with less than 200 or 200-349 CD4 cells/μl, respectively. Lower pre-cART cumulative viremia was associated with faster CD4 recovery. CD4 cell count increases after 4 years were either insignificant or very slow, irrespectively of baseline levels. Conclusion cART initiation before CD4 cell count drops below 350 cells/μl is crucial for achieving normal CD4 levels. These findings underline the importance of timely diagnosis and cART initiation as the risk of both AIDS and non-AIDS-related morbidity/mortality remains increased in patients with incomplete CD4 recovery.

The presence of human immunodeficiency virus type 1 (HIV-1) drug resistance among drug-naïve patients remains stable, although the proportion of patients with virological failure to therapy is decreasing. The dynamics of transmitted resistance among drug-naïve patients remains largely unknown. The prevalence of non-nucleoside reverse transcriptase inhibitors (NNRTI) resistance was 16.9% among treatment-naïve individuals in Greece. We aimed to investigate the transmission dynamics and the effective reproductive number (Re) of the locally transmitted NNRTI resistance. We analyzed sequences with dominant NNRTI resistance mutations (E138A and K103N) found within monophyletic clusters (local transmission networks (LTNs)) from patients in Greece. For the K103N LTN, the Re was >1 between 2008 and the first half of 2013. For all E138A LTNs, the Re was >1 between 1998 and 2015, except the most recent one (E138A_4), where the Re was >1 between 2006 and 2011 and approximately equal to 1 thereafter. K103N and E138A_4 showed similar characteristics with a more recent origin, higher Re during the first years of the sub-epidemics, and a declining trend in the number of transmissions during the last two years. In the remaining LTNs the epidemic was still expanding. Our study highlights the added value of molecular epidemiology to public health.