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Antibiotics (Basel) ; 11(9)2022 Sep 16.
Article in English | MEDLINE | ID: covidwho-2043552


BACKGROUND: Both healthcare-associated infections (HAIs) and antimicrobial resistance are associated with an increased length of stay and hospital costs, while they have also been linked to high morbidity and mortality rates. In 2016 and 2017, the latest point prevalence survey (PPS) of HAIs and antimicrobial use in European acute care hospitals highlighted an HAI prevalence of 6.5%, while Greece had a higher HAI prevalence of 10%. The aim of this PPS was to record the prevalence of HAIs and antimicrobial use in all eight public acute care hospitals in Crete, Greece during the COVID-19 pandemic in order to highlight the types of infections and antimicrobial practices that need to be prioritized for infection control initiatives. METHODS: The PPS was conducted between 30 March and 15 April 2022, according to the ECDC standardized relevant protocol (version 5.3). Statistics were extracted using the ECDC Helics.Win.Net application (software version 4.1.0). RESULTS: A total of 1188 patients were included. The overall point prevalence of patients with at least one HAI was 10.6%. The most frequent types of infections were pneumonia (34.3%), bloodstream infections (10.5%), systemic infections and urinary tract infections (10.5% and 9.1%, respectively). In 14 (12.4%) cases, the pathogen responsible for HAI was SARS-CoV-2 following onsite spread, accounting for almost 10% of all HAIs. Microorganisms were identified in 60.1% of HAIs. Antimicrobials were administered in 711 (59.8%) patients, with 1.59 antimicrobials used per patient. CONCLUSION: The prevalence of HAI and antimicrobial use among hospitalized patients in Crete, Greece was similar to the national HAI prevalence in 2016 despite the enormous pressure on public hospitals due to the COVID-19 pandemic. Nevertheless, both HAI prevalence and antimicrobial use remain high, underlining the need to implement adequate infection control and antimicrobial stewardship interventions.

Cell Host Microbe ; 29(8): 1277-1293.e6, 2021 Aug 11.
Article in English | MEDLINE | ID: covidwho-1293647


Immune deactivation of phagocytes is a central event in the pathogenesis of sepsis. Herein, we identify a master regulatory role of IL-6 signaling on LC3-associated phagocytosis (LAP) and reveal that uncoupling of these two processes during sepsis induces immunoparalysis in monocytes/macrophages. In particular, we demonstrate that activation of LAP by the human fungal pathogen Aspergillus fumigatus depends on ERK1/2-mediated phosphorylation of p47phox subunit of NADPH oxidase. Physiologically, autocrine IL-6/JAK2/Ninein axis orchestrates microtubule organization and dynamics regulating ERK recruitment to the phagosome and LC3+ phagosome (LAPosome) formation. In sepsis, loss of IL-6 signaling specifically abrogates microtubule-mediated trafficking of ERK, leading to defective activation of LAP and impaired killing of bacterial and fungal pathogens by monocytes/macrophages, which can be selectively restored by IL-6 supplementation. Our work uncovers a molecular pathway linking IL-6 signaling with LAP and provides insight into the mechanisms underlying immunoparalysis in sepsis.

Interleukin-6/metabolism , Microtubule-Associated Proteins/metabolism , Phagocytosis/immunology , Signal Transduction , Aspergillus fumigatus/metabolism , Cytokines/metabolism , Cytoskeletal Proteins/metabolism , Humans , Janus Kinase 2/metabolism , Macrophages , Monocytes , Nuclear Proteins/metabolism , Phagocytes , Phagocytosis/physiology , Sepsis/metabolism
Clin Infect Dis ; 72(2): 351-356, 2021 01 27.
Article in English | MEDLINE | ID: covidwho-695425


Cancer patients are traditionally considered at high risk for complicated respiratory viral infections, due to their underlying immunosuppression. In line with this notion, early case series reported high mortality rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with malignancy. However, subsequent large, prospective, epidemiological surveys indicate that the risk for severe coronavirus disease 2019 (COVID-19) may be largely attributed to the multiple confounders operating in this highly heterogeneous population of patients, rather than the cancer or its treatment per se. We critically discuss the conundrums of SARS-CoV-2 infection in cancer patients and underscore mechanistic insights on the outcome of COVID-19 as it relates to cancer therapy and the type and status of the underlying malignancy. Not all cancer patients are similarly at risk for a complicated COVID-19 course. A roadmap is needed for translational and clinical research on COVID-19 in this challenging group of patients.

COVID-19 , Neoplasms , Humans , Neoplasms/complications , Neoplasms/epidemiology , Prospective Studies , SARS-CoV-2