{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T11:47:53Z","timestamp":1767700073253,"version":"3.48.0"},"reference-count":34,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Healthcare-associated infections (HAIs) significantly increase morbidity and mortality in critically ill patients, and their burden became more pronounced during the COVID-19 pandemic. However, data describing the temporal evolution of HAIs, pathogen distribution, and associated risk factors across consecutive pandemic waves remain limited. This study aimed to characterize the epidemiology, microbiology, and outcomes of HAIs in COVID-19 intensive care units (ICU) patients and to identify clinical and laboratory predictors of mortality. Materials and Methods: This retrospective observational study included adult patients with RT-PCR\u2013confirmed COVID-19 who developed at least one HAI \u2265 48 h after ICU admission between March 2020 and December 2020, encompassing the first three pandemic waves in T\u00fcrkiye, in a tertiary-care ICU. Demographic, clinical, laboratory, and microbiological data were collected. Inflammatory markers and severity scores (SAPS-II, MCCI, and NLR) were analyzed. Receiver operating characteristic (ROC) curve analysis was used to determine optimal cut-off values for mortality prediction. Results: Among the 1656 ICU admissions, 145 patients (8.7%) developed HAIs; after exclusions, 136 patients were included in the final analysis. Bloodstream infections were the most frequent HAI (57%), followed by urinary tract infections (31%), ventilator-associated pneumonia (9%), and surgical site infections (1%). Klebsiella pneumoniae was the predominant pathogen, followed by Candida albicans and Acinetobacter baumannii. Multidrug-resistant organisms, including MRSA and VRE, showed variable distribution across pandemic periods. Overall in-hospital mortality was 74.3%. Non-survivors had significantly higher SAPS-II, MCCI, and NLR values. ROC analysis identified NLR &gt; 38.8 and SAPS-II &gt; 35.5 as mortality-predictive thresholds. Dynamic inflammatory marker patterns correlated with infection timing, and early peaks of CRP, WBC, and IL-6 were associated with worse outcomes. Conclusions: HAIs imposed a substantial clinical burden on critically ill COVID-19 patients, with high mortality driven predominantly by multidrug-resistant bloodstream infections. Severity indices and inflammation-based biomarkers demonstrated strong prognostic value. Temporal shifts in pathogen ecology across pandemic waves underscore the need for adaptive infection-prevention strategies, continuous microbiological surveillance, and strengthened antimicrobial stewardship in critical care settings.<\/jats:p>","DOI":"10.3390\/medicina62010118","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T11:13:18Z","timestamp":1767697998000},"page":"118","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Healthcare-Associated Infections in Critically Ill COVID-19 Patients Across Evolving Pandemic Waves: A Retrospective ICU Study"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6868-948X","authenticated-orcid":false,"given":"Nihan","family":"Altintepe Baskurt","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Intensive Care, Prof. Dr. Cemil Tascioglu State Hospital, 34384 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esra","family":"Akdas Tekin","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care, Prof. Dr. Cemil Tascioglu State Hospital, 34384 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6769-2054","authenticated-orcid":false,"given":"Onur","family":"Okur","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care, Prof. Dr. Cemil Tascioglu State Hospital, 34384 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Namigar","family":"Turgut","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care, Prof. Dr. Cemil Tascioglu State Hospital, 34384 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13756-024-01367-8","article-title":"Healthcare-associated infections and antimicrobial use in acute care hospitals in Greece, 2022; results of the third point prevalence survey","volume":"13","author":"Palaiopanos","year":"2024","journal-title":"Antimicrob. Resist. Infect. Control."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1017\/ice.2023.158","article-title":"Introduction to A Compendium of Strategies to Prevent Healthcare-Associated Infections In Acute-Care Hospitals: 2022 Updates","volume":"44","author":"Yokoe","year":"2023","journal-title":"Infect. Control. Hosp. Epidemiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1017\/ice.2022.93","article-title":"Healthcare-associated infections in Veterans Affairs acute-care and long-term healthcare facilities during the coronavirus disease 2019 (COVID-19) pandemic","volume":"44","author":"Evans","year":"2023","journal-title":"Infect. Control. Hosp. Epidemiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1016\/j.cmi.2020.06.027","article-title":"Reduction in healthcare-associated respiratory viral infections during a COVID-19 outbreak","volume":"26","author":"Wee","year":"2020","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.1016\/j.cmi.2021.06.001","article-title":"The interface between COVID-19 and bacterial healthcare-associated infections","volume":"27","year":"2021","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.cmi.2020.09.025","article-title":"Understanding the role of bacterial and fungal infection in COVID-19","volume":"27","author":"Rawson","year":"2021","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/S0899-9007(02)00868-7","article-title":"Nosocomial infection and outcome","volume":"18","author":"Vincent","year":"2002","journal-title":"Nutrition"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"181","DOI":"10.3233\/JRS-200056","article-title":"COVID-19 and healthcare-associated infections","volume":"31","author":"Cioffi","year":"2020","journal-title":"Int. J. Risk Saf. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.cmi.2020.07.041","article-title":"Incidence of co-infections and superinfections in hospitalized patients with COVID-19: A retrospective cohort study","volume":"27","author":"Sanjuan","year":"2021","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/S0195-6701(03)00150-6","article-title":"The preventable proportion of nosocomial infections: An overview of published reports","volume":"54","author":"Harbarth","year":"2003","journal-title":"J. Hosp. Infect."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ijid.2022.02.041","article-title":"The impact of COVID-19 on health care-associated infections in intensive care units in low- and middle-income countries: International Nosocomial Infection Control Consortium (INICC) findings","volume":"118","author":"Rosenthal","year":"2022","journal-title":"Int. J. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s15010-021-01643-4","article-title":"Multidrug-resistant Acinetobacter baumannii infections in COVID-19 patients hospitalized in intensive care unit","volume":"50","author":"Russo","year":"2022","journal-title":"Infection"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.cmi.2022.10.023","article-title":"Effect of SARS-CoV-2 infection and pandemic period on healthcare-associated infections acquired in intensive care units","volume":"29","author":"Lepape","year":"2023","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_14","unstructured":"(2026, January 01). CDC\/NHSN Surveillance Definitions for Specific Types of Infections, Available online: https:\/\/www.cdc.gov\/nhsn\/pdfs\/pscmanual\/17pscnosinfdef_current.pdf."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1111\/j.1469-0691.2011.03570.x","article-title":"Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance","volume":"18","author":"Magiorakos","year":"2012","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1001\/jama.1996.03530350048033","article-title":"Nosocomial pneumonia and mortality among patients in intensive care units","volume":"275","author":"Fagon","year":"1996","journal-title":"J. Am. Med. Assoc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s00134-004-2544-6","article-title":"One-year mortality of bloodstream infection-associated sepsis and septic shock among patients presenting to a regional critical care system","volume":"31","author":"Laupland","year":"2005","journal-title":"Intensive Care Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.jiph.2011.12.004","article-title":"Point prevalence and risk factors of hospital acquired infections in a cluster of university-affiliated hospitals in Shiraz, Iran","volume":"5","author":"Askarian","year":"2012","journal-title":"J. Infect. Public Health"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Musuuza, J.S., Watson, L., Parmasad, V., Putman-Buehler, N., Christensen, L., and Safdar, N. (2021). Prevalence and outcomes of co-infection and superinfection with SARS-CoV-2 and other pathogens: A systematic review and metaanalysis. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0251170"},{"key":"ref_20","first-page":"5667","article-title":"Healthcare workers\u2019 hand hygiene knowledge and compliance evaluation, in a Greek university hospital","volume":"26","author":"Sinopidis","year":"2022","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1086\/664048","article-title":"Prevalence of healthcare-associated infections in acute care hospitals in Jacksonville, Florida","volume":"33","author":"Magill","year":"2012","journal-title":"Infect. Control. Hosp. Epidemiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1056\/NEJMoa1801550","article-title":"Changes in Prevalence of Health Care-Associated Infections in U.S. Hospitals","volume":"379","author":"Magill","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"29","DOI":"10.12659\/MSM.881750","article-title":"Nosocomial infections and risk factors in the intensive care unit of a teaching and research hospital: A prospecive cohort study","volume":"17","author":"Ak","year":"2011","journal-title":"Med. Sci. Monit."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.7150\/ijms.46614","article-title":"Factors associated with death outcome in patients with severe coronavirus disease-19 (COVID-19): A case-control study","volume":"17","author":"Pan","year":"2020","journal-title":"Int. J. Med. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s13756-021-00959-y","article-title":"The impact of the COVID-19 pandemic on healthcare-associated infections in intensive care unit patients: A retrospective cohort study","volume":"10","author":"Baccolini","year":"2021","journal-title":"Antimicrob. Resist. Infect. Control."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e13378","DOI":"10.1111\/eci.13378","article-title":"Features of severe COVID-19: A systematic review and meta-analysis","volume":"50","author":"Farcomeni","year":"2020","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1186\/s13054-020-03374-8","article-title":"Predictive values of neutrophil-to-lymphocyte ratio on disease severity and mortality in COVID-19 patients: A systematic review and meta-analysis","volume":"24","author":"Li","year":"2020","journal-title":"Crit. Care"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e211","DOI":"10.1017\/S0950268820002071","article-title":"Ratios of Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Predict All-Cause Mortality in Inpatients with Coronavirus Disease 2019 (COVID-19): A Retrospective Cohort Study in A Single Medical Center","volume":"148","author":"Wang","year":"2020","journal-title":"Epidemiol. Infect."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.chest.2020.10.014","article-title":"Global Impact of Coronavirus Disease 2019 Infection Requiring Admission to the ICU: A Systematic Review and Meta-analysis","volume":"159","author":"Tan","year":"2021","journal-title":"Chest"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/j.dsx.2020.06.064","article-title":"Coronavirus disease (COVID-19): A systematic review and meta-analysis to evaluate the impact of various comorbidities on serious events","volume":"14","author":"Nandy","year":"2020","journal-title":"Diabetes Metab. Syndr. Clin. Res. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"S61","DOI":"10.1093\/cid\/cix103","article-title":"Prevalence of Healthcare-Associated Infections and Antimicrobial Use Among Adult Inpatients in Singapore Acute-Care Hospitals: Results From the First National Point Prevalence Survey","volume":"64","author":"Cai","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1001\/jama.2009.1754","article-title":"International study of the prevalence and outcomes of infection in intensive care units","volume":"302","author":"Vincent","year":"2009","journal-title":"JAMA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.jhin.2008.08.009","article-title":"Risk factors for death in a cohort of patients with and without healthcare-associated infections in Finnish acute care hospitals","volume":"70","author":"Kanerva","year":"2008","journal-title":"J. Hosp. Infect."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"31","DOI":"10.3892\/ijmm.2021.4864","article-title":"Nosocomial infection of COVID-19: A new challenge for healthcare professionals (Review)","volume":"47","author":"Du","year":"2021","journal-title":"Int. J. Mol. Med."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/1\/118\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T11:33:40Z","timestamp":1767699220000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/1\/118"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,6]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["medicina62010118"],"URL":"https:\/\/doi.org\/10.3390\/medicina62010118","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,6]]}}}