The Changing Pattern of Bacterial and Fungal Respiratory Isolates in Patients with COVID-19 Admitted to Intensive Care Unit

The Changing Pattern of Bacterial and Fungal Respiratory Isolates in Patients with COVID-19 Admitted to Intensive Care Unit | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Changing Pattern of Bacterial and Fungal Respiratory Isolates in Patients with COVID-19 Admitted to Intensive Care Unit Gianluca Zuglian, Diego Ripamonti, Alessandra Tebaldi, Marina Cuntrò, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-924270/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 22 Feb, 2022 Read the published version in BMC Infectious Diseases → Version 1 posted 8 You are reading this latest preprint version Abstract Objectives Severe acute respiratory syndrome 2 (SARS-CoV-2) pandemic has had a heavy impact on national health system, especially in the first wave. That impact hit principally the Intensive Care Units (ICUs). The large number of patients requiring hospitalization in ICUs lead to a complete upheaval of intensive wards. The increase in bed, the fewer number of nurses per patient, the constant use of personal protective equipment, the new antimicrobial surveillance protocols could have had deeply effects on microbiological flora of these wards. Moreover, the overconsumption of antimicrobial therapy in COVID-19 patients, like several studies report, could have impact of this aspect. Aim of this study is to evaluate the changing pattern of microbiological epidemiology during and before COVID-19 pandemic in a tertirary hospital ICUs. Methods A retrospective, observational study was conducted in ICUs of “ASST Papa Giovanni XXIII”, a large tertiary referral hospital in Northern Italy. We have retrospectively collected the microbiological data from BAL and TA of patients hospitalized in ICUs from 22 nd February 2020 to 31 st May 2020 (Period 1) and from 22 nd February 2019 to 31 st May 2019 (Period 2). We compared the prevalence and the antibiotic profile of bacterial and fungal species in the two time periods. Results The prevalence of Pseudomonas spp. shows a statistically significant increase from period 2 to period 1, as well as the prevalence of Enterococcus spp. On the contrary, the prevalence of Gram negative non fermenting bacteria (GN-NFB), Haemophilus influenzae and Streptococcus pneumoniae showed a significant reduction between two periods. Therewas a statistically significant increase in resistance of Pseudomonas spp. to carbapenems and piperacillin/tazobactam and Enterobacterales spp. for piperacillin/tazobactam, in period 1 compared to period 2, respectively. Conclusions A changing pattern in prevalence and resistance profiles of bacterial and fungal species was observed during COVID-19 pandemic. Infectious Diseases bacterial and fungal respiratory COVID-19 intensive care unit SARS-CoV-2 national health system Introduction Severe acute respiratory syndrome 2 (SARS-CoV-2) has spread worldwide since 2019. Patients with SARS-CoV-2 infections may develop a severe form of coronavirus disease (COVID-19) requiring hospitalization and admission to intensive care units (ICU) in approximately 30% of them 1 . A large proportion of COVID-19 patients received antimicrobial therapy for proven or suspected co-bacterial infections during their ICU stay 2 and several studies have highlighted the antibiotic over-exposure in this population, despite the low rate of culture-proven bacterial co-infections 3 . This may be caused by several factors including the severity of COVID-19, the uncertainties about this new disease and the limitations of invasive diagnostic procedures due to the SARS-Cov-2 transmission precautions. Moreover, COVID-19 pandemic has represented an exceptional stress for the hospital setting, especially for the ICU setting, due to the overwhelming number of patients requiring a prolonged ICU stay. The above-mentioned factors may have affected the local fungal and bacterial epidemiology. The aim of this study is to describe the prevalence of bacterial and fungal species in a cohort of COVID-19 patients admitted to ICUs compared to the patients observed at the same hospital during the previous year (before the COVID-19 pandemic). Materials And Methods “ASST Papa Giovanni XXIII” is a large tertiary referral hospital (990 beds) placed in Bergamo, one of the most affected provinces during the COVID-19 pandemic in Northern Italy in 2020. During the COVID-19 pandemic, following the large number of patients admitted to ICU wards, a surveillance program with collection of respiratory specimens [i.e. bronchoalveolar lavages (BAL) or tracheal aspirates (TA)] was performed every 48-72 hours or weekly in all the patients, according the different intensive wards, while such procedures, in not COVID-19 patients, had been previously performed only in selected individuals and according to clinical judgment. We have retrospectively collected the microbiological data from BAL and TA of patients hospitalized in ICUs from 22nd February 2020 to 31st May 2020 (Period 1) and from 22nd February 2019 to 31st May 2019 (Period 2). We compared the prevalence of bacterial and fungal species in the two time periods. Then, we have categorized the most prevalent bacterial species potentially pathogenic of the respiratory tract ( Enterobacterales , Pseudomonas spp. and Staphylococcus aureus ) on the basis of their antibiotic resistant profile as multidrug resistant (MDR) for Enterobacterales and Pseudomonas spp., (according to definitions by Magiorakos at all 4 ) and methicillin resistant (MR) for Staphylococcus aureus (according to cefoxitin screening). In addition, we calculated the odds ratio (OD) whit 95% confidence interval (CI) to evaluate the difference of the prevalence of bacterial and fungal species and the resistant pathogens in the two study periods. Results A total of 194 patients were admitted to ICU with COVID-19 in period 1 (namely 65% of 297 patients admitted in ICU in that time period), compared to 176 patients who were admitted in period 2. A total of 736 samples (3.8 patient) and 392 (2.2 per patient) were collected during the period 1 and period 2, respectively. The proportion of positive respiratory specimens (for at least 1 pathogen, either bacterial or fungal) was 48% (355/736 samples) and 47.7% (187/392 samples) in period 1 and 2, respectively. Table 1 shows the prevalence of bacterial and fungal species by group. In both periods, the most frequent bacterial isolates were Pseudomonas spp. and Enterobacterales; The prevalence of Pseudomonas spp. shows a statistically significant increase from period 2 to period 1, as well as the prevalence of Enterococcus spp. On the contrary, the prevalence of Gram negative non fermenting bacteria (GN-NFB), Haemophilus influenzae and Streptococcus pneumoniae showed a significant reduction in period 2 versus period 1. Table 1 Prevalence of fungal and bacterial pathogens from respiratory samples. Period 1, 2020 (%) Period 2, 2019 (%) OR 95% CI CoNS 10 (2.3) 5 (1,7) 1.38 0.47-4.09 Enterobacterales 101 (22.9) 102 (33.7) 0.59 0.42-0.81 Enterococcus spp. 35 (7.9) 7 (2.3) 3.65 1.6-8.32 GN-NFB 12 (2.7) 19 (6.3) 0.42 0.2-0.88 Haemophilus spp. 1 (0.2) 11 (3.6) 0.06 0.01-0.47 Pseudomonas spp. 114 (25.9) 40 (13.2) 2.29 1.54-3.4 Staphylococcus aureus 50 (11.3) 37 (12.2) 0.92 0.59-1.45 Streptococcus spp. 3 (0.7) 9 (3.0) 0.22 0.06-0.83 Other pathogens 8 (1.8) 8 (2.6) 0.68 0.26-1.89 Aspergillus spp. 48 (10.9) 21 (6.9) 1.64 0.96-2.8 Candida spp. 59 (13.4) 44 (14.5) 0.73 0.6-1.39 Total 441 303 - - CoNS: coagulase negative staphylococci; GN-NFB: gram negative non fermenting bacteria. Table 2 compares the prevalence of resistant pathogens and the resistance profile for the antibiotic of interest. There were no statistically significant differences between the proportion of resistant pathogens in the two study periods. Nevertheless, there was a statistically significant increase in resistance of Pseudomonas spp. to carbapenems and piperacillin/tazobactam and Enterobacterales spp. for piperacillin/tazobactam, in period 1 compared to period 2, respectively. Table 2 prevalence of antibiotic resistant pathogens according to the antibiotic of interest. Period 1- 2020 (%) Period 2 - 2019 (%) OR 95% CI Pseudomonas spp. MDR 42 (36.8) 14 (35) 1.08 0.51-2.3 Pseudomonas spp. PIP/TZ-R 75 (65.8) 15 (37.5) 3.21 1.52-6.77 Pseudomonas spp. CARBA-R 60 (52.6) 10 (25) 3.33 1.49-7.45 Pseudomonas spp. CTZ/CEF-R 40 (35.1) 14 (35) 1 0.47-2.14 Enterobacterales MDR 33 (32.7) 34 (33.3) 0.97 0.54-1.74 Enterobacterales PIP/TZ-R 33 (327) 18 (17.6) 2.27 1.17-4.37 Enterobacterales CARBA-R 0 (0) 0 (0) - - Enterobacterales 3GC-R 16 (15.8) 18 (17.6) 0.88 0.42-1.84 MDR: multi drug resistant; PIP/TZ-R/S: piperacillin/tazobactam resistant/susceptible; CARBA-R/S: carbapenem resistant/susceptible; CTZ/CEF-R/S: ceftazidime/cefepime resistant/susceptible. Discussion We observed a variation of microbiological respiratory isolates before and during COVID-19 pandemic. In period 2, the prevalence of potentially pathogenic bacterial isolates from respiratory samples in ICU patients was aligned with the one of previous studies in the same settings 5 . In period 1, we observed the reduction of several bacterial species, especially Enterobacterales and the parallel increase of Pseudomonas spp. and Enterococcus spp. In the interpretation of this changing epidemiology, some observations may be useful. Firstly, the isolation of bacterial and fungal species does not necessary imply an active infection caused by these pathogens and, certainly, the systematic respiratory tract sampling, aimed to early intercept an infectious complication in the context of the SAR-CoV-2 pneumonia, may have led to an overestimation of microbiological events compared to a standard and less aggressive approach. Secondly, with regard to the changing epidemiology for Enterococcus spp. and Pseudomonas spp., the longer ICU stay for COVID-19 patients compared to the ones hospitalized for other causes 6 represents an important risk factor for colonization and/or infection caused by these bacteria 7,8 . Thirdly, the tropism for respiratory tract by Pseudomonas spp. is well known, especially in patients with underlying lung disease (such as cystic fibrosis and chronic obstructive pulmonary diseases 9 ). In a recent surveillance of VAP in COVID-19 patients, Pseudomonas aeruginosa was the most common pathogen responsible for ventilator‐associated lower respiratory tract infections 10 and the most common isolate in a population of critically ill patients hospitalized for influenza-associated ARDS 10 . We can speculate that the combination of the lung impairment by SARS-CoV-2 and the predisposition of Pseudomonas spp. could act synergistically to put these patients at risk for colonization/infection by this pathogen. Fourthly, most COVID-19 patients during ICU hospitalization received empirical antibiotic therapy 2 . In the ICU departments the antibiotics belonging to beta lactams class are the most widely used 11 . In our study, we observed a high resistance rate for this antibiotic class by Pseudomonas spp. and Enterobacterales in period 2, that was dramatically increased compared to period 1. We can speculate that the antibiotic pressure may have favored the emergence of resistant bacteria 12 . Fifthly, the decrease of other bacterial species associated to respiratory tract infections is consistent with the low incidence rate of co-bacterial infections in COVID-19 patient 13 and the global reduction of prevalence of other respiratory pathogens, secondary to the public health measures against COVID-19 14 . Sixthly, the high degree of immunosuppression induced by steroid therapy, used as salvage therapy in COVID-19 patients during ICU stay in the first wave, may have influenced the rate and the microbiological pattern of respiratory bacterial/fungal complications compared to period 2 15 . Lastly, as mentioned above, the clinical significance of the colonization of the respiratory tract has not been investigated as the aim of the study was to describe the changing microbiological scenario during the COVID-19 pandemic which may help designing the antimicrobial stewardship programs. Declarations Ethic approval and consent to participant All methods were carried out in accordance with Declaration of Helsinki. This study was approved by the ethics committee of The Papa Giovanni XXIII Hospital (Protocol N. 257/2020). To maintain the principle of confidentiality, the data used were anonymized. The need for informed consent was waived by the ethical Committee of the “Papa Giovanni XXIII” Hospital due to retrospective nature of the study. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Availability of data and materials The data that support the findings of this study are available from the corresponding author, upon request. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors Authors' contributions G.Z., D.R and A.T. conceived of the presented clinical research. M.C and I.R. collected the clinical and microbiological data. G.Z. and D.R. verified the analytical methods and wrote the manuscript. M.R. and C.F. supervised the findings of this work. All authors discussed the results and contributed to the final manuscript. Acknowledgements Not applicable. Ethics declarations The Ethical Committee of the “Papa Giovanni XXIII” Hospital approved the study. All patients were enrolled in accordance with the Helsinki declaration Conflict of interest The authors declare that they have no conflict of interests. References Huang, C. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet 395 , 497–506 (2020). Grau, S. et al. Evolution of antimicrobial consumption during the first wave of covid-19 pandemic. Antibiotics 10 , 1–10 (2021). Langford, B., So, M., Raybardhan, S., … V. L.-C. M. & 2021, undefined. Antibiotic prescribing in patients with COVID-19: rapid review and meta-analysis. Elsevier . Magiorakos, A.-P. et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. (2012) doi:10.1111/j.1469-0691.2011.03570.x. Enne, V. I., Personne, Y., Grgic, L., Gant, V. & Zumla, A. Aetiology of hospital-acquired pneumonia and trends in antimicrobial resistance. Current Opinion in Pulmonary Medicine vol. 20 252–258 (2014). Rees, E. M. et al. COVID-19 length of hospital stay: A systematic review and data synthesis. BMC Medicine vol. 18 270 (2020). Moses, V. et al. Enterococcal bacteremia is associated with prolonged stay in the medical intensive care unit. Journal of Global Infectious Diseases 4 , 26–30 (2012). Fernández-Barat, L. et al. Intensive care unit-acquired pneumonia due to Pseudomonas aeruginosa with and without multidrug resistance. Journal of Infection 74 , 142–152 (2017). Valderrey, A. D. et al. Chronic colonization by Pseudomonas aeruginosa of patients with obstructive lung diseases: Cystic fibrosis, bronchiectasis, and chronic obstructive pulmonary disease. Diagnostic Microbiology and Infectious Disease 68 , 20–27 (2010). Rouzé, A. et al. Relationship between SARS-CoV-2 infection and the incidence of ventilator-associated lower respiratory tract infections: a European multicenter cohort study. Intensive Care Medicine 47 , (2021). Malacarne, P., Rossi, C. & Bertolini, G. Antibiotic usage in intensive care units: A pharmaco-epidemiological multicentre study. Journal of Antimicrobial Chemotherapy 54 , 221–224 (2004). Kolář, M., Urbánek, K. & Látal, T. Antibiotic selective pressure and development of bacterial resistance. International Journal of Antimicrobial Agents 17 , 357–363 (2001). Adler, H., Ball, R., Fisher, M., Mortimer, K. & Vardhan, M. S. Low rate of bacterial co-infection in patients with COVID-19. The Lancet Microbe 1 , e62 (2020). Oster, Y. et al. Decreased prevalence rate of respiratory pathogens in hospitalized patients during the COVID-19 pandemic: possible role for public health containment measures? Clinical Microbiology and Infection vol. 0 (2021). Li, Y. et al. Corticosteroid therapy in critically ill patients with COVID-19: a multicenter, retrospective study. Critical Care 24 , 1–10 (2020). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 22 Feb, 2022 Read the published version in BMC Infectious Diseases → Version 1 posted Editorial decision: Major revision 29 Oct, 2021 Reviews received at journal 11 Oct, 2021 Reviewers agreed at journal 11 Oct, 2021 Reviewers invited by journal 11 Oct, 2021 Editor assigned by journal 11 Oct, 2021 Editor invited by journal 11 Oct, 2021 Submission checks completed at journal 11 Oct, 2021 First submitted to journal 21 Sep, 2021 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-924270","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":56134852,"identity":"a0d7f5aa-11ba-4f90-9a01-d844a6e92430","order_by":0,"name":"Gianluca Zuglian","email":"data:image/png;base64,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","orcid":"","institution":"Azienda Socio-Sanitaria Territoriale \"Papa Giovanni XXIII,\" Bergamo","correspondingAuthor":true,"prefix":"","firstName":"Gianluca","middleName":"","lastName":"Zuglian","suffix":""},{"id":56134854,"identity":"5b9d9062-93f9-47e2-bcf9-8b7855b670b0","order_by":1,"name":"Diego Ripamonti","email":"","orcid":"","institution":"Azienda Socio-Sanitaria Territoriale \"Papa Giovanni XXIII,\" Bergamo","correspondingAuthor":false,"prefix":"","firstName":"Diego","middleName":"","lastName":"Ripamonti","suffix":""},{"id":56134856,"identity":"6a2a5749-c8f1-409b-80c8-707b62339d8d","order_by":2,"name":"Alessandra Tebaldi","email":"","orcid":"","institution":"Azienda Socio-Sanitaria Territoriale \"Papa Giovanni XXIII,\" Bergamo","correspondingAuthor":false,"prefix":"","firstName":"Alessandra","middleName":"","lastName":"Tebaldi","suffix":""},{"id":56134857,"identity":"5a211845-897f-4c5b-9fa6-dea516da5085","order_by":3,"name":"Marina Cuntrò","email":"","orcid":"","institution":"Azienda Socio-Sanitaria Territoriale \"Papa Giovanni XXIII,\" Bergamo","correspondingAuthor":false,"prefix":"","firstName":"Marina","middleName":"","lastName":"Cuntrò","suffix":""},{"id":56134859,"identity":"089625cb-1212-4901-8e79-f2a614ff0b45","order_by":4,"name":"Ivano Riva","email":"","orcid":"","institution":"Azienda Socio-Sanitaria Territoriale \"Papa Giovanni XXIII,\" Bergamo","correspondingAuthor":false,"prefix":"","firstName":"Ivano","middleName":"","lastName":"Riva","suffix":""},{"id":56134860,"identity":"1832770d-6743-49c8-bcef-cf357ebb8c5f","order_by":5,"name":"Claudio Farina","email":"","orcid":"","institution":"Azienda Socio-Sanitaria Territoriale \"Papa Giovanni XXIII,\" Bergamo","correspondingAuthor":false,"prefix":"","firstName":"Claudio","middleName":"","lastName":"Farina","suffix":""},{"id":56134862,"identity":"0deae55c-d3e6-445c-8ec4-937e3cf8efe8","order_by":6,"name":"Marco Rizzi","email":"","orcid":"","institution":"Azienda Socio-Sanitaria Territoriale \"Papa Giovanni XXIII,\" Bergamo","correspondingAuthor":false,"prefix":"","firstName":"Marco","middleName":"","lastName":"Rizzi","suffix":""}],"badges":[],"createdAt":"2021-09-21 11:29:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-924270/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-924270/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12879-022-07176-x","type":"published","date":"2022-02-23T00:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":18725949,"identity":"f94632c9-b94e-4a90-8c90-c6d2af68d45d","added_by":"auto","created_at":"2022-03-01 10:14:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":325127,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-924270/v1/1d2054a4-0db6-4b2d-a0c5-873fc2f869da.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eThe Changing Pattern of Bacterial and Fungal Respiratory Isolates in Patients with COVID-19 Admitted to Intensive Care Unit\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSevere acute respiratory syndrome 2 (SARS-CoV-2) has spread worldwide since 2019. Patients with SARS-CoV-2 infections may develop a severe form of coronavirus disease (COVID-19) requiring hospitalization and admission to intensive care units (ICU) in approximately 30% of them\u003csup\u003e1\u003c/sup\u003e. A large proportion of COVID-19 patients received antimicrobial therapy for proven or suspected co-bacterial infections during their ICU stay\u003csup\u003e2\u003c/sup\u003e and several studies have highlighted the antibiotic over-exposure in this population, despite the low rate of culture-proven bacterial co-infections\u003csup\u003e3\u003c/sup\u003e. This may be caused by several factors including the severity of COVID-19, the uncertainties about this new disease and the limitations of invasive diagnostic procedures due to the SARS-Cov-2 transmission precautions. Moreover, COVID-19 pandemic has represented an exceptional stress for the hospital setting, especially for the ICU setting, due to the overwhelming number of patients requiring a prolonged ICU stay.\u003c/p\u003e \u003cp\u003eThe above-mentioned factors may have affected the local fungal and bacterial epidemiology. The aim of this study is to describe the prevalence of bacterial and fungal species in a cohort of COVID-19 patients admitted to ICUs compared to the patients observed at the same hospital during the previous year (before the COVID-19 pandemic).\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cp\u003e\u0026ldquo;ASST Papa Giovanni XXIII\u0026rdquo; is a large tertiary referral hospital (990 beds) placed in Bergamo, one of the most affected provinces during the COVID-19 pandemic in Northern Italy in 2020. During the COVID-19 pandemic, following the large number of patients admitted to ICU wards, a surveillance program with collection of respiratory specimens [i.e. bronchoalveolar lavages (BAL) or tracheal aspirates (TA)] was performed every 48-72 hours or weekly in all the patients, according the different intensive wards, while such procedures, in not COVID-19 patients, had been previously performed only in selected individuals and according to clinical judgment. We have retrospectively collected the microbiological data from BAL and TA of patients hospitalized in ICUs from 22nd February 2020 to 31st May 2020 (Period 1) and from 22nd February 2019 to 31st May 2019 (Period 2). We compared the prevalence of bacterial and fungal species in the two time periods. Then, we have categorized the most prevalent bacterial species potentially pathogenic of the respiratory tract (\u003cem\u003eEnterobacterales\u003c/em\u003e, \u003cem\u003ePseudomonas\u003c/em\u003e spp. and \u003cem\u003eStaphylococcus aureus\u003c/em\u003e) on the basis of their antibiotic resistant profile as multidrug resistant (MDR) for \u003cem\u003eEnterobacterales\u003c/em\u003e and \u003cem\u003ePseudomonas\u003c/em\u003e spp., (according to definitions by Magiorakos at all\u003csup\u003e4\u003c/sup\u003e) and methicillin resistant (MR) for \u003cem\u003eStaphylococcus aureus\u003c/em\u003e (according to cefoxitin screening). In addition, we calculated the odds ratio (OD) whit 95% confidence interval (CI) to evaluate the difference of the prevalence of bacterial and fungal species and the resistant pathogens in the two study periods.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 194 patients were admitted to ICU with COVID-19 in period 1 (namely 65% of 297 patients admitted in ICU in that time period), compared to 176 patients who were admitted in period 2. A total of 736 samples (3.8 patient) and 392 (2.2 per patient) were collected during the period 1 and period 2, respectively. The proportion of positive respiratory specimens (for at least 1 pathogen, either bacterial or fungal) was 48% (355/736 samples) and 47.7% (187/392 samples) in period 1 and 2, respectively.\u003c/p\u003e\n\u003cp\u003eTable \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e shows the prevalence of bacterial and fungal species by group. In both periods, the most frequent bacterial isolates were \u003cem\u003ePseudomonas\u003c/em\u003e spp. and \u003cem\u003eEnterobacterales;\u003c/em\u003e The prevalence of \u003cem\u003ePseudomonas\u003c/em\u003e spp. shows a statistically significant increase from period 2 to period 1, as well as the prevalence of \u003cem\u003eEnterococcus\u003c/em\u003e spp. On the contrary, the prevalence of Gram negative non fermenting bacteria (GN-NFB), \u003cem\u003eHaemophilus influenzae\u003c/em\u003e and \u003cem\u003eStreptococcus pneumoniae\u003c/em\u003e showed a significant reduction in period 2 versus period 1.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable border=\"1\" id=\"Tab1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003ePrevalence of fungal and bacterial pathogens from respiratory samples.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"5\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePeriod 1, 2020 (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePeriod 2, 2019 (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOR\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eCoNS\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10 (2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (1,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.47-4.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eEnterobacterales\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e101 (22.9)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e102 (33.7)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.59\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.42-0.81\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eEnterococcus\u003c/em\u003e spp.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e35 (7.9)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e7 (2.3)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e3.65\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.6-8.32\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGN-NFB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e12 (2.7)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e19 (6.3)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.42\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.2-0.88\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eHaemophilus\u003c/em\u003e spp.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e1 (0.2)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e11 (3.6)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.06\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.01-0.47\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ePseudomonas\u003c/em\u003e spp.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e114 (25.9)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e40 (13.2)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.29\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.54-3.4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eStaphylococcus aureus\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50 (11.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37 (12.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.59-1.45\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eStreptococcus\u003c/em\u003e spp.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e3 (0.7)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e9 (3.0)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.22\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.06-0.83\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOther pathogens\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.26-1.89\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eAspergillus\u003c/em\u003e spp.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e48 (10.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21 (6.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.96-2.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eCandida\u003c/em\u003e spp.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59 (13.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44 (14.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.6-1.39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e441\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e303\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003eCoNS: coagulase negative staphylococci; GN-NFB: gram negative non fermenting bacteria.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eTable \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e compares the prevalence of resistant pathogens and the resistance profile for the antibiotic of interest. There were no statistically significant differences between the proportion of resistant pathogens in the two study periods. Nevertheless, there was a statistically significant increase in resistance of \u003cem\u003ePseudomonas\u003c/em\u003e spp. to carbapenems and piperacillin/tazobactam and \u003cem\u003eEnterobacterales\u003c/em\u003e spp. for piperacillin/tazobactam, in period 1 compared to period 2, respectively.\u0026nbsp;\u003c/p\u003e\u0026nbsp;\u003ctable border=\"1\" id=\"Tab2\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eprevalence of antibiotic resistant pathogens according to the antibiotic of interest.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePeriod 1- 2020 (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePeriod 2 - 2019 (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOR\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ePseudomonas\u003c/em\u003e spp. MDR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42 (36.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14 (35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.51-2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ePseudomonas\u003c/em\u003e spp. PIP/TZ-R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e75 (65.8)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e15 (37.5)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e3.21\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.52-6.77\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ePseudomonas\u003c/em\u003e spp. CARBA-R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e60 (52.6)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e10 (25)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e3.33\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.49-7.45\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ePseudomonas\u003c/em\u003e spp. CTZ/CEF-R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40 (35.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14 (35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.47-2.14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eEnterobacterales\u003c/em\u003e MDR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33 (32.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.54-1.74\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eEnterobacterales\u003c/em\u003e PIP/TZ-R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e33 (327)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e18 (17.6)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.27\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.17-4.37\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eEnterobacterales\u003c/em\u003e CARBA-R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eEnterobacterales\u003c/em\u003e 3GC-R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16 (15.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18 (17.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.42-1.84\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003eMDR: multi drug resistant; PIP/TZ-R/S: piperacillin/tazobactam resistant/susceptible; CARBA-R/S: carbapenem resistant/susceptible; CTZ/CEF-R/S: ceftazidime/cefepime resistant/susceptible.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe observed a variation of microbiological respiratory isolates before and during COVID-19 pandemic. In period 2, the prevalence of potentially pathogenic bacterial isolates from respiratory samples in ICU patients was aligned with the one of previous studies in the same settings\u003csup\u003e5\u003c/sup\u003e. In period 1, we observed the reduction of several bacterial species, especially \u003cem\u003eEnterobacterales\u003c/em\u003e and the parallel increase of \u003cem\u003ePseudomonas\u003c/em\u003e spp. \u0026nbsp;and \u003cem\u003eEnterococcus\u003c/em\u003e spp.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn the interpretation of this changing epidemiology, some observations may be useful.\u003c/p\u003e\n\u003cp\u003eFirstly, the isolation of bacterial and fungal species does not necessary imply an active infection caused by these pathogens and, certainly, the systematic respiratory tract sampling, aimed to early intercept an infectious complication in the context of the SAR-CoV-2 pneumonia, may have led to an overestimation of microbiological events compared to a standard and less aggressive approach. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSecondly, with regard to the changing epidemiology for \u003cem\u003eEnterococcus\u003c/em\u003e spp. and \u003cem\u003ePseudomonas\u003c/em\u003e spp., the longer ICU stay for COVID-19 patients compared to the ones hospitalized for other causes\u003csup\u003e6\u003c/sup\u003e represents an important risk factor for colonization and/or infection caused by these bacteria \u003csup\u003e7,8\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThirdly, the tropism for respiratory tract by \u003cem\u003ePseudomonas\u003c/em\u003e spp. is well known, especially in patients with underlying lung disease (such as cystic fibrosis and chronic obstructive pulmonary diseases\u003csup\u003e9\u003c/sup\u003e). In a recent surveillance of VAP in COVID-19 patients, \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e was the most common pathogen responsible for ventilator‐associated lower respiratory tract infections\u003csup\u003e10\u003c/sup\u003e and the most common isolate in a population of critically ill patients hospitalized for influenza-associated ARDS\u003csup\u003e10\u003c/sup\u003e. We can speculate that the combination of the lung impairment by SARS-CoV-2 and the predisposition of \u003cem\u003ePseudomonas\u003c/em\u003e spp. could act synergistically to put these patients at risk for colonization/infection by this pathogen. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFourthly, most COVID-19 patients during ICU hospitalization received empirical antibiotic therapy\u003csup\u003e2\u003c/sup\u003e. In the ICU departments the antibiotics belonging to beta lactams class are the most widely used\u003csup\u003e11\u003c/sup\u003e. In our study, we observed a high resistance rate for this antibiotic class by \u003cem\u003ePseudomonas\u003c/em\u003e spp. and \u003cem\u003eEnterobacterales\u003c/em\u003e in period 2, that was dramatically increased compared to period 1. We can speculate that the antibiotic pressure may have favored the emergence of resistant bacteria\u003csup\u003e12\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFifthly, the decrease of other bacterial species associated to respiratory tract infections is consistent with the low incidence rate of co-bacterial infections in COVID-19 patient\u003csup\u003e13\u003c/sup\u003e and the global reduction of prevalence of other respiratory pathogens, secondary to the public health measures against COVID-19\u003csup\u003e14\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSixthly, the high degree of immunosuppression induced by steroid therapy, used as salvage therapy in COVID-19 patients during ICU stay in the first wave, may have influenced the rate and the microbiological pattern of respiratory bacterial/fungal complications compared to period 2\u003csup\u003e15\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLastly, as mentioned above, the clinical significance of the colonization of the respiratory tract has not been investigated as the aim of the study was to describe the changing microbiological scenario during the COVID-19 pandemic which may help designing \u003cs\u003ethe\u003c/s\u003e antimicrobial stewardship programs.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eEthic approval and consent to participant\u003c/h2\u003e\n\u003cp\u003eAll methods were carried out in accordance with Declaration of Helsinki. This study was approved by the ethics committee of The Papa Giovanni XXIII Hospital (Protocol N. 257/2020). To maintain the principle of confidentiality, the data used were anonymized. The need for informed consent was waived by the \u0026nbsp;ethical Committee of the \u0026ldquo;Papa Giovanni XXIII\u0026rdquo; Hospital due to retrospective nature of the study.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eConsent for publication\u003c/h2\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch2\u003eCompeting interests\u003c/h2\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003ch2\u003eAvailability of data and materials\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the corresponding author, upon request.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eFunding\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eAuthors\u0026apos; contributions\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eG.Z., D.R and A.T. conceived of the presented clinical research. M.C and I.R. collected the clinical and microbiological data. G.Z. and D.R. verified the analytical methods and wrote the manuscript. M.R. and C.F. supervised the findings of this work. All authors discussed the results and contributed to the final manuscript.\u003c/p\u003e\n\u003ch2\u003eAcknowledgements\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch2 id=\"isPasted\"\u003eEthics declarations\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eThe Ethical Committee of the \u003cem\u003e\u0026ldquo;Papa Giovanni XXIII\u0026rdquo; Hospital\u0026nbsp;\u003c/em\u003eapproved the study. All patients were enrolled in accordance with the Helsinki declaration\u003c/p\u003e\n\u003ch2\u003eConflict of interest\u003c/h2\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interests.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eHuang, C. \u003cem\u003eet al.\u003c/em\u003e Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. \u003cem\u003eThe Lancet\u003c/em\u003e \u003cstrong\u003e395\u003c/strong\u003e, 497\u0026ndash;506 (2020).\u003c/li\u003e\n \u003cli\u003eGrau, S. \u003cem\u003eet al.\u003c/em\u003e Evolution of antimicrobial consumption during the first wave of covid-19 pandemic. \u003cem\u003eAntibiotics\u003c/em\u003e \u003cstrong\u003e10\u003c/strong\u003e, 1\u0026ndash;10 (2021).\u003c/li\u003e\n \u003cli\u003eLangford, B., So, M., Raybardhan, S., \u0026hellip; V. L.-C. M. \u0026amp; 2021, undefined. Antibiotic prescribing in patients with COVID-19: rapid review and meta-analysis.\u003cem\u003eElsevier\u003c/em\u003e.\u003c/li\u003e\n \u003cli\u003eMagiorakos, A.-P. \u003cem\u003eet al.\u003c/em\u003e Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. (2012) doi:10.1111/j.1469-0691.2011.03570.x.\u003c/li\u003e\n \u003cli\u003eEnne, V. I., Personne, Y., Grgic, L., Gant, V. \u0026amp; Zumla, A. Aetiology of hospital-acquired pneumonia and trends in antimicrobial resistance. \u003cem\u003eCurrent Opinion in Pulmonary Medicine\u003c/em\u003e vol. 20 252\u0026ndash;258 (2014).\u003c/li\u003e\n \u003cli\u003eRees, E. M. \u003cem\u003eet al.\u003c/em\u003e COVID-19 length of hospital stay: A systematic review and data synthesis. \u003cem\u003eBMC Medicine\u003c/em\u003e vol. 18 270 (2020).\u003c/li\u003e\n \u003cli\u003eMoses, V. \u003cem\u003eet al.\u003c/em\u003e Enterococcal bacteremia is associated with prolonged stay in the medical intensive care unit. \u003cem\u003eJournal of Global Infectious Diseases\u003c/em\u003e \u003cstrong\u003e4\u003c/strong\u003e, 26\u0026ndash;30 (2012).\u003c/li\u003e\n \u003cli\u003eFern\u0026aacute;ndez-Barat, L. \u003cem\u003eet al.\u003c/em\u003e Intensive care unit-acquired pneumonia due to Pseudomonas aeruginosa with and without multidrug resistance. \u003cem\u003eJournal of Infection\u003c/em\u003e \u003cstrong\u003e74\u003c/strong\u003e, 142\u0026ndash;152 (2017).\u003c/li\u003e\n \u003cli\u003eValderrey, A. D. \u003cem\u003eet al.\u003c/em\u003e Chronic colonization by Pseudomonas aeruginosa of patients with obstructive lung diseases: Cystic fibrosis, bronchiectasis, and chronic obstructive pulmonary disease. \u003cem\u003eDiagnostic Microbiology and Infectious Disease\u003c/em\u003e \u003cstrong\u003e68\u003c/strong\u003e, 20\u0026ndash;27 (2010).\u003c/li\u003e\n \u003cli\u003eRouz\u0026eacute;, A. \u003cem\u003eet al.\u003c/em\u003e Relationship between SARS-CoV-2 infection and the incidence of ventilator-associated lower respiratory tract infections: a European multicenter cohort study. \u003cem\u003eIntensive Care Medicine\u003c/em\u003e \u003cstrong\u003e47\u003c/strong\u003e, (2021).\u003c/li\u003e\n \u003cli\u003eMalacarne, P., Rossi, C. \u0026amp; Bertolini, G. Antibiotic usage in intensive care units: A pharmaco-epidemiological multicentre study. \u003cem\u003eJournal of Antimicrobial Chemotherapy\u003c/em\u003e \u003cstrong\u003e54\u003c/strong\u003e, 221\u0026ndash;224 (2004).\u003c/li\u003e\n \u003cli\u003eKol\u0026aacute;ř, M., Urb\u0026aacute;nek, K. \u0026amp; L\u0026aacute;tal, T. Antibiotic selective pressure and development of bacterial resistance. \u003cem\u003eInternational Journal of Antimicrobial Agents\u003c/em\u003e \u003cstrong\u003e17\u003c/strong\u003e, 357\u0026ndash;363 (2001).\u003c/li\u003e\n \u003cli\u003eAdler, H., Ball, R., Fisher, M., Mortimer, K. \u0026amp; Vardhan, M. S. Low rate of bacterial co-infection in patients with COVID-19. \u003cem\u003eThe Lancet Microbe\u003c/em\u003e \u003cstrong\u003e1\u003c/strong\u003e, e62 (2020).\u003c/li\u003e\n \u003cli\u003eOster, Y. \u003cem\u003eet al.\u003c/em\u003e Decreased prevalence rate of respiratory pathogens in hospitalized patients during the COVID-19 pandemic: possible role for public health containment measures? \u003cem\u003eClinical Microbiology and Infection\u003c/em\u003e vol. 0 (2021).\u003c/li\u003e\n \u003cli\u003eLi, Y. \u003cem\u003eet al.\u003c/em\u003e Corticosteroid therapy in critically ill patients with COVID-19: a multicenter, retrospective study. \u003cem\u003eCritical Care\u003c/em\u003e \u003cstrong\u003e24\u003c/strong\u003e, 1\u0026ndash;10 (2020).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"bacterial and fungal respiratory, COVID-19 , intensive care unit, SARS-CoV-2, national health system","lastPublishedDoi":"10.21203/rs.3.rs-924270/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-924270/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjectives \u003c/strong\u003e\u003c/p\u003e\u003cp\u003eSevere acute respiratory syndrome 2 (SARS-CoV-2) pandemic has had a heavy impact on national health system, especially in the first wave. That impact hit principally the Intensive Care Units (ICUs). The large number of patients requiring hospitalization in ICUs lead to a complete upheaval of intensive wards. The increase in bed, the fewer number of nurses per patient, the constant use of personal protective equipment, the new antimicrobial surveillance protocols could have had deeply effects on microbiological flora of these wards. Moreover, the overconsumption of antimicrobial therapy in COVID-19 patients, like several studies report, could have impact of this aspect. Aim of this study is to evaluate the changing pattern of microbiological epidemiology during and before COVID-19 pandemic in a tertirary hospital ICUs.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods \u003c/strong\u003e\u003c/p\u003e\u003cp\u003eA retrospective, observational study was conducted in ICUs of “ASST Papa Giovanni XXIII”, a large tertiary referral hospital in Northern Italy. We have retrospectively collected the microbiological data from BAL and TA of patients hospitalized in ICUs from 22 \u003csup\u003end \u003c/sup\u003eFebruary 2020 to 31 \u003csup\u003est \u003c/sup\u003eMay 2020 (Period 1) and from 22 \u003csup\u003end \u003c/sup\u003eFebruary 2019 to 31 \u003csup\u003est \u003c/sup\u003eMay 2019 (Period 2). We compared the prevalence and the antibiotic profile of bacterial and fungal species in the two time periods.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults \u003c/strong\u003e\u003c/p\u003e\u003cp\u003eThe prevalence of \u003cem\u003ePseudomonas \u003c/em\u003espp. shows a statistically significant increase from period 2 to period 1, as well as the prevalence of \u003cem\u003eEnterococcus \u003c/em\u003espp. On the contrary, the prevalence of Gram negative non fermenting bacteria (GN-NFB), \u003cem\u003eHaemophilus influenzae \u003c/em\u003eand \u003cem\u003eStreptococcus pneumoniae \u003c/em\u003eshowed a significant reduction between two periods. Therewas a statistically significant increase in resistance of \u003cem\u003ePseudomonas \u003c/em\u003espp. to carbapenems and piperacillin/tazobactam and \u003cem\u003eEnterobacterales \u003c/em\u003espp. for piperacillin/tazobactam, in period 1 compared to period 2, respectively.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions \u003c/strong\u003e\u003c/p\u003e\u003cp\u003eA changing pattern in prevalence and resistance profiles of bacterial and fungal species was observed during COVID-19 pandemic.\u003c/p\u003e","manuscriptTitle":"The Changing Pattern of Bacterial and Fungal Respiratory Isolates in Patients with COVID-19 Admitted to Intensive Care Unit","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-10-26 14:16:18","doi":"10.21203/rs.3.rs-924270/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2021-10-29T18:52:59+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2021-10-11T10:51:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"4b0a837d-4fb7-4431-a6aa-afbc410d921f","date":"2021-10-11T09:57:04+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2021-10-11T09:55:29+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2021-10-11T09:49:18+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2021-10-11T07:25:43+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2021-10-11T07:22:36+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2021-09-21T11:23:54+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"61496d9b-bf2e-4e7f-a4ed-18e8a19f5541","owner":[],"postedDate":"October 26th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":8100125,"name":"Infectious Diseases"}],"tags":[],"updatedAt":"2022-03-01T10:14:05+00:00","versionOfRecord":{"articleIdentity":"rs-924270","link":"https://doi.org/10.1186/s12879-022-07176-x","journal":{"identity":"bmc-infectious-diseases","isVorOnly":false,"title":"BMC Infectious Diseases"},"publishedOn":"2022-02-23 00:00:00","publishedOnDateReadable":"February 23rd, 2022"},"versionCreatedAt":"2021-10-26 14:16:18","video":"","vorDoi":"10.1186/s12879-022-07176-x","vorDoiUrl":"https://doi.org/10.1186/s12879-022-07176-x","workflowStages":[]},"version":"v1","identity":"rs-924270","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-924270","identity":"rs-924270","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}