This observational retrospective study aimed to analyze whether/how the spectrum of bacterial pathogens and their resistance to antibiotics changed during the worst part of the COVID-19 pandemic (1 November 2020 to 30 April 2021) among intensive care patients in University Hospital Olomouc, Czech Republic, as compared with the pre-pandemic period (1 November 2018 to 30 April 2019). A total of 789 clinically important bacterial isolates from 189 patients were cultured during the pre-COVID-19 period. The most frequent etiologic agents causing nosocomial infections were strains of Klebsiella pneumoniae (17%), Pseudomonas aeruginosa (11%), Escherichia coli (10%), coagulase-negative staphylococci (9%), Burkholderia multivorans (8%), Enterococcus faecium (6%), Enterococcus faecalis (5%), Proteus mirabilis (5%) and Staphylococcus aureus (5%). Over the comparable COVID-19 period, a total of 1500 bacterial isolates from 372 SARS-CoV-2-positive patients were assessed. While the percentage of etiological agents causing nosocomial infections increased in Enterococcus faecium (from 6% to 19%, p < 0.0001), Klebsiella variicola (from 1% to 6%, p = 0.0004) and Serratia marcescens (from 1% to 8%, p < 0.0001), there were significant decreases in Escherichia coli (from 10% to 3%, p < 0.0001), Proteus mirabilis (from 5% to 2%, p = 0.004) and Staphylococcus aureus (from 5% to 2%, p = 0.004). The study demonstrated that the changes in bacterial resistance to antibiotics are ambiguous. An increase in the frequency of ESBL-positive strains of some species (Serratia marcescens and Enterobacter cloacae) was confirmed; on the other hand, resistance decreased (Escherichia coli, Acinetobacter baumannii) or the proportion of resistant strains remained unchanged over both periods (Klebsiella pneumoniae, Enterococcus faecium). Changes in pathogen distribution and resistance were caused partly due to antibiotic selection pressure (cefotaxime consumption increased significantly in the COVID-19 period), but mainly due to clonal spread of identical bacterial isolates from patient to patient, which was confirmed by the pulse field gel electrophoresis methodology. In addition to the above shown results, the importance of infection prevention and control in healthcare facilities is discussed, not only for dealing with SARS-CoV-2 but also for limiting the spread of bacteria.

Department of Anesthesiology Resuscitation and Intensive Care University Hospital Olomouc 1 P Pavlova 6 779 00 Olomouc Czech Republic

Department of Medical Biophysics Faculty of Medicine and Dentistry Palacky University Olomouc Hnevotinska 3 779 00 Olomouc Czech Republic

Department of Microbiology Faculty of Medicine and Dentistry Palacky University Olomouc Hnevotinska 3 779 00 Olomouc Czech Republic

Department of Microbiology University Hospital Olomouc 1 P Pavlova 6 779 00 Olomouc Czech Republic

Department of Pharmacology Faculty of Medicine and Dentistry Palacky University Olomouc Hnevotinska 3 779 00 Olomouc Czech Republic

Zobrazit více v PubMed

Situation by Region, Country, Territory & Area—WHO Coronavirus (COVID-19) Dashboard. [(accessed on 30 May 2022)]. Available online: https://covid19.who.int/table.

O’Neill J. Review on Antimicrobial Resistance Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations. The Review on Antimicrobial Resistance; London, UK: 2014. [(accessed on 20 July 2021)]. Available online: https://amr-review.org/sites/default/files/AMR%20Review%20Paper%20-%20Tackling%20a%20crisis%20for%20the%20health%20and%20wealth%20of%20nations_1.pdf.

Beadling C., Slifka M.K. How do viral infections predispose patients to bacterial infections? Curr. Opin. Infect. Dis. 2004;17:185–191. doi: 10.1097/00001432-200406000-00003. PubMed DOI

Metzger D.W., Sun K. Immune dysfunction and bacterial coinfections following influenza. J. Immunol. 2013;191:2047–2052. doi: 10.4049/jimmunol.1301152. PubMed DOI PMC

Jia L., Xie J., Zhao J., Cao D., Liang Y., Hou X., Ligui W., Li Z. Mechanisms of severe mortality-associated bacterial co-infections following influenza virus infection. Front. Cell Infect. Microbiol. 2017;7:338. doi: 10.3389/fcimb.2017.00338. PubMed DOI PMC

Katsurada N., Suzuki M., Aoshima M., Yaegashi M., Ishifuji T., Asoh N., Hamashige N., Abe M., Ariyoshi K., Morimoto K. on behalf of the Adult Pneumonia Study Group-Japan. The impact of virus infections on pneumonia mortality is complex in adults: A prospective multicentre observational study. BMC Infect. Dis. 2017;17:755. doi: 10.1186/s12879-017-2858-y. PubMed DOI PMC

Quah J., Jiang B., Tan P.C., Siau C., Tan T.Y. Impact of microbial aetiology on mortality in severe community-acquired pneumonia. BMC Infect. Dis. 2018;18:451. doi: 10.1186/s12879-018-3366-4. PubMed DOI PMC

Morris D.E., Cleary D.W., Clarke S.C. Secondary bacterial infections associated with influenza pandemics. Front. Microbiol. 2017;8:1041. doi: 10.3389/fmicb.2017.01041. PubMed DOI PMC

Rawson T.M., Moore L.S.P., Zhu N., Ranganathan N., Skolimowska K., Gilchrist M., Satta G., Cooke G., Holmes A. Bacterial and Fungal Coinfection in Individuals With Coronavirus: A Rapid Review To Support COVID-19 Antimicrobial Prescribing. Clin. Infect. Dis. 2020;71:2459–2468. doi: 10.1093/cid/ciaa530. PubMed DOI PMC

Langford B.J., So M., Raybardhan S., Leung V., Westwood D., MacFadden D.R., Soucy J.R., Daneman N. Bacterial co-infection and secondary infection in patients with COVID-19: A living rapid review and meta-analysis. Clin. Microbiol. Infect. 2020;26:1622–1629. doi: 10.1016/j.cmi.2020.07.016. PubMed DOI PMC

Lansbury L., Lim B., Baskaran V., Lim W.S. Co-infections in people with COVID-19: A systematic review and meta-analysis. J. Infect. 2020;81:266–275. doi: 10.1016/j.jinf.2020.05.046. PubMed DOI PMC

Hughes S., Troise O., Donaldson H., Mughal N., Moore L.S.P. Bacterial and fungal coinfection among hospitalized patients with COVID-19: A retrospective cohort study in a UK secondary-care setting. Clin. Microbiol. Infect. 2020;26:1395–1399. doi: 10.1016/j.cmi.2020.06.025. PubMed DOI PMC

Garcia-Vidal C., Sanjuan G., Moreno-García E., Puerta-Alcalde P., Garcia-Pouton N., Chumbita M., Fernandez-Pittol M., Pitart C., Inciarte A., Bodro M., et al. Incidence of co-infections and superinfections in hospitalised patients with COVID-19: A retrospective cohort study. Clin. Microbiol. Infect. 2020;27:83–88. doi: 10.1016/j.cmi.2020.07.041. PubMed DOI PMC

Vaughn V.M., Gandhi T.N., Petty L.A., Patel P.K., Prescott H.C., Malani A.N., Ratz D., McLaughlin E., Chopra V., Flanders S.A. Empiric antibacterial therapy and community-onset bacterial co-infection in patients hospitalized with COVID-19: A multi-hospital cohort study. Clin. Infect. Dis. 2020;72:e533–e541. doi: 10.1093/cid/ciaa1239. PubMed DOI PMC

Youngs J., Wyncoll D., Hopkins P., Arnold A., Ball J., Bicanic T. Improving antibiotic stewardship in COVID-19: Bacterial co-infection is less common than with influenza. J. Infect. 2020;81:e55–e57. doi: 10.1016/j.jinf.2020.06.056. PubMed DOI PMC

Clancy C.J., Nguyen M.H. COVID-19, superinfections and antimicrobial development: What can we expect? Clin. Infect. Dis. 2020;71:2736–2743. doi: 10.1093/cid/ciaa524. PubMed DOI PMC

World Health Organization Clinical management of COVID-19: Interim Guidance, 27 May 2020. [(accessed on 20 July 2021)]. Available online: https://apps.who.int/iris/handle/10665/332196.

Raoof S., Nava S., Carpati C., Hill N.S. High-Flow, Noninvasive Ventilation and Awake (Nonintubation) Proning in Patients With Coronavirus Disease 2019 With Respiratory Failure. Chest. 2020;158:1992–2002. doi: 10.1016/j.chest.2020.07.013. PubMed DOI PMC

Alhazzani W., Møller M.H., Arabi Y.M., Loeb M., Gong M.N., Fan E., Oczkowski S., Levy M.M., Derde L., Dzierba A., et al. Surviving Sepsis Campaign: Guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19) Intensive Care Med. 2020;46:854–887. doi: 10.1007/s00134-020-06022-5. PubMed DOI PMC

Zhang W., Du R.H., Li B., Zheng X.S., Yang X.L., Hu B., Wang Y.Y., Xiao G.F., Yan B., Shi Z.L., et al. Molecular and serological investigation of 2019-nCoV infected patients: Implication of multiple shedding routes. Emerg. Microbes Infect. 2020;9:386–389. doi: 10.1080/22221751.2020.1729071. PubMed DOI PMC

European Committee on Antimicrobial Susceptibility Testing Breakpoint Tables for Interpretation of MICs and Zone Diameters. [(accessed on 12 July 2021)]. Available online: http://www.eucast.org/clinical_breakpoints.

Htoutou Sedlakova M., Hanulik V., Chroma M., Hricova K., Kolar M., Latal T., Schaumann R., Rodloff A.C. Phenotypic detection of broad-spectrum beta-lactamases in microbiological practice. Med. Sci. Monit. 2011;17:BR147–BR152. doi: 10.12659/MSM.881761. PubMed DOI PMC

Tamma P.D., Simner P.J. Phenotypic detection of carbapenemase producing organisms from clinical isolates. J. Clin. Microbiol. 2018;56:e01140-18. doi: 10.1128/JCM.01140-18. PubMed DOI PMC

Oliveira D.C., de Lencastre H. Multiplex PCR strategy for rapid identification of structural types and variants of the mec element in methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 2002;46:2155–2161. doi: 10.1128/AAC.46.7.2155-2161.2002. PubMed DOI PMC

Dutka-Malen S., Evers S., Courvalin P. Detection of glycopeptide resistance genotypes and identification to the species level of clinically relevant enterococci by PCR. J. Clin. Microbiol. 1995;33:24–27. doi: 10.1128/jcm.33.1.24-27.1995. PubMed DOI PMC

Standard Operating Procedure for PulseNet PFGE of Escherichia coli O157:H7, Escherichia coli non-O157 (STEC), Salmonella serotypes, Shigella sonnei and Shigella flexneri. [(accessed on 12 July 2021)]; Available online: https://www.cdc.gov/pulsenet/pdf/ecoli-shigella-salmonella-pfge-protocol-508c.pdf.

Zakaria A.M., Hassuna N.A. Modified PFGE protocol for improving typeability of DNA degradation susceptible nosocomial Klebsiella pneumoniae. J. Med. Microbiol. 2019;68:1787–1792. doi: 10.1099/jmm.0.001093. PubMed DOI

Mahenthiralingam E., Campbell M.E., Henry D.A., Speert D.P. Epidemiology of Burkholderia cepacia infection in patients with cystic fibrosis: Analysis by randomly amplified polymorphic DNA fingerprinting. J. Clin. Microbiol. 1996;34:2914–2920. doi: 10.1128/jcm.34.12.2914-2920.1996. PubMed DOI PMC

WHO Collaborating Centre for Drug Statistics Methodology ATC/DDD Index. 2020. [(accessed on 15 July 2021)]. Available online: https://www.whocc.no/atc_ddd_index/

van Berkel M., Kox M., Frenzel T., Pickkers P., Schouten J., On behalf of the RCI-COVID-19 Study Group Biomarkers for antimicrobial stewardship: A reappraisal in COVID-19 times? Crit. Care. 2020;24:600. doi: 10.1186/s13054-020-03291-w. PubMed DOI PMC

Pink I., Raupach D., Fuge J., Vonberg R.P., Hoeper M.M., Welte T., Rademacher J. C-reactive protein and procalcitonin for antimicrobial stewardship in COVID-19. Infection. 2021;49:935–943. doi: 10.1007/s15010-021-01615-8. PubMed DOI PMC

Klein E.Y., Monteforte B., Gupta A., Jiang W., May L., Hsieh Y.H., Dugas A. The frequency of influenza and bacterial coinfection: A systematic review and meta-analysis. Influenza Other Respir. Viruses. 2016;10:394–403. doi: 10.1111/irv.12398. PubMed DOI PMC

Saini V., Jain C., Singh N.P., Alsulimani A., Gupta C., Dar S.A., Haque S., Das S. Paradigm Shift in Antimicrobial Resistance Pattern of Bacterial Isolates during the COVID-19 Pandemic. Antibiotics. 2021;10:954. doi: 10.3390/antibiotics10080954. PubMed DOI PMC

Li J., Wang J., Yang Y., Cai P., Cao J., Cai X. Etiology and antimicrobial resistance of secondary bacterial infections in patients hospitalized with COVID-19 in Wuhan, China: A retrospective analysis. Antimicrob. Resist. Infect. Control. 2020;9:153. doi: 10.1186/s13756-020-00819-1. PubMed DOI PMC

Porretta A.D., Baggiani A., Arzilli G., Casigliani V., Mariotti T., Mariottini F., Scardina G., Sironi D., Totaro M., Barnini S., et al. Increased risk of acquisition of New Delhi metallo-beta-lactamase-producing carbapenem-resistant Enterobacterales (NDM-CRE) among a cohort of COVID-19 patients in a teaching hospital in Tuscany, Italy. Pathogens. 2020;9:635. doi: 10.3390/pathogens9080635. PubMed DOI PMC

Tiri B., Sensi E., Marsiliani V., Cantarini M., Priante G., Vernelli C., Martella L.A., Costantini M., Mariottini A., Andreani P., et al. Antimicrobial stewardship program, COVID-19, and infection control: Spread of carbapenem-resistant Klebsiella pneumoniae colonization in ICU COVID-19 patients. What did not work? J. Clin. Med. 2020;9:2744. doi: 10.3390/jcm9092744. PubMed DOI PMC

Lai C.C., Chen S.Y., Ko W.C., Hsueh P.R. Increased antimicrobial resistance during the COVID-19 pandemic. Int. J. Antimicrob. Agents. 2021;57:106324. doi: 10.1016/j.ijantimicag.2021.106324. PubMed DOI PMC

Pascale R., Bussini L., Gaibani P., Bovo F., Fornaro G., Lombardo D., Giannella M. Carbapenem-resistant bacteria in an intensive care unit during the coronavirus disease 2019 (COVID-19) pandemic: A multicenter before-and-after cross-sectional study. Infect. Control. Hosp. Epidemiol. 2021;43:461–466. doi: 10.1017/ice.2021.144. PubMed DOI PMC

Bentivegna E., Luciani M., Arcari L., Santino I., Simmaco M., Martelletti P. Reduction of multidrug-resistant (MDR) bacterial infections during the COVID-19 pandemic: A retrospective study. Int. J. Environ. Res. Public Health. 2021;18:1003. doi: 10.3390/ijerph18031003. PubMed DOI PMC

Kolar M., Htoutou Sedlakova M., Urbanek K., Mlynarcik P., Roderova M., Hricova K., Mezerova K., Kucova P., Zapletalova J., Fiserova K., et al. Implementation of Antibiotic Stewardship in a University Hospital Setting. Antibiotics. 2021;10:93. doi: 10.3390/antibiotics10010093. PubMed DOI PMC

Martak D., Meunier A., Sauget M., Cholley P., Thouverez M., Bertrand X., Valot B., Hocquet D. Comparison of pulsed-field gel electrophoresis and whole-genome-sequencing-based typing confirms the accuracy of pulsed-field gel electrophoresis for the investigation of local Pseudomonas aeruginosa outbreaks. J. Hosp. Infect. 2020;105:643–647. doi: 10.1016/j.jhin.2020.06.013. PubMed DOI

Papajk J., Mezerová K., Uvízl R., Štosová T., Kolář M. Clonal Diversity of Klebsiella spp. and Escherichia spp. Strains Isolated from Patients with Ventilator-Associated Pneumonia. Antibiotics. 2021;10:674. doi: 10.3390/antibiotics10060674. PubMed DOI PMC

Pudová V., Htoutou Sedláková M., Kolář M., working group Clonality of Bacterial Pathogens Causing Hospital-Acquired Pneumonia. Curr. Microbiol. 2016;73:312–316. doi: 10.1007/s00284-016-1058-0. PubMed DOI

Hanulík V., Uvízl R., Husičková V., Htoutou Sedláková M., Kolář M. Pneumonia-causing bacterial pathogens in intensive care patients. Klin. Mikrobiol. Infekc. Lek. 2011;17:135–140. PubMed

García-Meniño I., Forcelledo L., Rosete Y., García-Prieto E., Escudero D., Fernández J. Spread of OXA-48-producing Klebsiella pneumoniae among COVID-19-infected patients: The storm after the storm. J. Infect. Public Health. 2021;14:50–52. doi: 10.1016/j.jiph.2020.11.001. PubMed DOI PMC

Durán-Manuel E.M., Cruz-Cruz C., Ibáñez-Cervantes G., Bravata-Alcantará J.C., Sosa-Hernández O., Delgado-Balbuena L., León-García G., Cortés-Ortíz I.A., Cureño-Díaz M.A., Castro-Escarpulli G., et al. Clonal dispersion of Acinetobacter baumannii in an intensive care unit designed to patients COVID-19. J. Infect. Dev. Ctries. 2021;15:58–68. doi: 10.3855/jidc.13545. PubMed DOI

Patel A., Emerick M., Cabunoc M.K., Williams M.H., Preas M.A., Schrank G., Rabinowitz R., Luethy P., Johnson J.K., Leekha S. Rapid Spread and Control of Multidrug-Resistant Gram-Negative Bacteria in COVID-19 Patient Care Units. Emerg. Infect. Dis. 2021;27:1234–1237. doi: 10.3201/eid2704.204036. PubMed DOI PMC

Bogdanová K., Doubravská L., Vágnerová I., Hricová K., Pudová V., Röderová M., Papajk J., Uvízl R., Langová K., Kolář M. Clostridioides difficile and Vancomycin-Resistant Enterococci in COVID-19 Patients with Severe Pneumonia. Life. 2021;11:1127. doi: 10.3390/life11111127. PubMed DOI PMC

Patel M., Gangemi A., Marron R., Chowdhury J., Yousef I., Zheng M., Mills N., Tragesser L., Giurintano J., Gupta R., et al. Retrospective analysis of high flow nasal therapy in COVID-19-related moderate-to-severe hypoxaemic respiratory failure. BMJ Open Respir. Res. 2020;7:e000650. doi: 10.1136/bmjresp-2020-000650. PubMed DOI PMC

World Health Organization Interim Guidance for the Clinical Management of COVID-19. [(accessed on 18 July 2021)]. Available online: https://www.who.int/publications/i/item/clinical-management-of-severe-acute-respiratory-infection-when-novel-coronavirus-(ncov)-infection-is-suspected/

Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. [(accessed on 18 July 2021)]; Available online: https://www.covid19treatmentguidelines.nih.gov/ PubMed

Australian Guidelines for the Clinical Care of People with COVID-19. [(accessed on 18 July 2021)]. Available online: https://covid19evidence.net.au/

Hui D.S., Hall S.D., Chan M.T.V., Chow B., Ng S.S., Gin T., Sung J.J.Y. Exhaled Air Dispersion During Oxygen Delivery Via a Simple Oxygen Mask. Chest. 2007;132:540–546. doi: 10.1378/chest.07-0636. PubMed DOI PMC

Ip M., Tang J.W., Hui D.S., Wong A.L.N., Chan M.T.V., Joynt G.M., So A.T.P., Hall S.D., Chan P.K.S., Sung J.J.Y. Airflow and droplet spreading around oxygen masks: A simulation model for infection control research. Am. J. Infect. Control. 2007;35:684–689. doi: 10.1016/j.ajic.2007.05.007. PubMed DOI PMC

Leung C.C.H., Joynt G.M., Gomersall C.D., Wong W.T., Lee A., Ling L., Chan P.K.S., Lui P.C.W., Tsoi P.C.Y., Ling C.M., et al. Comparison of high-flow nasal cannula versus oxygen face mask for environmental bacterial contamination in critically ill pneumonia patients: A randomized controlled crossover trial. J. Hosp. Infect. 2019;101:84–87. doi: 10.1016/j.jhin.2018.10.007. PubMed DOI

Kotoda M., Hishiyama S., Mitsui K., Tanikawa T., Morikawa S., Takamino A., Matsukawa T. Assessment of the potential for pathogen dispersal during high-flow nasal therapy. J. Hosp. Infect. 2020;104:534–537. doi: 10.1016/j.jhin.2019.11.010. PubMed DOI PMC

Jermy M.C., Spence C.J.T., Kirton R., O’Donnell J.F., Kabaliuk N., Gaw S., Hockey H., Jiang Y., Zulkhairi Abidin Z., Dougherty R.L., et al. Assessment of dispersion of airborne particles of oral/nasal fluid by high flow nasal cannula therapy. PLoS ONE. 2021;16:e0246123. doi: 10.1371/journal.pone.0246123. PubMed DOI PMC

Li J., Fink J.B., Ehrmann S. High-flow nasal cannula for COVID-19 patients: Risk of bio-aerosol dispersion. Eur. Respir. J. 2020;55:2000892. doi: 10.1183/13993003.00892-2020. PubMed DOI PMC

Elshof J., Hebbink R., Duiverman M.L., Hagmeijer R. High-flow nasal cannula for COVID-19 patients: Risk of bio-aerosol dispersion. Eur. Respir. J. 2020;56:2003004. doi: 10.1183/13993003.03004-2020. PubMed DOI PMC

Li J., Fink J.B., Ehrmann S. High-flow nasal cannula for COVID-19 patients: Risk of bio-aerosol dispersion. Eur. Respir. J. 2020;56:2003136. doi: 10.1183/13993003.03136-2020. PubMed DOI PMC

Somsen G.A., van Rijn C., Kooij S., Bem R.A., Bonn D. Small droplet aerosols in poorly ventilated spaces and SARS-CoV-2 transmission. Lancet Respir. Med. 2020;8:658–659. doi: 10.1016/S2213-2600(20)30245-9. PubMed DOI PMC

Macias A.E., Huertas M., de Leon S.P., Munoz J.M., Chavez A.R., Sifuentes-Osornio J., Romero C., Bobadilla M. Contamination of intravenous fluids: A continuing cause of hospital bacteremia. Am. J. Inf. Control. 2010;38:217–221. doi: 10.1016/j.ajic.2009.08.015. PubMed DOI

Yuen J.W.M., Chung T.W.K., Loke A.Y. Methicillin-Resistant Staphylococcus aureus (MRSA) Contamination in Bedside Surfaces of a Hospital Ward and the Potential Effectiveness of Enhanced Disinfection with an Antimicrobial Polymer Surfactant. Int. J. Environ. Res. Public Health. 2015;12:3026–3041. doi: 10.3390/ijerph120303026. PubMed DOI PMC

Shaban R.Z., Maloney S., Gerrard J., Collignon P., Macbeth D., Cruickshank M., Hume A., Jennison A.V., Graham R., Bergh H., et al. Outbreak of health care-associated Burkholderia cenocepacia bacteremia and infection attributed to contaminated sterile gel used for central line insertion under ultrasound guidance and other procedures. Am. J. Inf. Control. 2017;45:954–958. doi: 10.1016/j.ajic.2017.06.025. PubMed DOI

Bacterial Community- and Hospital-Acquired Pneumonia in Patients with Critical COVID-19-A Prospective Monocentric Cohort Study