Prevalence of secondary infections, antimicrobial susceptibility and predictors for mortality among critically ill COVID 19 patients admitted to an Intensive Care Unit in India
Main Article Content
Abstract
Background: Critically ill COVID 19 patients requiring intensive care unit admission are at an increased risk of secondary infections owing to the need for invasive or non invasive oxygen therapy, prolonged indwelling catheters and long stay in intensive care unit. Secondary infections can further alter the clinical course and outcomes of these patients
Aims: In this study we aimed to investigate the prevalence, characteristics and factors associated with mortality in critically ill COVID 19 patients with secondary infections.
Methods: This was a single centre retrospective cohort study of adult critically ill COVID 19 patients admitted to the intensive care unit of a tertiary care hospital in India during one year period from May 2020 to April 2021.
Results: Among the 285 patients admitted to the intensive care unit 124 patients were identified with secondary infection. Out of the 250 isolates, 72.3% were gram negative bacilli with highest number of isolates recognised from blood (n=112, 44.8%). The most common organisms identified in our cohort were Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, Candida species and Enterococcus faecalis. Anti-microbial resistance was detected in 58.8% (n=147) of the isolates and majority of the patients received Carbapenem and Polymyxin. Patients with secondary infections were at increased risk of developing septic shock, acute kidney injury and also experienced higher mortality (50%, P-value <0.001). In our study cohort, increasing cumulative dose of steroids [OR 1.002, 95% CI: 1.001-1.004)] and increasing length of intensive care unit stay [OR 1.071, (95% CI: 1.030-1.113)] were found to be predictive of mortality among patients with secondary infection.
Conclusion: Secondary infections were high among the critically ill COVID 19 patients with high antimicrobial resistance and lead to high mortality. This being a single centre retrospective study, prospective evaluation with proper anti-microbial stewardship is needed for more precise results.
Keywords:
COVID 19, secondary infections, antimicrobial resistance, risk factors
Article Details
How to Cite
K, BabySailaja et al.
Prevalence of secondary infections, antimicrobial susceptibility and predictors for mortality among critically ill COVID 19 patients admitted to an Intensive Care Unit in India.
Medical Research Archives, [S.l.], v. 12, n. 8, aug. 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/5593>. Date accessed: 04 dec. 2024.
doi: https://doi.org/10.18103/mra.v12i8.5593.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. MacIntyre, C.R., Chughtai, A.A., Barnes, M. et al. The role of pneumonia and secondary bacterial infection in fatal and serious outcomes of pandemic influenza a(H1N1)pdm09. BMC Infect Dis 18, 637 (2018). https://doi.org/10.1186/s12879-018-3548-0
2. Saad M, Omrani AS, Baig K, Bahloul A, Elzein F, Matin MA, Selim MA, Al Mutairi M, Al Nakhli D, Al Aidaroos AY, Al Sherbeeni N. Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection: a single-center experience in Saudi Arabia. International journal of infectious diseases. 2014 Dec 1;29:301-6. https://doi.org/10.1016/j.ijid.2014.09.003
3. Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, Xie C, Ma K, Shang K, Wang W, Tian DS. Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China. Clinical infectious diseases. 2020 Jul 28;71(15):762-8. https://doi.org/10.1093/cid/ciaa248
4. Liu J, Liu Y, Xiang P, Pu L, Xiong H, Li C, Zhang M, Tan J, Xu Y, Song R, Song M. Neutrophil-to-lymphocyte ratio predicts critical illness patients with 2019 coronavirus disease in the early stage. Journal of translational medicine. 2020 Dec;18:1-2. https://doi.org/10.1186/s12967-020-02374-0
5. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. The lancet. 2020 Mar 28;395(10229):1033-4. https://doi.org/10.1016/S0140-6736(20)30628-0
6. RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19. New England Journal of Medicine. 2021 Feb 25;384(8):693-704. DOI: 10.1056/NEJMoa2021436
7. Langford BJ, So M, Raybardhan S, Leung V, Soucy JP, Westwood D, Daneman N, MacFadden DR. Antibiotic prescribing in patients with COVID-19: rapid review and meta-analysis. Clinical microbiology and infection. 2021 Apr 1;27(4):520-31. https://doi.org/10.1016/j.cmi.2020.12.018
8. Langford BJ, Soucy JP, Leung V, So M, Kwan AT, Portnoff JS, Bertagnolio S, Raybardhan S, MacFadden DR, Daneman N. Antibiotic resistance associated with the COVID-19 pandemic: a systematic review and meta-analysis. Clinical Microbiology and Infection. 2023 Mar 1;29(3):302-9. https://doi.org/10.1016/j.cmi.2022.12.006
9. Rehman S. A parallel and silent emerging pandemic: Antimicrobial resistance (AMR) amid COVID-19 pandemic. Journal of Infection and Public Health. 2023 Apr 1;16(4):611-7. https://doi.org/10.1016/j.jiph.2023.02.021
10. Petrakis V, Panopoulou M, Rafailidis P, Lemonakis N, Lazaridis G, Terzi I, Papazoglou D, Panagopoulos P. The impact of the COVID-19 pandemic on antimicrobial resistance and management of bloodstream infections. Pathogens. 2023 May 30;12(6):780. https://doi.org/10.3390/pathogens12060780
11. Sands KE, Blanchard EJ, Fraker S, Korwek K, Cuffe M. Health Care–Associated Infections Among Hospitalized Patients With COVID-19, March 2020-March 2022. JAMA Netw Open 2023;6(4):e238059. doi:10.1001/jamanetworkopen.2023.8059
12. Saini V, Jain C, Singh NP, Alsulimani A, Gupta C, Dar SA, Haque S, Das S. Paradigm shift in antimicrobial resistance pattern of bacterial isolates during the COVID-19 pandemic. Antibiotics. 2021 Aug 7;10(8):954. https://doi.org/10.3390/antibiotics10080954
13. Langford BJ, So M, Simeonova M, Leung V, Lo J, Kan T, Raybardhan S, Sapin ME, Mponponsuo K, Farrell A, Leung E. Antimicrobial resistance in patients with COVID-19: a systematic review and meta-analysis. The Lancet Microbe. 2023 Mar 1;4(3):e179-91. https://doi.org/10.1016/S2666-5247(22)00355-X
14. Yang X, Li X, Qiu S, Liu C, Chen S, Xia H, Zeng Y, Shi L, Chen J, Zheng J, Yang S. Global antimicrobial resistance and antibiotic use in COVID-19 patients within health facilities: a systematic review and meta-analysis of aggregated participant data. Journal of Infection. 2024 May 14:106183. https://doi.org/10.1016/j.jinf.2024.106183
15. Buetti, N., Ruckly, S., de Montmollin, E. et al. COVID-19 increased the risk of ICU-acquired bloodstream infections: a case–cohort study from the multicentric OUTCOMEREA network. Intensive Care Med 47, 180–187 (2021). https://doi.org/10.1007/s00134-021-06346-w
16. Li, J., Wang, J., Yang, Y. et al. Etiology and antimicrobial resistance of secondary bacterial infections in patients hospitalized with COVID-19 in Wuhan, China: a retrospective analysis. Antimicrob Resist Infect Control 9, 153 (2020). https://doi.org/10.1186/s13756-020-00819-1
17. Russell CD, Fairfield CJ, Drake TM, Turtle L, Seaton RA, Wootton DG, Sigfrid L, Harrison EM, Docherty AB, de Silva TI, Egan C. Co-infections, secondary infections, and antimicrobial use in patients hospitalised with COVID-19 during the first pandemic wave from the ISARIC WHO CCP-UK study: a multicentre, prospective cohort study. The Lancet Microbe. 2021 Aug 1;2(8):e354-65. https://doi.org/10.1016/S2666-5247(21)00090-2
18. Alshrefy AJ, Alwohaibi RN, Alhazzaa SA, et al. Incidence of Bacterial and Fungal Secondary Infections in COVID-19 Patients Admitted to the ICU. Int J Gen Med. 2022;15:7475-7485. Published 2022 Sep 24. doi:10.2147/IJGM.S382687
19. Zhang H, Zhang Y, Wu J, Li Y, Zhou X, Li X, Chen H, Guo M, Chen S, Sun F, Mao R. Risks and features of secondary infections in severe and critical ill COVID-19 patients. Emerging microbes & infections. 2020 Jan 1;9(1):1958-64. https://doi.org/10.1080/22221751.2020.1812437
20. De Bruyn, A., Verellen, S., Bruckers, L. et al. Secondary infection in COVID-19 critically ill patients: a retrospective single-center evaluation. BMC Infect Dis 22, 207 (2022). https://doi.org/10.1186/s12879-022-07192-x
21. Khurana S, Singh P, Sharad N, Kiro VV, Rastogi N, Lathwal A, Malhotra R, Trikha A, Mathur P. Profile of co-infections & secondary infections in COVID-19 patients at a dedicated COVID-19 facility of a tertiary care Indian hospital: Implication on antimicrobial resistance. Indian journal of medical microbiology. 2021 Apr 1;39(2):147-53. https://doi.org/10.1016/j.ijmmb.2020.10.014
22. Haque, Obaid I.1,; Shameem, Mohammad2; Hashim, Wamin3. Secondary infections in critically ill patients with COVID-19: A retrospective single-center study. Lung India 40(3):p 210-214, May–Jun 2023. DOI: 10.4103/lungindia.lungindia_293_22
23. Karuna T, Garg R, Kumar S, Singh G, Prasad L, Krishen Pandita K, Pakhare A, Saigal S, Khurana AK, Joshi R, Walia K. Clinico–Epidemio-Microbiological Exploratory Review Among COVID-19 Patients with Secondary Infection in Central India. Infection and Drug Resistance. 2022 Jan 1:1667-76. https://doi.org/10.2147/IDR.S355742
24. Boorgula SY, Yelamanchili S, Kottapalli P, Naga MD. An update on secondary bacterial and fungal infections and their antimicrobial resistance pattern (Amr) in COVID-19 confirmed patients. Journal of Laboratory Physicians. 2022 Sep;14(03):260-4. DOI: 10.1055/s-0041-1741438
25. Vijay S, Bansal N, Rao BK, Veeraraghavan B, Rodrigues C, Wattal C, Goyal JP, Tadepalli K, Mathur P, Venkateswaran R, Venkatasubramanian R. Secondary infections in hospitalized COVID-19 patients: Indian experience. Infection and drug resistance. 2021 May 24:1893-903. https://doi.org/10.2147/IDR.S299774
26. Ripa M, Galli L, Poli A, Oltolini C, Spagnuolo V, Mastrangelo A, Muccini C, Monti G, De Luca G, Landoni G, Dagna L. Secondary infections in patients hospitalized with COVID-19: incidence and predictive factors. Clinical Microbiology and Infection. 2021 Mar 1;27(3):451-7. https://doi.org/10.1016/j.cmi.2020.10.021
27. Signorini L, Moioli G, Calza S, Van Hauwermeiren E, Lorenzotti S, Del Fabro G, Renisi G, Lanza P, Saccani B, Zambolin G, Latronico N. Epidemiological and clinical characterization of superinfections in critically ill coronavirus disease 2019 patients. Critical care explorations. 2021 Jun 1;3(6):e0430 DOI: 10.1097/CCE.0000000000000430
28. Sanaie S, Rahnemayan S, Javan S, Shadvar K, Saghaleini SH, Mahmoodpoor A. Comparison of Closed vs Open Suction in Prevention of Ventilator-associated Pneumonia: A Systematic Review and Meta-analysis. Indian J Crit Care Med. 2022;26(7):839-845. https://doi.org/10.5005%2Fjp-journals-10071-24252
29. WHO Bacterial Priority Pathogens List, 2024: bacterial pathogens of public health importance to guide research, development and strategies to prevent and control antimicrobial resistance ISBN 978-92-4-009346-1 (electronic version) ISBN 978-92-4-009347-8 (print version)
30. Rouzé A, Martin-Loeches I, Povoa P, Makris D, Artigas A, Bouchereau M, Lambiotte F, Metzelard M, Cuchet P, Boulle Geronimi C, Labruyere M. Relationship between SARS-CoV-2 infection and the incidence of ventilator-associated lower respiratory tract infections: a European multicenter cohort study. Intensive care medicine. 2021 Feb;47:188-98. https://doi.org/10.1007/s00134-020-06323-9
31. Ritter LA, Britton N, Heil EL, Teeter WA, Murthi SB, Chow JH, Ricotta E, Chertow DS, Grazioli A, Levine AR. The impact of corticosteroids on secondary infection and mortality in critically ill COVID-19 patients. Journal of intensive care medicine. 2021 Oct;36(10):1201-8. https://doi.org/10.1177/08850666211032175
2. Saad M, Omrani AS, Baig K, Bahloul A, Elzein F, Matin MA, Selim MA, Al Mutairi M, Al Nakhli D, Al Aidaroos AY, Al Sherbeeni N. Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection: a single-center experience in Saudi Arabia. International journal of infectious diseases. 2014 Dec 1;29:301-6. https://doi.org/10.1016/j.ijid.2014.09.003
3. Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, Xie C, Ma K, Shang K, Wang W, Tian DS. Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China. Clinical infectious diseases. 2020 Jul 28;71(15):762-8. https://doi.org/10.1093/cid/ciaa248
4. Liu J, Liu Y, Xiang P, Pu L, Xiong H, Li C, Zhang M, Tan J, Xu Y, Song R, Song M. Neutrophil-to-lymphocyte ratio predicts critical illness patients with 2019 coronavirus disease in the early stage. Journal of translational medicine. 2020 Dec;18:1-2. https://doi.org/10.1186/s12967-020-02374-0
5. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. The lancet. 2020 Mar 28;395(10229):1033-4. https://doi.org/10.1016/S0140-6736(20)30628-0
6. RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19. New England Journal of Medicine. 2021 Feb 25;384(8):693-704. DOI: 10.1056/NEJMoa2021436
7. Langford BJ, So M, Raybardhan S, Leung V, Soucy JP, Westwood D, Daneman N, MacFadden DR. Antibiotic prescribing in patients with COVID-19: rapid review and meta-analysis. Clinical microbiology and infection. 2021 Apr 1;27(4):520-31. https://doi.org/10.1016/j.cmi.2020.12.018
8. Langford BJ, Soucy JP, Leung V, So M, Kwan AT, Portnoff JS, Bertagnolio S, Raybardhan S, MacFadden DR, Daneman N. Antibiotic resistance associated with the COVID-19 pandemic: a systematic review and meta-analysis. Clinical Microbiology and Infection. 2023 Mar 1;29(3):302-9. https://doi.org/10.1016/j.cmi.2022.12.006
9. Rehman S. A parallel and silent emerging pandemic: Antimicrobial resistance (AMR) amid COVID-19 pandemic. Journal of Infection and Public Health. 2023 Apr 1;16(4):611-7. https://doi.org/10.1016/j.jiph.2023.02.021
10. Petrakis V, Panopoulou M, Rafailidis P, Lemonakis N, Lazaridis G, Terzi I, Papazoglou D, Panagopoulos P. The impact of the COVID-19 pandemic on antimicrobial resistance and management of bloodstream infections. Pathogens. 2023 May 30;12(6):780. https://doi.org/10.3390/pathogens12060780
11. Sands KE, Blanchard EJ, Fraker S, Korwek K, Cuffe M. Health Care–Associated Infections Among Hospitalized Patients With COVID-19, March 2020-March 2022. JAMA Netw Open 2023;6(4):e238059. doi:10.1001/jamanetworkopen.2023.8059
12. Saini V, Jain C, Singh NP, Alsulimani A, Gupta C, Dar SA, Haque S, Das S. Paradigm shift in antimicrobial resistance pattern of bacterial isolates during the COVID-19 pandemic. Antibiotics. 2021 Aug 7;10(8):954. https://doi.org/10.3390/antibiotics10080954
13. Langford BJ, So M, Simeonova M, Leung V, Lo J, Kan T, Raybardhan S, Sapin ME, Mponponsuo K, Farrell A, Leung E. Antimicrobial resistance in patients with COVID-19: a systematic review and meta-analysis. The Lancet Microbe. 2023 Mar 1;4(3):e179-91. https://doi.org/10.1016/S2666-5247(22)00355-X
14. Yang X, Li X, Qiu S, Liu C, Chen S, Xia H, Zeng Y, Shi L, Chen J, Zheng J, Yang S. Global antimicrobial resistance and antibiotic use in COVID-19 patients within health facilities: a systematic review and meta-analysis of aggregated participant data. Journal of Infection. 2024 May 14:106183. https://doi.org/10.1016/j.jinf.2024.106183
15. Buetti, N., Ruckly, S., de Montmollin, E. et al. COVID-19 increased the risk of ICU-acquired bloodstream infections: a case–cohort study from the multicentric OUTCOMEREA network. Intensive Care Med 47, 180–187 (2021). https://doi.org/10.1007/s00134-021-06346-w
16. Li, J., Wang, J., Yang, Y. et al. Etiology and antimicrobial resistance of secondary bacterial infections in patients hospitalized with COVID-19 in Wuhan, China: a retrospective analysis. Antimicrob Resist Infect Control 9, 153 (2020). https://doi.org/10.1186/s13756-020-00819-1
17. Russell CD, Fairfield CJ, Drake TM, Turtle L, Seaton RA, Wootton DG, Sigfrid L, Harrison EM, Docherty AB, de Silva TI, Egan C. Co-infections, secondary infections, and antimicrobial use in patients hospitalised with COVID-19 during the first pandemic wave from the ISARIC WHO CCP-UK study: a multicentre, prospective cohort study. The Lancet Microbe. 2021 Aug 1;2(8):e354-65. https://doi.org/10.1016/S2666-5247(21)00090-2
18. Alshrefy AJ, Alwohaibi RN, Alhazzaa SA, et al. Incidence of Bacterial and Fungal Secondary Infections in COVID-19 Patients Admitted to the ICU. Int J Gen Med. 2022;15:7475-7485. Published 2022 Sep 24. doi:10.2147/IJGM.S382687
19. Zhang H, Zhang Y, Wu J, Li Y, Zhou X, Li X, Chen H, Guo M, Chen S, Sun F, Mao R. Risks and features of secondary infections in severe and critical ill COVID-19 patients. Emerging microbes & infections. 2020 Jan 1;9(1):1958-64. https://doi.org/10.1080/22221751.2020.1812437
20. De Bruyn, A., Verellen, S., Bruckers, L. et al. Secondary infection in COVID-19 critically ill patients: a retrospective single-center evaluation. BMC Infect Dis 22, 207 (2022). https://doi.org/10.1186/s12879-022-07192-x
21. Khurana S, Singh P, Sharad N, Kiro VV, Rastogi N, Lathwal A, Malhotra R, Trikha A, Mathur P. Profile of co-infections & secondary infections in COVID-19 patients at a dedicated COVID-19 facility of a tertiary care Indian hospital: Implication on antimicrobial resistance. Indian journal of medical microbiology. 2021 Apr 1;39(2):147-53. https://doi.org/10.1016/j.ijmmb.2020.10.014
22. Haque, Obaid I.1,; Shameem, Mohammad2; Hashim, Wamin3. Secondary infections in critically ill patients with COVID-19: A retrospective single-center study. Lung India 40(3):p 210-214, May–Jun 2023. DOI: 10.4103/lungindia.lungindia_293_22
23. Karuna T, Garg R, Kumar S, Singh G, Prasad L, Krishen Pandita K, Pakhare A, Saigal S, Khurana AK, Joshi R, Walia K. Clinico–Epidemio-Microbiological Exploratory Review Among COVID-19 Patients with Secondary Infection in Central India. Infection and Drug Resistance. 2022 Jan 1:1667-76. https://doi.org/10.2147/IDR.S355742
24. Boorgula SY, Yelamanchili S, Kottapalli P, Naga MD. An update on secondary bacterial and fungal infections and their antimicrobial resistance pattern (Amr) in COVID-19 confirmed patients. Journal of Laboratory Physicians. 2022 Sep;14(03):260-4. DOI: 10.1055/s-0041-1741438
25. Vijay S, Bansal N, Rao BK, Veeraraghavan B, Rodrigues C, Wattal C, Goyal JP, Tadepalli K, Mathur P, Venkateswaran R, Venkatasubramanian R. Secondary infections in hospitalized COVID-19 patients: Indian experience. Infection and drug resistance. 2021 May 24:1893-903. https://doi.org/10.2147/IDR.S299774
26. Ripa M, Galli L, Poli A, Oltolini C, Spagnuolo V, Mastrangelo A, Muccini C, Monti G, De Luca G, Landoni G, Dagna L. Secondary infections in patients hospitalized with COVID-19: incidence and predictive factors. Clinical Microbiology and Infection. 2021 Mar 1;27(3):451-7. https://doi.org/10.1016/j.cmi.2020.10.021
27. Signorini L, Moioli G, Calza S, Van Hauwermeiren E, Lorenzotti S, Del Fabro G, Renisi G, Lanza P, Saccani B, Zambolin G, Latronico N. Epidemiological and clinical characterization of superinfections in critically ill coronavirus disease 2019 patients. Critical care explorations. 2021 Jun 1;3(6):e0430 DOI: 10.1097/CCE.0000000000000430
28. Sanaie S, Rahnemayan S, Javan S, Shadvar K, Saghaleini SH, Mahmoodpoor A. Comparison of Closed vs Open Suction in Prevention of Ventilator-associated Pneumonia: A Systematic Review and Meta-analysis. Indian J Crit Care Med. 2022;26(7):839-845. https://doi.org/10.5005%2Fjp-journals-10071-24252
29. WHO Bacterial Priority Pathogens List, 2024: bacterial pathogens of public health importance to guide research, development and strategies to prevent and control antimicrobial resistance ISBN 978-92-4-009346-1 (electronic version) ISBN 978-92-4-009347-8 (print version)
30. Rouzé A, Martin-Loeches I, Povoa P, Makris D, Artigas A, Bouchereau M, Lambiotte F, Metzelard M, Cuchet P, Boulle Geronimi C, Labruyere M. Relationship between SARS-CoV-2 infection and the incidence of ventilator-associated lower respiratory tract infections: a European multicenter cohort study. Intensive care medicine. 2021 Feb;47:188-98. https://doi.org/10.1007/s00134-020-06323-9
31. Ritter LA, Britton N, Heil EL, Teeter WA, Murthi SB, Chow JH, Ricotta E, Chertow DS, Grazioli A, Levine AR. The impact of corticosteroids on secondary infection and mortality in critically ill COVID-19 patients. Journal of intensive care medicine. 2021 Oct;36(10):1201-8. https://doi.org/10.1177/08850666211032175