Appropriateness of antibiotic use and mortality risk factors in moderate to severe COVID-19 patients admitted to the intensive care unit of Bali Mandara Hospital in 2021
Main Article Content
Keywords
COVID-19, Antibiotics, Mortality, Antimicrobial Stewardship, Gyssens
Abstract
Introduction: The COVID-19 pandemic has been closely linked to the overuse of antibiotics, particularly in hospitalized patients. Early clinical uncertainty and lack of definitive treatments led to widespread empiric use. This study assessed the appropriateness of antibiotic use and identified mortality risk factors among moderate to severe COVID-19 patients in Bali Mandara Hospital's ICU.
Methods: A retrospective cross-sectional study of 72 moderate to severe COVID-19 patients was conducted from 200 ICU admissions in 2021. Simple random sampling was used. Antibiotic appropriateness was assessed using the Gyssens method. Variables such as age, sex, severity, comorbidities (hypertension, diabetes), and culture results were analyzed using Chi-square tests.
Result: Among 322 antimicrobials, 226 were antibiotics. Gyssens' classification showed 40% appropriate use and 60% inappropriate use, mainly due to lack of indication (Category V). Age over 60, sex, and disease severity were significantly associated with mortality (p<0.05). Bacterial co-infection was confirmed in 30.6%, predominantly Enterobacteriaceae.
Conclusion: Antibiotic appropriateness remains low, with substantial overuse. Mortality correlated significantly with age, sex, and disease severity. These findings underscore the need for enhanced antimicrobial stewardship and targeted clinical management in cases of severe COVID-19.
References
1. Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia. New England Journal of Medicine [Internet]. 2020;382(13):1199–207. Available from: https://doi.org/10.1056/NEJMoa2001316
2. Silva ARO, Salgado DR, Lopes LPN, Castanheira D, Emmerick ICM, Lima EC. Increased Use of Antibiotics in the Intensive Care Unit During Coronavirus Disease (COVID-19) Pandemic in a Brazilian Hospital. Front Pharmacol. 2021;12(December):1–11.
3. CDC C for DC and P. COVID-19: U.S. Impact on Antimicrobial Resistance, Special Report 2022. 2022.
4. Witt LS, Howard-Anderson JR, Jacob JT, Gottlieb LB. The impact of COVID-19 on multidrug-resistant organisms causing healthcare-associated infections: A narrative review. JAC Antimicrob Resist [Internet]. 2023;5(1):1–9. Available from: https://doi.org/10.1093/jacamr/dlac130
5. Feldman C, Anderson R. The role of co-infections and secondary infections in patients with COVID-19. Pneumonia [Internet]. 2021;13(1). Available from: https://doi.org/10.1186/s41479-021-00083-w
6. Karlsson PA, Pärssinen J, Danielsson EA, Fatsis-Kavalopoulos N, Frithiof R, Hultström M, et al. Antibiotic use during coronavirus disease 2019 intensive care unit shape multidrug resistance bacteriuria: A Swedish longitudinal prospective study. Front Med (Lausanne) [Internet]. 2023;10(February):1–12. Available from: https://doi.org/10.3389/fmed.2023.1087446
7. Giamarellou H, Galani L, Karavasilis T, Ioannidis K, Karaiskos I. Antimicrobial Stewardship in the Hospital Setting: A Narrative Review. Antibiotics [Internet]. 2023;12(10). Available from: https://doi.org/10.3390/antibiotics12101557
8. Knight GM, Glover RE, McQuaid CF, Olaru ID, Gallandat K, Leclerc QJ, et al. Antimicrobial resistance and covid-19: Intersections and implications. Elife [Internet]. 2021;10:1–27. Available from: https://doi.org/https://doi.org/10.7554/eLife.64139
9. Oliveira M, Antunes W, Mota S, Madureira-Carvalho Á, Dinis-Oliveira RJ, Dias da Silva D. An Overview of the Recent Advances in Antimicrobial Resistance. Microorganisms [Internet]. 2024;12(9):1–50. Available from: https://doi.org/10.3390/microorganisms12091920
10. Bendala Estrada AD, Calderón Parra J, Fernández Carracedo E, Muiño Míguez A, Ramos Martínez A, Muñez Rubio E, et al. Inadequate use of antibiotics in the covid-19 era: effectiveness of antibiotic therapy. BMC Infect Dis [Internet]. 2021;21(1):1–23. Available from: https://doi.org/10.1186/s12879-021-06821-1
11. Lai C cheng, Chen S ying, Ko W chien, Hsueh P ren. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID- 19 . The COVID-19 resource centre is hosted on Elsevier Connect , the company ’ s public news and information. 2020;(January). Available from: https://doi.org/10.1016/j.ijantimicag.2021.106324
12. Langford BJ, So M, Raybardhan S, Leung V, Soucy J paul R, Westwood D, et al. Antibiotic prescribing in patients with COVID-19: rapid review and meta-analysis. Clinical Microbiology and Infection [Internet]. 2020;27(January):520–31. Available from: https://doi.org/10.1016/j.cmi.2020.12.018
13. Ture Z, Güner R, Alp E. Antimicrobial stewardship in the intensive care unit. Journal of Intensive Medicine [Internet]. 2023;3(3):244–53. Available from: https://doi.org/10.1016/j.jointm.2022.10.001
14. Taha I, Abdou Y, Hammad I, Nady O, Hassan G, Farid MF, et al. Utilization of Antibiotics for Hospitalized Patients with Severe Coronavirus Disease 2019 in Al-Madinah Al-Munawara, Saudi Arabia: A Retrospective Study. Infect Drug Resist [Internet]. 2022;15(December):7401–11. Available from: https://doi.org/10.2147/IDR.S386162
15. Russo A, Gavaruzzi F, Ceccarelli G, Borrazzo C, Oliva A, Alessandri F, et al. Multidrug-resistant Acinetobacter baumannii infections in COVID-19 patients hospitalized in intensive care unit. Infection [Internet]. 2022;50(1):83–92. Available from: https://doi.org/10.1007/s15010-021-01643-4
16. Grau S, Echeverria-Esnal D, Gómez-Zorrilla S, Navarrete-Rouco ME, Masclans JR, Espona M, et al. Evolution of antimicrobial consumption during the first wave of covid-19 pandemic. Antibiotics [Internet]. 2021;10(2):1–10. Available from: https://doi.org/ 10.3390/antibiotics10020132
17. Capuozzo M, Zovi A, Langella R, Ottaiano A, Cascella M, Scognamiglio M, et al. Optimizing Antibiotic Use: Addressing Resistance Through Effective Strategies and Health Policies. Antibiotics [Internet]. 2024;13(12):1–14. Available from: https://doi.org/10.3390/ antibiotics13121112
18. Van Der Meer JWM, Gyssens IC. Quality of antimicrobial drug prescription in hospital. Clinical Microbiology and Infection [Internet]. 2001;7(SUPPL. 6):12–5. Available from: http://dx.doi.org/10.1046/j.1469-0691.2001.00079.x
19. Alimohamadi Y, Yekta EM, Sepandi M, Sharafoddin M, Arshadi M, Hesari E. Hospital length of stay for COVID-19 patients: a systematic review and meta-analysis. Multidiscip Respir Med [Internet]. 2022;17. Available from: https://doi.org/10.4081/mrm.2022.856
20. Fluck D, Fry CH, Rankin S, Lewis A, Robin J, Rees J, et al. Does the length of stay in hospital affect healthcare outcomes of patients without COVID-19 who were admitted during the pandemic? A retrospective monocentric study. Intern Emerg Med [Internet]. 2022;17(5):1385–93. Available from: https://doi.org/10.1007/s11739-022-02945-7
21. Malik SS, Mundra S. Increasing Consumption of Antibiotics during the COVID-19 Pandemic: Implications for Patient Health and Emerging Antimicrobial Resistance. Antibiotics [Internet]. 2023;12(1). Available from: https://doi.org/10.3390/ antibiotics12010045%0AAcademic
22. Cong W, Stuart B, AIhusein N, Liu B, Tang Y, Wang H, et al. Antibiotic Use and Bacterial Infection in COVID-19 Patients in the Second Phase of the SARS-CoV-2 Pandemic: A Scoping Review. Antibiotics [Internet]. 2022;11(8). Available from: https://doi.org/10.3390/antibiotics11080991
23. Burhan E, Susanto AD, Isbaniah F, Nasution SA, Ginanjar E. PEDOMAN TATALAKSANA COVID-19. Jakarta: PDPI, PERKI, PAPDI, PERDATIN, IDAI; 2022.
24. Epstein L, Diekema DJ, Morgan DJ, Fakih MG, Lee F, Gottlieb L, et al. Diagnostic stewardship and the coronavirus disease 2019 (COVID-19) pandemic: Lessons learned for prevention of emerging infectious diseases in acute-care settings. Infect Control Hosp Epidemiol [Internet]. 2024;45(3):277–83. Available from: https://doi.org/10.1017/ice.2023.195
25. Dhesi Z, Enne VI, O’Grady J, Gant V, Livermore DM. Rapid and Point-of-Care Testing in Respiratory Tract Infections: An Antibiotic Guardian? ACS Pharmacol Transl Sci. 2020;3(3):401–17.
26. Patton MJ, Orihuela CJ, Harrod KS, Bhuiyan MAN, Dominic P, Kevil CG, et al. COVID-19 bacteremic co-infection is a major risk factor for mortality, ICU admission, and mechanical ventilation. Crit Care [Internet]. 2023;27(1):1–12. Available from: https://doi.org/10.1186/s13054-023-04312-0
27. Wang IE, Cooper G, Mousa SA. Diagnostic approaches for covid-19 and its associated complications. Diagnostics [Internet]. 2021;11(11). Available from: https://doi.org/10.3390/diagnostics11112071
28. Wu YC, Wong LT, Wu CL, Chao WC. The association between culture positivity and long-term mortality in critically ill surgical patients. J Intensive Care [Internet]. 2021;9(1):1–10. Available from: https://doi.org/10.1186/s40560-021-00576-2
29. Fitero A, Bungau SG, Tit DM, Endres L, Khan SA, Bungau AF, et al. Comorbidities, Associated Diseases, and Risk Assessment in COVID-19 - A Systematic Review. Int J Clin Pract [Internet]. 2022;2022. Available from: https://doi.org/10.1155/2022/1571826
30. Mustafa L, Tolaj I, Baftiu N, Fejza H. Use of antibiotics in COVID-19 ICU patients. J Infect Dev Ctries. 2021;15(4):501–5.
31. Kariyawasam RM, Julien DA, Jelinski DC, Larose SL, Rennert-May E, Conly JM, et al. Antimicrobial resistance (AMR) in COVID-19 patients: a systematic review and meta-analysis (November 2019–June 2021). Antimicrob Resist Infect Control [Internet]. 2022;11(1). Available from: https://doi.org/10.1186/s13756-022-01085-z
32. Chavda VP, Patel AB, Pandya A, Vora LK, Patravale V, Tambuwala ZM, et al. Co-infection associated with SARS-CoV-2 and their management. Future Sci OA [Internet]. 2022;8(9). Available from: https://doi.org/10.2144/fsoa-2022-0011
2. Silva ARO, Salgado DR, Lopes LPN, Castanheira D, Emmerick ICM, Lima EC. Increased Use of Antibiotics in the Intensive Care Unit During Coronavirus Disease (COVID-19) Pandemic in a Brazilian Hospital. Front Pharmacol. 2021;12(December):1–11.
3. CDC C for DC and P. COVID-19: U.S. Impact on Antimicrobial Resistance, Special Report 2022. 2022.
4. Witt LS, Howard-Anderson JR, Jacob JT, Gottlieb LB. The impact of COVID-19 on multidrug-resistant organisms causing healthcare-associated infections: A narrative review. JAC Antimicrob Resist [Internet]. 2023;5(1):1–9. Available from: https://doi.org/10.1093/jacamr/dlac130
5. Feldman C, Anderson R. The role of co-infections and secondary infections in patients with COVID-19. Pneumonia [Internet]. 2021;13(1). Available from: https://doi.org/10.1186/s41479-021-00083-w
6. Karlsson PA, Pärssinen J, Danielsson EA, Fatsis-Kavalopoulos N, Frithiof R, Hultström M, et al. Antibiotic use during coronavirus disease 2019 intensive care unit shape multidrug resistance bacteriuria: A Swedish longitudinal prospective study. Front Med (Lausanne) [Internet]. 2023;10(February):1–12. Available from: https://doi.org/10.3389/fmed.2023.1087446
7. Giamarellou H, Galani L, Karavasilis T, Ioannidis K, Karaiskos I. Antimicrobial Stewardship in the Hospital Setting: A Narrative Review. Antibiotics [Internet]. 2023;12(10). Available from: https://doi.org/10.3390/antibiotics12101557
8. Knight GM, Glover RE, McQuaid CF, Olaru ID, Gallandat K, Leclerc QJ, et al. Antimicrobial resistance and covid-19: Intersections and implications. Elife [Internet]. 2021;10:1–27. Available from: https://doi.org/https://doi.org/10.7554/eLife.64139
9. Oliveira M, Antunes W, Mota S, Madureira-Carvalho Á, Dinis-Oliveira RJ, Dias da Silva D. An Overview of the Recent Advances in Antimicrobial Resistance. Microorganisms [Internet]. 2024;12(9):1–50. Available from: https://doi.org/10.3390/microorganisms12091920
10. Bendala Estrada AD, Calderón Parra J, Fernández Carracedo E, Muiño Míguez A, Ramos Martínez A, Muñez Rubio E, et al. Inadequate use of antibiotics in the covid-19 era: effectiveness of antibiotic therapy. BMC Infect Dis [Internet]. 2021;21(1):1–23. Available from: https://doi.org/10.1186/s12879-021-06821-1
11. Lai C cheng, Chen S ying, Ko W chien, Hsueh P ren. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID- 19 . The COVID-19 resource centre is hosted on Elsevier Connect , the company ’ s public news and information. 2020;(January). Available from: https://doi.org/10.1016/j.ijantimicag.2021.106324
12. Langford BJ, So M, Raybardhan S, Leung V, Soucy J paul R, Westwood D, et al. Antibiotic prescribing in patients with COVID-19: rapid review and meta-analysis. Clinical Microbiology and Infection [Internet]. 2020;27(January):520–31. Available from: https://doi.org/10.1016/j.cmi.2020.12.018
13. Ture Z, Güner R, Alp E. Antimicrobial stewardship in the intensive care unit. Journal of Intensive Medicine [Internet]. 2023;3(3):244–53. Available from: https://doi.org/10.1016/j.jointm.2022.10.001
14. Taha I, Abdou Y, Hammad I, Nady O, Hassan G, Farid MF, et al. Utilization of Antibiotics for Hospitalized Patients with Severe Coronavirus Disease 2019 in Al-Madinah Al-Munawara, Saudi Arabia: A Retrospective Study. Infect Drug Resist [Internet]. 2022;15(December):7401–11. Available from: https://doi.org/10.2147/IDR.S386162
15. Russo A, Gavaruzzi F, Ceccarelli G, Borrazzo C, Oliva A, Alessandri F, et al. Multidrug-resistant Acinetobacter baumannii infections in COVID-19 patients hospitalized in intensive care unit. Infection [Internet]. 2022;50(1):83–92. Available from: https://doi.org/10.1007/s15010-021-01643-4
16. Grau S, Echeverria-Esnal D, Gómez-Zorrilla S, Navarrete-Rouco ME, Masclans JR, Espona M, et al. Evolution of antimicrobial consumption during the first wave of covid-19 pandemic. Antibiotics [Internet]. 2021;10(2):1–10. Available from: https://doi.org/ 10.3390/antibiotics10020132
17. Capuozzo M, Zovi A, Langella R, Ottaiano A, Cascella M, Scognamiglio M, et al. Optimizing Antibiotic Use: Addressing Resistance Through Effective Strategies and Health Policies. Antibiotics [Internet]. 2024;13(12):1–14. Available from: https://doi.org/10.3390/ antibiotics13121112
18. Van Der Meer JWM, Gyssens IC. Quality of antimicrobial drug prescription in hospital. Clinical Microbiology and Infection [Internet]. 2001;7(SUPPL. 6):12–5. Available from: http://dx.doi.org/10.1046/j.1469-0691.2001.00079.x
19. Alimohamadi Y, Yekta EM, Sepandi M, Sharafoddin M, Arshadi M, Hesari E. Hospital length of stay for COVID-19 patients: a systematic review and meta-analysis. Multidiscip Respir Med [Internet]. 2022;17. Available from: https://doi.org/10.4081/mrm.2022.856
20. Fluck D, Fry CH, Rankin S, Lewis A, Robin J, Rees J, et al. Does the length of stay in hospital affect healthcare outcomes of patients without COVID-19 who were admitted during the pandemic? A retrospective monocentric study. Intern Emerg Med [Internet]. 2022;17(5):1385–93. Available from: https://doi.org/10.1007/s11739-022-02945-7
21. Malik SS, Mundra S. Increasing Consumption of Antibiotics during the COVID-19 Pandemic: Implications for Patient Health and Emerging Antimicrobial Resistance. Antibiotics [Internet]. 2023;12(1). Available from: https://doi.org/10.3390/ antibiotics12010045%0AAcademic
22. Cong W, Stuart B, AIhusein N, Liu B, Tang Y, Wang H, et al. Antibiotic Use and Bacterial Infection in COVID-19 Patients in the Second Phase of the SARS-CoV-2 Pandemic: A Scoping Review. Antibiotics [Internet]. 2022;11(8). Available from: https://doi.org/10.3390/antibiotics11080991
23. Burhan E, Susanto AD, Isbaniah F, Nasution SA, Ginanjar E. PEDOMAN TATALAKSANA COVID-19. Jakarta: PDPI, PERKI, PAPDI, PERDATIN, IDAI; 2022.
24. Epstein L, Diekema DJ, Morgan DJ, Fakih MG, Lee F, Gottlieb L, et al. Diagnostic stewardship and the coronavirus disease 2019 (COVID-19) pandemic: Lessons learned for prevention of emerging infectious diseases in acute-care settings. Infect Control Hosp Epidemiol [Internet]. 2024;45(3):277–83. Available from: https://doi.org/10.1017/ice.2023.195
25. Dhesi Z, Enne VI, O’Grady J, Gant V, Livermore DM. Rapid and Point-of-Care Testing in Respiratory Tract Infections: An Antibiotic Guardian? ACS Pharmacol Transl Sci. 2020;3(3):401–17.
26. Patton MJ, Orihuela CJ, Harrod KS, Bhuiyan MAN, Dominic P, Kevil CG, et al. COVID-19 bacteremic co-infection is a major risk factor for mortality, ICU admission, and mechanical ventilation. Crit Care [Internet]. 2023;27(1):1–12. Available from: https://doi.org/10.1186/s13054-023-04312-0
27. Wang IE, Cooper G, Mousa SA. Diagnostic approaches for covid-19 and its associated complications. Diagnostics [Internet]. 2021;11(11). Available from: https://doi.org/10.3390/diagnostics11112071
28. Wu YC, Wong LT, Wu CL, Chao WC. The association between culture positivity and long-term mortality in critically ill surgical patients. J Intensive Care [Internet]. 2021;9(1):1–10. Available from: https://doi.org/10.1186/s40560-021-00576-2
29. Fitero A, Bungau SG, Tit DM, Endres L, Khan SA, Bungau AF, et al. Comorbidities, Associated Diseases, and Risk Assessment in COVID-19 - A Systematic Review. Int J Clin Pract [Internet]. 2022;2022. Available from: https://doi.org/10.1155/2022/1571826
30. Mustafa L, Tolaj I, Baftiu N, Fejza H. Use of antibiotics in COVID-19 ICU patients. J Infect Dev Ctries. 2021;15(4):501–5.
31. Kariyawasam RM, Julien DA, Jelinski DC, Larose SL, Rennert-May E, Conly JM, et al. Antimicrobial resistance (AMR) in COVID-19 patients: a systematic review and meta-analysis (November 2019–June 2021). Antimicrob Resist Infect Control [Internet]. 2022;11(1). Available from: https://doi.org/10.1186/s13756-022-01085-z
32. Chavda VP, Patel AB, Pandya A, Vora LK, Patravale V, Tambuwala ZM, et al. Co-infection associated with SARS-CoV-2 and their management. Future Sci OA [Internet]. 2022;8(9). Available from: https://doi.org/10.2144/fsoa-2022-0011