COVID-19 and antibacterial therapy in the inpatient settings: to whom, when, why?

Although antibiotics (ABs) are ineffective against COVID-19, they are often prescribed to patients with the new coronavirus infection. Many of these prescriptions are uncalled for.

The aim of the work is to assess the frequency of prescribing antibiotics to hospitalized patients with confirmed COVID-19, identify the most commonly prescribed ABs, and determine the significance of various biomarkers for the diagnosis of bacterial infection.

Methods. A retrospective analysis of 190 inpatient cases with confirmed COVID-19 was carried out. The records of COVID-19 patients who were admitted to the intensive care unit were excluded from the analysis. Two groups were formed: 30 patients (group 1) with COVID-19, emergency or elective surgery, and exacerbation of chronic infectious diseases, and 160 patients (group 2) with manifestations of COVID-19 only.

Results. ABs were prescribed to 189 patients upon admission to the hospital. The most frequently prescribed ABs included macrolides (63.5%), respiratory fluoroquinolones (49.7%), and third or fourth-generation cephalosporins (57.1%). ABs were administered starting from the first day of admission and until the discharge. The patients in group 2 were more often prescribed respiratory fluoroquinolones and, less often, III - IV generation cephalosporins. Moreover, macrolides were used in the treatment regimens of both groups. Longer administration of respiratory fluoroquinolones to patients in group 2 than patients in group 1 (p < 0,05) was noted. Group 2 also tended to receive longer therapy with macrolides. On admission, the patients with signs of bacterial infection had more significant leukocytosis with a neutrophilic shift, a more common increase in ESR of more than 20 mm/h and an increase in the level of procalcitonin > 0,5 ng/ml.

Conclusion. ABs were administered to the overwhelming majority of hospitalized patients in the absence of clear therapeutic indications. The ABs are likely to have a minimal benefit as empirical treatment of COVID-19 and are associated with unintended consequences, including adverse effects and increased antibiotic resistance. According to our data, the most informative markers of a secondary bacterial infection in patients with COVID-19 are leukocytosis with a neutrophilic shift, an increase in ESR of more than 20 mm/h, and a procalcitonin level of more than 0,5 ng/ml.

1. Lu R., Zhao X., Li J. et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020; 395 (10224): 565-574. DOI: 10.1016/s0140-6736(20)30251-8.

2. Wang Z., Yang B., Li Q. et al. Clinical features of 69 cases with coronavirus disease 2019 in Wuhan, China. Clin. Infect. Dis. 2020; 71 (15): 769-777. DOI: 10.1093/cid/ciaa272.

3. Cevik M., Bamford C.G.G., Ho A. COVID-19 pandemic - a focused review for clinicians. Clin. Microbiol. Infect. 2020; 26 (7): 842-847. DOI: 10.1016/j.cmi.2020.04.023.

4. World Health Organization. Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected: interim guidance, 13 March 2020. Available at: https://apps.who.int/iris/handle/10665/331446 [Accessed: August 18, 2021].

5. Guan W.J., Ni Z.Y., Hu Y. et al. Clinical characteristics of coronavirus disease 2019 in China. N. Engl. J. Med. 2020; 382 (18): 1708-1720. DOI: 10.1056/NEJMoa2002032.

6. Joseph C., Togawa Y., Shindo N. Bacterial and viral infections associated with influenza. Influenza Other Respir. Viruses. 2013; 7 (Suppl. 2): 105-113. DOI: 10.1111/irv.12089.

7. Assiri A., Al-Tawfiq J.A., Al-Rabeeah A.A. et al. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study. Lancet Infect. Dis. 2013; 13 (9): 752-761. DOI: 10.1016/S1473-3099(13)70204-4.

8. Zahariadis G., Gooley T.A., Ryall P. et al. Risk of ruling out severe acute respiratory syndrome by ruling in another diagnosis: variable incidence of atypical bacteria coinfection based on diagnostic assays. Can. Resp. J. 2006; 13 (1): 17-22. DOI: 10.1155/2006/862797.

9. Zhang J., Wang X., Jia X. et al. Risk factors for disease severity, unimprovement, and mortality in COVID-19 patients in Wuhan, China. Clin. Microbiol. Infect. 2020; 26 (6): 767-772. DOI: 10.1016/j.cmi.2020.04.012.

10. Zhou F., Yu T., Du R. et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020; 395 (10229): 1054-1062. DOI: 10.1016/s0140-6736(20)30566-3.

11. Information letter MASRM. [COVID-19. Discussion of controversial questions related to the changes in the lungs caused by the virus, and approaches to the treatment. 2020]. Available at: https://www.antibiotics-chemotherapy.ru/jour/announcement/view/394?locale=ru_RU [Accessed: August 18, 2021] (in Russian).

12. Ministry of Health of the Russian Federation. [The Temporary Guidelines: Prevention, diagnosis and treatment of new coronavirus infection (COVID-19). Version 11 (May 05, 2021)]. Available at: https://static-0.minzdrav.gov.ru/system/attachments/attaches/000/055/735/original/B%D0%9C%D0%A0_COVID-19.pdf [Accessed: August 18, 2021] (in Russian).

13. Clancy C.J., Nguyen M.H. Coronavirus disease 19, superinfections, and antimicrobial development: what can we expect? Clin. Infect. Dis. 2020; 71 (10): 2736-2743. DOI: 10.1093/cid/ciaa524.

14. 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 (2): 266-275. DOI: 10.1016/j.jinf.2020.05.046.

15. Youngs J., Wyncoll D., Hopkins P. et al. Improving antibiotic stewardship in COVID-19: bacterial co-infection is less common than with influenza. J. Infect. 2020; 81 (3): e55—57. DOI: 10.1016/j.jinf.2020.06.056.

16. Dhesi Z., Enne V.I., Brealey D. et al. Organisms causing secondary pneumonia in COVID-19 patients in 5 UK ICUs as detected with the FilmArray test. Available at: https://www.medrxiv.org/content/10.1101/2020.06.22.20131573v1.full.pdf [Accessed: August 18, 2021].

17. Seaton R.A., Gibbons C.L., Cooper L. et al. Survey of antibiotic and antifungal prescribing in patients with suspected and confirmed COVID-19 in Scottish hospitals. J. Infect. 2020; 81 (6): 952—960. DOI: 10.1016/j.jinf.2020.09.024.

18. Russell C.D., Fairfield C.J., Drake T.M. et al. 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. Lancet Microbe. 2021; 2 (8): e354—365. DOI: 10.1016/S2666-5247(21)00090-2.

19. Karami Z., Knoop B.T., Dofferhoff A.S.M. et al. Few bacterial co-infections but frequent empiric antibiotic use in the early phase of hospitalized patients with COVID-19: results from a multicentre retrospective cohort study in The Netherlands. Infect. Dis. (Lond.). 2021; 53 (2): 102—110. DOI: 10.1080/23744235.2020.1839672.

20. Hughes S., Troise O., Donaldson H. et al. 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 (10): 1395—1399. DOI: 10.1016/j.cmi.2020.06.025.

21. Garcia-Vidal C., Sanjuan G., Moreno-Garcia E. et al. Incidence of co-infections and superinfections in hospitalised patients with COVID-19: a retrospective cohort study. Clin. Microbiol. Infect. 2021; 27 (1): 83—88. DOI: 10.1016/j.cmi.2020.07.041.

22. Vaughn V.M., Gandhi T.N., Petty L.A. et al. Empiric antibacterial therapy and community-onset bacterial coinfection in patients hospitalized with coronavirus disease 2019 (COVID-19): a multi-hospital cohort study. Clin. Infect. Dis. 2021; 72 (10): e533—541. DOI: 10.1093/cid/ciaa1239.

23. Rawson T.M., Moore L.P., Zhu N. et al. Bacterial and fungal coinfection in individuals with coronavirus: a rapid review to support COVID-19 antimicrobial prescribing. Clin. Infect. Dis. 2020; 71 (9): 2459—2468. DOI: 10.1093/cid/ciaa530.

24. Langford B.J., So M., Raybardhan S. et al. Bacterial co-infection and secondary infection in patients with COVID-19: a living rapid review and meta-analysis. Clin. Microbiol. Infect. 2020; 26 (12): 1622—1629. DOI: 10.1016/j.cmi.2020.07.016.

25. Langford B.J., So M., Raybardhan S. е! al. Antibiotic prescribing in patients with COVID-19: rapid review and meta-analysis. Clin. Microbiol. Infect. 2021; 27 (4): 520—531. DOI: 10.1016/j.cmi.2020.12.018.

26. Rothe K., Feihl S., Schneider J. et al. Rates of bacterial co-infections and antimicrobial use in COVID-19 patients: a retrospective cohort study in light of antibiotic stewardship. Eur. J. Clin. Microbiol. Infect. Dis. 2021; 40 (4): 859—869. DOI: 10.1007/s10096-020-04063-8.

27. Al-Kuraishy H.M., Al-Naimi M.S., Lungnier C.M., Al-Gareeb A.I. Macrolides and COVID-19: an optimum premise. Biomed. Biotechnol. Res. J. 2020; 4 (3): 189—192. DOI: 10.4103/bbrj.bbrj_103_20.

28. Mason J.W. Antimicrobials and QT prolongation. J. Antimicrob. Chemother. 2017; 72 (5): 1272—1274. DOI: 10.1093/jac/dkw591.

29. Kim D., Quinn J., Pinsky B. е1 al. Rates of co-infection between SARS-CoV-2 and other respiratory pathogens. JAMA. 2020; 323 (20): 2085—2086. DOI: 10.1001/jama.2020.6266.

30. Seaton R.A., Cooper L., Gibbons C.L. еt al. Antibiotic prescribing for respiratory tract infection in patients with suspected and proven COVID-19: results from an antibiotic point prevalence survey in Scottish hospitals. JACAntimicrob. Resist. 2021; 3 (2): dlab078. DOI: 10.1093/jacamr/dlab078.

31. Garcia-Vidal C., Sanjuan G., Moreno-Garcia E. et al. Incidence of co-infections and superinfections in hospitalised patients with COVID-19: a retrospective cohort study. Clin. Microbiol. Infect. 2021; 27 (1): 83—88. DOI: 10.1016/j.cmi.2020.07.041.

32. Rothe K., Feihl S., Schneider J. et al. Rates of bacterial co-infections and antimicrobial use in COVID-19 patients: a retrospective cohort study in light of antibiotic stew-ardship. Eur. J. Clin. Microbiol. Infect. Dis. 2021; 40 (4): 859—869. DOI: 10.1007/s10096-020-04063-8.

33. Hu R., Han C., Pei S. et al. Procalcitonin levels in COVID-19 patients. Int. J. Antimicrob. Agents. 2020; 56 (2): 106051. DOI: 10.1016/j.ijantimicag.2020.106051.

34. Van Berkel M., Kox M., Frenzel T. et al. Biomarkers for antimicrobial stewardship: a reappraisal in COVID-19 times? Crit. Care. 2020; 24 (1): 600. DOI: 10.1186/s13054-020-03291-w.

35. Williams E.J., Mair L., de Silva T.I. et al. Evaluation of procalcitonin as a contribution to antimicrobial stewardship in SARS-CoV-2 infection: a retrospective cohort study. J. Hosp. Infect. 2021; 110: 103—107. DOI: 10.1016/j.jhin.2021.01.006.

36. Schuetz P., Beishuizen A., Broyles M. et al. Procalcitonin (PCT) — guided antibiotic stewardship: an international experts consensus on optimized clinical use. Clin. Chem. Lab. Med. 2019; 57 (9): 1308— 1318. DOI: 10.1515/cclm-2018-1181.

37. National Institute for Health and Care Excellence (NICE). COVID-19 rapid guideline: Antibiotics for pneumonia in adults in hospital. 2020. Available at: https://www.nice.org.uk/guidance/ng173/chapter/4-Assessing-the-ongoing-need-for-antibiotics [Accessed: August 18, 2021].

38. Heesom L., Rehnberg L., Nasim-Mohi M. et al. Procalcitonin as an antibiotic stewardship tool in COVID-19 patients in the intensive care unit. J. Glob. Antimicrob. Resist. 2020; 22: 782—784. DOI: 10.1016/j.jgar.2020.07.017.

39. Mason C.Y., Kanitkar T., Richardson C.J. et al. Exclusion of bacterial co-infection in COVID-19 using baseline inflammatory markers and their response to antibiotics. J. Antimicrob. Chemother. 2021; 76 (5): 1323—1331. DOI: 10.1093/jac/dkaa563.

40.

41.

42.

43.