Arif Doğan HABİLOĞLU, Gönül ÇİÇEK ŞENTÜRK, Yunus GÜRBÜZ, Ezgi Gizem ŞIBAR, Esengül ŞENDAĞ, Nilgün ALTIN, İrfan ŞENCAN

Covid-19 pandemisinde antibiyotik kullanımının hastane enfeksiyonlarında mikroorganizma dağılımına ve antibiyotik direncine etkisi

Amaç: İki yılı aşkın süredir tüm dünyayı etkisi altına alan COVID-19 pnömonisi sağlık sistemini ciddi boyutlarda zorlamıştır. Sağlık hizmeti sunumunun tehlikeye girdiği bu dönemde uygun antibiyotik kullanımı geri planda kalmıştır. Bu çalışma ile pandemi döneminde değişen antibiyotik kullanımının hastane enfeksiyonlarına neden olan mikroorganizmaların dağılımı ve değişen antibiyotik dirençleri üzerine etkisininin araştırılması amaçlandı. Yöntem: Çalışma Dışkapı Yıldırım Beyazıt Eğitim ve Araştırma Hastanesinde gerçekleştirildi. 2016-2020 yılları arasında E. coli, Klebsiella penumonia, Enterobacter spp., P. aeruginosa ve Acinetobacter spp’nin etken olduğu hastane kaynaklı enfeksiyonlar değerlendirildi. Hastalar 2016 yılı 1. grup, 2017 yılı 2. grup, 2018 yılı 3. grup, 2019 yılı 4. grup ve 2020 yılı 5. grup şeklinde sınıflandırıldı. Gruplar hastane kaynaklı enfeksiyon etkenlerinin oranı, direnç durumları ve ilgili yıllarda kullanılan antibiyotik miktarları açısından birbirleri ile karşılaştırıldı. Anlamlı farklılığın sadece 5. yılda gösterildiği faktörler pandemi döneminde değişe sağlık hizmetlerine atfedildi ve irdelendi. Bulgular: Çalışmamızda en fazla kullanılan antibiyotik 150,72 DDD ile seftriaksondu. En sık kullanılan ikinci ve üçüncü antibiyotik sırasıyla piperasilin + tazobaktam ve levofloksasindi. Pandemi dönemine atfedilen piperasilin + tazobaktam kullanım miktarı 5. grupta, 1, 2, 3 ve 4. gruplara göre anlamlı düzeyde daha yüksektir. Pandemi döneminde meropenem, levofloksasin ve kolistin kullanım miktarı artmıştı. Ancak ikili karşılaştırmalarda 5. grup diğer grupların tümü ile farklılık göstermediği için 5. gruptaki bu artış pandemi dönemine atfedilmedi. Hastane enfeksiyonları etkeni olarak yıllara göre A. baumannii, P. aeruginosa, E. coli ve K. pneumoniae yüzdeleri karşılaştırıldı. Özellikle pandemi dönemine ait bir dağılım değişikliği görülmedi. Mikroorganzimaların antibiyotik direnç oranlarındaki değişimi açısından A. baumannii ve P. aeruginosa için pandemi dönemine ait değişim görülmedi. K. pneumonia ve E. coli için 5. gruptaki Piperasilin direnç oranı, 1, 2, 3 ve 4. gruplara göre anlamlı düzeyde daha yüksek bulundu. Piperasilin + tazobaktam kullanımı ile K. pneumoniae ve E. coli için piperasilin direnci arasında pozitif korelasyon görüldü. Sonuç: Çalışmamızda hastanemiz bünyesinde Piperasilin + tazobaktam ve levofloksasin kullanımının pandemi döneminde ciddi boyutlarda arttığını tespit ettik. Antimikrobiyal direnç açısındaın ise artan antibiyotik kullanımına paralel bir artış söz konusu değildi. Pandemi döneminde artan antibiyotik tüketim miktarının tetikleyeceği dirençli suşlar, önümüzdeki yıllarda da takibi gereken bir sorun olacaktır.

The effect of antibiotic use on microorganism distribution and antibiotic resistance in nosocomial infections in the Covid-19 pandemic

Objective: COVID-19 pneumonia, which has affected the whole world for more than two years, has forced the health system. In this period, when the delivery of health services is in danger, the use of appropriate antibiotics has remained in the background. With this study, we wanted to investigate the effect of changing antibiotic use during the pandemic period on the distribution of microorganisms that cause nosocomial infections and changing antibiotic resistances. Methods: The study was carried out in the Dışkapı Yıldırım Beyazıt Training and Research Hospital. Hospital-acquired infections caused by E. coli, Klebsiella penumonia, Enterobacter spp., P. aeruginosa and Acinetobacter spp. between 2016 and 2020 were evaluated for our study. We classified the patients in 2016 as 1st group, 2017 as a 2nd group, 2018 as a 3rd group, 2019 as a 4th group, 2020 as a 5th group. The groups were compared with each other in terms of the rate of hospital-acquired infection, their resistance status and the amount of antibiotics used in the relevant years. The factors that showed significant difference only in the 5th year were attributed to the changing health services during the pandemic period and were examined. Results: The most commonly used antibiotic in our study was ceftriaxone with a DDD of 150.72. Piperacillin + tazobactam and levofloxacin were the second and third most commonly used antibiotics, respectively.The amount of piperacillin + tazobactam use attributed to the pandemic period is significantly higher in the 5th group than in the 1st, 2nd, 3rd and 4th groups. Meropenem, levofloxacin, and colistin, which had increased usage during the pandemic period, were not attributed to the pandemic period since they did not differ with all other groups in pairwise comparisons. There was no change in the rates of microorganisms causing hospital infections for the pandemic period. Piperacillin resistance rate at 5th group for K. pneumonia and E. coli was significantly higher than at 1, 2, 3 and 4 groups. There was a positive correlation between the use of piperacillin/tazobactam and piperacillin resistance for K. pneumoniae and E. coli. Conclusion: In our study, we found that the use of piperacillin/tazobactam and levofloxacin in our hospital increased significantly during the pandemic period. There was no significant increase in the correlation between increasing antibiotic use and antibiotic resistance. Resistant strains, which will be triggered by the increasing amount of antibiotic consumption during the pandemic period, will be a problem that should be followed up in the coming years.

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1. Adebisi, Y. A., Jimoh, N. D., Ogunkola, I. O., Uwizeyimana, T., Olayemi, A. H., Ukor, N. A., et al. The use of antibiotics in COVID-19 management: a rapid review of national treatment guidelines in 10 African countries. Trop Med Health. 2021;49(1):51.
2. Iwu CJ, Jordan P, Jaja IF, Iwu CD, Wiysonge CS. Treatment of COVID-19: implications for antimicrobial resistance in Africa. Pan Afr Med J. 2020;35(2):119.
3. https://www.cdc.gov/drugresistance/covid19. html. Accessed date: 6 June 2021.
4. Llor C, Bjerrum L. Antimicrobial resistance: risk associated with antibiotic overuse and initiatives to reduce the problem. Ther Adv Drug Saf. 2014;5(6):229–41.
5. https://www.cdc.gov/drugresistance/about.html. Accessed date: 22 June 2021.
6. Kollef MH. Broad-spectrum antimicrobials and the treatment of serious bacterial infections: getting it right up front. Clin Infect Dis. 2008;47(1):3–13Sabtu N, Enoch DA, Brown NM. Antibiotic resistance: what, why, where, when and how? British Medical Bulletin, 2015;116:105–13.
7. https://www.who.int/news-room/fact-sheets/ detail/antimicrobial-resistance. Accessed date: 15 June 2021.
8. Sabtu, N., Enoch, D. A., Brown, N. M. Antibiotic resistance: what, why, where, when and how?. British medical bulletin. 2015;116(1):105-113.
9. https://www.cdc.gov/getsmart/healthcare/pdfs/ core-elements.pdf/ Accessed 30 May 2021.
10. https://www.whocc.no/ddd/definition_and_ general_considera/. Accessed 18 October 2021. 11. h t t p : / / w w w. s o c i n o r t e . c o m / w p - c o n t e n t / uploads/2013/03/Criterios-de-IN-2013.pdf. Accessed 15 May 2021.
12. https://www.eucast.org/fileadmin/src/media/ PDFs/EUCAST_files/Breakpoint_tables/v_11.0_ Breakpoint_Tables.pdf. Accessed 22 May 2021.
13. Metlay, J. P., Waterer, G. W., Long, A. C., Anzueto, A., Brozek, J., Crothers, K., et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. American journal of respiratory and critical care medicine, 2019;200(7):45-67.
14. Kalil, A. C., Metersky, M. L., Klompas, M., Muscedere, J., Sweeney, D. A., Palmer, L. B. et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clinical Infectious Diseases, 2016; 63(5):61- 111.
15. https://www.idsociety.org/covid-19-real-timelearning- network/disease-manifestations-- complications/co-infection-and-Antimicrobial- Stewardship/. Accessed 25 June 2021.
16. Nieuwlaat, R., Mbuagbaw, L., Mertz, D., Burrows, L. L., Bowdish, D. M., Moja, L., et al. Coronavirus Disease 2019 and antimicrobial resistance: parallel and interacting health emergencies. Clinical Infectious Diseases, 2021;72(9):1657-9.
17. Hamid, H., Abid, Z., Amir, A., Rehman, T. U., Akram, W., & Mehboob, T. Current burden on healthcare systems in low-and middle-income countries: recommendations for emergency care of COVID-19. Drugs & Therapy Perspectives, 2020;36(10):466-8.
18. Blandino, G. Cancer at the time of the COVID-19 hurricane. Journal of Experimental & Clinical Cancer Research, 2020;39(1):74.
19. https://hsgm.saglik.gov.tr/tr/bulasici-hastaliklar/ shie/shie-liste/shie-raporlar.html. Accessed 30 May 2021.
20. Lee, J., Oh, C. E., Choi, E. H., Lee, H. J. The impact of the increased use of piperacillin/tazobactam on the selection of antibiotic resistance among invasive Escherichia coli and Klebsiella pneumoniae isolates. International Journal of Infectious Diseases, 2103; 17(8): e638-e643.
21. Sedláková MH, Urbánek K, Vojtová V, Suchánková H, Imwensi P, Kolář M. Antibiotic consumption and its influence on the resistance in Enterobacteriaceae. BMC Res Notes. 2014;7:454.
22. Zemkova M, Kotlarova J, Merka V, Cermak P, Vlcek J, Jebavy L. Emergence of fluoroquinolone resistance in Escherichia coli isolates at the department of clinical hematology. New Microbiol. 2007;30(4):423–30.
23. Merlin, C. Reducing the consumption of antibiotics: would that be enough to slow down the dissemination of resistances in the downstream environment?. Frontiers in microbiology. 2020;11:33.
24. Yang, P., Chen, Y., Jiang, S., Shen, P., Lu, X., Xiao, Y. Association between the rate of fluoroquinolonesresistant gram-negative bacteria and antibiotic consumption from China based on 145 tertiary hospitals data in 2014. BMC infectious diseases, 2020, 20(1):269.
25. Kim, B., Kim, Y., Hwang, H., Kim, J., Kim, S.W. and Bae, I.G. (2018) Trends and Correlation between Antibiotic Usage and Resistance Pattern among Hospitalized Patients at University Hospitals in Korea, 2004 to 2012: A Nationwide Multicenter Study. Medicine, 97, e13719.
26. MULDER, Marlies, et al. Risk factors for resistance to ciprofloxacin in community-acquired urinary tract infections due to Escherichia coli in an elderly population. Journal of Antimicrobial Chemotherapy, 2016, 72.1: 281-HŞ9.