The investigation of adrenal involvement in carbapenem resistant Acinetobacter baumannii sepsis: experimental mouse model

Doganay, Mehmet; Eryilmaz-Eren, Esma; Dinc, Gokcen; Alp, Emine; KONTAŞ, OLGUN

doi:10.3906/sag-2001-163

The investigation of adrenal involvement in carbapenem resistant Acinetobacter baumannii sepsis: experimental mouse model

Esma EREN, (Kayseri İl Eğitim ve Araştırma Hastanesi, Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı, Kayseri, Türkiye)

Gokcen DİNÇ, (Erciyes Üniversitesi, Tıp Fakültesi, Mikrobiyoloji ve Klinik Mikrobiyoloji Anabilim Dalı, Kayseri, Türkiye)

Olgun KONTAŞ, (Erciyes Üniversitesi, Tıp Fakültesi, Mikrobiyoloji ve Klinik Mikrobiyoloji Anabilim Dalı, Kayseri, Türkiye)

Emine ALP, (Türkiye Cumhuriyeti Sağlık Bakanlığı, Ankara, Türkiye)

Mehmet DOĞANAY (Erciyes Üniversitesi, Tıp Fakültesi, Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı, Kayseri, Türkiye)

Turkish Journal of Medical Sciences

2 1

Yıl: 2021 Cilt: 51 Sayı: 6 Sayfa Aralığı: 3108 - 3114 Metin Dili: İngilizce DOI: 10.3906/sag-2001-163 İndeks Tarihi: 05-01-2022

The investigation of adrenal involvement in carbapenem resistant Acinetobacter baumannii sepsis: experimental mouse model

Öz:

Background/aim: In the last years, incidence of carbapenem resistant Acinetobacter baumannii sepsis is increasing with high mortality. However, it is not clear whether this is due to inadequate antimicrobial choice or a more severe clinical course. We aimed to evaluate the inflammation and adrenal involvement in the carbapenem resistant A. baumannii by using experimental mouse model sepsis. Materials and methods: Balb/c female mice were randomly put into control and three sepsis groups (A. baumannii susceptible to carbapenem-CSAB-, A. baumannii resistant to carbapenem-CRAB-, Escherichia coli). A total of sixty mice were included in this study with each group having 15 mice. Mice were sacrificed 72 h after bacterial inoculation, and blood was taken from each mouse for the assessment of cytokines and corticosterone. Both adrenal glands were dissected; one was used for culture and the other was used for histopathological examination. Bacterial loads of organs were calculated as CFU/g. The histopathological changes, bacterial levels in adrenal and cytokine and corticosterone levels were assessed and compared among the groups. Results: The bacterial level was higher in E. coli (108, 45 ±30, 55 log10 CFU/g) (mean±SD) than other sepsis groups. The lowest level of corticosterone was observed in the E. coli group (p < 0.001). TNF alpha level was highest in the CRAB and E. coli group and this difference was statistically significant than control group (p < 0.05). The IL-6 level in CRAB was significantly higher than the control group (10, 20 pg/mL). The adrenal gland congestion was significantly severe in all the sepsis groups compared to the control. In the group comparison, congestion was significantly more severe in the E. coli group than in CSAB and CRAB groups. Conclusion: Adrenal involvement and inflammatory reactions are seen in E. coli sepsis and in CRAB sepsis. These findings will be focused on in future clinical trials.Key words: Acinetobacter baumannii, adrenal insufficiency, corticosteroids, mice model, sepsis

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315: 801- 810. doi: 10.1001/jama.2016.0287
2. Angus DC, van der Poll T. Severe Sepsis and Septic Shock. New England Journal of Medicine 2013; 369: 840-851. doi: 10.1056/ NEJMra1208623
3. Venkatesh B, Finfer S, Cohen J, Rajbhandari D, Arabi Y et al. Adjunctive Glucocorticoid Therapy in Patients with Septic Shock. New England Journal of Medicine 2018; 378 (9): 797- 808. doi: 10.1056/NEJMoa1705835
4. Chrousos GP. The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. New England Journal of Medicine 1995; 332 (20): 1351-1362.doi: 10.1056/ NEJM199505183322008
5. Annane D. The Role of ACTH and Corticosteroids for Sepsis and Septic Shock: An Update. Frontier of Endocrinology 2016; 20: 7-70. doi: 10.3389/fendo.2016.00070
6. Guarner J, Paddock CD, Bartlett J, Zaki SR. Adrenal gland hemorrhage in patients with fatal bacterial infections. Modern Pathology 2008; 21 (9): 1113-1120. doi: 10.1038/ modpathol.2008.98
7. Aygen B, Inan M, Doğanay M, Keleştimur F. Adrenal functions in patients with sepsis. Experimental and Clinical Endocrinology and Diabetes 1997; 105 (3): 182-186. doi: 10.1055/s-0029-1211749
8. Peleg AY, Seifert H, Paterson DL. Acinetobacter baumannii: emergence of a successful pathogen. Clinical Microbiology Reviews 2008; 21: 538 –582. doi: 10.1128/CMR.00058-07
9. 2016 Surveying Records, Infection Control Board, Erciyes University
10. Dinc G, Demiraslan H, Elmali F, Ahmed SS, Alp E et al. Antimicrobial efficacy of doripenem and its combinations with sulbactam, amikacin, colistin, tigecycline in experimental sepsis of carbapenem-resistant Acinetobacter baumannii. New Microbiologica 2015; 38 (1): 67-73
11. Dinc G, Demiraslan H, Elmali F, Ahmed SS, Metan G et al. Efficacy of sulbactam and its combination with imipenem, colistin and tigecycline in an experimental model of carbapenem-resistant Acinetobacter baumannii sepsis. Chemotherapy 2013; 59 (5): 325-329. doi: 10.1159/000356755
12. Angus DC, Wax RS. Epidemiology of sepsis: an update. Critical Care Medicine 2001; 29: 109-116. doi: 10.1097/00003246- 200107001-00035
13. Kanczkowski W, Sue M, Zacharowski K, Reincke M, Bornstein SR. The role of adrenal gland microenvironment in the HPA axis function and dysfunction during sepsis. Molecular and Cellular Endocrinology 2015; 408: 241-248. doi: 10.1016/j. mce.2014.12.019
14. Paolo WF Jr1, Nosanchuk JD. Adrenal infections. International Journal of Infectious Disease 2006; 10: 343-353. doi: 10.1016/j. ijid.2005.08.001
15. Tormos LM, Schandl CA. The significance of adrenal hemorrhage: undiagnosed Waterhouse-Friderichsen syndrome, a case series. Journal of Forensic Sciences 2013; 58 (4): 1071-1074. doi: 10.1111/1556-4029.12099
16. Marik PE, Zaloga GP. Adrenal insufficiency during septic shock. Critical Care Medicine 2003; 31: 141-145. doi: 10.1097/00003246-200301000-00022
17. Annane D, Sebille V, Toche G, Raphael JC, Gajdos P et al. A 3-level prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin. JAMA 2000; 283: 1038-1045. doi: 10.1001/jama.283.8.1038
18. Soni A, Pepper GM, Wyrwinski PM, Ramirez NE, Simon R et al. Adrenal insufficiency occurring during septic shock: incidence, outcome, and relationship to peripheral cytokine levels. The American Journal of Medicine 1995; 98 (3): 266- 271. doi: 10.1016/S0002-9343(99)80373-8
19. Jäättelä M, Ilvesmäki V, Voutilainen R, Stenman UH, Saksela E. Tumor necrosis factor as a potent inhibitor of adrenocorticotropin-induced cortisol production and steroidogenic P450 enzyme gene expression in cultured human fetal adrenal cells. Endocrinology 1991; 128: 623-629. doi: 10.1210/endo-128-1-623
20. Zhu Q, Solomon S. Isolation and mode of action of rabbit corticostatic (antiadrenocorticotropin) peptides. Endocrinology 1992; 13M31: 1413-1423. doi: 10.1210/ endo.130.3.1311240
21. Mastorakos G, Chrousos GP, Weber JS. Recombinant interleukin-6 activates the hypothalamic-pituitary-adrenal axis in humans. Journal of Clinical Endocrinology and Metabolism 1993; 77: 1690-1694. doi: 10.1210/jcem.77.6.8263159
22. Marik PE, Zaloga GP.Adrenal insufficiency in the critically ill: a new look at an old problem. Chest 2002; 122: 1784-1796. doi: 10.1378/chest.122.5.1784
23. Annane D, Pastores SM, Arlt W, Balk RA, Beishuizen A et al. Critical illness-related corticosteroid insufficiency (CIRCI): a narrative review from a Multispecialty Task Force of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM). Intensive Care Med 2017; 43 (12): 1781-1792. doi: 10.1007/s00134-017-4914-x
24. Surbatovic M, Popovic N, Vojvodic D, Milosevic I, Acimovic G et al. Cytokine profile in severe Gram-positive and Gramnegative abdominal sepsis. Scientific Reports 2015; 16: 5-11355. doi: 10.1038/srep11355
25. Andaluz-Ojeda D1, Bobillo F, Iglesias V, Almansa R, Rico L et al. A combined score of pro- and anti-inflammatory interleukins improves mortality prediction in severe sepsis. Cytokine 2012; 57 (3): 332-336. doi: 10.1016/j.cyto.2011.12.002
26. Wu HP, Chen CK, Chung K, Tseng JC, Hua CC et al. Serial cytokine levels in patients with severe sepsis. Inflammation research 2009; 58 (7): 385-393. doi: 10.1007/s00011-009-0003-0

APA	Eryilmaz-Eren E, Dinc G, KONTAŞ O, Alp E, Doganay M (2021). The investigation of adrenal involvement in carbapenem resistant Acinetobacter baumannii sepsis: experimental mouse model. , 3108 - 3114. 10.3906/sag-2001-163
Chicago	Eryilmaz-Eren Esma,Dinc Gokcen,KONTAŞ OLGUN,Alp Emine,Doganay Mehmet The investigation of adrenal involvement in carbapenem resistant Acinetobacter baumannii sepsis: experimental mouse model. (2021): 3108 - 3114. 10.3906/sag-2001-163
MLA	Eryilmaz-Eren Esma,Dinc Gokcen,KONTAŞ OLGUN,Alp Emine,Doganay Mehmet The investigation of adrenal involvement in carbapenem resistant Acinetobacter baumannii sepsis: experimental mouse model. , 2021, ss.3108 - 3114. 10.3906/sag-2001-163
AMA	Eryilmaz-Eren E,Dinc G,KONTAŞ O,Alp E,Doganay M The investigation of adrenal involvement in carbapenem resistant Acinetobacter baumannii sepsis: experimental mouse model. . 2021; 3108 - 3114. 10.3906/sag-2001-163
Vancouver	Eryilmaz-Eren E,Dinc G,KONTAŞ O,Alp E,Doganay M The investigation of adrenal involvement in carbapenem resistant Acinetobacter baumannii sepsis: experimental mouse model. . 2021; 3108 - 3114. 10.3906/sag-2001-163
IEEE	Eryilmaz-Eren E,Dinc G,KONTAŞ O,Alp E,Doganay M "The investigation of adrenal involvement in carbapenem resistant Acinetobacter baumannii sepsis: experimental mouse model." , ss.3108 - 3114, 2021. 10.3906/sag-2001-163
ISNAD	Eryilmaz-Eren, Esma vd. "The investigation of adrenal involvement in carbapenem resistant Acinetobacter baumannii sepsis: experimental mouse model". (2021), 3108-3114. https://doi.org/10.3906/sag-2001-163

APA	Eryilmaz-Eren E, Dinc G, KONTAŞ O, Alp E, Doganay M (2021). The investigation of adrenal involvement in carbapenem resistant Acinetobacter baumannii sepsis: experimental mouse model. Turkish Journal of Medical Sciences, 51(6), 3108 - 3114. 10.3906/sag-2001-163
Chicago	Eryilmaz-Eren Esma,Dinc Gokcen,KONTAŞ OLGUN,Alp Emine,Doganay Mehmet The investigation of adrenal involvement in carbapenem resistant Acinetobacter baumannii sepsis: experimental mouse model. Turkish Journal of Medical Sciences 51, no.6 (2021): 3108 - 3114. 10.3906/sag-2001-163
MLA	Eryilmaz-Eren Esma,Dinc Gokcen,KONTAŞ OLGUN,Alp Emine,Doganay Mehmet The investigation of adrenal involvement in carbapenem resistant Acinetobacter baumannii sepsis: experimental mouse model. Turkish Journal of Medical Sciences, vol.51, no.6, 2021, ss.3108 - 3114. 10.3906/sag-2001-163
AMA	Eryilmaz-Eren E,Dinc G,KONTAŞ O,Alp E,Doganay M The investigation of adrenal involvement in carbapenem resistant Acinetobacter baumannii sepsis: experimental mouse model. Turkish Journal of Medical Sciences. 2021; 51(6): 3108 - 3114. 10.3906/sag-2001-163
Vancouver	Eryilmaz-Eren E,Dinc G,KONTAŞ O,Alp E,Doganay M The investigation of adrenal involvement in carbapenem resistant Acinetobacter baumannii sepsis: experimental mouse model. Turkish Journal of Medical Sciences. 2021; 51(6): 3108 - 3114. 10.3906/sag-2001-163
IEEE	Eryilmaz-Eren E,Dinc G,KONTAŞ O,Alp E,Doganay M "The investigation of adrenal involvement in carbapenem resistant Acinetobacter baumannii sepsis: experimental mouse model." Turkish Journal of Medical Sciences, 51, ss.3108 - 3114, 2021. 10.3906/sag-2001-163
ISNAD	Eryilmaz-Eren, Esma vd. "The investigation of adrenal involvement in carbapenem resistant Acinetobacter baumannii sepsis: experimental mouse model". Turkish Journal of Medical Sciences 51/6 (2021), 3108-3114. https://doi.org/10.3906/sag-2001-163