Impact of poly resistant bile flora on the development of infectious complications after pancreatoduodenectomy
https://doi.org/10.21294/1814-4861-2025-24-5-96-106
Abstract
Aim: to evaluate the impact of multidrug-resistant bile microflora on the development of infectious complications after pancreatoduodenectomy in patients undergoing standard perioperative antibiotic prophylaxis.
Material and Methods. This retrospective study included patients over 18 years of age who underwent pancreatoduodenectomy from January 2019 until May 2023. The inclusion criteria were the presence of pre/intraoperative bacteriological examination of a bile sample and perioperative antibiotic prophylaxis with amoxicillin + clavulanic acid at a dose of 1 ± 0.2 g 30 minutes before skin incision, followed by intraoperative administration every 4 hours. In the postoperative period, the drug was administered during the day at a dose of 1 ± 0.2 g every 6 hours. Of the 249 operated patients, 57 met the inclusion criteria; they were divided into two groups: patients without resistant strains in the bile and patients with resistant microflora. The postoperative period was assessed by tracking the incidence of surgical site infections (SSI), the likelihood of reoperations, hospitalizations, and one-year survival. Statistical data analysis was carried out using the statistical package R 3.4.2.
Results. The majority of patients – 24 (42 %) had a bile microflora with extended drug resistance, while 19 (33 %) patients had multiple drug resistance. Microflora without clinically significant resistance was found in 11 (25 %) patients, and no bacterial growth in the bile was observed in 3 (5 %) patients. Group 1 included 14 (25 %) and group 2 included 43 (75 %) patients. According to the data obtained, there were no superficial SSIs in patients with non-resistant microflora (group 1), whereas in the group of patients with resistant microflora (group 2) their frequency was 2 %. Organ/cavity SSIs were also observed with greater frequency in group 2 and amounted to 44 % versus 19 % in group 1. The probability of developing a surgical site infection was 28.6 % in group 1, versus 51.7 % in group 2 (p=0.2). There were no statistically significant differences in the re-operation and re-hospitalization rates between the groups (31.2 % for group 1 and 28.3 % for group 2, p=0.66; 5 % for group 1 and 7.4 % for group 2, p=0.42, respectively). No statistically significant difference in the 1-year survival rate between the study groups was found.
Conclusion. Multidrug-resistant microflora represents a serious burden for modern medicine, especially in the context of treating cancer patients requiring complex surgical interventions. Our study highlights the importance of timely monitoring of microflora and revision of approaches to perioperative antibiotic prophylaxis of infectious complications.
Keywords
About the Authors
I. E. KhatkovRussian Federation
Igor E. Khatkov - MD, DSc, Professor, Academician of the Russian Academy of Sciences, Director, Moscow Clinical Scientific Center named after A.S. Loginov; Head of the Department of Faculty-Based Surgery No. 2, Russian University of Medicine, MHR.
86, Entuziastov Highway, Moscow, 111123; 20/1, Delegatskaya St., Moscow, 127473
M. Yu. Drokov
Russian Federation
Mikhail Yu. Drokov - Head of the Research Sector for Chemotherapy of Hemoblastosis, Hematopoietic Depression and Bone Marrow Transplantation.
4, Zykovskiy Novyy proezd, Moscow, 125167
O. Yu. Gasieva
Russian Federation
Olga Yu. Gasieva - Head of the Clinical Pharmacology Department.
86, Entuziastov Highway, Moscow, 111123
References
1. Breijyeh Z., Jubeh B., Karaman R. Resistance of Gram-Negative Bacteria to Current Antibacterial Agents and Approaches to Resolve It. Molecules. 2020; 25(6): 1340. doi: 10.3390/molecules25061340.
2. Salam M.A., Al-Amin M.Y., Salam M.T., Pawar J.S., Akhter N., Rabaan A.A., Alqumber M.A.A. Antimicrobial Resistance: A Growing Serious Threat for Global Public Health. Healthcare (Basel). 2023; 11(13): 1946. doi: 10.3390/healthcare11131946.
3. Tamma P.D., Aitken S.L., Bonomo R.A., Mathers A.J., van Duin D., Clancy C.J. Infectious Diseases Society of America 2023 Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections. Clin Infect Dis. 2023: ciad428. doi: 10.1093/cid/ciad428. Epub ahead of print.
4. Tamma P.D., Aitken S.L., Bonomo R.A., Mathers A.J., van Duin D., Clancy C.J. Infectious Diseases Society of America Guidance on the Treatment of Extended-Spectrum β-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR-P. aeruginosa). Clin Infect Dis. 2021; 72(7): 1109–16. doi: 10.1093/cid/ciab295.
5. Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 2022; 399(10325): 629–55. doi: 10.1016/S0140-6736(21)02724-0. Erratum in: Lancet. 2022; 400(10358): 1102. doi: 10.1016/S0140-6736(21)02653-2.
6. Idris F.N., Nadzir M.M. Multi-drug resistant ESKAPE pathogens and the uses of plants as their antimicrobial agents. Arch Microbiol. 2023; 205(4): 115. doi: 10.1007/s00203-023-03455-6.
7. Foschi D., Yakushkina A., Cammarata F., Lamperti G., Colombo F., Rimoldi S., Antinori S., Sampietro G.M. Surgical site infections caused by multi-drug resistant organisms: a case-control study in general surgery. Updates Surg. 2022; 74(5): 1763–71. doi: 10.1007/s13304-022-01243-3.
8. Magiorakos A.P., Srinivasan A., Carey R.B., Carmeli Y., Falagas M.E., Giske C.G., Harbarth S., Hindler J.F., Kahlmeter G., Olsson-Liljequist B., Paterson D.L., Rice L.B., Stelling J., Struelens M.J., Vatopoulos A., Weber J.T., Monnet D.L. Multidrug-resistant, extensively drug-resistant and pandrugresistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012; 18(3): 268–81. doi: 10.1111/j.1469-0691.2011.03570.x.
9. European Food Safety Authority, European Centre for Disease Prevention and Control. The European Union summary report on antimicrobial resistance in zoonotic and indicator bacteria from humans, animals and food in 2022–2023. EFSA Journal. 2025; 23(3): e9237. doi: 10.2903/j.efsa.2025.9237.
10. Karaman R., Jubeh B., Breijyeh Z. Resistance of Gram-Positive Bacteria to Current Antibacterial Agents and Overcoming Approaches. Molecules. 2020; 25(12): 2888. doi: 10.3390/molecules25122888.
11. Sugimachi K., Iguchi T., Mano Y., Morita M., Mori M., Toh Y. Significance of bile culture surveillance for postoperative management of pancreatoduodenectomy. World J Surg Oncol. 2019; 17(1): 232. doi: 10.1186/s12957-019-1773-7.
12. Windisch O., Frossard J.L., Schiffer E., Harbarth S., Morel P., Bühler L. Microbiologic Changes Induced by Biliary Drainage Require Adapted Antibiotic Prophylaxis during Duodenopancreatectomy. Surg Infect (Larchmt). 2019; 20(8): 677–82. doi: 10.1089/sur.2019.088.
13. Cengiz T.B., Jarrar A., Power C., Joyce D., Anzlovar N., MorrisStiff G. Antimicrobial Stewardship Reduces Surgical Site Infection Rate, as well as Number and Severity of Pancreatic Fistulae after Pancreatoduodenectomy. Surg Infect (Larchmt). 2020; 21(3): 212–17. doi: 10.1089/sur.2019.108.
14. Mintziras I., Maurer E., Kanngiesser V., Lohoff M., Bartsch D.K. Preoperative Bacterobilia Is an Independent Risk Factor of SSIs after Partial PD. Dig Surg. 2020; 37(5): 428–35. doi: 10.1159/000508127.
15. Zagainov V.E., Ruina O.V., Zarechnova N.V., Kuchin D.M., Kiselev N.M., Naraliev N.U., Mukhanzaev Sh.Kh. Infectious complications after elective surgeries on the liver and pancreas. Annals of HPB Surgery. 2023; 28(4): 71–80. (in Russian). doi: 10.16931/1995-5464.2023-4-71-80. EDN: PWSQQQ.
16. Lillemoe K.D., Rikkers L.F. Pancreaticoduodenectomy: the golden era. Ann Surg. 2006; 244(1): 16–17. doi: 10.1097/01.sla.0000226042.37420.f9.
17. Cameron J.L., Riall T.S., Coleman J., Belcher K.A. One thousand consecutive pancreaticoduodenectomies. Ann Surg. 2006; 244(1): 10–15. doi: 10.1097/01.sla.0000217673.04165.ea.
18. Griffin J.F., Poruk K.E., Wolfgang C.L. Pancreatic cancer surgery: past, present, and future. Chin J Cancer Res. 2015; 27(4): 332–48. doi: 10.3978/j.issn.1000-9604.2015.06.07.
19. Sohn T.A., Yeo C.J., Cameron J.L., Koniaris L., Kaushal S., Abrams R.A., Sauter P.K., Coleman J., Hruban R.H., Lillemoe K.D. Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators. J Gastrointest Surg. 2000; 4(6): 567–79. doi: 10.1016/s1091-255x(00)80105-5.
20. Takahashi Y., Takesue Y., Fujiwara M., Tatsumi S., Ichiki K., Fujimoto J., Kimura T. Risk factors for surgical site infection after major hepatobiliary and pancreatic surgery. J Infect Chemother. 2018; 24(9): 739–43. doi: 10.1016/j.jiac.2018.05.007.
21. European Committee on Antimicrobial Susceptibility Testing (EUCAST), ‘Breakpoint tables for interpretation of MICs and zone diameters. Version 15.0EUCAST’, Växjö, Sweden, 2025. [Internet]. [cited 10.08.2025]. URL: https://www.eucast.org/clinical_breakpoints.
22. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing. 35th ed. CLSI supplement M100. Clinical and Laboratory Standards Institute, USA, 2025. ISBN: 978-1-68440-262-5.
23. Prevention of surgical site infections: methodological guidelines. National Association of Specialists for the Control of Infectious and Non-Infectious Diseases (NASCI). 2023. (in Russian)]. [Internet]. [cited 10.08.2025. URL: https://nasci.confreg.org/libs/files/2_mr_profilaktika_infekciy_oblasti_hirurgicheskogo_vmeshateljstva__2023.pdf.
24. Common Terminology Criteria for Adverse Events (CTCAE). Version 4.0. National Cancer Institute. 2009. [Internet]. [cited 10.08.2025]. URL: chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/Archive/CTCAE_4.0_2009-0529_QuickReference_8.5x11.pdf.
25. The SKAT (Strategy of Antimicrobial Therapy Control) Program for Inpatient Medical Care: Russian Clinical Guidelines. National Association of Specialists for the Control of Infectious and Non-Infectious Diseases (NASCI). 2018. Ed. by S.V. Yakovlev, N.I. Briko, S.V. Sidorenko, D.N. Protsenko. Moscow, 2018. 156 p. (in Russian). ISBN: 978-5-00122-157-9.
26. GBD 2021 Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance 1990–2021: a systematic analysis with forecasts to 2050. Lancet. 2024; 404(10459): 1199–226. doi: 10.1016/s0140-6736(24)01867-1.
27. Kimura W., Miyata H., Gotoh M., Hirai I., Kenjo A., Kitagawa Y., Shimada M., Baba H., Tomita N., Nakagoe T., Sugihara K., Mori M. A pancreaticoduodenectomy risk model derived from 8575 cases from a national single-race population (Japanese) using a web-based data entry system: the 30-day and in-hospital mortality rates for pancreaticoduodenectomy. Ann Surg. 2014; 259(4): 773–80. doi: 10.1097/SLA.0000000000000263.
28. Sandini M., Ruscic K.J., Ferrone C.R., Qadan M., Eikermann M., Warshaw A.L., Lillemoe K.D., Castillo C.F. Major Complications Independently Increase Long-Term Mortality After Pancreatoduodenectomy for Cancer. J Gastrointest Surg. 2019; 23(10): 1984–990. doi: 10.1007/s11605-018-3939-y.
29. Kim D., Park B.Y., Choi M.H., Yoon E.J., Lee H., Lee K.J., Park Y.S., Shin J.H., Uh Y., Shin K.S., Shin J.H., Kim Y.A., Jeong S.H. Antimicrobial resistance and virulence factors of Klebsiella pneumoniae affecting 30 day mortality in patients with bloodstream infection. J Antimicrob Chemother. 2019; 74(1): 190–99. doi: 10.1093/jac/dky397.
30. Righi E., Mutters N.T., Guirao X., Del Toro M.D., Eckmann C., Friedrich A.W., Giannella M., Kluytmans J., Presterl E., Christaki E., Cross E.L.A., Visentin A., Sganga G., Tsioutis C., Tacconelli E. ESCMID/ EUCIC clinical practice guidelines on perioperative antibiotic prophylaxis in patients colonized by multidrug-resistant Gram-negative bacteria before surgery. Clin Microbiol Infect. 2023; 29(4): 463–79. doi: 10.1016/j.cmi.2022.12.012.
Review
For citations:
Khatkov I.E., Drokov M.Yu., Gasieva O.Yu. Impact of poly resistant bile flora on the development of infectious complications after pancreatoduodenectomy. Siberian journal of oncology. 2025;24(5):96-106. (In Russ.) https://doi.org/10.21294/1814-4861-2025-24-5-96-106








































