Pattern of Multidrug Resistance Genes and Immunological Biomarkers in Post-Surgical wound infections in Nnewi, Nigeria
DOI:
https://doi.org/10.71637/tnhj.v25i2.1082Keywords:
post-surgical wound infections, cytokines , multidrug resistant genes , Serratia marcescens, Ectopseudomonas mendocinaAbstract
Background: Post-surgical wound infection (PSWI) can cause poor wound healing and longer period of hospitalization. The study evaluated the patterns of antibiotic multidrug-resistant genes and immunological biomarkers associated with PSWI in Nnewi, Nigeria.
Methods: Bacterial isolates that were difficult to identify using cultural and biochemical means were sent for sequencing. Enzyme linked immunosorbent assay method was used to evaluate Interleukin-10 (IL-10), Interleukin-4 (IL-4), tumor necrosis factor alpha (TNF-α,), interferon gamma (IFN-γ), and automated blood counting was used for haematological parameters. Polymerase chain reaction was used to detect the multidrug-resistant genes (MDR). Two hundred participants (100 patients with PSWI and 100 apparently healthy individuals (control group) aged between 17-70 years were recruited into the cross-sectional study using simple random sampling method. Data were analyzed using independent t-test and Pearson correlation with p<0.05 assumed to be statistically significant.
Results: The detection of Serratia marcescens, Ectopseudomonas mendocina, Providencia rettgeri, Providencia stuartii and Klebsiella grimontii using gene sequencing underscores a complex etiology in PSWI. We detected the presence of SHV, TEM, and gyrA MDR in patients with PSWI. The levels of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), IL-10, IL-4, TNF-α and IFN-γ were significantly elevated in the test group when compared with the control group (p<0.05).
Conclusion: The study detected the presence of SHV, TEM, and gyrA MDR genes in the isolates. The significantly elevated levels of TNF-α, IFN-γ, IL-4, NLR, and PLR in cases of PSWI suggest that these markers could be useful in the early detection, monitoring, and management of such cases.
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References
1.World Health Organization. (2015). Worldwide country situation analysis: response to antimicrobial resistance: summary. World Health Organization. https://iris.who.int/handle/10665/163473
2.Cassini A, Högberg LD, Plachouras D, Quattrocchi A, Hoxha A, Simonsen GS, Colomb-Cotinat M, Kretzschmar ME, Devleesschauwer B, Cecchini M, Ouakrim DA, Oliveira TC, Struelens MJ, Suetens C, Monnet DL; Burden of AMR Collaborative Group. Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis. The Lancet. Infectious Diseases. 2019; 19(1):56-66. doi: 10.1016/S1473-3099(18)30605-4.
3.Sánchez R, Thomas N, Richardson D. Microbial community disruptions and immune dysregulation caused by antibiotics. Frontiers in Immunology. 2020; 11(10):758-767.
4.Mengistu DA, Alemu A, Abdukadir AA, Mohammed Husen A, Ahmed F, Mohammed B, Musa I. Global Incidence of Surgical Site Infection Among Patients: Systematic Review and Meta-Analysis. Inquiry. 2023; 60:469580231162549. doi: 10.1177/00469580231162549.
5.Eze M, Nwokedi E. Epidemiology of surgical site infections in Nigeria: A review. African Journal of Health Sciences. 2021; 18(2),131-138.
6.Odimayo MS, Adedayo A, Kolawole G. Surgical site infection in a tertiary hospital in Nigeria: Surveillance diagnosis and strategies. International Journal of Infection Control. 2019; 15(2).
7.Kawalya EG. Prevalence and Risk Factors of Surgical Site Infections in Fort Portal Regional Referral Hospital: A Retrospective Cross-Sectional Study. Eurasian Experiment Journal of Public Health. 2024; 5(1): 62-68.
8.Ban KA, Minei JP, Laronga C, Harbrecht BG, Jensen EH, Fry DE, Itani KMF. American College of Surgeons and Surgical Infection Society: Surgical site infection guidelines. Journal of the American College of Surgeons. 2017; 224(1):59-74.
9.Barton RA, Peterson TS, Martin ME. The persistence of beta-lactam resistance genes in clinical isolates of Pseudomonas aeruginosa across hospital settings. Journal of Antimicrobial Chemotherapy. 2022; 78(1):56-65.
10.Monahan M, Jowett S, Pinkney T, Brocklehurst P, Morton DG, Abdali Z, Roberts TE. Surgical site infection and costs in low- and middle-income countries: A systematic review of the economic burden. PLoS One. 2020; 15(6):e0232960. doi: 10.1371/journal.pone.0232960.
11.Adisa AO, Lawal AO, Adejuyigbe O. Factors contributing to delays in the provision of surgical care in Nigeria. Nigerian Journal of Clinical Practice. 2017; 20(7):751–757.
12.Magill SS, Edwards JR, Bamberg W, Beldavs ZG, Dumyati G, Kainer MA, Lynfield R, Maloney M, McAllister-Hollod L, Nadle J, Ray SM, Thompson DL, Wilson LE, Fridkin SK; Emerging Infections Program Healthcare-Associated Infections and Antimicrobial Use Prevalence Survey Team. Multistate point-prevalence survey of health care-associated infections. New England Journal of Medicine. 2014; 370(13):1198-208. doi: 10.1056/NEJMoa1306801.
13.Hou Y, Collinsworth A, Hasa F, Griffin L. Incidence and impact of surgical site infections on length of stay and cost of care for patients undergoing open procedures. Surgery Open Science. 2022; 11:1-18. doi: 10.1016/j.sopen.2022.10.004.
14.Iheanacho CO, Eze UIH. Antimicrobial resistance in Nigeria: challenges and charting the way forward. European Journal of Hospital Pharmacy. 2022; 29(2):119. doi: 10.1136/ejhpharm-2021-002762.
15.Dhole S, Mahakalkar C, Kshirsagar S, Bhargava A. Antibiotic Prophylaxis in Surgery: Current Insights and Future Directions for Surgical Site Infection Prevention. Cureus. 2023; 15(10): e47858. doi: 10.7759/cureus.47858.
16.Iskandar K, Molinier L, Hallit S, Sartelli M, Catena F, Coccolini F, Hardcastle TC, Roques C, Salameh P. Drivers of Antibiotic Resistance Transmissionin Low- and Middle-Income Countriesfrom a "One Health" Perspective-A Review. Antibiotics (Basel). 2020; 9(7):372. doi: 10.3390/antibiotics9070372.
17.Shrestha J, Zahra F, Cannady, Jr P. Antimicrobial Stewardship. [Updated 2023 Jun 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK572068/
18.Spagnolo AM, Ottria G, Amicizia D, Perdelli F, Cristina ML. Operating theatre quality and prevention of surgical site infections. Journal of Preventive Medicine and Hygiene. 2013; 54(3):131-137.
19.Muteeb G, Rehman MT, Shahwan M, Aatif M. Origin of Antibiotics and Antibiotic Resistance, and Their Impacts on Drug Development: A Narrative Review. Pharmaceuticals. 2023; 16: 1615. doi: 10.3390/ph16111615
20.Dadgostar P. Antimicrobial Resistance: Implications and Costs. Infect Drug Resist. 2019; 12:3903-3910. doi: 10.2147/IDR.S234610.
21.van Hoek AH, Mevius D, Guerra B, Mullany P, Roberts AP, Aarts HJ. Acquired antibiotic resistance genes: an overview. Frontiers in Microbiology. 2011; 2:203. doi: 10.3389/fmicb.2011.00203.
22.Sakalauskienė GV, Malcienė L, Stankevičius E, Radzevičienė A. Unseen Enemy: Mechanisms of Multidrug Antimicrobial Resistance in Gram-Negative ESKAPE Pathogens. Antibiotics (Basel). 2025; 14(1):63. doi: 10.3390/antibiotics14010063.
23.Hooper DC, Jacoby GA. Topoisomerase Inhibitors: Fluoroquinolone Mechanisms of Action and Resistance. Cold Spring Harbor Perspectives in Medicine. 2016; 6(9): a025320. doi: 10.1101/cshperspect.a025320.
24.Kiiru J, Kariuki S, Goddeeris BM, Butaye P. Analysis of β-lactamase phenotypes and carriage of selected β-lactamase genes among Escherichia coli strains obtained from Kenyan patients during an 18-year period. BMC Microbiology. 2012; 12:155. doi: 10.1186/1471-2180-12-155.
25.Baya W, Adaily N, Mzabi A, Ben Fredj F, Bouattay A. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in bacterial infections: contributions to diagnostic strategies in a tertiary care hospital in Tunisia. F1000Res. 2024; 13:978. doi: 10.12688/f1000research.146952.1.
26.Martinez JM, Espírito Santo A, Ramada D, Fontes F, Medeiros R. Diagnostic accuracy of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and neutrophil-lymphocyte-to-platelet ratio biomarkers in predicting bacteremia and sepsis in immunosuppressive patients with cancer: literature review. Porto Biomedical Journal. 2024; 9(3):254. doi: 10.1097/j.pbj.0000000000000254.
27.Pujani M, Raychaudhuri S, Verma N, Kaur H, Agarwal S, Singh M, Jain M, Chandoke RK, Singh K, Sidam D, Chauhan V, Singh A, Katarya K. Association of Hematologic biomarkers and their combinations with disease severity and mortality in COVID-19- an Indian perspective. American Journal of Blood Research. 2021; 11(2):180-190.
28.Obeagu EI. Role of cytokines in immunomodulation during malaria clearance. Annals of Medicine and Surgery (Lond). 2024; 86(5):2873-2882. doi: 10.1097/MS9.0000000000002019.
29.Kany S, Vollrath JT, Relja B. Cytokines in Inflammatory Disease. International Journal of Molecular Sciences. 2019; 20(23):6008. doi: 10.3390/ijms20236008.
30.Gao W, Liu X, Zhang S, Wang J, Qiu B, Shao J, Huang W, Huang Y, Yao M, Tang L-L. Alterations in gut microbiota and inflammatory cytokines after administration of antibiotics in mice. Microbiology Spectrum. 2024; 12(8): e0309523. doi: 10.1128/spectrum.03095-23.
31.Chinemerem Nwobodo D, Ugwu MC, Oliseloke Anie C, Al-Ouqaili MTS, Chinedu Ikem J, Victor Chigozie U, Saki M. Antibiotic resistance: The challenges and some emerging strategies for tackling a global menace. Journal of Clinical Laboratory Analysis. 2022; 36(9): e24655. doi: 10.1002/jcla.24655.
32.Naing L, Nordin RB, Abdul Rahman H, Naing YT. Sample size calculation for prevalence studies using Scalex and ScalaR calculators. BMC Medical Research Methodology. 2022; 22(1):209. doi: 10.1186/s12874-022-01694-7.
33.World Health Organization (WHO). Worldwide country situation analysis (2015): Response to antimicrobial resistance; WHO Library Cataloguing-in-Publication Data. Geneva: World Health Organization.
34.Chukwuagwu IU, Ukibe NR, Ogbu II, Ikimi CG, Agu VO, Kalu OA, Ukibe SN, Awalu JC. Evaluation of Serum Interleukin 6, Tumor Necrosis Factor-Alpha, and Interferon-Gamma Levels in Relation to Body Mass Index and Blood Pressure in HIV Seropositive Pregnant Women Coinfected with Malaria. Interdisciplinary Perspectives on Infectious Diseases. 2020; 2020:2424802. doi: 10.1155/2020/2424802.
35.Hillyer LM, Woodward B. Interleukin-10 concentration determined by sandwich enzyme-linked immunosorbent assay is unrepresentative of bioactivity in murine blood. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2003; 285(6): R1514-9. doi: 10.1152/ajpregu.00378.2003.
36.Cheesbrough, M. Microbiological Tests. In: Cheesbrough, M., Ed., District Laboratory Practice in Tropical Countries, Part II, Low Priced Edition, Cambridge University Press, Cambridge, 2000, 105-130.
37.Alali WQ, Abdo NM, AlFouzan W, Dhar R. Antimicrobial resistance pattern in clinical Escherichia coli and Pseudomonas aeruginosa isolates obtained from a secondary-care hospital prior to and during the COVID-19 pandemic in Kuwait. Germs. 2022; 12(3):372-383. doi: 10.18683/germs.2022.1341.
38.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.
39.Muteeb G, Rehman MT, Shahwan M, Aatif M. Origin of Antibiotics and Antibiotic Resistance, and Their Impacts on Drug Development: A Narrative Review. Pharmaceuticals (Basel). 2023; 16(11):1615. doi: 10.3390/ph16111615.
40.Ozkurt ZG, Ergin C, Tekin A. Etiology and management of complex wound infections. Wound Repair and Regeneration. 2021; 29(5): 744-753.
41.Ghasemian A, Ghavidel F, Bakhshi B. Polymicrobial infections and their diagnostic challenges. Infection and Drug Resistance. 2020; 13: 2355-2371.
42.Dryden M. Complicated skin and soft tissue infection. Journal of Antimicrobial Chemotherapy. 72(suppl_1), i4-i10. doi:10.1093/jac/dkx017.
43.Brown AE, Smith RD, Jones BA. Advanced molecular diagnostics for wound care. Clinical Microbiology and Infection. 2018; 24(7):715-721. doi: 10.1016/j.cmi.2018.01.017.
44.Lanteri M, Tschan T, Oppenheim B. Targeted therapies for complex wound infections. Journal of Wound Care. 2022; 31(4): 232-240.
45.Löffler T, Löffler B, Kramer A. Innovative diagnostic methods for wound infections. Current Opinion in Infectious Diseases. 2019; 32(2): 104-110.
46.López-Perales M, Schwartz CA, Koh E. Patterns of multidrug resistance in clinical pathogens: A study of gram-positive and gram-negative bacteria. Journal of Clinical Pathology. 2023; 77(3): 243-249.
47.Schreiner HA. Preventing and managing surgical site infections: Global perspectives on infection prevention. Infection Control and Hospital Epidemiology. 2020; 41(3): 362-371.
48.Koh E, Gauthier S, Lee KS. Assessing antibiotic stewardship programs: A systematic review. Journal of Global Health. 2024; 14(2): 98
49.Salam MA, Al-Amin MY, Salam MT, Pawar JS, Akhter N, Rabaan AA, Alqumber MAA. Antimicrobial Resistance: A Growing Serious Threat for Global Public Health. Healthcare (Basel). 2023; 11(13):1946. doi: 10.3390/healthcare11131946.
50.Martinez C, Wong D. The immune implications of repeated antibiotic misuse. International Journal of Antimicrobial Agents. 2019; 53(6): 453-465.
51.Barton RA, Peterson TS, Martin ME. The persistence of beta-lactam resistance genes in clinical isolates of Pseudomonas aeruginosa across hospital settings. Journal of Antimicrobial Chemotherapy. 2022; 78(1): 56-65. doi:10.1093/jac/dkab354.
52.Schwartz CA, Koh E, Peterson TS. Horizontal gene transfer and the spread of resistance genes in clinical pathogens. Microbial Genomics. 2023; 9(1): 12-24.
53.Husna A, Rahman MM, Badruzzaman ATM, Sikder MH, Islam MR, Rahman MT, Alam J, Ashour HM. Extended-Spectrum β-Lactamases (ESBL): Challenges and Opportunities. Biomedicines. 2023;11(11):2937. doi: 10.3390/biomedicines11112937.
54.Bradford PA. Extended-spectrum beta-lactamases in the 21st century: characterization, epidemiology, and detection of this important resistance threat. Clinical Microbiology Reviews. 2001; 14(4):933-951. doi: 10.1128/CMR.14.4.933-951.2001.
55.Glen KA, Lamont IL. β-lactam Resistance in Pseudomonas aeruginosa: Current Status, Future Prospects. Pathogens. 2021; 10(12):1638. doi: 10.3390/pathogens10121638.
56.Johnning A, Kristiansson E, Fick J, Weijdegård B, Larsson DG. Resistance Mutations in gyrA and parC are Common in Escherichia Communities of both Fluoroquinolone-Polluted and Uncontaminated Aquatic Environments. Frontiers in Microbiology. 2015; 6:1355. doi: 10.3389/fmicb.2015.01355.
57.Dalhoff A. Global fluoroquinolone resistance epidemiology and implictions for clinical use. Interdisciplinary Perspectives on Infectious Diseases. 2012; 2012:976273. doi: 10.1155/2012/976273.
58.Harris M, Fasolino T, Ivankovic D, Davis NJ, Brownlee N. Genetic Factors That Contribute to Antibiotic Resistance through Intrinsic and Acquired Bacterial Genes in Urinary Tract Infections. Microorganisms. 2023; 11(6):1407. doi: 10.3390/microorganisms11061407.
59.Sarma PR. Red Cell Indices. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 152. Available from: https://www.ncbi.nlm.nih.gov/books/NBK260
60.Zahorec R. Neutrophil-to-lymphocyte ratio: A marker of systemic inflammation in critical conditions. Intensive Care Medicine. 2021; 47(2): 135-137.
61.Russell C, Evans M, Wright D, Jackson R. The significance of NLR and PLR in clinical practice: Current insights and future directions. Clinical Immunology. 2023; 238: 108883.
62.Li X, Zhu Y, Zhang L, Wang J. TNF and its role in immune regulation and chronic inflammation. Autoimmunity Reviews. 2022; 20(5): 102765.
63.Rogers R, Pranab D. IL-4 in autoimmune diseases and the immune response. Immunology Letters. 2019; 212: 65-72.
64.Chen L, Deng H, Cui H, Fang J, Zuo Z, Deng J, Li Y, Wang X, Zhao L. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget. 2017; 9(6):7204-7218. doi: 10.18632/oncotarget.23208.
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