Comparative outcomes of standard wound care versus a triple-combination topical regimen including metronidazole in post-debridement necrotizing fasciitis wounds: a retrospective cohort study

Ifeanyi C. Agwulonu; Udemeobong Obong; Moses Oyewumi; Chinoso Osuala; Aikomien Usuanlele; Hakeem Badmus; Oluyemisi Okwudishu

doi:10.18203/2349-2902.isj20253009

Authors

Ifeanyi C. Agwulonu Department of Surgery, Babcock University Teaching Hospital, Ilishan Remo, Nigeria
Udemeobong Obong Department of Surgery, Babcock University Teaching Hospital, Ilishan Remo, Nigeria
Moses Oyewumi Department of Surgery, Babcock University Teaching Hospital, Ilishan Remo, Nigeria
Chinoso Osuala Department of Orthopedics, Ebonyi State Teaching Hospital, Abakaliki, Nigeria
Aikomien Usuanlele Department of Orthopedics, National Orthopaedic Hospital Igbobi, Nigeria
Hakeem Badmus Hospital for Trauma and Surgery, Lekki, Nigeria
Oluyemisi Okwudishu Department of Surgery, Babcock University Teaching Hospital, Ilishan Remo, Nigeria

DOI:

https://doi.org/10.18203/2349-2902.isj20253009

Keywords:

Wound infection, Wound healing, Topical therapy, Resource limited settings, Hydrogen peroxide, Metronidazole, Necrotizing fasciitis, Povidone iodine

Abstract

Background: Necrotizing fasciitis (NF) is a rapidly progressive soft tissue infection requiring prompt surgical and antimicrobial management. While systemic antibiotics are essential, topical therapy may enhance local control. This study compares the clinical efficacy of standard topical therapy (saline+honey) versus a triple combination regimen (metronidazole, povidone iodine and hydrogen peroxide) in NF wound care.

Methods: This retrospective cohort study analyzed 50 patients with NF treated at a tertiary center in Nigeria between January 2022 and March 2024. Patients were divided into two groups: a standard therapy group (n=25) and a triple-combination therapy group (n=25). Primary outcomes included final white blood cell (WBC) count, percent wound effluent reduction and time to granulation tissue appearance. Secondary outcomes were treatment success rate and need for repeat debridement. Independent t-tests and chi-square analyses were used. A p-value<0.05 was considered significant.

Results: Baseline WBC counts were similar between groups (p=0.341). The triple-combination group achieved significantly lower final WBC counts (4,900±1234 cells/µl) compared to the standard group (5,125±1435 cells/µl; p=0.001). Wound effluent reduction was also greater in the triple group (81.97%±8.92) vs. standard (64.67%±10.11; p=0.001). Granulation tissue appeared earlier in the triple group (4.48±0.79 days) than in the standard group (6.89±1.98 days; p=0.001). Treatment success was significantly higher with triple therapy (84.0%) versus standard (56.0%; χ²=4.667, p=0.031).

Conclusions: Triple-combination topical therapy with metronidazole, povidone iodine and hydrogen peroxide led to superior clinical outcomes compared to standard care, achieving faster infection resolution, enhanced wound granulation and higher treatment success rates. This approach may offer a cost-effective, accessible adjunct in NF care, particularly in resource-limited settings.

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References

Van SF, Vries J, Bijker. Review of 58 patients with necrotizing fasciitis in the Netherlands. World J Emerg Surg. 2016;11(1):21. DOI: https://doi.org/10.1186/s13017-016-0080-7

Peetermans M, Prost N, Eckmann C. Necrotizing skin and soft tissue infections in the intensive care unit. Clinical microbiology and infection. European Soc Clin Microbiol Infect Dis. 2020;2:98. DOI: https://doi.org/10.1016/j.cmi.2019.06.031

Vieira RA, Zucca Mathes AG, Michelli RA, Ribeiro GH, Haikel RL, Viana CR, et al. Necrotizing soft tissue infection of the breast: case report and literature review. Surg Infect. 2012;13(4):270-5. DOI: https://doi.org/10.1089/sur.2011.029

Golger A, Ching S, Goldsmith CH, Pennie RA, Bain JR. Mortality in patients with necrotizing fasciitis. Plast Reconst Surg. 2007;119(6):1803-7. DOI: https://doi.org/10.1097/01.prs.0000259040.71478.27

Nawijn F, de Gier B, Brandwagt DA, Groenwold RH, Keizer J, Hietbrink F. Incidence and mortality of necrotizing fasciitis in The Netherlands: the impact of group A Streptococcus. BMC Infect Dis. 2021;21(1):1217. DOI: https://doi.org/10.1186/s12879-021-06928-5

Abdallah T, Challita C, Daou C. A 10-year retrospective review of necrotizing fasciitis at a tertiary referral hospital in a low/middle income country. Open Forum Infect Dis. 2025;12:631. DOI: https://doi.org/10.1093/ofid/ofae631.947

Paul P, Prabhakaran I, Chisthi M. Mortality from necrotizing fasciitis: a cross-sectional study. 2020. DOI: https://doi.org/10.18203/2349-2902.isj20201036

Gore MR. Odontogenic necrotizing fasciitis: a systematic review of the literature. BMC Ear, Nose and Throat Disorders. 2018;18(1):14. DOI: https://doi.org/10.1186/s12901-018-0059-y

Lohawatcharagul T, Jamjittrong S, Suenghataiphorn T. P-754. Retrospective study of necrotizing fasciitis: a review of 99 cases in a tertiary care center in eastern Thailand from 2022 to 2023. Open Forum Infectious Diseases. 2023;2:67.

Davies HD. Flesh-eating disease: A note on necrotizing fasciitis. Paediatr Child Health. 2001;6(5):243-7. DOI: https://doi.org/10.1093/pch/6.5.243

Misiakos EP, Bagias G, Patapis P, Sotiropoulos D, Kanavidis P, Machairas A. Current concepts in the management of necrotizing fasciitis. Front. Surg. 2014;1:36. DOI: https://doi.org/10.3389/fsurg.2014.00036

Mirghani R, Saba T, Khaliq H, Mitchell J, Do L, Chambi L, et al. Biofilms: Formation, drug resistance and alternatives to conventional approaches. AIMS Microbiol. 2022;8(3):239-77. DOI: https://doi.org/10.3934/microbiol.2022019

Linge CC, Kullberg RF, Chouchane O, Roelofs JJ, Goessens WH, van ‘t Veer C, et al. Topical adjunctive treatment with flagellin augments pulmonary neutrophil responses and reduces bacterial dissemination in multidrug-resistant K. pneumoniae infection. Front Immunol. 2024;15:1450486. DOI: https://doi.org/10.3389/fimmu.2024.1450486

Leitsch D. A review on metronidazole: an old warhorse in antimicrobial chemotherapy. Parasitology. 2019;146(9):1167-78. DOI: https://doi.org/10.1017/S0031182017002025

Li FF, Zhang PL, Tangadanchu VK, Li S, Zhou CH. Novel metronidazole-derived three-component hybrids as promising broad-spectrum agents to combat oppressive bacterial resistance. Bioorg Chemist. 2022;122:105718. DOI: https://doi.org/10.1016/j.bioorg.2022.105718

Dingsdag SA, Hunter N. Metronidazole: an update on metabolism, structure–cytotoxicity and resistance mechanisms. J Antimicrob Chemoth. 2018;73(2):265-79. DOI: https://doi.org/10.1093/jac/dkx351

Brook I. Spectrum and treatment of anaerobic infections. J Infect Chemoth. 2016;22(1):1-3. DOI: https://doi.org/10.1016/j.jiac.2015.10.010

Lyvers E, Elliott DP. Topical metronidazole for odor control in pressure ulcers. The Consultant Pharmacist®. 2015;30(9):523-6. DOI: https://doi.org/10.4140/TCP.n.2015.523

Harano H, Matsunuma R, Tanaka-Yagi Y. Malodour from oral malignant fungating wound: sprayed metronidazole – case report. BMJ Support Pall Care. 2013;13:966-7. DOI: https://doi.org/10.1136/spcare-2022-004137

Reimer K, Wichelhaus TA, Schäfer V, Rudolph P, Kramer A, Wutzler P, et al. Antimicrobial effectiveness of povidone-iodine and consequences for new application areas. Dermatology. 2002;204(1):114-20. DOI: https://doi.org/10.1159/000057738

Bigliardi P, Alsagoff S, El-Kafrawi H. Povidone iodine in wound healing: A review of current concepts and practices. Int J Surg. 2017;44:260-8. DOI: https://doi.org/10.1016/j.ijsu.2017.06.073

Barreto R, Barrois B, Lambert J, Malhotra-Kumar S, Santos-Fernandes V, Monstrey S. Addressing the challenges in antisepsis: focus on povidone iodine. International J Antimicrob Agen. 2020;56(3):106064. DOI: https://doi.org/10.1016/j.ijantimicag.2020.106064

Ríos-Castillo A, González‐Rivas F, Rodríguez-Jerez J. Bactericidal efficacy of hydrogen peroxide-based disinfectants against gram-positive and gram-negative bacteria on stainless steel surfaces. J Food Sci. 82(10):2351-6. DOI: https://doi.org/10.1111/1750-3841.13790

Sen A, Imlay JA. How microbes defend themselves from incoming hydrogen peroxide. Front Immunol. 2021;12:667343. DOI: https://doi.org/10.3389/fimmu.2021.667343

Almasaudi S. The antibacterial activities of honey. Saudi J Biol Sci. 2020;28:2188-96. DOI: https://doi.org/10.1016/j.sjbs.2020.10.017

Zhu G, Wang Q, Lu S, Niu Y. Hydrogen peroxide: a potential wound therapeutic target. Med Princ Pract. 2017;26(4):301-8. DOI: https://doi.org/10.1159/000475501

Zubko EI, Zubko MK. Co-operative inhibitory effects of hydrogen peroxide and iodine against bacterial and yeast species. BMC Res. 2013;6:272. DOI: https://doi.org/10.1186/1756-0500-6-272

Wan L, Sankaranarayanan J, Lee CY, Zhou H, Yoon TR, Seon JK, et al. Povidone-iodine and hydrogen peroxide combination improves the anti-biofilm activity of the individual agents on Staphylococcus aureus. Int J Mol Sci. 2025;6;26(9):4390. DOI: https://doi.org/10.3390/ijms26094390

Ding M, Zhang Y, Li X, Li Q, Xiu W, He A, et al. Simultaneous biofilm disruption, bacterial killing, and inflammation elimination for wound treatment using silver embellished polydopamine nanoplatform. Small. 2024;20(36):2400927. DOI: https://doi.org/10.1002/smll.202400927

Wong CH, Khin LW, Heng KS, Tan KC, Low CO. The LRINEC (Laboratory Risk Indicator for Necrotizing Fasciitis) score: a tool for distinguishing necrotizing fasciitis from other soft tissue infections. Crit Care Med. 2004;32(7):1535-41. DOI: https://doi.org/10.1097/01.CCM.0000129486.35458.7D