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Antibiotic resistance and biofilm-forming ability of α-toxin-positive Clostridium septicum isolates worsen patient prognosis

. 2023 Aug ; 131 (8) : 434-441. [epub] 20230625

Language English Country Denmark Media print-electronic

Document type Journal Article

Grant support
Faculty of Medicine Ostrava, University of Ostrava
APVV 19-0519 Slovak Research and Development Agency

A total of, 78 Clostridium septicum (CLSE) isolates were screened for genes encoding: α-toxin, flagellin, and resistance to vancomycin (VANg). The isolates were also tested for their ability to form biofilm and their antibiotic susceptibility. All isolates were positive for α-toxin and flagellin genes. However, only 19 isolates (24.3%) showed prevalence for VANg. We observed the strongest capacity to form a biofilm (100%) in isolates from patients with oncologic or septic and febrile diagnoses. This percentage was also very high in patients with colitis and gastrointestinal hemorrhage (72.7%). No less than 43 isolates showed antibiotic resistance, and 21 were multidrug-resistant (MDR). Interestingly, our studies showed a correlation between antibiotic resistance and biofilm formation. A statistically significant difference was observed between biofilm-forming MDR isolates and those with low/no biofilm-forming ability. However, the most impressive observation was the correlation with mortality rate. While the overall mortality rate for CLSE infections was 16.7% (13/78), the mortality rate for patients infected with MDR isolates forming biofilm moderately or strongly reached 38.1% (8/21). This number increased even further when only infections with the biofilm-forming VANg-positive isolates were considered (61.5%; 8/13). Therefore, the ability of a VANg-positive CLSE isolate to form a biofilm has been suggested as a biomarker of poor prognosis.

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Jing W, Pilato JL, Kay C, Feng S, Tuipulotu DE, Mathur A, et al. Clostridium septicum α- toxin activates the NLRP3 inflammasome by engaging GPI-anchored proteins. Sci Immunol. 2022;7:71.

Macfarlane S, Hopkins MJ, Macfarlane GT. Toxin synthesis and mucin breakdown are related to swarming phenomenon in Clostridium septicum. Infect Immun. 2001;69(2):1120-6.

Kousa O, Essa A, Ramadan B, Aly A, Awad D, Zhao X, et al. Multiorgan fatal gas gangrene in the setting of Clostridium septicum bacteremia: a case report. J Emerg Crit Care Med. 2020;4:21-1.

Stevens DL, Musher DM, Watson DA, Eddy H, Hamill RJ, Gyorkey F, et al. Spontaneous, nontraumatic gangrene due to Clostridium septicum. Clin Infect Dis. 1990;12(2):286-96.

Granok AB, Mahon PA, Biesek GW. Clostridium septicum empyema in an immunocompetent woman. Case Rep Med. 2010;20(ID231738):1-4.

Gordon VM, Nelson KL, Buckley JT, Stevens VL, Tweten RK, Elwood PC, et al. Clostridium septicum alpha toxin uses glycosylphosphatidylinositol-anchored protein receptors. J Biol Chem. 1999;274(38):27274-80.

Kennedy CL, Krejany EO, Young LF, O'Connor JR, Awad MM, Boyd RL, et al. The α-toxin of Clostridium septicum is essential for virulence. Mol Microbiol. 2005;57(5):1357-66.

Sedarat Z, Taylor-Robinson AW. Biofilm formation by pathogenic bacteria: applying a Staphylococcus aureus model to appraise potential targets for therapeutic intervention. Pathogens. 2022;11(4):388.

Mann R, Holmes A, McNeilly O, Cavaliere R, Sotiriou GA, Rice SA, et al. Evolution of biofilm-forming pathogenic bacteria in the presence of nanoparticles and antibiotic: adaptation phenomena and cross-resistance. J Nanobiotechnol. 2021;19(1):291.

Thomas P, Abdel-Glil MY, Subbaiyan A, Busch A, Eichhorn I, Wieler LH, et al. First comparative analysis of Clostridium septicum genomes provides insights into the taxonomy, species genetic diversity, and virulence related to gas gangrene. Front Microbiol. 2021;12(771945):1-18.

Kennedy CL, Lyras D, Cordner LM, Melton-Witt J, Emmins JJ, Tweten RK, et al. Pore-forming activity of alpha-toxin is essential for Clostridium septicum-mediated Myonecrosis. Infect Immun. 2009;77(3):943-51.

Melton-Witt JA, Bentsen LM, Tweten RK. Identification of functional domains of Clostridium septicum alpha toxin. Biochemistry. 2006;45(48):14347-54.

Sivasubramanian G. Rapidly progressive and fatal distant spontaneous gas gangrene due to Clostridium septicum after biopsy of malignant cecal mass. IDCases. 2021;24:e01129.

Sharma P, Tanveer N, Dixit S. Histopathological features of gas gangrene. Indian J Pathol Microbiol. 2022;65(1):211-2.

Haruka K, Harumi G, Kazutaka F, Yukiko K, Taijiro S, Kousei M, et al. Rapidly progressive fatal gas gangrene due to Clostridium septicum in a patient with colon cancer revealed by autopsy. Int J Crit Care Emerg Med. 2017;3:2.

Justesen US, Nielsen SL, Jensen TG, Dessau RB, Møller JK, Coia JE, et al. Bacteremia with anaerobic bacteria and association with colorectal cancer: a population-based cohort study. Clin Infect Dis. 2022;75(10):1747-53.

Alvarez VF, Alvarez VF, Linares-Sanchez M, Botas-Velasco M, Canto-Peruyera PD, Alvarez-Garcia L, et al. Emphysematous abdominal aortic aneurysm by Clostridium septicum with synchronous colon cancer. Int J Surg Case Rep. 2022;5(3):1-3.

Seely KD, Morgan AD, Hagenstein LD, Florey GM, Small JM. Bacterial involvement in progression and metastasis of colorectal neoplasia. Cancer. 2022;14(4):1019.

Sidhu JS, Mandal A, Virk J, Gayam V. Early detection of colon cancer following incidental finding of Clostridium septicum bacteremia. J Investig Med High Impact Case Rep. 2019;7:232470961983205.

Zurmeyer S, Fotopoulou C, Braicu E, Schlichting U, Sehouli J. Clostridium septicum can cause distant myonecrosis in patients with ovarian cancer. Anticancer Res. 2013;33(4):1585-9.

Panikkath R, Konala V, Panikkath D, Umyarova E, Hardwicke F. Fatal Clostridium septicum infection in a patient with a hematological malignancy. Proc (Bayl Univ Med Cent). 2014;27(2):111-2.

Nagy E, Justesen US, Eitel Z, Urbán E. Development of EUCAST disk diffusion method for susceptibility testing of the Bacteroides fragilis group isolates. Anaerobe. 2015;31:65-71.

Erikstrup LT, Danielsen TKL, Hall V, Olsen KEP, Kristensen B, Kahlmeter G, et al. Antimicrobial susceptibility testing of Clostridium difficile using EUCAST epidemiological cutoff values and disk diffusion correlates. Clin Microbiol Infect. 2012;18(8):E266-72.

Takeuchi S, Hashizume N, Kinoshita T, Kaidoh T, Tamura Y. Detection of Clostridium septicum Hemolysin gene by polymerase chain reaction. J Vet Med A. 1997;59(9):853-5.

Aldape MJ, Bayer CR, Rice SN, Bryant AE, Stevens DL. Comparative efficacy of antibiotics in treating experimental Clostridium septicum infection. Int J Antimicrob Agents. 2018;52(4):469-73.

Gazioglu A, Karagülle B, Yüksel H, Nuri Açık M, Keçeci H, Dörtbudak MB, et al. Sudden death due to gas gangrene caused by Clostridium septicum in goats. BMC Vet Res. 2018;14(1):406.

Stepanovic S, Vukovic D, Hola V, Bonaventura GD, Djukic S, Ćirkovic I, et al. Quantification of biofilm in microtiter plates: overview of testing conditions and practical recommendations for assessment of biofilm production by Staphylococci. APMIS. 2007;115(8):891-9.

Stoodley P, Sauer K, Davies DG, Costerton JW. Biofilms as complex differentiated communities. Annu Rev Microbiol. 2002;56(1):187-209.

Costerton J. Introduction to biofilm. Int J Antimicrob Agents. 1999;11(3-4):217-21.

Hernández-Jiménez E, del Campo R, Toledano V, Vallejo-Cremades MT, Muñoz A, Largo C, et al. Biofilm vs. planktonic bacterial mode of growth: which do human macrophages prefer? Biochem Biophys Res Commun. 2013;441(4):947-52.

Dahmus JD, Kotler DL, Kastenberg DM, Kistler CA. The gut microbiome and colorectal cancer: a review of bacterial pathogenesis. J Gastrointest Oncol. 2018;9(4):769-77.

Minasyan H. Sepsis and septic shock: pathogenesis and treatment perspectives. J Crit Care. 2017;40:229-42.

Skrupky LP, Kerby PW, Hotchkiss RS. Advances in the management of sepsis and the understanding of key immunologic defects. Anesthesiology. 2011;115(6):1349-62.

Raimondi S, Musmeci E, Candeliere F, Amaretti A, Rossi M. Identification of mucin degraders of the human gut microbiota. Sci Rep. 2021;11(1):11094.

Wan J, Zhang Y, He W, Tian Z, Lin J, Liu Z, et al. Gut microbiota and metabolite changes in patients with ulcerative colitis and clostridioides difficile infection. Front Microbiol. 2022;13:1-13.

Jessamy K, Ojevwe FO, Ubagharaji E, Sharma A, Anozie O, Gilman CA, et al. Clostridium septicum: an unusual link to a lower gastrointestinal bleed. Case Rep Gastroenterol. 2016;10(2):489-93.

Banawas SS. Systematic review and meta-analysis on the frequency of antibiotic-resistant clostridium species in Saudi Arabia. Antibiotics. 2022;11(9):1165.

Alexander CJ, Citron DM, Brazier JS, Goldstein EJ. Identification and antimicrobial resistance patterns of clinical isolates of Clostridium clostridioforme, Clostridium innocuum, and Clostridium ramosum compared with those of clinical isolates of clostridium perfringens. J Clin Microbiol. 1991;33(12):3209-15.

Evans DJ, Allison DG, Brown MRW, Gilbert P. Susceptibility of Pseudomonas aeruginosa and Escherichia coli biofilms towards ciprofloxacin: effect of specific growth rate. J Antimicrob Chemother. 1991;27(2):177-84.

Suci PA, Mittelman MW, Yu FP, Geesey GG. Investigation of ciprofloxacin penetration into Pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother. 1994;38(9):2125-33.

Elhadi M, Khaled A, Msherghi A. Infectious diseases as a cause of death among cancer patients: a trend analysis and population-based study of outcome in the United States based on the surveillance, epidemiology, and end results database. Infect Agents Cancer. 2021;16(1):72.

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