In Vitro Susceptibility and Synergistic Effect of Bismuth Against

Overview

Journal Antibiotics (Basel)

Specialty Pharmacology

Date 2024 Nov 27

PMID 39596699

Authors

Jieun Woo

Chang Seok Bang

Jae Jun Lee

Ji Yong Ahn

Jung Mogg Kim

Hwoon-Yong Jung

Eun Jeong Gong

Affiliations

Soon will be listed here.

Abstract

Bismuth is commonly used in () eradication therapy. However, few studies have examined the in vitro susceptibility of to bismuth. Moreover, the exact mechanism of action of bismuth on remains unclear. The aim of this study was to identify the anti-bacterial effect of bismuth as well as to evaluate potential synergistic effects between bismuth and various antibiotics. The minimum inhibitory concentrations (MICs) of three bismuth preparations, bismuth subsalicylate, bismuth potassium citrate, and colloidal bismuth subcitrate (CBS, De-Nol) were determined for strains using the agar dilution technique. Agar plates of varying pH values from 5.0 to 8.0 were used to investigate whether acidity influences the anti-bacterial effect of bismuth. A checkerboard assay was performed to assess the synergism between CBS and antibiotics (amoxicillin, clarithromycin, and metronidazole). Twelve strains, including three reference strains ( 26695, J99, and ATCC 43504), and nine clinically isolated strains were tested. The MICs for bismuth subsalicylate, bismuth potassium citrate, and CBS ranged from 4 to 32 μg/mL, 2 to 16 μg/mL, and 1 to 8 μg/mL, respectively. The bismuth MICs for the reference strains were similar at pH 5-8. In the checkerboard assay, no interactions between CBS and any of the antibiotics were observed in the reference strains. Bismuth showed in vitro susceptibility against . The enhanced eradication efficacy of bismuth-containing regimens appears to be due to mechanisms other than direct synergy with antibiotics.

References

Ko S, Kim Y, Chung W, Lee S . Bismuth supplements as the first-line regimen for Helicobacter pylori eradication therapy: Systemic review and meta-analysis. Helicobacter. 2019; 24(2):e12565. DOI: 10.1111/hel.12565. View

Armstrong J, Wee S, Goodwin C, Wilson D . Response of Campylobacter pyloridis to antibiotics, bismuth and an acid-reducing agent in vitro--an ultrastructural study. J Med Microbiol. 1987; 24(4):343-50. DOI: 10.1099/00222615-24-4-343. View

Kumar S, Vinella D, De Reuse H . Nickel, an essential virulence determinant of Helicobacter pylori: Transport and trafficking pathways and their targeting by bismuth. Adv Microb Physiol. 2022; 80:1-33. DOI: 10.1016/bs.ampbs.2022.01.001. View

Bland M, Ismail S, Heinemann J, Keenan J . The action of bismuth against Helicobacter pylori mimics but is not caused by intracellular iron deprivation. Antimicrob Agents Chemother. 2004; 48(6):1983-8. PMC: 415606. DOI: 10.1128/AAC.48.6.1983-1988.2004. View

Gong E, Yun S, Jung H, Lim H, Choi K, Ahn J . Meta-analysis of first-line triple therapy for helicobacter pylori eradication in Korea: is it time to change?. J Korean Med Sci. 2014; 29(5):704-13. PMC: 4024949. DOI: 10.3346/jkms.2014.29.5.704. View

Meyer J, Ryu S, Pendland S, Danziger L . In vitro synergy testing of clarithromycin and 14-hydroxyclarithromycin with amoxicillin or bismuth subsalicylate against Helicobacter pylori. Antimicrob Agents Chemother. 1997; 41(7):1607-8. PMC: 163970. DOI: 10.1128/AAC.41.7.1607. View

Marshall B, Warren J . Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet. 1984; 1(8390):1311-5. DOI: 10.1016/s0140-6736(84)91816-6. View

Marshall B, Valenzuela J, McCallum R, Dooley C, Guerrant R, Cohen H . Bismuth subsalicylate suppression of Helicobacter pylori in nonulcer dyspepsia: a double-blind placebo-controlled trial. Dig Dis Sci. 1993; 38(9):1674-80. DOI: 10.1007/BF01303177. View

Jin L, Szeto K, Zhang L, Du W, Sun H . Inhibition of alcohol dehydrogenase by bismuth. J Inorg Biochem. 2004; 98(8):1331-7. PMC: 7126473. DOI: 10.1016/j.jinorgbio.2004.03.016. View

10.

Lee J, Kim N, Nam R, Kim J, Park J, Lee S . High Efficacy of Finafloxacin on Helicobacter pylori Isolates at pH 5.0 Compared with That of Other Fluoroquinolones. Antimicrob Agents Chemother. 2015; 59(12):7629-36. PMC: 4649160. DOI: 10.1128/AAC.01467-15. View

11.

Dore M, Graham D, Mele R, Marras L, Nieddu S, Manca A . Colloidal bismuth subcitrate-based twice-a-day quadruple therapy as primary or salvage therapy for Helicobacter pylori infection. Am J Gastroenterol. 2002; 97(4):857-60. DOI: 10.1111/j.1572-0241.2002.05600.x. View

12.

Odds F . Synergy, antagonism, and what the chequerboard puts between them. J Antimicrob Chemother. 2003; 52(1):1. DOI: 10.1093/jac/dkg301. View

13.

Lambert J, Midolo P . The actions of bismuth in the treatment of Helicobacter pylori infection. Aliment Pharmacol Ther. 1997; 11 Suppl 1:27-33. DOI: 10.1046/j.1365-2036.11.s1.13.x. View

14.

Cun S, Li H, Ge R, Lin M, Sun H . A histidine-rich and cysteine-rich metal-binding domain at the C terminus of heat shock protein A from Helicobacter pylori: implication for nickel homeostasis and bismuth susceptibility. J Biol Chem. 2008; 283(22):15142-51. PMC: 3258894. DOI: 10.1074/jbc.M800591200. View

15.

Ge R, Sun X, Gu Q, Watt R, Tanner J, Wong B . A proteomic approach for the identification of bismuth-binding proteins in Helicobacter pylori. J Biol Inorg Chem. 2007; 12(6):831-42. DOI: 10.1007/s00775-007-0237-7. View

16.

Rauws E, Langenberg W, Houthoff H, Zanen H, Tytgat G . Campylobacter pyloridis-associated chronic active antral gastritis. A prospective study of its prevalence and the effects of antibacterial and antiulcer treatment. Gastroenterology. 1988; 94(1):33-40. View

17.

Van Caekenberghe D, Breyssens J . In vitro synergistic activity between bismuth subcitrate and various antimicrobial agents against Campylobacter pyloridis (C. pylori). Antimicrob Agents Chemother. 1987; 31(9):1429-30. PMC: 174956. DOI: 10.1128/AAC.31.9.1429. View

18.

Grayson M, Eliopoulos G, Ferraro M, Moellering Jr R . Effect of varying pH on the susceptibility of Campylobacter pylori to antimicrobial agents. Eur J Clin Microbiol Infect Dis. 1989; 8(10):888-9. DOI: 10.1007/BF01963775. View

19.

Lee S . A potential mechanism of action of colloidal bismuth subcitrate: diffusion barrier to hydrochloric acid. Scand J Gastroenterol Suppl. 1982; 80:17-21. View

20.

Koo J, Ho J, Lam S, Wong J, Ong G . Selective coating of gastric ulcer by tripotassium dicitrato bismuthate in the rat. Gastroenterology. 1982; 82(5 Pt 1):864-70. View