Quadruple therapy with furazolidone for retreatment in patients with peptic ulcer disease

Felga, Guilherme Eduardo Gonçalves; Silva, Fernando Marcuz; Barbuti, Ricardo Correa; Navarro–Rodriguez, Tomás; Zaterka, Schlioma; Eisig, Jaime Natan

doi:10.3748/wjg.14.6224

Cited by 18 publications

(15 citation statements)

References 31 publications

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“…We have read with great interest the study performed in Brazil by Felga et al [1] on the efficacy and safety of a 'rescue' therapy to cure Helicobacter pylori (H pylori) infection. Briefly, following a quadruple therapy including PPI, bismuth salts, amoxicillin and furazolidone, a 68.8% eradication rate was achieved, a side-effect incidence of 31.4% was observed, and treatment interruption occurred in 3 (6.7%) out of 45 controlled patients.…”

Section: To the Editormentioning

confidence: 99%

Furazolidone therapy for Helicobacter pylori: Is it effective and safe?

Francesco¹,

Ierardi²,

Hassan³

et al. 2009

WJG

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Section: To the Editormentioning

confidence: 99%

Furazolidone therapy for Helicobacter pylori: Is it effective and safe?

Francesco¹,

Ierardi²,

Hassan³

et al. 2009

WJG

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“…In the 3 decades since the discovery of the bacterium, treatment strategies for H. pylori infection have undergone tremendous evolutionary changes that span from monotherapy to multidrug therapy for extended periods of treatment (15). Though initially favored, monotherapy and dual therapy for 4 to 7 days were the first treatments to be shown to result in eradication failure (21).…”

mentioning

confidence: 99%

The Oligo-Acyl Lysyl Antimicrobial Peptide C ₁₂ K-2β ₁₂ Exhibits a Dual Mechanism of Action and Demonstrates Strong In Vivo Efficacy against Helicobacter pylori

Makobongo

Gancz

Carpenter

et al. 2012

Antimicrob Agents Chemother

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Helicobacter pylori has developed antimicrobial resistance to virtually all current antibiotics. Thus, there is a pressing need to develop new anti-H. pylori therapies. We recently described a novel oligo-acyl-lysyl (OAK) antimicrobial peptidomimetic, C 12 K-2␤ 12 , that shows potent in vitro bactericidal activity against H. pylori. Herein, we define the mechanism of action and evaluate the in vivo efficacy of C 12 K-2␤ 12 against H. pylori after experimental infection of Mongolian gerbils. We demonstrate using a 1-N-phenylnaphthylamine (fluorescent probe) uptake assay and electron microscopy that C 12 K-2␤ 12 rapidly permeabilizes the bacterial membrane and creates pores that cause bacterial cell lysis. Furthermore, using nucleic acid binding assays, Western blots, and confocal microscopy, we show that C 12 K-2␤ 12 can cross the bacterial membranes into the cytoplasm and tightly bind to bacterial DNA, RNA, and proteins, a property that may result in inhibition of enzymatic activities and macromolecule synthesis. To define the in vivo efficacy of C 12 K-2␤ 12 , H. pylori-infected gerbils were orogastrically treated with increasing doses and concentrations of C 12 K-2␤ 12 1 day or 1 week postinfection. The efficacy of C 12 K-2␤ 12 was strongest in animals that received the largest number of doses at the highest concentration, indicating dose-dependent activity of the peptide (P < 0.001 by analysis of variance [ANOVA]) regardless of the timing of the treatment with C 12 K-2␤ 12 . Overall, our results demonstrate a dual mode of action of C 12 K-2␤ 12 against the H. pylori membrane and cytoplasmic components. Moreover, and consistent with the previously reported in vitro efficacy, C 12 K-2␤ 12 shows significant in vivo efficacy against H. pylori when used as monotherapy. Therefore, OAK peptides may be a valuable resource for therapeutic treatment of H. pylori infection.

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“…Since the original isolation of H. pylori in the early 1980s, treatment of the bacterial infection has undergone a significant evolutionary development from initial monotherapy to dual, triple, and in more recent trials quadruple therapy (8,18). Current treatment strategies employ combination therapy, since single-antibiotic therapy often results in failure to eradicate the infection (21).…”

mentioning

confidence: 99%

In Vitro Antibacterial Activity of Acyl-Lysyl Oligomers againstHelicobacter pylori

Makobongo

Kovachi

Gancz

et al. 2009

Antimicrob Agents Chemother

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The gastric pathogen Helicobacter pylori has developed resistance to virtually all current antibiotics; thus, there is a pressing need to develop new anti-H. pylori therapies. The goal of this work was to evaluate the antibacterial effect of oligo-acyl-lysyl (OAK) antimicrobial peptidomimetics to determine if they might represent alternatives to conventional antibiotic treatment of H. pylori infection. A total of five OAK sequences were screened for growthinhibitory and/or bactericidal effects against H. pylori strain G27; four of these sequences had growth-inhibitory and bactericidal effects. The peptide with the highest efficacy against strain G27, C 12 K-2␤ 12 , was selected for further characterization against five additional H. pylori strains (26695, J99, 7.13, SS1, and HPAG1). C 12 K-2␤ 12 displayed MIC and minimum bactericidal concentration (MBC) ranges of 6.5 to 26 M and 14.5 to 90 M, respectively, across the six strains after 24 h of exposure. G27 was the most sensitive H. pylori strain (MIC ‫؍‬ 6.5 to 7 M; MBC ‫؍‬ 15 to 20 M), whereas 26695 was the least susceptible strain (MIC ‫؍‬ 25 to 26 M; MBC ‫؍‬ 70 to 90 M). H. pylori was completely killed after 6 to 8 h of incubation in liquid cultures containing two times the MBC of C 12 K-2␤ 12 . The OAK demonstrated strong in vitro stability, since efficacy was maintained after incubation at extreme temperatures (4°C, 37°C, 42°C, 50°C, 55°C, 60°C, and 95°C) and at low pH, although reduced killing kinetics were observed at pH 4.5. Additionally, upon transient exposure to the bacteria, C 12 K-2␤ 12 showed irreversible and significant antibacterial effects and was also nonhemolytic. Our results show a significant in vitro effect of C 12 K-2␤ 12 against H. pylori and suggest that OAKs may be a valuable resource for the treatment of H. pylori infection.Helicobacter pylori is a microaerophilic gram-negative bacterium that colonizes the gastric mucosa. It is known to be a principal gastric pathogen of humans and is associated with the development of gastritis, gastric ulcers, duodenal ulcers, and gastric cancer (46,55,56,60). Approximately half of the world's population is infected with H. pylori (79). Thus, the bacterium poses a significant public health problem, which is further compounded by the fact that H. pylori has developed antimicrobial resistance to virtually all current antibiotics, a phenomenon that is hampering efforts to treat the infection (40, 51).Since the original isolation of H. pylori in the early 1980s, treatment of the bacterial infection has undergone a significant evolutionary development from initial monotherapy to dual, triple, and in more recent trials quadruple therapy (8, 18). Current treatment strategies employ combination therapy, since single-antibiotic therapy often results in failure to eradicate the infection (21). The highest H. pylori eradication rates have been reported with triple therapy, which involves the utilization of two antibiotics in combination with bismuth or a proton pump inhibitor, PPI (34,44). Amoxicillin (amoxicil...

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Quadruple therapy with furazolidone for retreatment in patients with peptic ulcer disease

Cited by 18 publications

References 31 publications

Furazolidone therapy for Helicobacter pylori: Is it effective and safe?

Furazolidone therapy for Helicobacter pylori: Is it effective and safe?

The Oligo-Acyl Lysyl Antimicrobial Peptide C ₁₂ K-2β ₁₂ Exhibits a Dual Mechanism of Action and Demonstrates Strong In Vivo Efficacy against Helicobacter pylori

In Vitro Antibacterial Activity of Acyl-Lysyl Oligomers againstHelicobacter pylori

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Quadruple therapy with furazolidone for retreatment in patients with peptic ulcer disease

Cited by 18 publications

References 31 publications

Furazolidone therapy for Helicobacter pylori: Is it effective and safe?

Furazolidone therapy for Helicobacter pylori: Is it effective and safe?

The Oligo-Acyl Lysyl Antimicrobial Peptide C 12 K-2β 12 Exhibits a Dual Mechanism of Action and Demonstrates Strong In Vivo Efficacy against Helicobacter pylori

In Vitro Antibacterial Activity of Acyl-Lysyl Oligomers againstHelicobacter pylori

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Resources

About

The Oligo-Acyl Lysyl Antimicrobial Peptide C ₁₂ K-2β ₁₂ Exhibits a Dual Mechanism of Action and Demonstrates Strong In Vivo Efficacy against Helicobacter pylori