Additive Effect of Pronase on the Efficacy of Eradication Therapy Against <i>Helicobacter pylori</i>

Gotoh, Akira; Akamatsu, Taiji; Shimizu, Toshiki; Shimodaira, Kazuhisa; Kaneko, Taimei; Kiyosawa, Kendo; Ishida, Kumiko; Ikeno, Tatsuo; Sugiyama, Atsushi; Kawakami, Yoshiyuki; Ota, Hiroyoshi; Katsuyama, Tsutomu

doi:10.1046/j.1523-5378.2002.00079.x

Cited by 35 publications

(24 citation statements)

References 30 publications

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“…Pronase alone did not exhibit an inhibitory effect on H. pylori in vitro, even at concentrations of 3.3 ϫ 10 3 mg/liter, in previous studies (data not shown), which was consistent with previous reports demonstrating that pronase did not inhibit the growth of H. pylori (11). Misoprostol is a mucosal protective agent (26).…”

Section: Discussionsupporting

confidence: 91%

“…A potentially useful method would be to directly improve the local drug concentration in the deep GML. According to Gotoh et al (11), quadruple therapy with lansoprazole, pronase, amoxicillin, and metronidazole could improve the efficacy of H. pylori eradication in humans, which may be due to the increased delivery of antibiotics at the site of infection by virtue of pronase's ability to remove and disrupt the GML. However, the doses of antibiotics were 500 mg of amoxicillin and 250 mg of metronidazole, and the times of therapy were three times daily for 2 weeks, which worsens compliance due to an additional drug being administered at the same time.…”

Section: Discussionmentioning

confidence: 99%

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Efficacy and Pharmacological Mechanism of Pronase-Enhanced Low-Dose Antibiotics for Helicobacter pylori Eradication

Liu

et al. 2014

Antimicrob Agents Chemother

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bThis study examined the efficacy and pharmacological mechanism of pronase-assisted low-dose antibiotics for eradication of Helicobacter pylori. Mongolian gerbils infected with H. pylori received 7-day treatment (omeprazole, different concentrations of pronase, amoxicillin, and clarithromycin), and the efficacy was assessed using the eradication rate and the colonization of H. pylori. In Mongolian gerbils orally administered pronase, the thickness of the gastric mucous layer (GML) was examined using immunohistochemical and alcian blue staining, and the concentrations of amoxicillin in gastric tissue and serum were detected using high-performance liquid chromatography (HPLC). The eradication rates were 80.0% (12/15) in the high-pronase quadruple group (HPQG) and 86.7% (13/15) in the high-antibiotic group (HAG) (P ‫؍‬ 1.000). The antibiotic dose in the HPQG was only 1/20 that in the HAG. Thirty minutes after oral treatment with pronase, the sticky protein of the GML was hydrolyzed, and the GML became thinner. Higher amoxicillin concentrations in both the gastric tissue and serum were observed in the pronase group than in the Am10 group. The concentration of amoxicillin in the Am10-plus-Pr108 group in gastric tissue was 3.8 times higher than in the Am10 group in 5 min. Together, these data suggest that pronase significantly reduced the dose of antibiotics used in H. pylori eradication. The pharmacological mechanism is likely pronase removal of the mucus layer, promoting chemical factor (i.e., gastric acid and pepsinogen) distribution and increasing the antibiotic concentrations in the deep GML, which acted on H. pylori collectively. Thus, pronase may enhance the level of antibiotics for eradication of H. pylori in the clinic.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Efficacy and Pharmacological Mechanism of Pronase-Enhanced Low-Dose Antibiotics for Helicobacter pylori Eradication

Liu

et al. 2014

Antimicrob Agents Chemother

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“…Taking these considerations into account, bioadhesive rifaximin formulations able to better and persistently cover gastric mucosa [70, 71], or combination with mucolytic agents, such as pronase or acetylcysteine [72, 73], need to be evaluated in order to better define the place of this antibiotic in our therapeutic armamentarium.…”

Section: Discussionmentioning

confidence: 99%

Eradication of <i>Helicobacter pylori</i>: Are Rifaximin-Based Regimens Effective?

Gasbarrini

Pelosini

et al. 2006

Digestion

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Rifaximin is a non-absorbed semisynthetic rifamycin derivative with a broad spectrum of antibacterial activity including Gram-positive and Gram-negative bacteria, both aerobes and anaerobes. Although originally developed for the treatment of infectious diarrhea, the appreciation of the pathogenic role of gut bacteria in several organic and functional gastrointestinal diseases has increasingly broadened its clinical use. Being the antibiotic active against Helicobacter pylori, even towards clarithromycin-resistant strain, and being the primary resistance very rare, several investigations explored its potential use for eradication of the microorganism. Rifaximin alone proved to be effective, but even the highest dose (1,200 mg daily) gave a cure rate of only 30%. Dual and triple therapies were also studied, with the better results obtained with rifaximin-clarithromycin and rifaximin-clarithromycin-esomeprazole combinations. However, the eradication rates (60–70%) obtained with these regimens were still below the standard set by the Maastricht Consensus guidelines. Although rifaximin-based eradication therapies are promising, new antimicrobial combinations (with and without proton pump inhibitors) need to be explored in well-designed clinical trials including a large cohort of H. pylori-infected patients. The remarkable safety of rifaximin will allow high-dose regimens of longer duration (e.g. 10 or 14 days) to be tested with confidence in the hope of achieving better eradication rates. A drawback of rifaximin could be its inability to reach sufficiently high concentrations in the gastric mucus layer under and within which H. pylori is commonly located and this would likely affect eradication rate. Taking these considerations into account, bioadhesive rifaximin formulations able to better and persistently cover gastric mucosa, or combination with mucolytic agents, such as pronase or acetylcysteine, need to be evaluated in order to better define the place of this antibiotic in our therapeutic armamentarium.

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“…Pronase and N-acetyl cysteine have been used to change the mucus layer and potentially expose the bacteria. In one trial pronase given as 18,000 tyrosine units of pronase thrice daily for 2 weeks significantly increased the effectiveness of traditional triple therapy (eg, from 76.5 to 94%) 72 . Clearly, additional studies are needed.…”

Section: Thinking Outside the Box: The Use Of Treatment Enhancersmentioning

confidence: 99%

New concepts of resistance in the treatment of Helicobacter pylori infections

Graham

Shiotani

2008

Nat Rev Gastroenterol Hepatol

316

368

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SummaryThe prevalence of antimicrobial resistance is now such that all patients should be considered as having resistant infections. Ideally therapy is based on pretreatment susceptibility testing. Empiric therapies should assume antimicrobial resistance and use higher doses for 14 days. Acceptable results are 90-94% cure intention to treat (Grade B) or greater. Clarithromycin-containing triple therapies now typically produce ≤80% cure ITT (Grade F) and are no longer acceptable empiric therapy. Current initial therapy options are between sequential therapy, concomitant therapy, and bismuth containing quadruple therapy. Sequential therapy has the potential to be improved to ≥95% cure ITT (Grade A) by continuing the amoxicillin through the second and/or by increasing the duration. Better appreciation of the role of acidity in phenotypic resistance has resulted in high cure rates with high dose PPI plus amoxicillin dual therapy; additional studies to devise better dual-based multidrug regimes are still needed. Antimicrobial choices following treatment failure is best approached by susceptibility testing. If not available, we recommended a bismuth containing quadruple therapy substituting a new drug for metronidazole/tinidazole and/or clarithromycin if they have been used previously. The alternate would be to use a 14 day high dose PPI, amoxicillin-based triple therapy with rifabutin, a fluoroquinolone, or furazolidone. KeywordsHelicobacter pylori; therapy; resistance; antibiotics; anti-secretory drugs; phenotypic drug resistance; cytochrome P450 "To read without reflecting is like eating without digesting". -86-462-1111-86-462- , FAX 81-86-464-1195 Review criteria: We searched the relevant papers by using computer-assisted bibliographic searches of PubMed through November 30, 2007 using combinations of the following terms: H. pylori combined with resistance, therapy, eradication, second, triple, quadruple, sequential, or rescue. We also reviewed the recent literature on pharmacokinetics and pharmacodynamics in relation to the drugs used in H. pylori therapy and the relation to host cytochrome P450 genotypes to treatment outcome. We did not perform meta-analyses. We reviewed only articles published in English.

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Additive Effect of Pronase on the Efficacy of Eradication Therapy Against Helicobacter pylori

Abstract: Pronase has an additive effect in curing H. pylori infection. Pronase has no apparent in vitro activity against H. pylori, but may improve the local delivery of antibiotics by virtue of its removal and disruption of the SMGL.

Cited by 35 publications

References 30 publications

Efficacy and Pharmacological Mechanism of Pronase-Enhanced Low-Dose Antibiotics for Helicobacter pylori Eradication

Efficacy and Pharmacological Mechanism of Pronase-Enhanced Low-Dose Antibiotics for Helicobacter pylori Eradication

Eradication of <i>Helicobacter pylori</i>: Are Rifaximin-Based Regimens Effective?

New concepts of resistance in the treatment of Helicobacter pylori infections

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