Bismuth Concentrations in Patients Treated in Real-Life Practice with a Bismuth Subcitrate-Metronidazole-Tetracycline Preparation: The SAPHARY Study

Guiard, Estelle; Lelièvre, Bénédicte; Rouyer, M.; Zerbib, Frank; Diquet, Bertrand; Mégraud, Françis; Tison, François; Bignon, Emmanuelle; Lassalle, R.; Droz–Perroteau, C.; Moore, Nicholas; Blin, Patrick

doi:10.1007/s40264-019-00821-6

Cited by 12 publications

(8 citation statements)

References 32 publications

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“…Neurological symptoms associated with the use of bismuth are associated with increased blood levels, especially in elderly patients . Nonetheless, only mild dizziness or headache was reported in seven patients irrespective of age in this study.…”

Section: Discussioncontrasting

confidence: 62%

“…19 Neurological symptoms associated with the use of bismuth are associated with increased blood levels, especially in elderly patients. 20 Nonetheless, only mild dizziness or headache was reported in seven patients irrespective of age in this study. Abdominal pain, discomfort, and distention occurred more frequently in the four times a day group which required two times the dose and frequency than in the twice a day group.…”

Section: Ta B L Ementioning

confidence: 50%

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Efficacy and safety of twice a day, bismuth‐containing quadruple therapy using high‐dose tetracycline and metronidazole for second‐line Helicobacter pylori eradication

et al. 2020

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Background/Aims Conventional second‐line, bismuth‐containing quadruple therapy is administered four times a day. We aimed to evaluate the efficacy and safety of twice a day administration compared to the four times a day therapy. Methods Medical records of consecutive patients with positive 13C‐urea breath tests (UBTs) after first‐line eradication were reviewed. From December 2018 to June 2019, 100 consecutive 13C‐UBT‐positive patients received tetracycline 1 g, metronidazole 750 mg, bismuth subcitrate 300 mg, and pantoprazole 20 mg twice a day for one week. The same number of consecutive13C‐UBT‐positive patients before December 2018 was included as controls. The control group received tetracycline 500 mg and bismuth subcitrate 300 mg four times a day, metronidazole 500 mg three times a day, and pantoprazole 20 mg twice a day for one week. Eradication was confirmed based on a 13C‐UBT performed in the 5th week after taking quadruple therapy. Results Ninety‐eight patients from the twice a day group and 99 patients from the four times a day group were analyzed. The eradication rate did not differ between the twice a day group (92/98, 93.9%) and the four times a day group (92/99, 92.9%). Adverse drug effects were found in 36 patients from the twice a day group and 50 patients from the four times a day group (P = .051). Abdominal pain, discomfort, and distention were more common with four times a day intake (13.1%) than with twice a day intake (4.1%; P = .024). Conclusions We determined for the first time that twice a day intake of bismuth‐containing quadruple therapy using 2 g/d of tetracycline, 1.5 g/d of metronidazole, and 600 mg/d of bismuth subcitrate for one week is effective and safe as the conventional four times a day therapy. Twice a day intake decreased abdominal pain, discomfort, and distention.

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Section: Discussioncontrasting

confidence: 62%

Section: Ta B L Ementioning

confidence: 50%

Efficacy and safety of twice a day, bismuth‐containing quadruple therapy using high‐dose tetracycline and metronidazole for second‐line Helicobacter pylori eradication

et al. 2020

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“…It is known that the serum concentration of bismuth after intake of one tablet of CBS can only reach a rather low level (44.5 μg/L or 0.2129 μM) ( Vanhoe et al, 1993 ). In addition, the standard use of bismuth subcitrate, metronidazole, and tetracycline (BMT) for targeting Helicobacter pylori generates a relatively low concentration of blood bismuth (16.9 μg/L or 0.081 μM) ( Guiard et al, 2019 ). Taken together, these findings indicate that such oral dosage of bismuth is far away from providing effective control of P. gingivalis in terms of its MIC (1,306 μg/L or 6.25 μM).…”

Section: Discussionmentioning

confidence: 99%

Eradication of Porphyromonas gingivalis Persisters Through Colloidal Bismuth Subcitrate Synergistically Combined With Metronidazole

Wang

Xuan²,

Cheng³

et al. 2021

Front. Microbiol.

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Microbial persisters enable the development of certain intrinsic strategies for survival with extreme tolerance to multiple antimicrobials. Porphyromonas gingivalis is considered to be the “keystone” periodontopathogen. Indeed, periodontitis, as a highly common inflammatory disease, is the major cause of severe tooth loss and edentulism in adults globally, and yet it is crucially involved in various systemic comorbidities like diabetes. We have recently revealed P. gingivalis persisters-induced perturbation of immuno-inflammatory responses and effective suppression of this key pathogen by bismuth drugs. This study further explored novel approaches to eradicating P. gingivalis persisters through synergistic combination of colloidal bismuth subcitrate (CBS) with traditional antibiotics. P. gingivalis (ATCC 33277) cells in planktonic and biofilm states were cultured to stationary phase, and then treated with metronidazole (100 mg/L), amoxicillin (100 mg/L), CBS, (100 μM) and combinations of these medications, respectively. Persister survival rate was calculated by colony-forming unit. Cell viability and cytotoxicity of CBS were assessed in human gingival epithelial cells (HGECs). Notably, CBS combined with metronidazole enabled the effective eradication of P. gingivalis persisters in planktonic mode, and nearly eliminated their existence in biofilm mode. Importantly, CBS exhibited no effects on the viability of HGECs, along with minimal cytotoxicity (<5%) even at a high concentration (400 μM). This pioneering study shows that P. gingivalis persisters could be well eliminated via the synergistic combination of CBS with metronidazole. Our findings may contribute to developing novel approaches to tackling periodontitis and inflammatory systemic comorbidities.

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“…Dose reduction is required when there is a risk of drug interactions 8 . Furthermore, adverse neurological effects are associated with increased blood levels of bismuth, especially in older patients 9 . Patients with low body weight also show more adverse drug effects; however, their eradication rate is higher than that of their counterparts 10 .…”

Section: Introductionmentioning

confidence: 99%

“…8 Furthermore, adverse neurological effects are associated with increased blood levels of bismuth, especially in older patients. 9 Patients with low body weight also show more adverse drug effects; however, their eradication rate is higher than that of their counterparts. 10 Altogether, a shorter duration and dose reduction might be helpful for patients with low body weight and those with comorbidities.…”

Section: Introductionmentioning

confidence: 99%

Twice‐daily intake of bismuth‐based quadruple therapy for first‐line Helicobacter pylori eradication: A retrospective study on 10‐day, 14‐day, and half‐dose antibiotic therapy

et al. 2023

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Background/Aims: In areas with >15% clarithromycin resistance, bismuth-based quadruple therapy is recommended for first-line Helicobacter pylori eradication. This study aimed to determine the efficacy of the twice-daily intake of bismuth-based quadruple therapy among 10-day, 14-day, and half-dose antibiotic regimens. Methods:From May 2021 to March 2023, H. pylori-infected Korean adults were administered tetracycline (1 g), metronidazole (750 mg), bismuth potassium citrate (300 mg), and lansoprazole (30 mg) twice daily, after breakfast and dinner, for 10 days.The regimen was administered for 14 days if the body weight was ≥70 kg or if the patient had reinfection. Half doses of antibiotics were administered for 14 days if there was a risk of drug interactions or if the patient was aged ≥75 years. The 13 C-urea breath test was performed after 6 weeks.Results: Among the 1258 infected Koreans, 85.1% (412/484) in the 10-day, 84.3% (498/591) in the 14-day, and 86.3% (158/183) in the half-dose antibiotic groups followed the instructions. In the per-protocol (PP) analysis, eradication rates were higher in the 10-day (90.5%, p = 0.019) and 14-day (90.2%, p = 0.023) groups than in the halfdose group (83.5%). In the intention-to-treat (ITT) analysis, eradication rates were higher in the 10-day group (80.6%) than in the half-dose group (73.2%, p = 0.039). In the half-dose group, the eradication rate was lower in patients aged ≥75 years (PP: 74.6%, ITT: 66.2%) than in those with a risk of drug interactions (PP: 89.7% [p = 0.017], ITT: 82.4% [p = 0.019]).Conclusions: Twice-daily intake of bismuth-based quadruple therapy for 10-14 days showed an eradication rate of >90% in the PP analysis. A 10-day regimen could be administered to eradication-naive patients with a body weight below 70 kg. A half-dose antibiotic regimen might be recommended to patients with a risk of drug interactions but not to those aged ≥75 years simply due to old age.

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Bismuth Concentrations in Patients Treated in Real-Life Practice with a Bismuth Subcitrate-Metronidazole-Tetracycline Preparation: The SAPHARY Study

Cited by 12 publications

References 32 publications

Efficacy and safety of twice a day, bismuth‐containing quadruple therapy using high‐dose tetracycline and metronidazole for second‐line Helicobacter pylori eradication

Efficacy and safety of twice a day, bismuth‐containing quadruple therapy using high‐dose tetracycline and metronidazole for second‐line Helicobacter pylori eradication

Eradication of Porphyromonas gingivalis Persisters Through Colloidal Bismuth Subcitrate Synergistically Combined With Metronidazole

Twice‐daily intake of bismuth‐based quadruple therapy for first‐line Helicobacter pylori eradication: A retrospective study on 10‐day, 14‐day, and half‐dose antibiotic therapy

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