CYP2C19 genotype

[dawnxding]

Hi,
My 12-year-old daughter, who is allergic to penicillin, failed 2 rounds of H pylori treatment. Round 1:prilosec 20 mg BID, Biaxin 500 mg BID, and metronidazole 250 mg TID 10 day course. Round 2: Levofloxacin 500 mg QD, Doxycycline 100 mg BID, Alinia (nitazoxanide) 500mg BID, Prilosec 20 mg BID. She had uper GI endoscopy a week ago, and is waiting for H pylor culture and sensitivity results.

Recently emerging evidence suggests that in addition to antibiotic sensitivity, genotype of CYP2C19, is a determining factor for H pylori treatment success. CYP2C19, is a liver enzyme. Proton pump inhibitor (PPI) is destroyed by the enzyme. If one has a high activity level of the enzyme, standard dose of PPI is not enough to inhibit acid production in stomach. As a result, antibiotics will not work because pH is too low.

I seek expert opinion regarding your experience of CYP2C19 genotyping and selection and dosing of PPI. Thank you so much.

[Helico_expert]

You are doing the right thing. get antibiotic sensitivity test done and you'll get a more effective treatment.

nevertheless, is your daughter's health affected by H. pylori? there are some studies that suggest that H. pylori may be beneficial for children against food allergies and asthma.

[Helico_expert]

In regards to CYP2C19 genotype. Prof. Marshall share us the following.

Efficacy of Clarithromycin-Susceptibility Based Tailored Helicobacter pylori Eradication Treatment Maintaining Acid Secretion for a Full 24 Hours
Management of H. pylori infection

https://forums.helico.com/PDF/H-mediaobj ... Sa1903.pdf

Author(s):
Mitsushige Sugimoto1, Takahiro Uotani1, Shu Sahara1, Hitomi Ichikawa1, Mihoko Yamade1, Takanori Yamada1, Satoshi Osawa1, Ken Sugimoto1, Takahisa Furuta2

Affiliation:
1First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan; 2Hamamatsu University School of Medicine, Center for Clinical Research, Hamamatsu, Japan

Category:
Esophageal, Gastric and Duodenal Disorders

Abstract
Background: Over the years, the eradication rate of Helicobacter pylori during treatment has gradually decreased for two reasons: increased prevalence of clarithromycin (CAM)-resistant strains and acid inhibition during treatment, as insufficient acid inhibition during treatment makes antimicrobial agents unstable and leads to their degradation in stomach. During treatment, when respective percent time of pH < 4.0 and 24-h pH values of < 10% and > 6.0 were attained, most cases of infection were able to be resolved, irrespective of bacterial susceptibility. However, the optimum regimen of proton pump inhibitors (PPIs) is unknown at present. We therefore assessed acid inhibitory effects of multiple PPI dosing methods with respect to CYP2C19 genotype status and efficacy of CAM-susceptibility-based H. pylori eradication efforts by maintaining acid secretion for a full 24 h.
Methods: [Study 1] Using pH monitoring, we evaluated the efficacy of multiple dosing regimens with the PPI rabeprazole (40 mg sid, 20 mg bid, and 10 mg qid). [Study 2] A total of 200 H. pylori-positive patients were randomly assigned to the standard regimen group (rabeprazole 10 mg bid, amoxicillin (AMPC) 750 mg bid and CAM 400 mg bid for 1 week) or the tailored regimen group based on bacterial susceptibility to CAM. Patients infected with CAM-sensitive H. pylori were treated with rabeprazole 10 mg qid, AMPC 500 mg qid and CAM 400 mg bid for 1 week, and patients infected with CAM-resistant H. pylori were treated with rabeprazole 10 mg qid, AMPC 500 mg qid, and metronidazole (MNZ) 250 mg bid for 1 week.
Results: [Study 1] Respective median 24-h pH values for rabeprazole 40 mg sid, 20 mg bid, and 10 mg qid were 4.8 (3.6-6.4), 5.7 (4.1-7.4), and 6.6 (4.9-8.4). Increasing the dosing times effectively increased pH throughout a 24-h period. In CYP2C19 poor metabolizers, acid inhibition by a PPI was enhanced in comparison with that in CYP2C19 intermediate or rapid metabolizers. Further, rabeprazole 10 mg qid maintained pH > 4 for 24 h in rapid metabolizers. [Study 2] The intention-to-treat eradication rate in tailored regimen group was 96.0% (95% confidence interval [CI]: 90.1%-98.9%, 96/100), which was significantly higher than that in the standard regimen group (70.0%, 95% CI: 60.0%-78.8%, 70/100) (P < 0.001). In the tailored regimen group, the eradication rate in the PPI/AMPC/CAM regimen was 93.2% (95% CI: 83.5%-98.1%, 55/59), and that in the PPI/AMPC/MNZ regimen was 100% (95% CI: 93.0%-100%, 41/41).
Discussion: Four-times daily dosing of rabeprazole 10 mg achieved potent acid inhibition, including at night, in CYP2C19 rapid metabolizers, suggesting its potential usefulness in patients refractory to PPI therapeutic regimens. Using this PPI qid treatment for all patients made CAM-susceptibility-based H. pylori eradication treatment effective, with an eradication rate exceeding 95%.

Disclosure(s):
The following people have nothing to disclose: Mitsushige Sugimoto, Takahiro Uotani, Shu Sahara, Hitomi Ichikawa, Mihoko Yamade, Takanori Yamada, Satoshi Osawa, Ken Sugimoto, Takahisa Furuta