A pharmacometric grey zone reconciles high metronidazole resistance rates with bismuth quadruple therapy efficacy in Helicobacter pylori

The article addresses a paradox where Helicobacter pylori resistance to metronidazole exceeds 50-60 percent globally, yet bismuth quadruple therapy containing metronidazole achieves over 90 percent eradication even in metronidazole-resistant infections. Researchers hypothesize that this discordance stems from a pharmacometric grey zone between the 128 and 256 microgram per milliliter breakpoints, where treatable isolates are systematically misclassified as high-level resistance. The study included 4,610 treatment-naive children from 2019-2024. Researchers used checkerboard assays to determine the synergy factor between bismuth and metronidazole. Population pharmacokinetic-pharmacodynamic modeling simulated metronidazole exposure in the stomach.