# A128 ANTIBIOTIC RESISTANCE DOES NOT FULLY EXPLAIN HELICOBACTER PYLORI TREATMENT FAILURES

## TL;DR

This study shows that many Helicobacter pylori treatment failures happen even when patients are not resistant to the antibiotics used, suggesting other factors like treatment adherence or regimen choice may play a role.

## Contribution

The study quantifies the proportion of H. pylori treatment failures not explained by antibiotic resistance, highlighting the need for broader clinical evaluation.

## Key findings

- 27-41% of patients failed treatment despite being sensitive to antibiotics like clarithromycin, metronidazole, and levofloxacin.
- Metronidazole resistance can be partially overcome with combination therapies like PBMT or PAMC.
- Resistance to amoxicillin and tetracycline is rare, with no tetracycline resistance observed in the study.

## Abstract

Most treatment failures of Helicobacter pylori are attributed to antibiotic resistance or patient nonadherence. Commonly used 1st-line treatment regimens include 14 day concomitant [proton pump inhibitor(P), amoxicillin(A), metronidazole(M), and clarithromycin(C):PAMC], or bismuth-based quadruple therapy [P, Bismuth(B), M, and tetracycline(T):PBMT]. Levofloxacin(L)-based PAL is also suggested for 14 days and rifabutin(R)-based PAR for 10 days. Analyses of data on the frequency of treatment failures in antibiotic sensitive cases are scarce.

To determine the proportion of H. pylori treatment failures not explained by antibiotic resistance.

Cultures of H. pylori positive patients (by histology, urea breath test, or stool antigen test) at the University of Alberta Hospital in Edmonton, Canada were assessed for resistance by E-test according to EUCAST thresholds to C, M, A, T, and L measuring minimum inhibitory concentrations.

There were 68 positive cultures from 64 individuals in 292 cases. Treatment adherence was high in patients with follow-up (FU) testing available. Median number of antibiotic regimens received prior to culture was 2 (IQR 0-3). In patients not previously treated, overall cure rate was 10/17 (59%) vs 21/47 (45%) for those who had been previously treated (p=.32). Summary data on outcomes are shown in Fig 1.

Clarithromycin: 14/63 (22%) cases had C-sensitive cultures. Regimens containing C were successful in 5/8 (63%), failures were PAC(1), Sequential therapy (1), and PMC(1). Of C-sensitive cases, 5/14 (36%) had been previously treated with C: further treatment success was 1/2 with PAR and 0/1 with PAL.

Metronidazole: 25/52 (48.0%) cases were M-sensitive: 11 cases were treated with M-containing regimens. 80% (8/10) were successfully treated with PBMT or PAMC, 1 case failed. Success with non-M regimens was 67% (4/6) with PAR and 1/2 with PAL. PBMT was successful in 60% (3/5) of M-sensitive patients with prior M-exposure.

43% (22/51) of cases had dual resistance to C and M. In 5 cases who were sensitive to both C and M, 60% (3/5) were cured with PAMC, 1 declined treatment and 1 was lost to FU.

Levofloxacin: 22/57 (39%) cases were L-sensitive of which 41% (9/22) had been previously treated with PAL. Successful treatment with PAL was 67% (4/6) in L-sensitive cases.

There were no cases of T-resistance (0/66). Borderline A-resistance was observed in 9% (4/46) of cases.

H. pylori treatment failures are not fully explained by antibiotic resistance. A substantial proportion (27-41%) of patients failed despite being sensitive to the antibiotics used (C, M, L). M resistance can be partially overcome with combination treatment. Resistance to A and T is rare. Clinical history including adherence is an important complement to antibiotic resistance testing in H. pylori, especially to determine previous C exposure.

Figure 1: Treatment success in confirmed cases with antibiotic-sensitive H. pylori cultures.

Abbreviations: PPI, proton pump inhibitor; PAMC, PPI-amoxicillin-metronidazole-clarithromycin; PAC, PPI-amoxicillin-clarithromycin; PMC, PPI-metronidazole-clarithromycin; PAR, PPI-amoxicillin-rifabutin; PAL, PPI-amoxicillin-levofloxacin; PBMT, PPI-bismuth-metronidazole-tetracycline; PAM, PPI-amoxicillin-metronidazole; PBAT, PPI-bismuth-amoxicillin-tetracycline

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