H. pylori‐primary resistance increasing; sequential therapy effective
Primary antibiotic resistance is on the rise and represents the most crucial factor affecting the efficacy of Helicobacter pylori treatments, as shown in a recent study from Italy. Sequential therapy appears to be effective, eradicating more than 80 percent of strains resistant to both clarithromycin and metronidazole.
“Reliable estimates of the effectiveness of a given regimen in patients harbouring resistant strains can be obtained only by assessing a large number of strains,” the investigators said.
Between 2010 and 2015, the investigators examined H. pylori cultures from 1,325 consecutive treatment-naïve patients (median age 50 years; 61.1 percent female) for resistance to clarithromycin, metronidazole and levofloxacin via E-test. H. pylori‐primary resistance to antimicrobials tested was found to be high, with 60.9 percent (95 percent CI, 58.3–63.5) showing resistance to one, two or all three agents. [Aliment Pharmacol Ther 2018;47:1261-1269]
In the group of 1,185 patients who received sequential therapy, the overall eradication rates were 91.1 percent in the intention-to-treat analysis and 93.7 percent in thte per-protocol analysis.
When susceptibility to individual agents was analysed, eradication rates were as follows: 97.3 percent in strains susceptible to both clarithromycin and metronidazole (n=527), 93.4 percent in strains resistant to clarithromycin but susceptible to metronidazole (n=151), 96.1 percent in strains resistant to metronidazole but susceptible to clarithromycin (n=152), and 83.1 percent in strains resistant to both clarithromycin and metronidazole (n=236).
For therapies with eradication rates ranging between 75 percent and 85 percent (an average cure rate achieved by several regimens in real world), some 98–144 patients with resistant strains should be examined to get a reliable and consistent estimate of eradication rate.
H. pylori‐primary resistance increasing
Multivariate logistic regression analysis showed a significant upward trend in the risk of carrying strains resistant to clarithromycin (odds ratio [OR], 1.15; 1.08–1.23; p<0.0001), metronidazole (OR, 1.11; 1.04–1.19; p= 0.002) and levofloxacin (OR, 1.16; 1.08–1.25; p<0.0001) over the years.
“The statistically significant increase in resistance rates for all the antimicrobial agents, tested between 2010 and 2015, was also corroborated from the retrospective analysis of historical data from our centre, which were previously included in published papers,” the investigators said. [Aliment Pharmacol Ther 2003;17:719-726; Aliment Pharmacol Ther 2007;25:1429-1434]
The investigators pointed out that the present data have important implications given that “[c]hanges in prevalence of primary resistance mainly depend on the antibiotic consumption in a given geographic area.”
First, regional health authorities should consider setting up regular monitoring of primary resistance for H. pylori (as well as for other microorganisms), because nearly all the eradication regimens are based on antimicrobials used also for other infectious diseases. Second, the high primary resistance rate to levofloxacin suggest that any levofloxacin-based regimen (be it triple or quadruple) should be used with caution. Finally, trials evaluating the efficacy of a H. pylori regimen, especially in naïve patients, should always include susceptibility testing.
The present study has several limitations. Among the investigators cited were the lack of data on previous exposure to antibiotics, enrolment of patients from a single referral centre and the use of E-test to examine antibiotic resistance. This test might have exaggerated the rate of metronidazole resistance, as the E-test could show significantly higher minimal inhibitory concentration values than that of agar dilution.