Gastric mucosal distribution and clinical efficacy of azithromycin in patients with Helicobacter pylori related gastritis

Abstract

The gastric mucosal distribution of azithromycin, the prototype of a new class of macrolide antibiotics named azalides, was studied in patients with duodenal ulcer and Helicobacter pylori-related gastritis. The time course of ulcer healing, H. pylori infection, and gastritis activity was also evaluated. Twenty patients (median age 50 years) received the following treatment for 1 month: three cycles of azithromycin (500 mg/day for 3 consecutive days) on days 1-3, 11-13 and 21-23 plus omeprazole (40 mg/day) for 30 consecutive days. Endoscopic biopsy specimens of gastric mucosa and blood samples were collected on days 0, 4, 7, 10, 20 and 30. An additional follow-up endoscopy was carried out on day 60. H. pylori infection was determined by both histology and rapid urease test. Azithromycin concentrations in both plasma and gastric mucosa were measured by a microbiological plate assay, using Micrococcus luteus NCTC 8440 as the reference organism. Azithromycin concentrations in plasma ranged between 0.17 mg/L (95% CI: 0.08-0.26; n = 5) and 0.32 mg/L (95% CI: 0.21-0.43; n = 5) throughout the treatment period. In addition, azithromycin concentrations in gastric mucosa were significantly higher than plasma concentrations at all times examined and ranged from 18.5 mg/kg (95% CI: 15-20; n = 20) to 24.6 mg/kg (95% CI: 16.8-32.4; n = 5), Indicating that the drug was highly retained in the target tissue. Accordingly, the ratio of azithromycin mucosal level to plasma concentration varied between 77.9 (95% CI: 56.5-99.3; n = 5) and 112.7 (95% CI: 100.2-125.2; n = 5). At the end of treatment (day 30) H. pylori was no longer detected in 16 of 20 patients (80%), and this finding was consistent with a marked decrease in the grading of gastritis activity. At the follow-up endoscopy (day 60) the infection was eradicated in only four patients (20%). These data indicate a favourable distribution of azithromycin into gastric mucosa of patients with H. pylori infection and suggest that this new macrolide antibiotic represents a valuable option for treatment regimens against H. pylori. However, the low eradication rate achieved with azithromycin plus omeprazole is a source of concern and requires further investigation.

Helicobacter pyloriresistance to antibiotics in Europe and its relationship to antibiotic consumption

“…However, this association became significant when the use of long-acting macrolides only (azithromycin) was considered in the analysis. Azithromycin is known to achieve high concentrations in the gastric mucus and gastric juice for several weeks after its administration, and this may lead to local subinhibitory concentrations in the vicinity of H pylori which could favour the selection of macrolide-resistant mutants 21 22…”

Helicobacter pylori eradication using tetracycline and furazolidone versus amoxicillin and azithromycin in lansoprazole based triple therapy: an open randomized clinical trial

“…Azithromycin is a potentially attractive agent for H. pylori eradication given its excellent inhibitory concentration for this organism and long biologic half-life (4,16) . However, clinical trials with azithromycin have displayed considerable variation with respect to the regimens used and the results obtained.…”

Comparison of Azithromycin and Clarithromycin Triple Therapy Regimens for Helicobacter Pylori Eradication in hemodialysis Patients

“…In vitro, azithromycin is bactericidal against H. pylori. In 1998, a study revealed that azithromycin becomes concentrated in the gastric mucosa in much higher levels than in the plasma (17). The finding supported the hypothesis that azithromycin is an effective antibiotic for treating H. pylori infections (28).…”

“…Azithromycin is an azalide similar to clarithromycin but less expensive and less prone to select for resistance (13). Most of the clinical trials examined short-duration azithromycin regimens in treating H. pylori (2–7 days of therapy), which may explain the range of eradication rates observed, from 44% to 93% (17-19). …”