Helicobacter pylori has been considered to be non-invasive and to rarely infiltrate the gastric mucosa, even though there is an active Th1 immune response in the lamina propria of the H. pylori-infected stomach. To elucidate whether H. pylori invades the lamina propria and translocates to the gastric lymph nodes, we examined H. pylori in formalin-fixed and paraffin-embedded tissue sections of stomach and gastric lymph nodes obtained from 51 cancer patients using real-time PCR and immunohistochemistry (IHC) with a novel anti-H. pylori monoclonal antibody that recognizes lipopolysaccharides. Fresh gastric lymph nodes were used to culture for H. pylori. In 46 patients with H. pylori in the stomach, the bacterium was found in the lymph nodes from 21 patients by culture, 37 patients by PCR, and 29 patients by IHC. H. pylori captured by macrophages was found in the lamina propria of 39 patients. In the lymph nodes, the bacterium was found in many macrophages and a few interdigitating dendritic cells at the paracortical areas. H. pylori was also found in the intracellular canaliculi of parietal cells in 21 patients, but intracytoplasmic invasion into gastric epithelial cells was not identified. When compared to the commercially available anti-H. pylori antibodies, the novel antibody showed the highest sensitivity to detect H. pylori-positive macrophages, whereas no difference was found for H. pylori in the mucous layer. The H. pylori-positive macrophages in the lamina propria correlated with chronic gastritis as well as translocation of such cells to the lymph nodes. These results suggest that H. pylori-induced gastric epithelial damage allows the bacteria to invade the lamina propria and translocate to the gastric lymph nodes, which may chronically stimulate the immune system. The bacteria captured by macrophages, whether remaining alive or not, may contribute to the induction and development of H. pylori-induced chronic gastritis.

A high resistance rate (47.9%) to gatifloxacin (GAT; 8-methoxy fluoroquinolone) in Helicobacter pylori (H. pylori) strains from 48 Japanese patients is observed after unsuccessful H. pylori eradication. A significant association between MICs for GAT equal to or above 1 g/ml and mutations of the gyrA gene of H. pylori was demonstrated.Resistance to antibiotics is the major cause of the failure to eradicate Helicobacter pylori. For such cases, alternative regimens need to be developed.Perri et al. have reported an unacceptable low eradication rate of only 68% with a 7-day regimen of levofloxacin (LVX), amoxicillin (AMX), and pantoprazole (12). However, Sharara et al. have recently reported an excellent eradication rate of 92% with a 7-day regimen of gatifloxacin (GAT), AMX, and rabeprazole (14). It is important to note the superior in vitro activity of GAT over that of LVX against H. pylori (1). Therefore, GAT-based triple therapy might be a promising option for an alternative treatment regimen.Several studies have shown that the "quinolone resistancedetermining region" (QRDR) of the gyrA gene plays a critical role in the resistance of H. pylori to ciprofloxacin (CIP) (8,15). H. pylori does not contain genes for topoisomerase IV, an important fluoroquinolone target in other bacteria (15). The present study demonstrated a correlation between MICs to GAT and mutations of the gyrA and gyrB genes in H. pylori isolated from Japanese patients after unsuccessful eradication of infection.A total of 48 patients (32 males and 16 females; mean age, 57.8) with H. pylori infection after treatment failure were enrolled at Keio University Hospital between September 2004 and June 2005. Of the total, 42 patients had one treatment failure, 4 patients had two treatment failures, and 2 patients had three treatment failures (first-line treatment, triple therapy with clarithromycin [CLR], AMX, and proton pump inhibitor [PPI]; second-line treatment, triple therapy with metronidazole [MNZ], AMX, and PPI; and third-line treatment, triple therapy with LVX, AMX, and PPI). All patients underwent upper gastrointestinal endoscopy and gastric biopsy at Keio University Hospital.The susceptibility of H. pylori isolates to CRL, GAT, and MNZ was determined by the agar dilution method according to the guidelines established by the CLSI (formerly NCCLS) (9). Isolates were considered resistant to MNZ if the MIC of the drug was Ն8 g/ml and resistant to CLR and GAT if the MIC of these drugs was Ն1 g/ml (3, 7, 10). The resistance rates to GAT, CLR, and MNZ were 47.9%, 79.2%, and 6.3%, respectively. The GAT resistance rates were 22.2% (2/9) in the strains susceptible to both CLR and MNZ, 50% (18/36) in the strains resistant to CLR but susceptible to MNZ, 100% (1/1) in the strains resistant to MNZ but susceptible to CLR, and 100% (2/2) in the strains resistant to both CLR and MNZ.Studies in Europe have suggested that the primary resistance rate might be as low as 8% for CIP (2, 16) and that only 9% of the isolates show resistance to CIP after failure of pr...

The efflux pump of H. pylori is associated with the development of resistance to CLR, in addition to 23S rRNA point mutations. Efflux pumps could be a novel target for reversing drug resistance in H. pylori.