We show that quinolone resistance in Helicobacter pylori has reached an alarming level in Germany. Our data suggest that the use of quinolones requires prior antimicrobial susceptibility testing, especially for isolates from patients who have already undergone previous unsuccessful eradication treatments, and also underline the further need for surveillance studies to monitor antibiotic resistance in H. pylori.Helicobacter pylori infection causes gastritis and can result in complications such as peptic ulcer diseases, mucosa-associated lymphoid tissue lymphoma, or gastric cancer (22). In Germany, antibiotic chemotherapy that includes amoxicillin, clarithromycin, and a proton pump inhibitor is recommended for the eradication of these bacteria in infected individuals (14). After treatment failures, quinolone-based triple therapies have been shown to be highly effective and therefore have been proposed as rescue regimens (4,20).The aim of this study was to estimate the prevalence of quinolone resistance in H. pylori by testing the antimicrobial susceptibilities of clinical isolates obtained between 2001 and 2005. We analyzed H. pylori isolates from patients who had already been treated (n ϭ 805; 86%) or who had not been treated (n ϭ 126; 14%). Susceptibilities to ciprofloxacin, metronidazole, and clarithromycin were determined by the Etest method, according to the manufacturer's instructions and a modified protocol, as described previously (9). Isolates were classified as resistant to ciprofloxacin and clarithromycin when the MIC was Ͼ1 mg/liter and were classified as resistant to metronidazole when the MIC was Ͼ8 mg/liter (9, 12).Due to the predominance of previously treated patients, the overall rates of resistance to metronidazole (Mtz r ; 67.8%), clarithromycin (Cla r ; 62.9%), and to both antimicrobials (Mtz r Cla r ; 39.8%) were expectedly high. We also observed a large number (n ϭ 150; 16.1%) of ciprofloxacin-resistant isolates; detailed analysis showed that the majority of these isolates (n ϭ 95; 10.2%) were also resistant to metronidazole and clarithromycin, whereas only a minority (n ϭ 17; 1.8%) were exclusively resistant to ciprofloxacin.Previous unsuccessful eradication trials appear to be an important risk factor for the development of overall quinolone resistance and triple-drug resistance, since those patterns of resistance were more common among isolates from previously treated patients (Cip r , 17.1%; Mtz r Cla r Cip r , 11.8%) than among those derived from previously untreated individuals (Cip r , 9.5%; Mtz r Cla r Cip r , 0.0%). A chi-square test confirmed these differences to be significant at an error level of 5% (Fig. 1). Next, we also analyzed the average MICs of ciprofloxacin and compared the annual differences in the proportions of quinolone-resistant isolates.The (Fig. 2). Logistic regression analysis showed a significant positive trend for the proportions of Cip r isolates and Mtz r Cla r Cip r isolates. Similar high rates of quinolone resistance were reported from Korea (12) and Italy (...