Primary and combined resistance to four antimicrobial agents in Helicobacter pylori in Sofia, Bulgaria

The aim of this study was to evaluate the primary and combined resistance o f Helicobacter pylori against four antimicrobial agents by a screening agar method (SAM) and a modified disk diffusion method (MDDM) alone and in comb ination. Pre-treatment H, pylori isolates from 192 consecutive H, pylori-po sitive patients at three hospitals in Sofia were investigated. MDDM was per formed with disks containing metronidazole (5 mu g), clarithromycin (15 mu g) or erythromycin (15 mu g), ciprofloxacin (5 mu g) and tetracycline (30 m u g). Resistance was determined by an inhibitory zone of <16 mm for metroni dazole and less than or equal to 30 mm for other agents tested. The cut-off concentrations used to define resistance by SAM were: metronidazole >8mg/L , clarithromycin >2mg/L, tetracycline >4 mg/L and ciprofloxacin >1 mg/L, Pr imary resistance rates in H. pylori were: metronidazole 28,6%, clarithromyc in 9,7%, metronidazole + clarithromycin 2,8%, ciprofloxacin 3,9%, metronida zole + ciprofloxacin 2,3%, tetracycline 1.9% and metronidazole + tetracycli ne 1,2%, Among metronidazole-resistant isolates, combined resistance to cla rithromycin, ciprofloxacin and tetracycline was present in 11.4% (5 of 44 s trains), 8.3% (3 of 36) and 4.9% (2 of 41), respectively. Two strains exhib ited triple resistance to macrolides, metronidazole and either ciprofloxaci n or tetracycline. Three tetracycline-resistant strains were detected in 19 99; however, resistance rates to other agents mere relatively stable during the 6 years. Primary H, pylori resistance to metronidazole is moderate and resistance to clarithromycin and to ciprofloxacin is considerable in compa rison with results in most other countries, The alarming appearance of stra ins harbouring combined resistance or multiresistance provides the motivati on for continued surveillance of H, pylori at global, national and regional levels.