title: Primary and combined resistance to four antimicrobial agents in Helicobacter pylori in Sofia, Bulgaria.
abstract: The aim of this study was to evaluate the primary and combined resistance of Helicobacter pylori against four antimicrobial agents by a screening agar method (SAM) and a modified disk diffusion method (MDDM) alone and in combination. Pre-treatment H. pylori isolates from 192 consecutive H. pylori-positive patients at three hospitals in Sofia were investigated. MDDM was performed with disks containing metronidazole (5 microg), clarithromycin (15 microg) or erythromycin (15 microg), ciprofloxacin (5 microg) and tetracycline (30 microg). Resistance was determined by an inhibitory zone of <16 mm for metronidazole and < or =30 mm for other agents tested. The cut-off concentrations used to define resistance by SAM were: metronidazole >8 mg/L, clarithromycin >2 mg/L, tetracycline >4 mg/L and ciprofloxacin >1 mg/L. Primary resistance rates in H. pylori were: metronidazole 28.6%, clarithromycin 9.7%, metronidazole + clarithromycin 2.8%, ciprofloxacin 3.9%, metronidazole + ciprofloxacin 2.3%, tetracycline 1.9% and metronidazole + tetracycline 1.2%. Among metronidazole-resistant isolates, combined resistance to clarithromycin, ciprofloxacin and tetracycline was present in 11.4% (5 of 44 strains), 8.3% (3 of 36) and 4.9% (2 of 41), respectively. Two strains exhibited triple resistance to macrolides, metronidazole and either ciprofloxacin or tetracycline. Three tetracycline-resistant strains were detected in 1999; however, resistance rates to other agents were relatively stable during the 6 years. Primary H. pylori resistance to metronidazole is moderate and resistance to clarithromycin and to ciprofloxacin is considerable in comparison with results in most other countries. The alarming appearance of strains harbouring combined resistance or multiresistance provides the motivation for continued surveillance of H. pylori at global, national and regional levels.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Boyanova
authors.affiliation: Department of Microbiology, Medical University, Sofia, *Department of Gastroenterology, Hospital of the Ministry of Internal Affairs, Sofia, †Department of Gastroenterology, University Hospital 'St Ivan Rilski', Sofia and ‡Department of Gastroenterology, University Paediatric Hospital, Sofia, Bulgaria.
authors.forename: Irina
authors.initials: I
authors.lastname: Stancheva
authors.affiliation: Department of Microbiology, Medical University, Sofia, *Department of Gastroenterology, Hospital of the Ministry of Internal Affairs, Sofia, †Department of Gastroenterology, University Hospital 'St Ivan Rilski', Sofia and ‡Department of Gastroenterology, University Paediatric Hospital, Sofia, Bulgaria.
authors.forename: Zoya
authors.initials: Z
authors.lastname: Spassova
authors.affiliation: Department of Microbiology, Medical University, Sofia, *Department of Gastroenterology, Hospital of the Ministry of Internal Affairs, Sofia, †Department of Gastroenterology, University Hospital 'St Ivan Rilski', Sofia and ‡Department of Gastroenterology, University Paediatric Hospital, Sofia, Bulgaria.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Katzarov
authors.forename: Ivan
authors.initials: I
authors.lastname: Mitov
authors.affiliation: Department of Microbiology, Medical University, Sofia, *Department of Gastroenterology, Hospital of the Ministry of Internal Affairs, Sofia, †Department of Gastroenterology, University Hospital 'St Ivan Rilski', Sofia and ‡Department of Gastroenterology, University Paediatric Hospital, Sofia, Bulgaria.
authors.forename: Radka
authors.initials: R
authors.lastname: Koumanova
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002031:Bulgaria; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D002939:Ciprofloxacin / Q000494:pharmacology; D017291:Clarithromycin / Q000494:pharmacology; D004338:Drug Combinations; D004352:Drug Resistance, Microbial; D005260:Female; D005756:Gastritis / Q000382:microbiology; D016481:Helicobacter Infections / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests / Q000379:methods; D008875:Middle Aged; D010437:Peptic Ulcer / Q000382:microbiology; D013270:Stomach / Q000382:microbiology; D013752:Tetracycline / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D008795:Metronidazole; D002939:Ciprofloxacin; D013752:Tetracycline; D017291:Clarithromycin