Downloaded from www.microbiologyresearch.org by IP: 54.70.40.11 On: Mon, 15 Jul 2019 08:07:21 Prevalence of multidrug-resistant Helicobacter pylori in Bulgaria Lyudmila Boyanova Correspondence Lyudmila Boyanova l.boyanova@hotmail.com Chair of Microbiology, Medical University of Sofia, Sofia, Bulgaria Received 3 February 2009 Accepted 13 March 2009 The aim of this study was to evaluate the presence and prevalence of multidrug antibacterial resistance in Helicobacter pylori in Bulgaria from 2005 to 2008. The resistance in 828 untreated adults, 124 treated adults and 105 untreated children was, respectively, 26.5, 50.8 and 16.2 % for metronidazole; 18.4, 45.2 and 19 % for clarithromycin; 1, 2.4 and 0 % for amoxicillin; 4.4, 10.6 and 1.9 % for tetracycline; and 9, 14.5 and 5.8 % for ciprofloxacin. Triple resistance to the evaluated agents was uncommon and was detected in 1 % of the untreated children, 3.5 % of the untreated adults and 13.6 % of the treated adults. Five H. pylori strains were resistant to amoxicillin, metronidazole and clarithromycin, two of them exhibiting quadruple resistance. Resistance to four of the five antibacterials tested was found in 0.7 % of the untreated and 1.8 % of the treated adults. The overall level of multidrug resistance in the treated adults (15.4 %) was higher than that in the untreated adults (4.2 %, P50.0001) and the untreated children (1 %, P50.0001). The presence of multidrug H. pylori resistance in Bulgaria could be associated with many factors, among them the slightly increasing national use of macrolides, lincosamides and streptogramins and of quinolones since 2000, the significant increase in primary H. pylori clarithromycin resistance, the high tetracycline use between 1994 and 1999, and, in individual cases, the use of azithromycin-based regimens or reuse of nitroimidazoles. In conclusion, for the first time in a European country during the last 5 years, H. pylori strains harbouring a worrying quadruple antibacterial resistance were found in treated as well as in untreated patients. H. pylori susceptibility patterns have a tendency to become unpredictable and should be monitored constantly at both national and global levels. INTRODUCTION One important reason for the failure of Helicobacter pylori eradication is antibacterial resistance (Morgner et al., 2006). This resistance is most often due to point mutations and can result from inappropriate or frequent antibiotic use (Megraud & Lehours, 2007). The genes responsible for the mutations are the 23S rRNA gene for the macrolides, rdxA and frxA for metronidazole, gyrA for the quinolones, rpoB for rifampin, pbp1 for amoxicillin and the 16S rRNA gene for tetracycline (Megraud & Lehours, 2007). In addition, some non-specific proteins, such as HP1092 and the hefC gene product, have been associated with H. pylori multidrug resistance (Kutschke & de Jonge, 2005; Saidijam et al., 2006). In adults, the primary H. pylori resistance rates to clarithromycin vary from 0 to 25 % (Megraud & Lehours, 2007). Macrolide resistance is sometimes higher in children than in adults because children are treated with macrolides for respiratory infections more often than adults (Koletzko et al., 2006). Primary resistance rates to metronidazole have been 20–40 % in the USA and Europe, but in developing countries, the rates have been higher (from 50 to .80 %), whilst conversely, in Japan, the rates have been low (1.1–12 %) (Kobayashi et al., 2007; Megraud & Lehours, 2007). Primary H. pylori resistance to amoxicillin is uncommon (often 0–2 %) and has been detected in only a few countries; similarly, tetracycline resistance is low except for several countries such as South Korea and Taiwan (Hu et al., 2007). Conversely, because of the increasing use of fluoroqui- nolones in many countries, quinolone resistance in H. pylori has increased and has reached .20 % in adult patients in Japan and Portugal (Megraud & Lehours, 2007; Miyachi et al., 2006). Post-treatment resistance to gatifloxacin has been found to be 47.9 % in Japan (Nishizawa et al., 2006). The double-drug H. pylori resistance rate has usually been ,10 % in Europe (Koletzko et al., 2006; Megraud & Lehours, 2007), whilst triple resistance to amoxicillin, metronidazole and clarithromycin in H. pylori has been only occasional (Torres et al., 2001). Abbreviations: BST, breakpoint susceptibility testing; DID, defined daily doses per 1000 inhabitants per day; GORD, gastro-oesophageal reflux disease; PPI, proton pump inhibitor. Journal of Medical Microbiology (2009), 58, 930–935 DOI 10.1099/jmm.0.009993-0 930 009993 G 2009 SGM Printed in Great Britain