Antimicrobial Susceptibility of Helicobacter pylori Strains Isolated in Bangladesh

Abstract

Antimicrobial susceptibility of 120 Helicobacter pylori isolates to metronidazole, tetracycline, clarithromycin, and amoxicillin was determined, and 77.5, 15, 10, and 6.6% of the isolates, respectively, were resistant. Only rdxA inactivation and both rdxA and frxA inactivation were responsible for metronidazole resistance in 66% (8 of 12) and 33% (4 of 12) of the isolates, respectively. Eradication ofHelicobacter pylori infection by treatment with two antimicrobial agents (clarithromycin and amoxicillin or metronidazole) and a proton pump inhibitor is recommended by various consensus groups (10,16,20). Antimicrobial resistance in H. pylori is a growing problem as it is the most important factor in determining treatment outcome. The prevalence of antimicrobial resistance varies with geographical regions (3, 25). Metronidazole resistance in H. pylori has been shown to be due to mutation in rdxA; mutation in frxA has also been shown to be associated with metronidazole resistance (11,12,23). In Bangladesh, the prevalences of H. pylori infection among infants, children, and adults are 61, 84, and 92%, respectively (1, 21, 22); however, information on antimicrobial susceptibility to commonly used drugs in H. pylori treatment is lacking. This study was conducted to evaluate (i) the prevalence of primary antibiotic resistance to commonly used antimicrobial agents and (ii) the genetic basis for metronidazole resistance in H. pylori isolates from Bangladesh.Consecutive patients attending the Gastroenterology Department of Dhaka Medical College Hospital for upper gastrointestinal endoscopy were enrolled during 1999 to 2001. Diagnosis of peptic ulcer (PU) and non-ulcer dyspepsia (NUD) or gastritis was based on endoscopic examination of the stomach and duodenum. Biopsy samples were taken from each patient for culture.Bacteria were grown in brain heart infusion agar with 7% sheep blood and incubated at 37°C in 5% O 2 , 10% CO 2 , and 85% N 2 for 3 to 6 days. The MICs of amoxicillin, clarithromycin, metronidazole, and tetracycline for the isolates were determined by the agar dilution method as described elsewhere (18,19). All tests were repeated twice, and H. pylori 26695 was used as a control. ␤-Lactamase production was tested by the chromogenic cephalosporin method (6). The molecular mechanism of susceptibility and resistance to metronidazole was studied in 12 isolates. Metronidazole-susceptible (Mtz s ) isolates were further studied (by inactivation of rdxA alone or rdxA and frxA for conversion into an Mtz r phenotype) by transformation of Mtz s isolates with plasmids pBS-rdxA-cam (rdxA::cat) and pBS-frxA-kan (frxA::kan) as described earlier (11,12).A total of 278 consecutive patients between 15 and 78 years of age were enrolled, and among them, 72.7% (202 patients) were male and 27.3% (76 patients) were female. Among the patients, 162 had PU and 116 had NUD and 62.6% (174 of 278) were culture positive for H. pylori. Among the culturepositive patients, 121 (69.5%) were male and 53 (30.4%) were female and 112 (64.3%) had PU ...

Helicobacter pylori antibiotic susceptibility patterns in Bangladesh: Emerging levofloxacin resistance

“…The previous study reported that H. pylori resistance to antibiotics is linked to consumption of antibiotics in the region [23]. It is concordance with our results showing increased prevalence of CAM resistance compared to the approximately 10% rate reported in the previous study [12]. The Maastricht III guidelines on H. pylori infection management recommend substituting MNZ for CAM when resistance to this antibiotic exceeds 15% to 20% [24].…”

“…Interestingly H. pylori showed a higher rate of resistance to CAM and MNZ (22/56, 39.3% and 53/56, 94.6%; Table 1) than previously reported in Bangladesh [12]. Moreover, the LVX resistance rate also indicated emerging antimicrobial resistance (37/56, 66.1%), a similar phenomenon to that reported in India [11].…”

“…Levofloxacin (LVX)-based triple regimens or bismuthbased quadruple therapy has therefore been suggested to be most effective in this region. Although a previous study reported antibiotic resistance rates in Bangladesh, it was performed approximately 15 years ago (1999)(2000)(2001) [12]. Moreover, the previous study did not measure the resistance rate for LVX, which has recently been used in second-line regimens and as a rescue treatment for H. pylori eradication.…”

“…Moreover, the previous study did not measure the resistance rate for LVX, which has recently been used in second-line regimens and as a rescue treatment for H. pylori eradication. The previous study reported rates of resistance to CAM, AMX, MNZ and TCN to be 10%, 6.6%, 77.5%, and 15%, respectively [12]. The standard CAM-based triple regimen for 7-14 days is still the first option for eradicating H. pylori in Bangladesh, and LVX-based is the second line treatment [13].…”

Julian Davies and the discovery of kanamycin resistance transposon Tn5

“…[67][68][69] In addition, we and others showed that resistance to erythromycin-related macrolides, which is also common, stems from a point mutation at any of several sites in 23 S ribosomal RNA genes; and that tetracycline resistance, which is rare, typically involves a cluster of substitution mutations in its 16 S ribosomal RNA target. [70][71][72] AR GENES IN DEVELOPING COUNTRY LOW-INCOME SETTINGS As a final illustration of Julian's impact on me, I was pleased to help Washington University colleague Gautam Dantas and his students set-up collaborations with my long-term collaborators in Peru (Bob Gilman) and El Salvador (Teresita Bertoli) to examine the 'resistomes' in a peri-urban low-income community in Lima, Peru and in a Salvadorean agricultural community. Many resistance genes were found, were widely disseminated, and were often tightly associated with transposase-or phage integrase-like sequences.…”