A 9 year study of clarithromycin and metronidazole resistance in Helicobacter pylori from Spanish children

López-Brea, M; Martínez, María Josefa García; Domingo, Diego; Alarcón, Teresa

doi:10.1093/jac/48.2.295

Cited by 44 publications

(45 citation statements)

References 7 publications

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“…New macrolides were marketed in Spain at the beginning of the 1990, and clarithromycin began to be marketed in 1991. Children have had more exposure to macrolides, and nowadays, respiratory infections in young children are very frequently treated with this group of antibiotics (1,23).…”

Section: Discussionmentioning

confidence: 99%

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High Prevalence of Clarithromycin-Resistant Helicobacter pylori Strains and Risk Factors Associated with Resistance in Madrid, Spain

et al. 2010

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Clarithromycin is one of the antibiotics used for the treatment of Helicobacter pylori infections, and clarithromycin resistance is the most important factor when it comes to predicting eradication failure. The present study analyzed H. pylori isolates for the presence of 23S rRNA gene mutations and determined the risk factors associated with resistance among H. pylori isolates collected in Madrid, Spain, in 2008. We studied 118 H. pylori strains isolated from the same number of patients. A total of 76.3% of the patients were born in Spain, 52.7% were children, 20.3% had previously been treated, and 66.1% were female. Clarithromycin resistance was determined by Etest. H. pylori strains were considered resistant if the MIC was >1 mg/liter. DNA extraction was carried out by use of the NucliSens easyMAG platform with NucliSens magnetic extraction reagents (bioMérieux). The DNA sequences of the 23S rRNA genes of clarithromycin-resistant and -sensitive strains were determined to identify specific point mutations. The vacA genotype and cagA status were determined by PCR. We found that 42 (35.6%) strains were resistant to clarithromycin by Etest. Etest results were confirmed by detection of the presence of point mutations in 34 (88.1%) of these strains. Eight H. pylori strains were resistant to clarithromycin by Etest but did not have a point mutation in the 23S rRNA gene. Mutation at A2143G was found in 85.3% of the strains, mutation at A2142G in 8.8%, and mutation at T2182C in 5.9%. Dual mutations were found in 8.8% of the strains. H. pylori clarithromycin-resistant strains were strongly associated with pediatric patients, with patients born in Spain, and with patients who had previously been treated (P < 0.02). In addition, H. pylori strains resistant to clarithromycin more frequently presented the vacA s2/m2 genotype and were more likely to be cagA negative than susceptible strains (39.1% and 11.2%, respectively; P value < 0.001). We concluded that, in the present study, H. pylori clarithromycin-resistant strains are more frequently found in children, in patients mostly born in Spain, and in individuals who were previously treated for H. pylori infection and that these individuals are more likely colonized with a less virulent H. pylori strain.

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Section: Discussionmentioning

confidence: 99%

“…Fewer studies have focused on the prevalence of clarithromycin resistance among H. pylori strains from children compared with that among strains from the adult population. These studies will be useful for estimating the rate of clarithromycin-resistant H. pylori isolates among children and adults in Spain in the future (1,23).…”

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High Prevalence of Clarithromycin-Resistant Helicobacter pylori Strains and Risk Factors Associated with Resistance in Madrid, Spain

et al. 2010

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“…In some countries resistance is higher in children than in adults (9), although not in others (21). An increase of resistance to clarithromycin and metronidazole in children has also been described elsewhere (3,8,15).…”

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Clarithromycin Resistance among Helicobacter pylori Strains Isolated from Children: Prevalence and Study of Mechanism of Resistance by PCR-Restriction Fragment Length Polymorphism Analysis

et al. 2003

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Clarithromycin and metronidazole resistance was 29.1 and 23.9%, respectively, in 96 Helicobacter pylori strains obtained from pediatric patients. No resistance to amoxicillin was observed. Resistance according to patients' ages to clarithromycin and metronidazole was 45.4 and 18.2% in 22 patients from 4 to 8 years old, 30.2 and 20.7% in 53 patients from 9 to 13 years old, and 9.5 and 38.1% in 21 patients from 14 to 18 years old, respectively. The A2143G mutation was the most prevalent (82.1%) among clarithromycin-resistant strains.Helicobacter pylori is a gram-negative microaerophilic rod found in the human gastric mucosa associated with different digestive diseases, such as peptic ulcer, gastritis, and mucosaassociated lymphoid tissue lymphoma (7), and it is considered a risk factor in the development of gastric cancer (24). H. pylori infection is frequently acquired during childhood, and symptoms such as vomiting and epigastric or recurrent abdominal pain are associated with H. pylori infection (6).Amoxicillin, tetracycline, metronidazole, and clarithromycin are frequently used, combined with proton pump inhibitors or bismuth salts, for the treatment of H. pylori infections (22). However, side effects, poor compliance, and resistance to antibiotics are causes of treatment failure (4, 16). Resistance to metronidazole and clarithromycin is population dependent, and several studies suggest that clarithromycin resistance is higher in strains obtained from children than in those from adults (9).The aim of this study was to determine the rate of resistance to clarithromycin in H. pylori strains obtained from pediatric patients according to the age of the patients. Metronidazole and amoxicillin resistance was also studied. The mutation involved in clarithromycin resistance was detected by PCR-restriction fragment length polymorphism analysis.Ninety-six pediatric patients, aged from 4 to 18 years (mean age Ϯ standard deviation, 10.86 Ϯ 3.3 years), attending the Gastroenterology Unit at the Hospital del Niño Jesus during 1999 and 2000, were included in this study. Patients were referred for endoscopy due to different symptoms, with epigastric pain (74.2%), vomiting (33.3%), and recurrent abdominal pain (25.8%) being the most prevalent. Parents signed an informed consent form for the endoscopy, and the Ethical Committee supervised the study. Patients previously treated for H. pylori infections were not included. Strains were grouped according to the age of the patient at the time of endoscopy.Only culture-positive patients were included. H. pylori clinical isolates were obtained from gastric biopsy specimens according to standard procedures.Clarithromycin was obtained from Abbott Laboratories SA, Madrid, Spain, and metronidazole and amoxicillin were obtained from Sigma-Aldrich, Madrid, Spain. MICs were determined by an agar dilution technique with Mueller-Hinton agar plus 7% horse blood according to NCCLS recommendations (17). Plates with twofold dilutions of each antibiotic were inoculated with 1 to 2 l of 10 9 CFU/ml ...

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“…The most commonly used treatments are triple therapies consisting of a proton pump inhibitor with clarithromycin and metronidazole or amoxicillin or quadruple therapy with a proton pump inhibitor, a bismuth compound, tetracycline, and metronidazole (3,8,21,39). The primary and secondary resistance rates reported worldwide vary from 1 to 58% for clarithromycin and from 5 to 76% for metronidazole (1,5,15,17,26,28,32,43). Resistance to one or both of these antibiotics significantly reduces treatment success (2,11,19,22,35,37,42,44).…”

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Multilaboratory Comparison of Proficiencies in Susceptibility Testing of Helicobacter pylori and Correlation between Agar Dilution and E Test Methods

Best

Haldane

Keelan

et al. 2003

Antimicrob Agents Chemother

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Susceptibility testing was performed at seven Canadian microbiology laboratories and the Helicobacter Reference Laboratory, Halifax, Nova Scotia, Canada, to assess susceptibility testing proficiency and the reproducibility of the results for clarithromycin and metronidazole and to compare the Epsilometer test (E test) method to the agar dilution reference method. Control strain Helicobacter pylori ATCC 43504 (American Type Culture Collection) and 13 clinical isolates (plus duplicates of four of these strains including ATCC 43504) were tested blindly. The National Committee for Clinical Laboratory Standards (NCCLS) guidelines for agar dilution testing were followed, and the same suspension of organisms was used for agar dilution and E test. Antimicrobials and E test strips were provided to the investigators. Methods were provided on a website (www.Helicobactercanada.org). Each center reported MICs within the stated range for strain ATCC 43504. Compared to the average MICs, interlaboratory agreements within 2 log 2 dilutions were 90% (range, 69 to 100%) for clarithromycin by agar dilution, with seven very major errors [VMEs], and 85% (range, 65 to 100%) by E test, with three VMEs. Interlaboratory agreements within 2 log 2 dilutions were 83% (range, 50 to 100%) for metronidazole by agar dilution, with six VMEs and eight major errors (MEs), and 75% (range, 50 to 94%) by E test, with four VMEs and four MEs. At lower and higher concentrations of antibiotic, E test MICs were slightly different from agar dilution MICs, but these differences did not result in errors. When a standardized protocol based on NCCLS guidelines was used, most participants in this study correctly identified clarithromycin-and metronidazole-susceptible and -resistant strains of H. pylori 93% of the time by either the agar dilution or E test method, and the numbers of errors were relatively equivalent by both methods.

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A 9 year study of clarithromycin and metronidazole resistance in Helicobacter pylori from Spanish children

Cited by 44 publications

References 7 publications

High Prevalence of Clarithromycin-Resistant Helicobacter pylori Strains and Risk Factors Associated with Resistance in Madrid, Spain

High Prevalence of Clarithromycin-Resistant Helicobacter pylori Strains and Risk Factors Associated with Resistance in Madrid, Spain

Clarithromycin Resistance among Helicobacter pylori Strains Isolated from Children: Prevalence and Study of Mechanism of Resistance by PCR-Restriction Fragment Length Polymorphism Analysis

Multilaboratory Comparison of Proficiencies in Susceptibility Testing of Helicobacter pylori and Correlation between Agar Dilution and E Test Methods

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