- Open Access
Primary resistance to clarithromycin, metronidazole and amoxicillin of Helicobacter pylori isolated from Tunisian patients with peptic ulcers and gastritis: a prospective multicentre study
- Khansa Ben Mansour1Email author,
- Christophe Burucoa2,
- Meriem Zribi1,
- Afef Masmoudi1,
- Sami Karoui3,
- Lamia Kallel3,
- Soufiène Chouaib4,
- Samira Matri3,
- Monia Fekih3,
- Sonia Zarrouk5,
- Mounir Labbene5,
- Jalel Boubaker3,
- Imed Cheikh4,
- Mongi Ben Hriz6,
- Nadia Siala6,
- Abdelkarim Ayadi7,
- Azza Filali3,
- Nabil Ben Mami4,
- Taoufik Najjar8,
- Ahmed Maherzi6,
- Mohamed Tahar Sfar7 and
- Chedlia Fendri1
© Ben Mansour et al; licensee BioMed Central Ltd. 2010
- Received: 9 June 2010
- Accepted: 13 August 2010
- Published: 13 August 2010
The frequency of primary resistance to antibiotics in H. pylori isolates is increasing worldwide. In Tunisia, there are limited data regarding the pattern of H. pylori antibiotic primary resistance.
To evaluate the primary resistance of H. pylori to clarithromycin, metronidazole and amoxicillin and to detect the mutations involved in clarithromycin resistance.
Materials and methods
273 strains isolated from adults and children were enrolled. The primary resistance to clarithromycin, metronidazole and amoxicillin was evaluated by means of E-test minimal inhibitory concentration (MIC). The real-time PCR using Scorpion primers was performed in all cases to assess clarithromycin primary resistance and point mutations involved.
No resistance to amoxicillin was detected. For adults, resistance to clarithromycin and metronidazole was found respectively in 14.6% and 56.8%, and respectively in 18.8% and 25% in children. Overall, the rates of global primary resistance to clarithromycin and metronidazole in Tunisia were respectively determined in 15.4% and 51.3%.
By the use of Scorpion PCR, the A2143G was the most frequent point mutation observed (88.1%), followed by the A2142G (11.9%); the A2142C was not found and 18 of 42 patients (42.8%) were infected by both the resistant and the susceptible genotype.
The association of clarithromycin resistance with gender was not statistically significant, but metronidazole resistant strains were isolated more frequently in females (67.8%) than in males (32.2%) and the difference was significant. As for gastroduodenal diseases, the difference between strains isolated from patients with peptic ulceration and those with non peptic ulceration was not statistically significant. When about the distribution of resistant strains to clarithromycin and metronidazole between the three Tunisian cities (Tunis, Menzel Bourguiba and Mahdia), the difference was not statistically significant.
Local data regarding the primary resistance of H. pylori to clarithromycin, metronidazole and amoxicillin and the main genetic mutation involved in clarithromycin resistance in vivo (A2143G) are necessary to prove a clear need for a periodic evaluation of antibiotic consumption and new therapeutic strategies in Tunisia in order to avoid the emergence of resistant strains.
- Primary Resistance
- Clarithromycin Resistance
Helicobacter pylori (H. pylori) colonizes the human stomach and it has emerged as an important pathogen in the field of gastroenterology . In Tunisia, his prevalence is average 90% in peptic ulcer . Since 2005, the Tunisian consensus had recommended the eradication of H. pylori by a triple therapy which includes amoxicillin, clarithromycin or metronidazole combined with proton pump inhibitors (PPI) for 7 to 10 days . Resistance to these drugs reduces the success rate of treatment regimens both in adults and children. Several studies have demonstrated that primary resistance to clarithromycin is a major predictive factor for therapeutic failure ; the mechanism of this resistance decreased binding of the antibiotic to the 50 S ribosomal subunit of the microorganism and is due to three distinct point mutations (A2142G, A2143G and A2142C) within the peptidyltransferase region encoded in domain V of the H. pylori bacterial 23 S rRNA gene . The detection of mutations was performed by the use of several real-time PCR methods [5–9]. Resistance to metronidazole is mainly due to mutations in the rdxA gene encoding RdxA, an oxygen-insensitive nitroreductase . When about primary resistance to metronidazole, conflicting results have been reported on its impact in the treatment outcome . Prevalence rates of primary clarithromycine and metronidazole resistance were documented to be higher in developing countries than in industrialized ones [12, 13]. Because of limited data on the resistance of H. pylori to antibiotics in Tunisia, the aims of the present prospective and multicentre study were: (i) to evaluate, by means of E-test and Scorpion PCR the prevalence of primary resistance to clarithromycin, and by means of E-test, the rates of primary resistance to metronidazole and amoxicillin of 273 clinical strains isolated from children and adults, (ii) to detect, for the first time in Tunisia, the mutations involved in clarithromycin resistance by Scorpion PCR as previously described .
Patients and biopsies
In this study, the biopsy samples were taken over a 2 years-period (March 2005 to August 2007) from patients referred for endoscopy at 6 different units of gastroenterology in three Tunisian cities (Tunis, Menzel Bourguiba and Mahdia). 273 patients had H. pylori positive culture; 48 children (aged from 2 to 14 years; mean age 8.75 years) were distributed into gastritis in 47 cases and one case of duodenal ulcer and, 225 adults (aged from 18 to 88 years; mean age 38.3 years) in which 148 cases were defined as gastritis, 66 cases as duodenal ulcer and gastric ulcer was observed in 11 cases. All patients had not been treated before. Regarding the total group, patients were distributed into gastritis in 195 cases, duodenal ulcer in 67 cases and gastric ulcer in 11 cases. The biopsy specimens were cultured on Columbia agar plates supplemented with 10% horse blood and Skirrow supplement (Oxoid, England) under microaerobic conditions for a maximum of 6 days as described by Ben Mansour et al .
6 gastroenterology centers in 3 Tunisian cities: 1/Tunis (Adult Units A and B in Rabta University Hospital, Adult Gastroenterology Unit-Charles-Nicolle University Hospital, and Paediatric Unit in Mongi-Slim University Hospital); 2/Adult Gastroenterology Unit-Menzel Bourguiba Regional Hospital, and 3/Paediatric Unit-Mahdia Regional Hospital, between March 2005 and August 2007.
Genomic DNA was extracted with the QIAamp DNA mini kit (Qiagen, Germany) according to the manufacturer's instructions. The isolated DNA was eluted in 200 μl of 1 × TE buffer (10 mM Tris-HCl, 1 mM EDTA [pH 8.0]) and stored at -20°C until use.
The inoculum was adjusted to an opacity equivalent to a 3-4 McFarland turbidity standard and was flooded on Columbia agar plates containing 10% horse blood. The E-test strip (AB Biodisk, Sweden) was placed on the plate when it was dry and according to the instructions of the manufacturer. Incubation was performed in a microaerobic atmosphere for 48 to 72 hours at 37°C. Strains were considered resistant to clarithromycin when the MIC was ≥ 1 μg/ml for clarithromycin, ≥ 8 μg/ml for metronidazole and ≥ 0.5 μg/ml for amoxicillin. These breakpoints were used on the basis of recommendations as previously described .
Determination of point mutations in the 23 S rRNA gene of H. pylori by Scorpion PCR
Scorpion primers and primer sequences
TACC BHQ1 HEG GGACCACGGGGTCTTT-3'
5'-Texas red AAGGTAGGTGAAAATTCCTCC
TACC BHQ2 HEG GGACCACGGGGTCTTT-3'
TACC BHQ1 HEG GGACCACGGGGTCTTC-3'
TACC BHQ1 HEG GGACCACGGGGTCTTG-3'
Data were analyzed using X2 test. A p value of < 0.05 was considered to be statistically significant.
Detection of resistance to clarithromycin, metronidazole and amoxicillin by E-test
Distribution of resistant strains to clarithromycin, metronidazole and amoxicillin among children, adults and a total group
(N = 48)
(N = 225)
(N = 273)
Among children, the primary resistance to clarithromycin and to metronidazole was found respectively in 9 cases (18.8%) and in 12 cases (25%) of all 48 isolates (Table 2). 8 strains (16.7%) were resistant to both clarithromycin and metronidazole.
Overall, the rates of global primary resistance to clarithromycin and metronidazole in Tunisia were respectively determined in 15.4% (42 of 273) and in 51.3% (140/273) and the rate of primary resistance to both clarithromycin and metronidazole resistance was 13.6% (37/273) in all studied strains. No resistance to amoxicillin was found in the present study.
Detection of clarithromycin resistance and point mutations conferring resistance to clarithromycin by Scorpion PCR
Relationship between mutations conferring clarithromycin resistance and pathologies
Relationship between the sex of patients and resistance rates
Relationship between the gastroduodenal diseases and resistance rates
When about gastroduodenal diseases, no statistically difference was found between strains isolated from patients having peptic ulceration and those with non peptic ulceration (p > 0.05).
Resistance rates among the 3 Tunisian cities
(N = 181)
(N = 83)
(N = 9)
(N = 273)
In Tunisia, it's very important to know the rates of primary resistance of H. pylori strains to clarithromycin, metronidazole and amoxicillin, especially when antibiotic resistance in H. pylori represents a serious public health problem.
In adults, the rates of primary resistance to clarithromycin and metronidazole were documented as 17.5% for clarithromycin and 56% for metronidazole in 2002 . There is a decrease in the rate of clarithromycin resistance with 14.6% founded in our present study and a slightly variation (56.8%) among metronidazole. In terms of clarithromycin primary resistance, our prevalence would seem higher than that computed in Malaysia (2.1%) , in Germany (2.2%) , in Canada (less than 4%) , in Hong-Kong (4.5%) , in Korea (5-6%)  and in one European multicentre study (9.9%) . This prevalence was almost similar to those found in the USA (10-15%) , in France  but was lower to that detected in Iran (17%) , in Turkish (27.6%)  and in one European study (43.5%) . This difference in clarithromycin resistance rate between several countries might be due to the prescription and administration of this antibiotic. Indeed, since clarithromycin is a widely used antimicrobial drug to treat infection in other organ systems than gastric tract, e.g., respiratory tract infections, the prevalence of clarithromycin-resistant H. pylori is increasing continuously. No differences in gastroduodenal diseases were seen between patients with non peptic ulceration and those with peptic ulceration (p > 0.05); the majority of studies have mentioned no differences in prevalence in accordance with disease status, but two studies did mention such differences, and they concluded that duodenal ulcer and non-ulcer dyspepsia patients should be managed differently in medical practice and considered independently in eradication trials . A2143G and A2142G are the most prevalent point mutations, and studies have claimed that these mutations play a major role in clarithromycin resistance [5, 23]. The prevalence distribution of A2143G (78.6%) and A2142G (9.6%) in adults was similar to those of patients in Taiwan study and in a prospective multicentre survey carried out in Europe . We have not found the A2142C mutation which is less common, e.g., it was found in 5 of 129 resistant strains .
As for metronidazole resistance, it is well known that the prevalence of H. pylori is much higher in developing countries (50-80%). Our prevalence was much higher than that documented in an European multicentre study and in Bulgaria where the rates were evaluated respectively to 33.1% and 26.5% [11, 28], but was lower to that computed in Columbia (82%) , in Mexico (76.3%)  and in Sweden (76%) . In one Indian study, the resistance to metronidazole was evaluated to 41.9% . When regarding risk factors, we showed a higher primary metronidazole resistance in female patients compared with male ones, most likely due to the wide use of imidazoles for gynaecological infection. In agreement with data presented by Glupczynski et al and Batnavala et al, metronidazole resistant isolates were found significantly more frequently in females than in males and in non-European natives than in subjects born in European countries [33, 34]. The same cause was explained by Koletzko et al in their study where they found that metronidazole was widely used in Africa and Asia to treat parasitic diseases and gynaecological infections .
For children, the prevalence of clarithromycin primary resistance (18.8%) was in agreement with a French one where resistance to clarithromycin was detected in 18% , and slightly lower than those founded in a European prospective multicentre study and in Spain study where the rates were evaluated respectively to 20% and 21.1% [35, 37], but more lower than that documented in an Argentinean study (29.1%) . Our prevalence was lower than that reported by one previous Tunisian study conducted with 46 treated children, where the susceptibility testing was performed in 10 cases and where the rates of resistance to clarithromycin and metronidazole were respectively 30% and 90% .
When regarding the point mutations conferring resistance to clarithromycin, we found that A2143G was dominant followed by A2142G mutation, the A2142C was not detected. Domingo et al and Pina et al showed that the A2143G was more prevalent. De Francesco et al reported that the A2143G was prevalent in their study and concluded that this mutation reduces markedly the eradication therapy efficacy. As for metronidazole resistance, our prevalence (25%) was much higher than that reported in 105 untreated children in Bulgaria (16.2%) , but was slightly higher than that documented from children in Argentina (23.9%), in Spain (23%)  and in a European study (23%) .
Overall, the resistance rate for clarithromycin was lower in adults than in children (14.6% vs. 18.8%), which points to an acquisition of the resistance during childhood. Indeed, macrolides are very often used nowadays to treat respiratory infections in young children. By contrast, for metronidazole the resistance rate was markedly higher in adults than in children (56.8% vs. 25%). Our results were not in agreement with those founded in a European study , where the rates were very similar in adults and children and where they concluded that the similar rate was in favour of transmission of a resistant strain to the children mostly from their mothers who widely used metronidazole to treat gynaecologic infections. In contrast to clarithromycin and metronidazole, no amoxicillin resistance was observed; this finding was similar to those determined by Kim et al and Wolle et al in their studies. This is despite the wide use of this antibiotic, both alone and combined with clavulanic acid for the treatment of respiratory tract infections or H. pylori infection in children and adults. However, resistance to amoxicillin has appeared in some countries with low frequencies and could increase. The determination of resistant strains to antibiotics by the E-test method has proven clinically reliable except in the case of metronidazole for which the E-test has a tendency to overestimate the presence of resistance. The reason is not known, but it may be that a pre-incubation of the media in an anaerobic atmosphere has been shown a factor that increasing metronidazole activity . For that reason and for the lack of clinicobacteriological correlation, the Maastricht III 2005 Consensus Report discourages routine metronidazole susceptibility testing . Then, further standardization should be performed regarding the medium, the inoculum and the growth atmosphere.
In conclusion, we believe that the widespread use of macrolides in our country for the treatment of upper respiratory tract infections could have an undesirable outcome in the emergence of clarithromycin resistant strains of H. pylori, reducing the success of therapy rate. Moreover, the rate of annual consumption of antibiotics in Tunisia was evaluated to 4% which is a risk factor for increasing resistant strains to antibiotics; when regarding macrolides, for example, the rate of consumption in Tunisia exceed 4 millions units per year . The clarithromycin resistance decreases the effectiveness of antibiotic therapy and is the main risk factor for treatment failure: resistance reduces the efficacy of the first line therapy by up to 70% . Among the Maastricht III consensus report , treatment should achieve an eradication rate of ≥ 80%. The threshold of clarithromycin resistance at which this antibiotic should not be used, or a clarithromycin susceptibility test should be performed, is 15-20% [43, 45]. In Tunisia, physicians can continue the prescription of clarithromycin as a treatment for H. pylori infection in adults, in whom 14.6% of strains are resistant to this antibiotic, but in our paediatric population where the rate of this resistance was 18.8%, clarithromycin should not be used. Our study is the first to show that A2143G is the main genetic mutation involved in H. pylori clarithromycin resistance in vivo, thus suggesting that new therapeutic strategies are needed. When about metronidazole, we think that physicians might well refrain from using this antibiotic in order to prevent the emergence of more resistant strains especially because of the high rate of metronidazole resistant strains in Tunisia. In one study performed in North India, Bhatia et al have concluded that imidazole-based eradication regimens should be abandoned in North India regardless of in vitro susceptibility results (41.9%).
Because of the emergence of resistant strains in our country, there is a clear need for a periodic evaluation of antibiotic consumption, particularly of clarithromycin in public hospitals and in private clinical sector.
There are no competing interests to declare for this study.
- Solerman A, Perren A, Schmid S, Eigenmann F, Guller R, Weher KB, Meier F, Eichenberger P, Komminoth P: Assesment of Helicobacter pylori clarithromycin resistance mutations in archival gastric biopsy samples. Swiss Med Wkly 2005, 135: 327-332.Google Scholar
- Djmel N, Khamassi S, Bouzaïdi S, Labbene M, Ben Ammar A, Fendri C, Arrouji Z, Ben Jilani S, Zermani R: Prevalence of Helicobacter pylori in Tunisia: in asymptomatic controls and in none ulcerous dyspepsia and in duodenal ulcer: a prospective study of 183 cases. Tunis Med 1995, 73: 373-377.Google Scholar
- Consensus: Actualisation du consensus du traitement de la maladie ulcéreuse gastro-duodénale non compliquée de l'adulte en Tunisie. Journal Officiel de la République Tunisienne Ministère de la santé publique 2006. Avril-MaiGoogle Scholar
- Murakami K, Sato R, Okimoto T, Nasu M, Fujioka T, Kodama M, Kagawa J, Sato S, Abe H, Arita T: Eradication rates of clarithromycin-resistant Helicobacter pylori using either rabeprazole or lansoprazole plus amoxicillin and clarithromycin. Aliment Pharmacol Ther 2002, 16: 1933-8. 10.1046/j.1365-2036.2002.01368.xView ArticlePubMedGoogle Scholar
- Versalovic J, Shortridge D, Kibler K, Griffy MV, Beyer J, Flamm RK, Tanaka SK, Graham DY, Go MF: Mutations in 23 S rRNA are associated with clarithromycin resistance in Helicobacter pylori . Antimicrob Agents Chemother 1996, 40: 477-480.PubMed CentralPubMedGoogle Scholar
- Gibson JR, Saunders NA, Burke B, Owen RJ: Novel method for rapid determination of calrithromycin sensitivity in Helicobacter pylori . J Clin Microbiol 1999, 37: 3746-3748.PubMed CentralPubMedGoogle Scholar
- Marais A, Monteiro L, Occhialini A, Pina M, Lamouliatte H, Mégraud F: Direct detection of Helicobacter pylori resistance to macrolides by a polymerase chain reaction/DNA enzyme immunoassay in gastric biopsy specimens. Gut 1999, 44: 463-467. 10.1136/gut.44.4.463PubMed CentralView ArticlePubMedGoogle Scholar
- Occhialini A, Urdaci M, Doucet-Populaire F, Bébéar CM, Lamouliatte H, Mégraud F: Macrolides resistance in Helicobacter pylori : rapid detection of point mutations and assays of macrolides binding to ribosomes. Antimicrob Agents Chemother 1997, 41: 2724-2728.PubMed CentralPubMedGoogle Scholar
- Pina M, Occhialini A, Monteiro L, Doermann HP, Mégraud F: Detection of point mutations associated with resistance of Helicobacter pylori to clarithromycin by hybridization in liquid phase. J Clin Microbiol 1998, 36: 3285-3290.PubMed CentralPubMedGoogle Scholar
- Goodwin A, Kersulyte D, Sisson G, Veldhuyzen van Zanten SJ, Berg DE, Hoffman PS: Metronidazole resistance in Helicobacter pylori is due to null mutations in a gene (rdxA) that encodes an oxygen-insensitive NADPH nitroreductase. Mol Microbiol 1998, 28: 383-393. 10.1046/j.1365-2958.1998.00806.xView ArticlePubMedGoogle Scholar
- Lerang F, Moum B, Haug JB, Tolås P, Breder O, Aubert E, Høie O, Søberg T, Flaaten B, Farup P, Berge T: Highly effective twice-daily triple therapies for Helicobacter pylori infection and peptic ulcer disease: does in vitro metronidazole resistance have any clinical relevance? Am J Gastroenterol 1997, 92: 248-53.PubMedGoogle Scholar
- Osato MS, Reddy R, Graham DY: Metronidazole and clarithromycin resistance amongst Helicobacter pylori isolates from a large metropolitan hospital in the United States. Int J Antimicrob Agents 1999, 12: 341-7. 10.1016/S0924-8579(99)00079-5View ArticlePubMedGoogle Scholar
- Glupczynski Y, Megraud F, Lopez-Brea M, Andersen LP: European multicentre survey of in vitro antimicrobial resistance in Helicobacter pylori. Eur J Clin Microbiol Infect Dis 2001, 20: 820-3. 10.1007/s100960100611View ArticlePubMedGoogle Scholar
- Burucoa C, Garnier M, Silvain C, Fauchère JL: Quadruplex real-time PCR assay using allele-specific scorpion primers for detection of mutations conferring clarithromycin resistance to Helicobacter pylori. J Clin Microbiol 2008, 46: 2320-2326. 10.1128/JCM.02352-07PubMed CentralView ArticlePubMedGoogle Scholar
- Ben Mansour K, Fendri C, Zribi M, Masmoudi A, Labbene M, Fillali A, Ben Mami N, Najjar T, Meherzi A, Sfar T, Burucoa C: Prevalence of Helicobacter pylori vacA, cagA, iceA and oipA genotypes in Tunisian patients. Annals of Clinical Microbiology and Antimicrobials 2010,9(10):1-7.Google Scholar
- Chaabouni H, Bouzid H, Masmoudi A, Cheikh I, Fendri C, Ben Ammar A: Evaluation in vitro de la résistance primaire de Helicobacter pylori aux antibiotiques chez les maladies souffrant d'ulcère duodénal en Tunisie. Gastroenterol Clin Biol 2004, 28: A135.Google Scholar
- Norazah A, Zakaria WR, Abdullah SA, Mohamed R: Characterization of clarithromycin resistance in Malaysian isolates of Helicobacter pylori . World J Gastroenterol 2009, 15: 3161-3165. 10.3748/wjg.15.3161View ArticleGoogle Scholar
- Wolle K, Leodolter A, Malfertheiner P, König W: Antibiotic susceptibility of Helicobacter pylori in Germany: stable primary resistance from 1995 to 2000. J Med Microbiol 2002, 51: 705-709.View ArticlePubMedGoogle Scholar
- Fellone CA: Epidemiology of the antibiotic resistance of Helicobacter pylori in Canada. Can J Gastroenterol 2000, 14: 879-882.Google Scholar
- Ling TKW, Leung WK, Lee CC, Ng EK, Yung MY, Chung MY, Chung SS, Sung JJ, Cheng AF: The antimicrobial susceptibility of Helicobacter pylori in Hong Kong (1997-2001). Helicobacter 2002, 7: 327-329. 10.1046/j.1523-5378.2002.00101_1.xView ArticlePubMedGoogle Scholar
- Kim JJ, Reddy R, Lee M, Kim JG, El-Zaatari FA, Osato MS, Graham DY, Kwon DH: Analysis of metronidazole, clarithromycin and tetracycline resistance of Helicobacter pylori isolates form Korea. J Antimicrob Chemother 2001, 47: 459-461. 10.1093/jac/47.4.459View ArticlePubMedGoogle Scholar
- Laine L, Fennerty MB, Osato M, Sugg J, Suchower L, Probst P, Levine JG: Esomeprazole-based Helicobacter pylori eradication therapy and the effect of antibiotic resistance: results of three US multicenter, double-blind trials. Am J Gastroenterol 2000, 95: 3393-3398. 10.1111/j.1572-0241.2000.03349.xView ArticlePubMedGoogle Scholar
- Mégraud F: H.pylori antibiotic resistance: prevalence, importance, and advances in testing. Gut 2004, 53: 1374-1384. 10.1136/gut.2003.022111PubMed CentralView ArticlePubMedGoogle Scholar
- Mohammedi M, Doroud D, Massarrat S, Farahvach MJ: Clarithromycin resistance in Iranian Helicobacter pylori strains before introduction of clarithromycin. Helicobater 2003, 8: 79-80.Google Scholar
- Baglan PH, Bozdayi G, Ozkan M, Ahmed K, Bozdayi AM, Ozden A: Clarithromycin resistance prevalence and iceA gene status in Helicobacter pylori clinical isolates in Turkish patients with duodenal ulcer and functional dyspepsia. J Microbiol 2006, 44: 409-416.PubMedGoogle Scholar
- van Doorn LJ, Glupczynski Y, Kusters JG, Megraud R, Midolo P, Maggi-Soloca N, Quiroz DMM, Nouhan N, Stet E, Quint WGV: Accurate prediction of macrolide resistance in Helicobacter pylori by a PCR line probe assay for detection of mutations in the 23 S rRNA gene: multicenter validation study. Antimicrob Agent Chemother 2001, 45: 1500-1504. 10.1128/AAC.45.5.1500-1504.2001View ArticleGoogle Scholar
- Broutet N, Tchamgoué S, Pereira E, Lamouliatte H, Salamon R, Mégraud F: Risk factors for failure of Helicobacter pylori therapy-results of individual data analysis of 2751 patients. Aliment Pharmacol Ther 2003, 17: 99-109. 10.1046/j.1365-2036.2003.01396.xView ArticlePubMedGoogle Scholar
- Boyanova L: Prevalence of multidrug-resistant Helicobacter pylori in Bulgaria. J Med Microbiol 2009, 58: 930-935. 10.1099/jmm.0.009993-0View ArticlePubMedGoogle Scholar
- Alvarez A, Moncayo JI, Santacruz JJ, Santacoloma M, Corredor LF, Reinosa E: Antimicrobial Susceptibility and Mutations Involved in Clarithromycin Resistance in Helicobacter pylori Isolates from Patients in the Western Central Region of Columbia. Antimicrob Agent Chemother 2009, 53: 4022-4024. 10.1128/AAC.00145-09View ArticleGoogle Scholar
- Torres J, Camorlinga-Ponce M, Perez-Perez G, Madrazo-De La Garza, Dehesa M, Conza'lez-Valencia G, Munoz O: Increasing multidrug resistance in Helicobacter pylori strains isolated from children and adults in Mexico. J Clin Microbiol 2001, 39: 2677-2680. 10.1128/JCM.39.7.2677-2680.2001PubMed CentralView ArticlePubMedGoogle Scholar
- Wheeldon TU, Granstrom M, Hoang TT, Phuncarg DC, Nilsson LE, Sorberg M: The importance of the level of metronidazole resistance for the success of Helicobacter pylori eradication. Aliment Pharmacol Ther 2004,19(12):1315-1321. 10.1111/j.1365-2036.2004.01959.xView ArticlePubMedGoogle Scholar
- Bhatia V, Ahuja V, Das B, Bal C, Sharma MP: Use of imidazole-based eradication regimens for Helicobacter pylori should be abandoned in North India regardless of in vitro antibiotic sensitivity. J Gastroenterol Hepathol 2004,19(6):619-625. 10.1111/j.1440-1746.2003.03276.xView ArticleGoogle Scholar
- Glupczynski Y: European Multicentre Study Group on Antibiotic Susceptibility of Helicobacter pylori . Results of a multicentre European survey in 1991 of metronidazole resistance in Helicobacter pylori . Eur J Clin Microbiol Infect Dis 1992, 11: 777-781. 10.1007/BF01960875View ArticleGoogle Scholar
- Batnavala N, Bavies GR, Abdi Y, Clements L, Rampton DS, Hardie JM: High prevalence of Helicobacter pylori metronidazole resistance in migrants to east London: relation with previous nitroimidazole exposure and gastroduodénale disease. Gut 1994, 35: 1562-1566. 10.1136/gut.35.11.1562View ArticleGoogle Scholar
- Koletzko S, Richy F, Bontems P, Crone J, Kalach N, Monteiro ML, Gottrand F, Celinska-Cedro D, Roma-Giannikou E, Orderda G, Kolacek S, Urruzuno P, Martinez-Gomez MJ, Casswall T, Ashorn M, Bodanszky H, Mégraud F: Prospective multicentre study on antibiotic resistance of Helicobacter pylori strains obtained from children living in Europe. Gut 2006, 55: 1711-1716. 10.1136/gut.2006.091272PubMed CentralView ArticlePubMedGoogle Scholar
- Kalach N, Benhamou PH, Campeotto F, Bergeret M, Dupont C, Raymond J: Clarithromycin Resistance and Eradication of Helicobacter pylori in Children. Antimicrob Agent Chemother 2001, 45: 2134-2135. 10.1128/AAC.45.7.2134-2135.2001View ArticleGoogle Scholar
- Lopez-Brea M, Martinez MJ, Domingo D, Alarcon T: A 9 year study of clarithromycin and metronidazole resistance in Helicobacter pylori from Spanish children. J Antimicrob Chemother 2001, 48: 295-297. 10.1093/jac/48.2.295View ArticlePubMedGoogle Scholar
- Alarcon T, Vega AE, Domingo D, Martinez MJ, Lopez-Brea M: Clarithromycin resistance among Helicobacter pylori strains isolated from children: prevalence and study of mechanism of resistance by PCR-Restriction Fragment Length Polymorphism analysis. J Clin Microbiol 2003, 41: 486-488. 10.1128/JCM.41.1.486-488.2003PubMed CentralView ArticlePubMedGoogle Scholar
- Mrad S, Boukthir S, Fdhila F, Fendri C, Barsaoui S: Children helicobacter pylori infection: antibiogram results. Tunis Med 2005, 83: 599-602.PubMedGoogle Scholar
- Domingo D, Alarcon T, Sanz JC, Sanchez I, Lopez-Brea M: High frequency of mutations at position 2144 of 23 S rRNA gene in clarithromycin-resistant Helicobacter pylori strains isolated in Spain. J Antimicrob Chemother 1998, 41: 573-574. 10.1093/jac/41.5.573View ArticlePubMedGoogle Scholar
- De FrancescoV, Zullo A, Ierardi E, Giorgio F, Perna F, Hassan C, Morini S, Panella C, Vaira D: Phenotypic and genotypic Helicobacter pylori clarithromycin resistance and therapeutic outcome: benefits and limits. J Antimicrobiol Chemother 2010, 65: 327-332. 10.1093/jac/dkp445View ArticleGoogle Scholar
- Cederbrant G, Kahlmeter G, Ljungh A: Proposed mechanism for metronidazole resistance in Helicobacter pylori . J Antimicrob Chemother 1992, 29: 115-120. 10.1093/jac/29.2.115View ArticlePubMedGoogle Scholar
- Malfertheiner P, Mégraud F, O'Morain C, Bazzoli F, El-Omar E, Graham D, Hunt R, Rokkas T, Vakil N, Kuipers EJ: Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut 2007.Google Scholar
- Zouiten F, Ben Rachid A, Neifer N: About antibiotic consumption in Tunisia. Tunis Med 1999, 77: 467-471.PubMedGoogle Scholar
- Delchier JC: Quelles recommandations pour le management de l'infection à Helicobacter pylori après la troisième conférence de consensus européenne (Maastricht III) ? Gastroenterol Clin Biol 2006, 30: 1361-1364. 10.1016/S0399-8320(06)73555-2View ArticlePubMedGoogle Scholar
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