The resistance of Helicobacter pylori to the recently available antibiotic treatment regimens has been a growing problem. We investigated the prevalence of H. pylori resistance to clarithromycin, metronidazole, and amoxicillin among 51 H. pylori isolates from Japanese children. In addition, the mutations of the corresponding gene were studied by PCR and restriction fragment length polymorphism analysis. Primary resistance to clarithromycin, metronidazole, and amoxicillin was detected in 29, 24, and 0% of strains, respectively. The eradication rates in clarithromycin-susceptible and -resistant strains were 89 and 56%, respectively (P < 0.05). The prevalence of strains with acquired resistance to clarithromycin (78%) was higher than that of strains with primary resistance (P < 0.01). Among the clarithromycin-resistant strains studied, 92% showed cross-resistance to azithromycin. No acquired resistance to amoxicillin was demonstrated. The A2144G mutation in the 23S rRNA gene was detected in 11 of 12 (92%) clarithromycin-resistant strains tested, whereas the mutation was not detected in any of the 15 susceptible strains. The deletion of the rdxA gene was not demonstrated in any of the strains. The results indicate that a high prevalence of clarithromycin-resistant strains is associated with eradication failure. Testing of susceptibility to clarithromycin is recommended.
Recently, the development of antibiotic resistance emerged as a significant clinical problem in the eradication of Helicobacter pylori. We investigated the MICs of antibiotics for 135 H. pylori isolates from adults in Seoul, South Korea, over the past 16 years. The MICs of amoxicillin, clarithromycin, metronidazole, tetracycline, azithromycin, and ciprofloxacin increased from 1987 to 2003. Rates of primary resistance to clarithromycin increased from 2.8% in 1994 to 13.8% in 2003. The A2144G mutation was frequently observed in the 23S rRNA gene in clarithromycin-resistant isolates. The increase in resistance to clarithromycin seems to result in a decrease in eradication efficacy for H. pylori. These results suggest that the MICs of several antibiotics for H. pylori have increased over the past 16 years in Seoul.
The study evaluated the antibiotic resistance patterns of Helicobacter pylori strains against metronidazole and clarithromycin in a hospital in Havana, Cuba. Eighty-five percent, 22.5%, and 10% of 40 H. pylori strains investigated were resistant to metronidazole, ciprofloxacin, and clarithromycin respectively but all were susceptible to amoxicillin and tetracycline. RdxA truncation was found only in metronidazole-resistant strains. In such strains, reported are eight and two novel mutations in the rdxA and frxA genes respectively. Two-point mutations in the 23S rRNA genes of clarithromycin-resistant strains were detected. A high prevalence of metronidazole resistance was found in Cuban H. pylori strains. Mutations in the rdxA gene may contribute more significantly than frxA gene to the high level of resistance to metronidazole. This study supports the need to continue monitoring the antibiotic susceptibility in H. pylori in Cuba to guide the treatment of such infection.
Antibiotic resistance; Gene mutations; Helicobacter pylori; Cuba
Background—Resistance of Helicobacter pylori to the more frequently used antibiotics (metronidazole and clarithromycin) reduces eradication rates even with triple treatment. Determining the antibiogram profile of H pylori can take up to 14 days and delays appropriate treatment.
Aims—To determine the role of screening agar plates for more rapid in vitro susceptibility of H pylori to metronidazole, amoxicillin, and clarithromycin.
Methods—Routine gastric biopsy specimens from 507 dyspeptic patients were inoculated on to 10% lysed blood agar plates containing metronidazole (8 µg/ml), clarithromycin (2 µg/ml), or amoxicillin (0.5 µg/ml). The minimum inhibitory concentration (MIC) of the 90 isolates was determined using the E test.
Results—Metronidazole resistance was detected in 28 of 90 isolates by E test and nine of 98 by screening agar. The screening agar detected none of the four clarithromycin resistant isolates detected by the E test.
Conclusions—The screening agar method is not sufficiently sensitive to be used alone.
Key Words: Helicobacter pylori • metronidazole • clarithromycin • susceptibility testing
Background. Failure of anti-Helicobacter therapy is the result noncompliance and resistance to the prescribed antibiotics. Aim. Antibiotic susceptibility of H. pylori was determined in native Dutch patients and patients of Turkish descent. Methods. In a period of eight years a total of 925 strains of H. pylori were cultured. Bacterial susceptibility was successfully determined in 746 (80.6%) of these isolates. Three hundred and nine strains (33%) originated from patients of Turkish descent. Results. In total clarithromycin resistance was found in 146 (20.5%) strains, metronidazole resistance in 147 (19.9%) strains. Amoxicillin resistance was found to be present in five strains. There is a slight but nonsignificant decrease in the percentage of clarithromycin-resistant strains in the consecutive period of eight years from 20% to 18%. No changes were seen in the consecutive years in metronidazole resistance. The number of clarithromycin-resistant strains decreased in Turkish patients, not in native Dutch patients. Conclusion. Resistance did not change significantly in consecutive years. But clinicians should take not only the antibiotic history into account but also ethnicity before prescribing metronidazole or clarithromycin.
The aim of the study was to evaluate the prevalence of resistance to amoxicillin, metronidazole, and clarithromycin before treatment of Helicobacter pylori infection in children and to assess the evolution of resistance with time. The study was carried out between 1994 and 1999 with 150 H. pylori-positive children through gastric culture (antimicrobial susceptibility) and histology. All cultured H. pylori strains were sensitive to amoxicillin, 64 (43%) were resistant to metronidazole, 32 (21%) were resistant to clarithromycin, and 14 (9%) were resistant to both metronidazole and clarithromycin. The overall prevalence of resistance to metronidazole and clarithromycin did not change significantly with time. The study highlights the generalized high-level and stable metronidazole and clarithromycin resistance of H. pylori strains from children.
The aim of this study was to compare the efficacy and tolerability of the first-line Helicobacter pylori (H. pylori) eradication regimen composed of proton pump inhibitor, clarithromycin, and amoxicillin, with those of a regimen composed of proton pump inhibitor, metronidazole, and amoxicillin. Data of patients, who were administered the first-line H. pylori eradication regimen at Tokyo Medical Center between 2008 and 2011, were reviewed. All patients had H. pylori gastritis without peptic ulcer disease. The 7-day triple regimen composed of lansoprazole, clarithromycin, and amoxicillin was administered to 55 patients, and that composed of omeprazole, metronidazole, and amoxicillin was administered to 55 patients. Intention-to-treat and per-protocol eradication rates were 74.5 and 80.4%, respectively, for the regimen of lansoprazole, clarithromycin, and amoxicillin, whereas the corresponding rates were 96.4 and 100%, respectively, for the regimen of omeprazole, metronidazole, and amoxicillin. In conclusion, first-line H. pylori eradication therapy composed of omeprazole, metronidazole, and amoxicillin was significantly more effective than that composed of lansoprazole, clarithromycin, and amoxicillin, without differences in tolerability.
Helicobacter pylori; eradication; antibiotics
We isolated 45 Helicobacter pylori strains from 217 child patients. Resistance to clarithromycin, metronidazole, amoxicillin, and tetracycline was detected in 27%, 13%, 4%, and 0% of strains, respectively. The A2143G mutation was the most prevalent (67%) among clarithromycin-resistant strains. In addition, strain genotyping revealed a significant association between gastritis severity and the simultaneous presence of cagA, vacA s1m1, iceA2, and babA2 genes.
Antibiotic combination therapy for Helicobacter pylori eradication must be adapted to local resistance patterns, but the epidemiology of H. pylori resistance to antibiotics is poorly documented in Africa. The aim was to determine the antibiotic resistance rates, as well as the associated molecular mechanisms, of strains isolated in Dakar, Senegal.
One hundred and eight H. pylori strains were isolated between 2007 and 2009 from 108 patients presenting with upper abdominal pain to the Gastroenterology Department of Le Dantec Hospital. Antimicrobial susceptibility testing was performed for amoxicillin, clarithromycin, metronidazole, levofloxacin and tetracyclin using the E-test method. Mutations in the 23S rRNA gene of clarithromycin-resistant strains and in gyrA and gyrB of levofloxacin-resistant strains were investigated.
Isolates were characterized by no resistance to amoxicillin (0%), tetracycline (0%), and very low rate of resistance to clarithromycin (1%), but a high rate of resistance to metronidazole (85%). The clarithromycin-resistant strain displayed the A2143G mutation. A worrying rate of levofloxacin resistance was detected (15%). N87I and D91N were the most common mutations in the quinolone-resistance-determining region of gyrA.
The first-line empirical regimen for H. pylori eradication in Senegal should include clarithromycin. Increasing rates of fluoroquinolone resistance detected should discourage the use of levofloxacin-containing regimens without prior antimicrobial susceptibility testing.
Helicobacter pylori; Levofloxacin; Clarithromycin; Antibiotic resistance; Senegal
AIM: To investigate the resistance of Helicobacter pylori (H. pylori) to 6 commonly used antibiotics from 2000 to 2009 in Shanghai.
METHODS: A total of 293 H. pylori strains were collected from 2000 to 2009 in Shanghai and tested for their susceptibility to metronidazole, clarithromycin, amoxicillin, furazolidone, levofloxacin and tetracycline using agar dilution.
RESULTS: The resistant rates of H. pylori to clarithromycin (8.6%, 9.0% and 20.7%) and levofloxacin (10.3%, 24.0% and 32.5%) increased from 2000 to 2009 in Shanghai. The resistant rate of H. pylori to metronidazole remained stable (40%-50%). Only one strain of H. pylori isolated in 2005 was resistant to tetracycline. All strains were sensitive to amoxicillin and furazolidone. The resistant rate of H. pylori to antibiotics was not related with the sex, age and clinical outcome of patients.
CONCLUSION: Resistance of H. pylori to antibiotics plays an important role in making treatment strategies against H. pylori-associated diseases.
Helicobacter pylori; Antibiotic resistance; Agar dilution; Metronidazole; Clarithromycin; Levofloxacin; Tetracycline; Amoxicillin; Furazolidone
Resistance to metronidazole, clarithromycin, and amoxicillin (amoxicilline) was found in 82, 3.8, and 1.9% of 106 Helicobacter pylori isolates, respectively. No tetracycline-resistant isolates were found. In all of the clarithromycin-resistant isolates, only one point mutation was present, either A2143G or A2142G. Our results indicate that metronidazole should not be included in the empirical treatment of H. pylori infection in this region.
Helicobacter pylori is the primary cause of peptic ulcer disease and an etiologic agent in the development of gastric cancer. H. pylori infection is curable with regimens of multiple antimicrobial agents, and antimicrobial resistance is a leading cause of treatment failure. The Helicobacter pylori Antimicrobial Resistance Monitoring Program (HARP) is a prospective, multicenter U.S. network that tracks national incidence rates of H. pylori antimicrobial resistance. Of 347 clinical H. pylori isolates collected from December 1998 through 2002, 101 (29.1%) were resistant to one antimicrobial agent, and 17 (5%) were resistant to two or more antimicrobial agents. Eighty-seven (25.1%) isolates were resistant to metronidazole, 45 (12.9%) to clarithromycin, and 3 (0.9%) to amoxicillin. On multivariate analysis, black race was the only significant risk factor (p < 0.01, hazard ratio 2.04) for infection with a resistant H. pylori strain. Formulating pretreatment screening strategies or providing alternative therapeutic regimens for high-risk populations may be important for future clinical practice.
Helicobacter pylori; antimicrobial resistance; risk factors
In this study, we evaluated the prevalence of primary resistance of Brazilian H. pylori isolates to metronidazole, clarithromycin, amoxicillin, tetracycline, and furazolidone. In addition, the vacA, iceA, cagA and cagE genotypes of strains isolated from Brazilian patients were determined and associated with clinical data in an effort to correlate these four virulence markers and antibiotic resistance.
H. pylori was cultured in 155 H. pylori-positive patients and MICs for metronidazole, clarithromycin, amoxicillin, tetracycline, and furazolidone were determined by the agar dilution method. Genomic DNA was extracted, and allelic variants of vacA, iceA, cagA and cagE were identified by the polymerase chain reaction.
There was a strong association between the vacA s1/cagA -positive genotype and peptic ulcer disease (OR = 5.42, 95% CI 2.6–11.3, p = 0.0006). Additionally, infection by more virulent strains may protect against GERD, since logistic regression showed a negative association between the more virulent strain, vacA s1/cagA-positive genotype and GERD (OR = 0.26, 95% CI 0.08–0.8, p = 0.03). Resistance to metronidazole was detected in 75 patients (55%), to amoxicillin in 54 individuals (38%), to clarithromycin in 23 patients (16%), to tetracycline in 13 patients (9%), and to furazolidone in 19 individuals (13%). No significant correlation between pathogenicity and resistance or susceptibility was detected when MIC values for each antibiotic were compared with different vacA, iceA, cagA and cagE genotypes.
The analysis of virulence genes revealed a specific association between H. pylori strains and clinical outcome, furthermore, no significant association was detected among pathogenicity and resistance or susceptibility.
AIM: To improve our understanding of Iranian regional variation in Helicobacter pylori (H. pylori) antibiotic resistance rates to find the best antibiotic therapy for eradication of H. pylori infections.
METHODS: A total of 266 patients undergoing endoscopy in Shiraz, Southern Iran, were included in this study. H. pylori strains were isolated from antral biopsies by culture and confirmed by the rapid urease-test and gram staining. Antibiotic susceptibility of H. pylori isolates was determined by E-test.
RESULTS: A total of 121 H. pylori strains were isolated, 50 from male and 71 from female patients. Data showed that 44% (n = 53), 20% (n = 24), 5% (n = 6), and 3% (n = 4) of all strains were resistant to the antibiotics metronidazole, amoxicillin, clarithromycin, and tetracycline, respectively. When the antibiotics were considered together we found 11 sensitivity patterns for the strains. Resistance to metronidazole was significantly higher in female than in male patients (P < 0.05). In about 71% of the metronidazole-resistant isolates, the minimum inhibitory concentrations (MICs) exceeded 256 μg/mL.
CONCLUSION: We found a moderate rate of primary resistance to metronidazole. However, a high MIC (> 256 mg/L) which was found in 71% of the isolates is considerable. In the case of amoxicillin, an increased resistance rate of 20% is worrying. Resistance to clarithromycin and tetracycline is also emerging among the H. pylori strains in our region.
Gastric disorders; Helicobacter pylori; Iran; Sensitivity; Treatment
We analyzed the rates of antimicrobial resistance of Helicobacter pylori strains isolated from patients from 1990 to 2009 and identified risk factors associated with resistance. Gastric biopsy specimens were collected from several digestive disease centers in Brussels, Belgium. We routinely performed antimicrobial susceptibility testing for clarithromycin (CLR), metronidazole, amoxicillin, tetracycline, and ciprofloxacin. Evaluable susceptibility testing was obtained for 9,430 strains isolated from patients who were not previously treated for Helicobacter pylori infection (1,527 isolates from children and 7,903 from adults) and 1,371 strains from patients who were previously treated (162 isolates from children and 1,209 from adults). No resistance to amoxicillin was observed, and tetracycline resistance was very rare (<0.01%). Primary metronidazole resistance remained stable over the years, with significantly lower rates for isolates from children (23.4%) than for isolates from adults (30.6%). Ciprofloxacin resistance remained rare in children, while it increased significantly over the last years in adults. Primary clarithromycin resistance increased significantly, reaching peaks in 2000 for children (16.9%) and in 2003 for adults (23.7%). A subsequent decrease of resistance rates down to 10% in both groups corresponded to a parallel decrease in macrolide consumption during the same period. Multivariate logistic regression revealed that female gender, age of the patient of 40 to 64 years, ethnic background, the number of previously unsuccessful eradication attempts, and the different time periods studied were independent risk factors of resistance to clarithromycin, metronidazole, and ciprofloxacin. Our study highlights the need to update local epidemiological data. Thus, the empirical CLR-based triple therapy proposed by the Maastricht III consensus report remains currently applicable to our population.
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 has been implicated in the formation of chronic gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma and gastric cancer. Eradication of H. Pylori has been recommended as treatment and prevention for these complications. This review is based on a search of Medline, the Cochrane Database of Systemic Reviews, and citation lists of relevant publications. Subject heading and key words used include H. Pylori, current treatment and emerging therapy. Only articles in English were included. There has been a substantial decline in the H. pylori eradication rates over the years, despite the use of proton pump inhibitor and bismuth salts for triple and quadruple therapies respectively. The reasons for eradication failure are diverse, among them, antibiotic resistance is an important factor in the treatment failure. Primary resistance to clarithromycin or metronidazole significantly affects the efficacy of eradication therapy. This has led to the introduction of second line, third line “rescue,” and sequential therapies for resistant cases. Subsequently, new antibiotic combinations with proton-pump inhibitors and bismuth salts are being studied in the last decade, to find out the antibiotics that are capable of increasing the eradication rates. Some of these antibiotics include Levofloxacin, Doxycycline, Rifaximin, Rifampicin, Furazolidone based therapies. Studies are ongoing to determine the efficacy of Lactoferrin based therapy.
Bismuth salts; emerging therapies; Helicobacter pylori; proton-pump inhibitor
AIM: To determine antibiotic resistance of Helicobacter pylori (H. pylori) in Pakistan and its correlation with host and pathogen associated factors.
METHODS: A total of 178 strains of H. pylori were isolated from gastric biopsies of dyspeptic patients. Susceptibility patterns against first and second-line antibiotics were determined and trends of resistance were analyzed in relation to the sampling period, gastric conditions and cagA gene carriage. The effect of cagA gene on the acquisition of resistance was investigated by mutant selection assay.
RESULTS: The observations showed that monoresistant strains were prevalent with rates of 89% for metronidazole, 36% for clarithromycin, 37% for amoxicillin, 18.5% for ofloxacin and 12% for tetracycline. Furthermore, clarithromycin resistance was on the rise from 2005 to 2008 (32% vs 38%, P = 0.004) and it is significantly observed in non ulcerative dyspeptic patients compared to gastritis, gastric ulcer and duodenal ulcer cases (53% vs 20%, 18% and 19%, P = 0.000). On the contrary, metronidazole and ofloxacin resistance were more common in gastritis and gastric ulcer cases. Distribution analysis and frequencies of resistant mutants in vitro correlated with the absence of cagA gene with metronidazole and ofloxacin resistance.
CONCLUSION: The study confirms the alarming levels of antibiotic resistance associated with the degree of gastric inflammation and cagA gene carriage in H. pylori strains.
Helicobacter pylori; Antibiotic resistance; cagA; Pakistan; Clarithromycin; Metronidazole; Fluoroquinolones
The purpose of this study was to evaluate the primary resistance rates of recent clinical Helicobacter pylori isolates to the most commonly used antibiotics in Iran.
Materials and Methods
210 patients presenting with gastric maladies between January and July of 2009 were enrolled in this study. Endoscopy was performed, and biopsy specimens were collected from each patient for subsequent bacterial culture of H. pylori. Single colony isolates from each patient were then used for antimicrobial susceptibility testing. The disk diffusion method was used to determine susceptibility patterns.
197 of the patients were H. pylori positive (93.8%). The rates of resistance to tetracycline, amoxicillin, ciprofloxacin, metronidazole, clarithromycin, and furizoladone were 37.1%, 23.9%, 34.5%, 65.5%, 45.2%, and 61.4%, respectively. A significant association between amoxicillin resistance and disease state (P <0.05) was identified. Furthermore, some double, triple, quadruple, and quintuple combinations of antibiotic resistance were found to be associated with disease state.
This study evaluated the prevalence of H. pylori resistance to the most commonly prescribed antibiotics used in Iran and showed that resistance rates were generally higher than previously reported. This data adds to the growing body of evidence that suggests there is increasing antibiotic resistance among H. pylori isolates, which likely is responsible for the decreasing efficacy of anti-H. pylori therapy at the local and global level. Hence, there is a need for continued monitoring of resistance patterns, especially at the local level, and for incorporation of that information into treatment regimens for H. pylori infections.
Helicobacter; antibiotic resistance; Iran; multidrug resistance; amoxicillin; metronidazole
Helicobacter pylori is an important pathogen for gastroduodenal diseases. Infection with H. pylori can be limited by regimens of multiple antimicrobial agents. However, antibiotic resistance is a leading cause of treatment failure. The aim of this study has been to determine the resistance patterns of H. pylori strains isolated from gastric biopsies of patients with dyspepsia by agar dilution method, in Tehran, Iran
Patients and Methods:
H. pylori isolates from patients with gastrointestinal diseases were evaluated for susceptibility testing by agar dilution method. Susceptibility testing was performed to commonly used antibiotics including clarithromycin, tetracycline, amoxicillin, metronidazole and ciprofloxacin.
Among 92 patients with dyspepsia, H. pylori strains were isolated from 42 patients. Seventeen (40.5%) of the isolates were resistant to metronidazole (MICs ≥ 8 μg/l), whereas one isolate (2.4%) was resistant to amoxicillin (MICs ≤ 0. 5 μg/ml) and ciprofloxacin (MICs ≤ 1μg/ml). The resistance rates to other antibiotics in H. pylori isolates are recorded as follows: clarithromycin 6 (14.3 %), tetracycline 2 (4.8%). In 5 of 42 resistant cases, combined resistance was found.
These data suggest that metronidazole should be used among Iranian patients in first-line therapy with caution, and ciprofloxacin in association with amoxicillin and a proton pump inhibitor is more recommended.
Antibiotic susceptibility; Helicobacter pylori; Iranian patients
The MICs of clarithromycin, amoxicillin, and metronidazole for 150 Helicobacter pylori isolates were determined using the AnaeroPack system and were compared with those determined using a microaerophilic incubator. The MICs of clarithromycin, amoxicillin, and metronidazole determined under both microaerophilic atmospheres were mostly within one twofold dilution for 146 (97.3%), 150 (100%), and 149 (99.3%) of the isolates, respectively.
AIM: To survey the antibiotic resistance pattern of Helicobacter pylori (H. pylori) strains isolated from Bhutanese population.
METHODS: We isolated 111 H. pylori strains from the gastric mucosa of H. pylori-infected patients in Bhutan in 2010. The Epsilometer test was used to determine the minimum inhibitory concentrations (MICs) of amoxicillin (AMX), clarithromycin (CLR), metronidazole (MNZ), levofloxacin (LVX), ciprofloxacin (CIP), and tetracycline (TET).
RESULTS: Nineteen of the isolated H. pylori strains were susceptible to all antibiotics tested. The isolated strains showed the highest rate of antibiotic resistance to MNZ (92/111, 82.9%). Among the 92 MNZ-resistant strains, 74 strains (80.4%) showed high-level resistance (MIC ≥ 256 μg/mL). Three strains were resistance to LVX (2.7%). These strains were also resistance to CIP. None of the strains showed resistance to CLR, AMX and TET.
CONCLUSION: CLR-based triple therapy is a more effective treatment approach over MNZ-based triple therapy for H. pylori infection in Bhutan.
Helicobacter pylori; Drug resistance; Bhutan
Culture and susceptibility testing of Helicobacter pylori strains was performed in a large multinational, multicenter randomized clinical trial. Culture was carried out on gastric biopsy samples obtained from 516 patients at entry and had a sensitivity of 99% when the [13C]urea breath test was used as a reference. Susceptibility testing was performed for clarithromycin and metronidazole on 485 strains by an agar dilution method and the epsilometer test (Etest) and for amoxicillin by an agar dilution method only. Resistance to clarithromycin (>1 μg/ml) was found in 3% of the H. pylori strains, with a perfect correlation between Etest and agar dilution methods. Resistance to metronidazole (>8 μl/ml) was found in 27% of the strains by agar dilution, but there were important discrepancies between it and the Etest method. No resistance to amoxicillin was found. The logarithms of the MICs of the three antibiotics against susceptible strains had a distribution close to normal. The impact of resistance was tested in the four arms of the trial. There were not enough clarithromycin-resistant strains to evaluate the impact of resistance on the cure rate of clarithromycin-based regimens. For metronidazole-resistant strains, the impact noted in the clarithromycin-metronidazole arm was partially overcome when omeprazole was added (76% eradication for resistant strains versus 95% for susceptible strains). Secondary resistance to clarithromycin occurred in strains from 12 of 105 patients (11.4%) after the failure of a clarithromycin-based regimen to effect eradication. The detection of point mutations in clarithromycin-resistant strains was performed by a combination of PCR and restriction fragment length polymorphism. Mutations (A2142G and 2143G) were found in all strains tested except one. This study stresses the importance of performing susceptibility tests in clinical trials in order to explain the results of different treatments.
Background and aims: The success of Helicobacter pylori eradication regimens depends on gastric pH, inflammation, and mucus thickness. Our aim was to investigate the effects of acid secretion, inflammation, and mucolysis on gastric antibiotic transfer.
Subjects and methods: A total of 134 anaesthetised rats were given metronidazole, amoxicillin, or clarithromycin intravenously and gastric contents were aspirated via an indwelling cannula. Acid secretion was controlled by either omeprazole or pentagastrin while gastritis was induced by infection with H pylori or dosing with iodoacetamide. Mucolysis was achieved by instilling pronase into the gastric lumen.
Results: Metronidazole transfer increased with acid secretion and fell with omeprazole, independently of gastric pH. Clarithromycin was also transferred with acid but was then rapidly degraded. Omeprazole prevented this degradation, raising gastric luminal concentrations. Omeprazole did not alter amoxicillin transfer. Gastritis induced by H pylori did not alter gastric transfer of metronidazole and amoxicillin but that of clarithromycin was increased by 23%. However, gastritis induced by iodoacetamide reduced clarithromycin transfer without any effect on metronidazole or amoxicillin transfer. Pronase treatment increased amoxicillin transfer fourfold and metronidazole by 66% but reduced clarithromycin transfer by 35%.
Conclusions: Metronidazole and clarithromycin are predominantly transferred with gastric acid rather than by an acid trapping mechanism. Pronase increases the appearance of amoxicillin and metronidazole in gastric secretions.
acid secretion; gastritis; mucus thickness; gastric transfer; antibiotics; rats
A proton-pump inhibitor (PPI), clarithromycin-based, triple therapy has been the recommended treatment for Helicobacter pylori eradication for the past 15 years. Due to a steady increase in H. pylori resistance to clarithromycin, this triple clarithromycin-based treatment has become progressively less efficacious. Several approaches are available to address this situation: one is to test for clarithromycin resistance so that this triple clarithromycin-based regimen is given only to those who will benefit; a second is to prescribe the drugs sequentially, beginning with amoxicillin and a PPI followed by clarithromycin and metronidazole, again with a PPI or the four drugs prescribed concomitantly; a third alternative is to use bismuth-based quadruple therapy, PPI plus a standardized three-in-one capsule, bismuth subcitrate potassium, metronidazole, and tetracycline (BMT, sold under licence as Pylera®). The advantages of these different approaches are reviewed, including the relevance of BMT three-in-one capsule in clinical practice.
bismuth salts; clarithromycin; BMT (Pylera®); sequential therapy; antimicrobial susceptibility testing