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1.  Antibiotic Resistance of Helicobacter pylori Strains in Japanese Children 
Journal of Clinical Microbiology  2002;40(2):649-653.
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.
PMCID: PMC153406  PMID: 11825987
2.  Resistance pattern of Helicobacter pylori strains to clarithromycin, metronidazole, and amoxicillin in Isfahan, Iran 
Helicobacter pylori (H. pylori) resistance to antibiotics has become a global problem and is an important factor in determining the outcome of treatment of infected patients. The purpose of this study was to determine the H. pylori resistance to clarithromycin, metronidazole, and amoxicillin in gastrointestinal disorders patients.
Materials and Methods:
In this study, a total of 260 gastric antrum biopsy specimens were collected from patients with gastrointestinal disorders who referred to Endoscopy Section of the Isfahan Hospitals. The E-test and Modified Disk Diffusion Method (MDDM) were used to verify the prevalence of antibiotic resistance in 78 H. pylori isolates to the clarithromycin, metronidazole, and amoxicillin.
H. pylori resistance to clarithromycin, metronidazole, and amoxicillin were 15.3, 55.1, and 6.4%, respectively. In this study, we had one multidrug resistance (MDR) isolates from patient with gastritis and peptic ulcer disease.
Information on antibiotic susceptibility profile plays an important role in empiric antibiotic treatment and management of refractive cases. According to the results obtained in this study, H. pylori resistance to clarithromycin and metronidazole was relatively high. MDR strains are emerging and will have an effect on the combination therapy.
PMCID: PMC3908526  PMID: 24523796
Amoxicillin; clarithromycin; Helicobacter pylori; metronidazole
3.  Distribution of Antibiotic MICs for Helicobacter pylori Strains over a 16-Year Period in Patients from Seoul, South Korea 
Antimicrobial Agents and Chemotherapy  2004;48(12):4843-4847.
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.
PMCID: PMC529181  PMID: 15561865
4.  Phenotypic and Genetic Characterization of Antimicrobial Profiles of Helicobacter pylori Strains in Cuba 
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.
PMCID: PMC2980873  PMID: 20411674
Antibiotic resistance; Gene mutations; Helicobacter pylori; Cuba
5.  Role of screening agar plates for in vitro susceptibility testing of Helicobacter pylori in a routine laboratory setting 
Journal of Clinical Pathology  2001;54(5):408-411.
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
PMCID: PMC1731429  PMID: 11328845
6.  Changes in Antibiotic Susceptibility of Helicobacter pylori in the Course of Eight Years in the Zaanstreek Region in The Netherlands 
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.
PMCID: PMC3610376  PMID: 23573077
7.  High Levels of Resistance to Metronidazole and Clarithromycin in Helicobacter pylori Strains in Children 
Journal of Clinical Microbiology  2001;39(1):394-397.
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.
PMCID: PMC87742  PMID: 11136811
8.  Proton pump inhibitor-amoxicillin-clarithromycin versus proton pump inhibitor-amoxicillin-metronidazole as first-line Helicobacter pylori eradication therapy 
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.
PMCID: PMC3432820  PMID: 22962528
Helicobacter pylori; eradication; antibiotics
9.  High Prevalence of Clarithromycin Resistance and cagA, vacA, iceA2, and babA2 Genotypes of Helicobacter pylori in Brazilian Children▿  
Journal of Clinical Microbiology  2010;48(11):4266-4268.
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.
PMCID: PMC3020848  PMID: 20826649
10.  Primary antibiotic resistance and associated mechanisms in Helicobacter pylori isolates from Senegalese patients 
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.
PMCID: PMC3552979  PMID: 23298145
Helicobacter pylori; Levofloxacin; Clarithromycin; Antibiotic resistance; Senegal
11.  Resistance of Helicobacter pylori to antibiotics from 2000 to 2009 in Shanghai 
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.
PMCID: PMC2965290  PMID: 20976850
Helicobacter pylori; Antibiotic resistance; Agar dilution; Metronidazole; Clarithromycin; Levofloxacin; Tetracycline; Amoxicillin; Furazolidone
12.  Antimicrobial Susceptibility and Mutations Involved in Clarithromycin Resistance in Helicobacter pylori Isolates from Patients in the Western Central Region of Colombia ▿  
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.
PMCID: PMC2737890  PMID: 19546360
13.  Antibiotic Resistance in Helicobacter pylori Strains and its Effect on H. pylori Eradication Rates in a Single Center in Korea 
Annals of Laboratory Medicine  2013;33(6):415-419.
Clarithromycin, amoxicillin, metronidazole, tetracycline, and levofloxacin have been commonly used for the eradication of Helicobacter pylori. We compared the change in antibiotic resistance of H. pylori strains during two separate periods and investigated the effect of antibiotic resistance on H. pylori eradication.
H. pylori strains were isolated from 71 patients between 2009 and 2010 and from 94 patients between 2011 and 2012. The distribution of minimal inhibitory concentration (MIC) of 5 antibiotics was assessed using the agar dilution method, and H. pylori eradication based on the antimicrobial susceptibility of the isolates was investigated retrospectively.
Antibiotic resistance rate against clarithromycin, amoxicillin, tetracycline, metronidazole, and levofloxacin for the 2009-2010 isolates were 7.0% (5/71), 2.8% (2/71), 0% (0/71), 45.1% (32/71), and 26.8% (19/71), respectively, and for the 2011-2012 isolates were 16.0% (15/94), 2.1% (2/94), 0% (0/94), 56.3% (53/94), and 22.3% (21/94), respectively. Multi-drug resistance for 2 or more antibiotics increased slightly from 16.9% (12/71) in the 2009-2010 isolates to 23.4% (22/94) in the 2011-2012 isolates. In follow-up testing of 66 patients, first-line treatment successfully eradicated H. pylori in 50 patients (75.8%) and failed in 4 of 7 patients (57.1%) in a clarithromycin-resistant and amoxicillin-susceptible group.
We observed an increase in resistance to clarithromycin and an overall increase in multi-drug resistance during the 2 study periods. The effectiveness of the eradication regimen was low with combinations of clarithromycin and amoxicillin, particularly in the clarithromycin-resistant group. Thus, eradication of H. pylori depends upon periodic monitoring of antimicrobial susceptibility.
PMCID: PMC3819440  PMID: 24205490
Helicobacter pylori; Antibiotic resistance; Eradication
14.  Antimicrobial Resistance Incidence and Risk Factors among Helicobacter pylori–Infected Persons, United States 
Emerging Infectious Diseases  2004;10(6):1088-1094.
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.
PMCID: PMC3323181  PMID: 15207062
Helicobacter pylori; antimicrobial resistance; risk factors
15.  Analysis of antimicrobial susceptibility and virulence factors in Helicobacter pylori clinical isolates 
BMC Gastroenterology  2003;3:20.
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.
PMCID: PMC194586  PMID: 12911839
16.  Antimicrobial susceptibility of Helicobacter pylori strains isolated from patients in Shiraz, Southern Iran 
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.
PMCID: PMC2997992  PMID: 21128326
Gastric disorders; Helicobacter pylori; Iran; Sensitivity; Treatment
17.  The Bactericidal Activity of Carbon Monoxide–Releasing Molecules against Helicobacter pylori 
PLoS ONE  2013;8(12):e83157.
Helicobacter pylori is a pathogen that establishes long life infections responsible for chronic gastric ulcer diseases and a proved risk factor for gastric carcinoma. The therapeutic properties of carbon-monoxide releasing molecules (CORMs) led us to investigate their effect on H. pylori. We show that H. pylori 26695 is susceptible to two widely used CORMs, namely CORM-2 and CORM-3. Also, several H. pylori clinical isolates were killed by CORM-2, including those resistant to metronidazole. Moreover, sub-lethal doses of CORM-2 combined with metronidazole, amoxicillin and clarithromycin was found to potentiate the effect of the antibiotics. We further demonstrate that the mechanisms underpinning the antimicrobial effect of CORMs involve the inhibition of H. pylori respiration and urease activity. In vivo studies done in key cells of the innate immune system, such as macrophages, showed that CORM-2, either alone or when combined with metronidazole, strongly reduces the ability of H. pylori to infect animal cells. Hence, CORMs have the potential to kill antibiotic resistant strains of H. pylori.
PMCID: PMC3873287  PMID: 24386154
18.  Multicenter Survey of Routine Determinations of Resistance of Helicobacter pylori to Antimicrobials over the Last 20 Years (1990 to 2009) in Belgium▿ 
Journal of Clinical Microbiology  2011;49(6):2200-2209.
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.
PMCID: PMC3122765  PMID: 21450969
19.  Clarithromycin Resistance among Helicobacter pylori Strains Isolated from Children: Prevalence and Study of Mechanism of Resistance by PCR-Restriction Fragment Length Polymorphism Analysis 
Journal of Clinical Microbiology  2003;41(1):486-488.
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.
PMCID: PMC149579  PMID: 12517902
20.  Helicobacter pylori eradication therapy: A review of current trends 
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.
PMCID: PMC3644737  PMID: 23661891
Bismuth salts; emerging therapies; Helicobacter pylori; proton-pump inhibitor
21.  Antibiotic Susceptibility Profile of Helicobacter pylori Isolated from the Dyspepsia Patients in Tehran, Iran 
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.
PMCID: PMC3133984  PMID: 21727733
Antibiotic susceptibility; Helicobacter pylori; Iranian patients
22.  Frequency of Antibiotic Resistance in Helicobacter pylori Strains Isolated from the Northern Population of Iran 
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.
PMCID: PMC3275342  PMID: 22203563
Helicobacter; antibiotic resistance; Iran; multidrug resistance; amoxicillin; metronidazole
23.  Antibiotic resistance and cagA gene correlation: A looming crisis of Helicobacter pylori 
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.
PMCID: PMC3351776  PMID: 22611319
Helicobacter pylori; Antibiotic resistance; cagA; Pakistan; Clarithromycin; Metronidazole; Fluoroquinolones
24.  Antimicrobial Susceptibilities of Helicobacter pylori Isolates under Microaerophilic Atmospheres Established by Two Different Methods 
Journal of Clinical Microbiology  2001;39(7):2646-2647.
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.
PMCID: PMC88201  PMID: 11427585
25.  Antibiotics resistance rate of Helicobacter pylori in Bhutan 
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.
PMCID: PMC3761104  PMID: 24023494
Helicobacter pylori; Drug resistance; Bhutan

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