| Abstract|| |
The objective was to determine over two periods, seven years apart, the sensitivity of H. pylori isolates to metronidazole, tetracycline and erythromycin. The study periods were 1987/88 and 1995/96 and the population consisted of 133 patients undergoing upper gastrointestinal endoscopy for peptic ulcer disease in KFHU. The sensitivity of H. pylori isolates from their biopsy specimens was tested to three antibiotics using the disc diffusion method. In 1987/88, 62%, 97.0% and 98.6% of isolates were sensitive to metronidazole, erythromycin and tetracycline respectively. The corresponding sensitivities in 1995/96 were 14.5, 93.5% and 100% respectively. In 1987/88 there was no difference in the metronidazole resistant H. pylori isolates from men and women (38.2% vs 37.5%) but in 1995/96 slightly more women than men had metronidazole resistant isolates (89% vs 82.9%). The resistance of H. pylori to metronidazole increased over time. In order to improve outcome of treatment, sensitivity of H. pylori isolates needs to be determined for each patient. The recommended triple therapy requires to be modified if the prevailing sensitivity pattern of H pylori in our environment is taken into account.
|How to cite this article:|
Larbi EB. The changing sensitivity of Helicobacter pylori to metronidazole. Saudi J Gastroenterol 1999;5:124-8
< Helicobacter pylori ori) plays a major role in the pathogenesis of chronic gastritis, peptic ulceration and probably gastric malignancy, especially, lymphoma of mucosa-associated lymphoid tissue (MALT) ,,,,,. Successful treatment of H. pylori not only results in the healing of gastritis and peptic ulceration and remission of low grade MALT lymphoma but also prevents their recurrence ,,,,,, Eradication of H. pylori from the stomach is thus of paramount importance in such patients. In a number of successful regimens including the recommended triple regimen for the eradication of H. pylori, metronidazole has been the primary ingredient ,,, . However, the presence of metronidazole-resistant organisms has reduced the efficacy of the metronidazole-containing regimens , . Cure rates have been low ,, and recurrence rates high ,
Resistance of H. pylori to metronidazole has varied in different populations ,, but has been highest in developing countries ,, In Saudi Arabia resistant strains of H. pylori to metronidazole have been reported from the south and western provinces in 40% and 66% of cases respectively ,. There have been no studies on changes in the resistance pattern of H. pylori to metronidazole over time. This paper reports the changing pattern of resistance of H. pylori to metronidazole over a seven-year period in the eastern province of Saudi Arabia.
| Methods|| |
This study was conducted in King Fahd Hospital of the University, Al-Khobar. As part of a clinical trial on H. pylori, a random sample of patients with dyspepsia were evaluated over two separate periods, seven years apart. Patients were included, if they had symptoms of peptic ulcer disease and antral biopsy grew Helicobacter pylori and had no history or evidence of previous treatment with metronidazole. They were excluded if they had been previously treated with antibiotics or bismuth for peptic ulcer disease. All patients included in the initial evaluation (1987/88) were excluded from the second evaluation period (1995/96). Patients had upper gastrointestinal endoscopy and antral mucosa biopsied within 5 cm of the pylorus. The specimens were transported immediately in sterile normal saline to the microbiology laboratory and processed in the standard manner required to isolate H. pylori. Thus, within three hours of collection each specimen was homogenized in sterile ground glass grinder. The resulting suspension was inoculated onto Butzler medium and Skirrow medium (containing vancomycin, trimethoprim and polymyxin) and incubated at 37° C under microaerophilic conditions for 4-7 days. Plates were then examined for bacterial growth and typical colonies were selected for identification. The identity of H. pylori was confirmed by Gram stain and by the production of urease, oxidase and catalase , . The isolates were subcultured on chocolate agar for standard susceptibility testing to metronidazole, erythromycin and tetracycline. Thus a disk diffusion method was used with disks containing metronidazole 5µg, erythromycin 5µg or tetracycline 10µg and a zone of > l0mm clear of H. pylori around the disk indicated sensitivity. The results were statistically analyzed using Chi square test with Yates correction.
| Results|| |
The two periods of study were April 1987 - March 1998 and April 1995 - March 1996. [Table - 1] shows the demographic features of the patients included in the study. The patients were predominantly of Saudi nationality. There were more males than females in each study period. Those studied in 1987/88 were slightly older than the 1995/96 group.
The number of isolates of H. pylori subjected to sensitivity testing in 1987/88 and 1995/96 were 71 and 62 respectively, and [Table - 2] shows the sensitivity to metronidazole, erythromycin and tetracycline. Over the two periods of study, the resistance of H. pylori to metronidazole increased from 38% to 85.5%. This difference was statistically significant (p>0.0001). There was a slight increase in resistance to erythromycin from 3.0% to 6.5%. All the isolates were sensitive to tetracycline. There was no difference in the sensitivity to metronidazole of the H. pylori isolates from men and women in 1987/88. However, in 1995/96 slightly more isolates from women were resistant to metronidazole [Table - 3].
| Discussion|| |
The resistance of H. pylori to metronidazole varies from population to population ,, . It is highest in the developing and lowest in the developed countries ,, . In this study, the 38% prevalence of metronidazole-resistant H. pylori isolated in 1987/88 was higher than that observed in Brussels, similar in those born in the UK, but much lower than the 84% recorded in Zairians , . However, over the seven-year period, there occurred a marked increase in metronidazole resistant H. pylori isolates in the same area. The resistance rate of 85.5% is among the highest so far recorded ,,, as seen in [Table - 4] and [Figure - 1] which show some of the published resistant rates of H. pylori to metronidazole in Saudi Arabia and five other countries. In contrast to other areas  but similar to the observations of Glupczynski et al  , there was no difference in the prevalence of resistant strains in men and women in 1987/88. This pattern, however, changed and in 1995/96 women had a slightly higher prevalence rate of metronidazole resistant H. pylori strains than men, as observed elsewhere ,28]
Resistance of H. pylori to metronidazole is related to previous exposure to the drug ,, . It has been suggested that the high prevalence rate of metronidazole-resistant H. pylori in women may be due to its use in the treatment of vaginal infections such as trichomoniasis and Gardnerella and as prophylaxis in uterine surgery  . Previous use for the treatment of amoebiasis and other diarrheal diseases, and prophylaxis for colonic surgery also contribute to resistance in others  . The rapid increase in resistance of H. pylori to metronidazole observed over the seven years may be related to possible increased use for protozoal and diarrheal diseases and anaerobic infections in our environment.
The prevalence of H. pylori in Saudi Arabia varies from region to region. In the Eastern region, in patients undergoing upper gastrointestinal endoscopy, 72% - 76% of those with chronic gastritis and 89% with peptic ulcer or gastroduodenitis had H. pylori ,, In a recent study from the south, Al-Knawy et al found that 37% of the population had H. pylorr  . Its eradication is associated not only with healing and reduced recurrence of peptic ulceration but also remission of low grade MALT lymphoma ,,,,,,
Monotherapy of H. pylori is associated with low rates of eradication and rapid development of resistance. Triple therapy, consisting of bismuth subcitrate, metronidazole and another antibiotic, is thus standard ,,, . It provides eradication in over 85% of patients. However, the efficacy of the triple therapy is markedly reduced in patients who have metronidazole-resistant H. pylori ,,,, . The efficacy of such therapy in our patients will thus be diminished. The addition of proton pump inhibitors to the triple therapy increases its efficacy even in patients with metronidazole resistant H. pylori  . Such therapy may thus be required in our patients who have a high prevalence of metronidazole-resistant H. pylori. Furthermore, in order to improve outcome of treatment, sensitivity of H. pylori may need to be done to select the most appropriate treatment for each individual. Although this will make management more expensive, it will in the long term be cost effective since it will provide better eradication of the organism.
This study provides evidence of the changing pattern of sensitivity of H. pylori to the antibiotics tested. This phenomenon is likely to vary in different populations and it stresses the need for periodic, if not routine monitoring of the sensitivity of H. pylori to the routinely used antibiotics. This will enhance the efficient management of patients.
In conclusion, the rate of resistance of H. pylori to metronidazole varies in different populations and can change over time within the same population.
The high rate of resistance in our patients would suggest that sensitivity testing is necessary for the selection of the most appropriate drug regimen for individual patients. The addition of proton pump inhibitor to the triple therapy would seem appropriate in this environment to enhance the eradication of metronidazole-resistant strains. Therapeutic regimens recommended in other environments are not necessarily suitable for our patients, but must be modified by taking into account our prevailing sensitivity pattern of H. pylori.
| Acknowledgement|| |
I acknowledge with gratitude Prof. Abdulaziz Al Quorain for his help and encouragement, Prof. Lade Wosornu for a critical review of the manuscript, Irene San Augustine and Saud Hwelm for their technical assistance.
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Emmanuel Bekoe Larbi
College of Medicine & Medical Sciences, King Faisal University, Dammam, P.O. Box 2114, Dammam 31451
Source of Support: None, Conflict of Interest: None
[Figure - 1]
[Table - 1], [Table - 2], [Table - 3], [Table - 4]