helicobacter pylori sensitivity to antibiotics in the sudan

184 Pages·2003·0.57 MB·English

UNIVERSITY OF KHARTOUM
FACULTY OF PHARMACY
DEPARTMENT OF Pharmaceutics

HELICOBACTER PYLORI SENSITIVITY

TO ANTIBIOTICS IN THE SUDAN

A Thesis

Submited By

HEKMA YOUSIF MOHAMED ELZIN

For the Degree of M.Pharm.

Under Supervision of

Dr . ELSKEIKH ALI ELOBEID
DEDICATION

TO MY

Family
To My Late Mother , Who Would
Have Loved To See

Me Succeed , MY
Father ,

To Whom Iove
Every Thing . I`m Proud of My
Brothers And

Ssters who Spared No Effort To Bring This
Work
Into Existance
MY

Teachers

And my

Dear friends

List of contents

Acknowledgement--------------------------------------------------------I
Abbreviations-------------------------------------------------------------II
Arabic Abstract---------------------------------------------------------III
Abstract-------------------------------------------------------------------.V
List of contents--------------------------------------------------------Vll
list of tables--------------------------------------------------------------X
List of figures ----------------------------------------------------------XII
Chapter One
1 - Introduction and Literature Review…………………..1
1.1 Peptic ulcer diseases…………………………………….1
1.2 Factors of peptic ulcer disease………………………….2
1.3 Discovery of H.pylori………………………………………. 4
1.3.1 H.pylori characteristics………………………………… 4
1.3.2 Historical ……………………………………………….4
1.3.3 H.pylori: Metabolism………………………………….5
1.3.4 Infection of H. pylori ………………………………....5
1.3.5 Pathological changes ……………………………….....7
1.3.6 Transmission…………………………………………...8
1.3.7 Diagnosis of H.pylori……………………………………….8
1.3.7.1 Urea Breath test…………………………………………11
1 .3.7.2 Serology………………………………………………..11
1.3.7.3 Molecular Test ………………………………………...12
1.3.7.4 Urease test……………………………………………..12
1.3.7.5. Culture…………………………………………………13
1.3.7.6 Histology……………………………………………-..13
1.3.7.8. The treatment of pepetic ulcers…………………..14
1.3.7.9 Treatment of H.pylori …………………………….8
1.3.9.1. Antibacterial Therapy …………………………….18
1.4. The problem of antimicrobial resistance …………..21
1.5. Pharmacological Resistance ……………….…….. 23
1.6. The stomach as a difficult environment……...........23

1.2. Aim of the study ………………………………...25

Chapter Two
2. Materials and Methods………………………….26
2.1. Materials……………………………………………26
2.1.1 Culture Media……………………………………..26
2.1.2 Skirrow’s, supplements……………………………26
2.1.3 Chemicals and Reagents…………………………..26
2.1.4. Biological Materials……………………………….27
2.1.5. Instruments…………………………………………..27
2.1.6. Sensitivity Feels for Antibiotic……………………….28
2.2 Methods and Patients……………………………....29
2 2.1. Media used …………………………………………………..30
2.2.1.1. Heart infusion Agar…………………………………………..30
2.2.1.2. Special transport Media……………………………………....30
2.2.1.3. Sensitivity testing Agar……………………………………….31
2.2.1.4. Skirrow’s H.pylori Medium…………………………………..31
2.3. Blood addition……………………………………………….31
2.4. Methods ……………………………………………………..32
2.4.1. Culture……………………………………………………….33
2.4.2. Gram-stain …………………………………………………..33
2.4.3. Biochemical tests …………………………………………….34
2.4.3.1. Rapid urease test…………………………………………….35
2.4.3.2. Catalase test…………………………………………………35
2..5. Antimicrobial sensitivity testing ………………………………36
2.6. Preparation of Plates ………………………………………… .37
2.7. Preparation of Inoculum and inoculation………………… ..37
2.8. Application of sensitivity test………………………………… 38
2.9. Interpretation of results ………………………………………38
Chapter Three

1.3. Results ………………………………………………………..40
1.3.1. Sensitivity test results …………………………………………40

Chapter Four
4.1 Discussion…………………………………………………….71
4.1. 1. Sensitivity testing of H.pylori………………………………………74
4.1. 2. Tinidazole …………………………………………………….75
4.1..3. Metronidazole………………………………………………...75
4.1.4
Amoxycillin……………………………………………………76
4.1.5. Clarithromycin………………………………………………… 77
4.2 . Conclusions………………………………………………….. .79
4.3. Recommendations…………………………………………… 80

Chapter Five
1.5. References …………………………………………………. ...81
List of Tables

Page
Table (1) Application of tests for the detection of H.pylori in
routine clinical diagnosis…………………………..10
Table (2) The doses of the anti -ulcer drugs………………………15

Table (3) Antimicrobial therapies of H.pylori (H.P) infection………16

Table (4) Sex distribution…………………………………………...41

Table (5) Age distribution of the study population………………….43

Table (6) Residence of patients…………………………………….45

Table (7) The distribution of the study group according to their
Occupation……………………………………………….47

Table (8) Symptoms presented in the study group…………………..49

Table (9) The endoscopic finding in the study population (65)……. 51

Table (10) Percentage of sensitivity and resistance of H.pylori
strains to Tinidazole (20µg/ml)……………………….53

Table (11) Percentage of sensitivity and resistance of H.pylori
strains to Tinidazole (100µg/ml)……………………..53

Table (12) Percentage of sensitivity and resistance of H.pylori
strains to Metronidazole (40µg/ml)………………… 56

Page
Taple (13) Percentage of sensitivity and resistance of H.pylori
strains to Metronidazole (160µg/ml)……………….56

Table (14) Percentage of sensitivity and resistance of H.pylori
strains to Amoxycillin (60µg/ml)…………………….59

Table (15) Percentage of sensitivity and resistance of H.pylori
strains to Amoxycillin (120µg/ml)………………… .59

Table (16) Percentage of sensitivity and resistance of H.pylori
strains to Clavulinated Amoxycillin (25µg/ml)…….. 62

Table (17) Percentage of sensitivity and resistance of H.pylori
strains to Clavulinated Amoxycillin (50µg/ml)…….. 62

Table (18) Percentage of sensitivity and resistance of H.pylori
strains to Tetracycline (10µg/ml)…………………… 65

Table (19) Precentage of sensitivity and resistance of H.pylori
strains to Tetracycline (30µg/ml)…………………. .65

Taple (20) Percentage of sensitivity and resistance of H.pylori
strains to clarithromycin ( 0.03µg/ml)…………….. 68

Table (21) Percentage of sensitivity and resistance of H.pylori
srtains to clarithromycin (0.06µg/ml)……………… 68
List of Figures

Page

Fig (1) The mechanisms involved in the secretion of acid into the
stomach and the effect and site of action of H blockers…..14
2

Fig (2) The male to female ratio in the study population (65)…..…42

Fig (3) The age distribution in the study group……………………44.

Fig (4) The distribution of the study group according to their place of
residence …………………………………………………46

Fig (5) The distribution of the study group according to their
occupation ……………………………………………..48

Fig (6) The presenting symptoms in the study group ……………....50.

Fig (7) The endoscopic finding in the study population …………..52

Fig (8) Percentage of sensitivity of H.pylori strains to Tinidazole
(20µg/ml) …… …………………………………………..54

Fig (9) Percentage of sensitivity of H.pylori strains toTinidazole
(120µg /ml)………………………………………………..55

Fig (10) Percentage of sensitivity of H.pylori strains to Metrondizole
(40µg/ml)… ……………………………………………..57

Fig (11) Percentage of sensitivity of H.pylori strains to Metrondizole
(160µg/ml) ………………………………………………58

Fig (12) Percentage of sensitivity of H.pylori strains to Amoxycillin
(60µg/ml)… ……………………………………………60

Fig (13) Percentage of sensitivity of H.pylori strains To Amoxycillin
(120µg/ml) … …………………………………………….61