A500 AGA ABSTRACTS

2680

PRIMARY METRONIDAZOLE AND CLARITHROMYCIN RESIS­TANCE RATES FOR HELICOBACTER PYLORI IN THE U.S.Michael S. Osato, Rita Reddy, Siddharta G. Reddy. Rebecca L. Penland,David Y. Graham, Hoda M. Malath, VAMC and Baylor Coil of Medicine,Houston, TX.

Background: Knowledge of the frequency of clarithromycin and metroni­dazole resistance is critical for optimum choice of anti-Helicobacter pyloritherapy. Aim: To assess the overall prevalence of metronidazole andc1arithromycin resistance in the United States, as well as to determine theeffect of patient demographics. Methods: Agar dilution susceptibility re­sults were obtained from US based clinical trial data collected between1993 to 1999. Breakpoints used for metronidazole and clarithromycinresistance were >8mg/mL and Img/mL, respectively. Results: 3,193 pa­tients were available for overall metronidazole and clarithromycin resis­tance rates. Information on the gender and age of the patient was availableon 557 and 1,555 individuals, respectively. Overall metronidazole resis­tance averaged 25.7% (317/1,234) and ranged between 22.1% (46/208) and66.7% (417). Clarithromycin resistance ranged from 9% (19/211) to 11%(117/1,050), with an overall resistance rate of 10.6% (150/1,414). Womenwere more apt to harbor metronidazole and clarithromycin resistant H.pylori (F:M = 34.8% [58/166] vs 22.6% [68/301] [p = 0.04] for metro­nidazole and 19% [371195] vs 13% [47/362] [p = 0.07] for clarithromycin,respectively). After age 70 both metronidazole and clarithromycin resis­tance decreased significantly (p <0.05). When the U.S. was divided into 4regions (West, Central, Southeast, Northeast), the resistance patternshowed that metronidazole resistance was highest in the SE (27.5%) andlowest in the NE (22.1%). For clarithromycin resistance, the NE had thehighest rates (13%) while the West had the lowest rates (8.6%). Conclu­sion: Age and gender of the patient had a significant effect on the resistancerates, with the younger individuals and females having higher rates. Re­gional differences were detected, but there were no significant differencesin the prevalence of resistance to either antibiotic.

2681TRANSFER OF CLARITHROMYCIN TO GASTRIC JUICE IS EN­HANCED BY OMEPRAZOLE IN HEUCOBACTER PYWRI IN­FECTED INDIVIDUALS.Silvana A. Calafatti, Fernanda E. Dias, Maristela Deguer, Fabiana D.Mendes, Jose G. Ferraz, Ana P. Bento, Alex A. Pereira, Helenice Piovesan,Gilberto De Nucci, Federico E. Lerner, Rodrigo A. Ortiz, Jose Pedrazzoli,Sao Francisco Univ Med Sch, Braganca Pta. Brazil; State Univ of Campi­nas, Campinas, Brazil; Sao Paulo Univ, Sao Paulo, Brazil.

Background and aims: The effects of H. pylori infection associated withgastric acid blockade on the distribution of drugs used to eradicate thismicroorganism are poorly understood. The aim of this study was toinvestigate the effect of a 7 day administration of 20 mg of omeprazole onthe distribution of clarithromycin in the gastric juice of individuals with anH. pylori infection. Methods: Eighteen H. pylori positive male volunteerswere enrolled in a study with an open randomised two-period crossoverdesign and a 21-day washout period between phases. Plasma and gastricjuice concentrations of c1arithromycin in subjects with and without ome­prazole pre-treatment were measured by liquid chromatography coupled totandem mass spectrometry. Results: Omeprazole did not alter the plasmabioavailability of clarithromycin, as shown by the AUCO_2h CLk Pre­treatment with omeprazole did affect the clarithromycin peak concentration(Cmax) in gastric juice and significantly increased AUC{}-zh CLA and Cmax­

CLA in the gastric juice from H. pylori positive individuals. Conclusion:Short-term treatment of H. pylori positive volunteers with omeprazoleincreased the amount of clarithromycin transferred to gastric juice, con­firming a synergism between these drugs. These results also suggested thepresence of an omeprazole sensitive active transport mechanism for clar­ithromycin between plasma and the gastric lumen.

2682

EFFECT OF ACID SECRETION BLOCKADE BY OMEPRAZOLEON THE BIOAVAILABILITY OF ORALLY ADMINISTEREDFURAZOLIDONE IN HEALTHY VOLUNTEERS.Silvana A. Calafatti, Rodrigo A. Ortiz, Fernanda E. Dias, MaristelaDeguer, Marcio Martinez, Jose Pedrazzoli, Sao Francisco Univ Med Sch,Braganca Pta, Brazil.

Background: The administration of omeprazole may interfere with theabsorption of orally administered drugs by reducing gastric pH and thustablets dissolution. The aim of this study was to investigate the effects ofa five day administration of omeprazole on furazolidone pharmacokinetics.Methods: Eighteen healthy (male, female) volunteers were selected. Thestudy had an open randomized two-period crossover design with a 21 daywashout period between the phases. Plasma concentrations of furazolidonewere measured by reversed-phase HPLC with ultraviolet detection. Re­sults: Administration of omeprazole caused a significant reduction of Cmax(0.3426 + 0.042 vs. 0.2440 + 0.046) and a not significant reduction of T liZ

(4.869 + 1.06 vs, 3.904 + 0.85 ) but did not interfere with other pharma­cokinetic parameters of orally administered furazolidone. Conclusion: Ourresults indicate that furazolidone is well absorbed after oral administration.Short-term treatment with omeprazole does not alter the bioavailablitity offurazolidone. The observed reduction in Cmax and T liZ induced by acid

GASTROENTEROWGY Vol. 118, No.4

blockade suggests a possible interference with the absorption kinetics ofthe drug.

2683

EPIDEMIOLOGY OF HELICOBACTER PYLORI RESISTANCETO ANTffiIOTICS IN NORTH EAST OF ITALY: A MULTI­CENTER STUDY.Alberto Pilotto, Mario Rassu, Marilisa Franceschi, Gioacchino Leandro,Francesca Furlan, Francesco Di Mario, on behalf of GISU InterdisciplinaryGroup Study Ulcer, Dept of Geriatrics, Vicenza, Italy; Microbiology Ser­vice, Vicenza, Italy; Dept Gastroenterology, Castellana G., Italy; DeptGastroenterology Univ, Padova, Italy.

Aims: I) to evaluate the prevalence of primary H pylori antibiotic resis­tances in North East of Italy and 2) to identify whether some risk factor isassociated with such antibiotic resistance. Materials and Methods. 248consecutive patients undergoing for the fisrt time an upper GI endoscopyand who were diagnosed H pylori-positive by rapid urease test (CLO test)were enrolled from 19 Endoscopy Units during three months. From eachpatient, 4 gastric biopsies were taken for histological confirmation of Hpylori infection (modified Giemsa stain) and 2 biopsies were send to theMicrobiology Unit for culture and determination of antibiotic activityagainst H pylori by means of the E-test. Strains were considered resistantwhen the MIC was > 8 ~g/mL for metronidazole, > 2 ~g/mL forclarithromycin and > I ~g/mL for amoxicillin. In all patients epidemio­logical (sex, age, smoking, alcohol) and clinical data (concomitant diseasesand therapies, endoscopic diagnoses) were recorded. Statistical analysiswas performed by means of X squared test and Fisher exact test. Results:243/248 patients were confirmed to be H pylori positive by gastric histol­ogy; culture of H pylori was successfully performed in 167/243 (68.7%)patients (M=90, F=77, mean age=58.6 years, range=23-94). 27/167(16.2%) patients were infected with H pylori strains resistant to antibiotics.Primary resistance rates to metronidazole, clarithromycin and amoxicillinwere 14.9%, 1.79% and 0% respectively. Subjects infected with H pyloristrains resistant to antibiotics were more frequently females than males(70.3% vs 41.4%, p=O.OI), while mean age (59.2 vs 55.1 years), smoking(21.3% vs 23.8%), alcohol (34.1% vs 28.6%), concomitant diseases (46.7%vs 33.3%) concomitant treatments (41.1% vs 30%) and endoscopic diag­noses (DU=24.7% vs 31.8%, GU=3.4% vs 9.1%, gastritis=47.8% vs18.2%, esophagitis=5.9% vs 13.6%, non lesions= 17.9% vs 27.7%) werenot different between patients with susceptible and resistant strains. Uni­variate analysis demonstrated that female sex was the only factor signifi­cantly associated with H pylori strains resistant to antibiotics. Conclusions.The prevalence ofH pylori resistance to antibiotics was lower compared toprevious european studies; 2) resistance to metronidazole resulted higherthan to clarithromycin; 3) female sex was the only factor significantlyassociated with H pylori strains resistant to antibiotics.

2684

RANDOMIZED TRIAL OF USING ANTIMICROBIAL SUSCEPTI­BILITY TESTING OR NOT WITH PPI TRIPLE THERAPY FORHELICOBACTER PYLORI INFECTION.Margherita Idda, Monica Carta, Bianca M. Are, Ida Mura, Maria P. Dore,Giuseppe Realdi, Institute of Internal Medicine, Univ of Medicine, Sassari,Italy; Institute of Hygiene, Univ of Medicine, Sassari, Italy.

One-week of proton-pump inhibitor based triple therapies containing twoantibiotics (MOC and MOA) for H. pylori infection achieve controversialresults in relation to several factors (1,2). Aim: To identify a successfultherapy for treatment of H. pylori infection on the basis of pre-treatmentsusceptibility test. Methods: 110 dyspeptic patients positive for H. pylori­infection were randomized to receive H.pylori eradication treatment basedon or without knowledge of pre-treatment susceptibility results. 53 patientsreceived omeprazole (20 mg bid), metronidazole (500 mg bid), and tetra­cycline (500 mg qid) (OMT) for 7 days, or omeprazole (20 mg bid),clarithromycin (500 mg bid), and amoxycillin (1000 mg bid) (OCA) for 10days based on pre-treatment susceptibility test. 57 patients received OMTor OCA treatments without regard of the pre-treatment susceptibility testresults. H. pylori status was assessed by histology, culture, rapid ureasetesting of gastric biopsies and urea breath test. Antibiotic susceptibilitytesting was performed by the E-test method for amoxycillin, clarithromy­cin, metronidazole, and tetracycline. 40 to 50 days after ending antimicro­bial therapy, H. pylori status was determined by UBT. Results: The curerate for OMT was 92% (23\25) and 93% for OCA based on pre-treatmentsusceptibility. The successful eradication rate in patients with unknownpre-treatment susceptibility results was lower: 86% for OMT and 68% forOCA. Conclusions: Use of pre-treatment susceptibility testing to choosethe appropriate therapy markedly improved the outcomes (e. g. 93% vs.68% for OCA,p= 0.04) and should become the standard of care inlocations where the prevalence of antibiotic resistance is high ReferencesI.Realdi G, Dore MP, Piana A, et al. Pretreatment antibiotic resistance inHelicobacter pylori infection: results of three randomized controlled stud­ies. Helicobacter 1999;4:106-12. 2.Dore MP, Piana A, Carta M, et al.Amoxycillin resistance is one reason for failure of amoxycillin-omeprazoletreatment of Helicobacter pylori infection. Aliment Pharmacol Ther 1998;12:635-9.