BSS quadruple “Salvage” therapy for patients with culture proven metronidazole-resistant Helicobacter pylori

A138 AGA ABSTRACTS

GASTROENTEROLOGYVol. 114, No. 4

G0562 ANTI-REFLUX THERAPY IMPROVES SYMPTOMS IN PATIENTS WITH REFLUX LARYNGITIS. Y. Govil, P. Katz, R. Srinivasan, R, Khoury, D. Castell. Allegheny University Hospitals, Graduate, Philadelphia, PA. Gastroesnphageal reflux may be an etiologic factor in many patients with chronic laryngeal symptoms. However, limited data are available on frequency of symptoms and their response to therapy. Methods: 52 patients with suspected reflux laryngitis documented by abnormal pH monitoring prior to therapy between 1/93 and 12/96 were mailed a questionnaire designed to assess symptomatic response to antireflux treatment. Patients were asked to rate presence of and improvement in laryngeal (hoarseness, change in voice quality, throat clearing and globus sensation) and esophageal (heartburn, dysphagia, regurgitation) symptoms. Patients' self reported current status of symptoms at time of survey were compared to initial symptoms, rated as 0 (worse) to 4 (excellent). Results: 27 (52%) patients responded to the questionnaire. There were 12 (44%) males and 15 (56%) females; mean age 47 (range 29-71) years. Symptom

Pre-treatment frequency

Hoarseness Change in voice Frequency throat clearing Globus Heartburn Dysphagia Regurgitation

21/27 (78%) 20/27 (74%)

Improvement frequency (good/excellent) 16/24 (76%) 11/20 (55%)

21/27 (78%)

13/21 (62%)

14/27 (52%) 19/27 (70%) 10127 (37%) 17/27 (63%)

10/14 (71%) 15/19 (79%) 5/10 (50%) 13/17 (78%)

Maximum level of treatment reported was as follows: Life style modification (22%), H2RA (15%), PPI (30%) and surgery (33%). Treatment response was similar between esophageal and laryngeal symptoms: Conclusion: Antireflux therapy resulted in improvement of both laryngeal and esophageal symptoms in response to a wide range of treatment options. Heartburn was seen in greater frequency in this population than previously reported. • G0563 BSS QUADRUPLE "SALVAGE" THERAPY FOR PATIENTS WITH CULTURE PROVEN METRONIDAZOLE-RESISTANT HELICOBACTER PYLORL D.Y. Graham, J. Hoffman, M.S. Osato, H.M.T. E1-Zimaity. VA Medical Center and Baylor College of Medicine, Houston, TX. Background: Increasingly antibiotic resistance has begun to jeopardize the ability of clinicians to cure H. pylori infection. Salvage therapies for patients with metronidazole and clarithromycin resistant H. pylori are needed. Aim: To investigate the role of quadruple therapy for the treatment of culture proven metronidazole-resistant H. pylori. Methods: Patients with histologically and culture proven 1-1.pylori infection with isolates proven to be resistant to metronidazole by E-test (MIC > 16 rag/L) received BSS (2 Pepto-Bismol swallowable caplets q.i.d.) tetracycline HC1 (500 mg q.i.d.), metronidazole (500 mg t.i.d.), and omeprazole (20 mg daily) for 14 days. 4 or more weeks after the end of therapy outcome was assessed by repeat endoscopy with histology and culture or in 2 cases with urea breath tests. Results: 6 patients with proven metronidazole-resistant H. pylori have completed therapy. There were 4 men and 2 women. The ages ranged from 38 to 73 years. 3 (50%) had previously been treated with metronidazole and 4 (67%) also had clarithromycin resistant H. pylori. All (100%) of infections were cured. Conclusions: Despite the presence of H. pylori with cultureproven metronidazole resistance, quadruple therapy proved effective in curing the H. pylori infection. The difference between standard triple therapy and quadruple therapy is the increase in the dose of metronidazole to 500 mg t.i.d., and the addition of a proton pump inhibitor. Quadruple therapy should be considered as salvage therapy after treatment failure, or as primary therapy in situations where metronidazole and clarithromycin resistance is common. Supported, in part, by a grant from Procter & Gamble Pharmaceuticals • G0564 DRUG-INDUCED GASTRIC ULCERS ARE CAUSED BY MORE THAN JUST NSAIDS: ALENDRONATE GASTRIC ULCERS. D.Y. Graham. H.M. Malaty, VA Medical Center and Baylor College of Medicine, Houston, TX. Background: It has become increasingly recognized that many peptic ulcers in the US are not directly related to 1-1.pylori infection. As patients using NSAIDs are routinely excluded from clincial trials of H. pylori therapy, and yet ulcer recurrence despite H. pylori cure is reported, it appears likely that drugs in addition to NSAIDs may also be associated with ulcers and ulcer complications (e.g., potassium chloride). Alendronate (Fosamax) is a primary amino-bisphosphonate used in the treatment of metabolic bone disease. Alendronate has been associated with severe esophageal damage and stricture. We previously showed that the dose of alendronate used for Paget's disease

(40 mg) caused gastric damage similar to NSAIDs. The usual dose for the prevention of osteoporosis is I0 mg per day. Aim: To investigate whether the lower dose of alendronate causes ulcers. Methods: We performed a blinded, crossover, randomized, singlecenter comparison of 10 mg of alendronate/day and placebo in volunteers age 40 or older. Video-endoscopy was used to evaluate the presence and degree of mucosal damage to the esophagus, stomach, or duodenal bulb. Results: 15 normal volunteers were studied both before and after 7 and 14 days of drug therapy. Alendronate caused visible gastric mucosal injury in 7 (47%). Gastric ulcers developed in the antrum of 3 volunteers. There were no symptoms associated with the presence of the ulcers. Condusion: The primary amino-bisphosphonate alendronate causes mucosal injury to the upper gastrointestinal tract similar to NSAIDs. The fact that it causes ulcers suggests that like NSAIDs, alendronate use will be associated with ulcer complications such as acute UGI bleeding. Even when used according to manufacturer's dosing instructions alendronate should be used with caution. Supported, in part, by a grant from Procter & Gamble Pharmaceuticals G0565 HOW DOES CITRIC ACID INCREASE UREASE ACTIVITY IN VIVO? D.Y, Graham, D. Runke-Garcia, S.Y. Anderson, H.M. Malaty. Department of Medicine, VA Medical Center and Baylor College of Medicine; P.D. Klein, Meretek Diagnostics, Houston, TX. Background: It has been suggested that citric acid may be the best test meal for the UBT. Test meals were designed to slow gastric emptying and to increase the area of contact with the substrate. The effect of citric acid and its sodium salts on gastric emptying has been extensively studied in the past. Maximum slowing is with citric acid and is successively less as the three hydrogens are replaced by sodium. The minimum concentration of citric acid required to reduce gastric emptying is the range of 30 raN. Citric acid solutions have a pH of~2.4 vs. 8.2 for sodium citrate. Sodium citrate also increases gastric acid secretion. Aim: (a) To evaluate the effect of citric acid on urea hydrolysis and (b) to identify why it has an effect on urea hydrolysis. Methods: 13-C-urea was given in 200 mL of water with or without citric acid. Results: We studied 9 healthy Hp infected individuals. The median urea hydrolysis without citric acid was 83 gg/min and increased to 120, 131, and 193 ~g/min, respectively, as the amount of citric acid was increased from 1, 2, or 4 g (78, 172, or 315 raN), respectively (p < 0.05 vs control for each). The response in urease activity was very rapid; at 10 minutes it was significantly higher with citric acid than without it. There was a small but significant increase (to 95.4 pg/min, p < 0.05) in urea hydrolysis with sodium citrate. In a separate experiment we tested 50 g Polycose, 4 g ascnrbic acid (slowing of gastric emptying =-130 mN citric acid, pH ~2.4), 4 g citric acid, and pentagastrin (6 ~g/kg SC) to evaluate the effect of the pH of the test meal. As predicted from the 1st experiment, citric acid increased the urease hydrolysis-3-fold (p < 0.05 against all others); ascorbic acid, Polycose, and pentagastrin approximately doubled urease activity (p <0.05 for each). Conclusions: Slowing of gastric emptying is largely responsible for the enhanced urease activity seen with citric acid. Supported in part by Meretek Diagnostics, Houston, TX. G0566 NEW THERAPY FOR METRONIDAZOLE OR CLARITHROMYCIN RESISTANT HELICOBACTER PYLORI: FOC OR FOM. D.Y. Graham, J. Hoffman, M.S. Osato, H.M.T. E1-Zimaity. VA Medical Center and Baylor College of Medicine, Houston, TX. Background: Increasingly, antibiotic resistance has begun to jeopardize the ability of clinicians to cure H. pylori infection. New therapies for patients with metronidazole or clarithromycin resistant H. pylori are needed. Aim: To investigate the role of furazolidone triple therapy for the treatment of 11. pylori in the U.S. Furazolidone replaced metronidazole or clarithrnmycin in MOC to yield FOC or FOM. Methods: Patients with histologically and culture proven H. pylori infection with isolates proven to be sensitive to metronidazole or clarithromyin (by E-test) received furazolidone (100 mg t.i,d.), omeprazole (20 mg daily.), and either metronidazole (500 mg t.i.d.) or clarithromycin (500 mg t.i.d.) (depending on the sensitivity of the organism) for 14 days. 4 or more weeks after the end of therapy outcome was assessed by repeat endoscopy with histology and culture or urea breath testing. Results: 12 patients completed therapy; 9 patients had proven metronidazolesensitive 11. pylori, and 3 patients had clarithromycin-sensitive H. pylori. There were 10 men and 2 women. The ages ranged from 26 to 74 years. All (100%) of infections were cured. Severe side effects were seen in 4 (33%) and necessitated treatment stoppage in 1 (at 5 days). Nevertheless, the infection was cured. Conclusions: Furazolidone-containing therapy proved effective in curing the 14. pylori infection in the US. Furazolidone salvage therapy should be considered as therapy after treatment failure, or as primary therapy in situations where metronidazole and clarithromycin resistance is common. We previously showed that 7 mg of furazolidone 7 times a day for one day changed the UBT to negative. That experiment suggests that lower doses may