Antonella Ferrieri

Intestinal Bacterial Overgrowth During Chronic Pancreatitis

INTRODUCTION The presence of an intestinal bacterial overgrowth (IBO) in patients with pancreatic insufficiency has been recently suggested to justify the worsening of their clinical conditions despite pancreatic enzyme supplementation. AIM The purposes of this study were (a) to verify IBO frequency in patients with pancreatic insufficiency owing to chronic pancreatitis and (b) to evaluate the effect of chronic administration of a non-absorbable antibiotic, Rifaximin, in reducing IBO frequency and influencing the clinical picture of the disease. MATERIAL AND METHODS Thirty-five patients with pancreatic insufficiency owing to chronic pancreatitis and 61 gastro-resected patients without pancreatic disease were studied. The presence of IBO was tested in both groups of patients using the hydrogen breath test with glucose. Chronic pancreatitis patients were subsequently treated with Rifaximin, 400 mg t.i.d for seven consecutive days each month for three months. RESULTS A positive hydrogen breath test was present in 12 out of 35 (34%) chronic pancreatitis patients and in 13 out 61 (21%) controls (p < 0.002). In chronic pancreatitis patients an IBO was most likely to be present in the presence of a high ethanol intake, pancreatic microcalcifications, concomitant gallstones, diarrhoea and a history of gastric resection. In all patients with IBO, Rifaximin administration normalised the hydrogen breath test and reduced symptoms. CONCLUSIONS IBO is frequent in patients with pancreatic insufficiency, particularly in those with a history of gastroduodenal surgery. Treatment with Rifaximin reduces IBO frequency and improves symptoms.

Rifaximin, a non-absorbable rifamycin, for the treatment of hepatic encephalopathy. A double-blind, randomised trial

The aim of this study was to evaluate the efficacy and tolerability of rifaximin, a non-absorbable intestinal antibiotic, in comparison to neomycin in the short- and long-term treatment of hepatic encephalopathy (HE). Forty-nine patients with a definite diagnosis of cirrhosis were included in this double-blind, randomised, controlled trial. Patients were randomly assigned to one of the following treatments: (1) rifaximin 400 mg three times daily; (2) neomycin 1 g three times daily. Both drugs were administrated orally as tablets during 14 consecutive days each month, for a period of six months. The neuropsychiatric signs and blood ammonia levels were examined before starting the treatment, and every 30 days, until the final assessment. In all patients a progressive and important reduction in HE grade was observed, and no statistically significant difference between the two treatments was detected. In both groups the disturbances in speech, memory, behaviour and mood, gait, asterixis, writing, and serial subtraction of 7 s and five-pointed star tests all showed the highest proportion of improvement. During the study blood ammonia levels decreased in both the rifaximin and in the neomycin groups, and again no statistically significant difference was found between groups. Our findings confirm, therefore, the usefulness of rifaximin in the treatment of HE, supporting its use as a first-choice antibiotic, particularly in patients intolerant to neomycin or with impaired renal function.

Rifaximin in the treatment of chronic hepatic encephalopathy

A study was performed to assess the efficacy and tolerability of rifaximin in the treatment of encephalopathy during cirrhosis of the liver. Fifty-five patients suffering from grade 1, 2 and 3 portosystemic encephalopathy, with a mean age of 58.9 years (range 30 to 86 years) were evaluated. The patients were treated for 15 consecutive days with rifaximin, an antibiotic which is not absorbed by the intestinal wall, at a dosage of 1200 mg/day in association with sufficient lactulose to induce 2 or 3 evacuations per day. Combined use of the 2 drugs proved an efficient means of controlling the majority of signs and symptoms. After just a few days, an improvement in the signs of encephalopathy was noted in all patients. The treatment was well tolerated and the patients completed the trial without any drug-related side-effects. The results of our trial, although in the context of an open assessment, confirm the clinical efficacy of rifaximin in association with a non-absorbable disaccharide such as lactulose. The 2 compounds have a synergetic effect in reducing ammonia-producing flora. Its efficacy and good tolerability make rifaximin a valid alternative to the use of aminoglycoside antibiotics associated with disaccharides in the treatment of patients with liver disease, particularly in the case of prolonged therapy.

Evaluation of the effect of rifaximin in colon diverticular disease by means of lactulose hydrogen breath test

To understand better the mechanism by which rifaximin produces symptomatic relief in diverticular disease of the colon, the effect of this antibiotic on orocaecal transit time and on the production of hydrogen by intestinal microflora after ingestion of lactulose was studied in 33 patients with this disease and in 11 healthy subjects. An hydrogen breath test was carried out to measure pulmonary hydrogen excreted during the 3 hours after ingestion of 10 g lactulose. In patients, the hydrogen breath test with lactulose was repeated after treatment with 400 mg rifaximin twice daily for 10 days. In patients under basal conditions and controls, orocaecal transit time did not differ significantly, but hydrogen production was significantly higher in the former (p < 0.02). In patients, transit time and hydrogen excretion in response to lactulose administration did not differ significantly before and after treatment with rifaximin, and these two parameters were inversely correlated both before (r = 0.49, p < 0.01) and after rifaximin (r = 0.58, p < 0.001). Fifteen of the 33 patients showed accelerated transit time after treatment with the antibiotic, 10 showed no variation, and 8 showed prolonged transit. In 19 patients a reduction in hydrogen production was noted after rifaximin, while in 14 an increase was demonstrated. Twenty-one of the 33 patients reported an improvement in their symptoms with rifaximin; of these, only 10 showed accelerated transit time and 9 a reduction in hydrogen production after rifaximin.(ABSTRACT TRUNCATED AT 250 WORDS)

Rifaximin suspension for the eradication of Helicobacter pylori

Abstract The in vitro sensitivity of Helicobacter pylori to rifaximin, a new rifamycin antibiotic, was evaluated in 40 clinical isolates by the agar dilution method. Rifaximin showed good activity, with a 50% minimum inhibitory concentration of 4 mg/L −1 . Consequently, we assessed rifaximin in H pylori —positive patients. Overall, 71 patients with upper gastrointestinal symptoms (35 men and 36 women; aged 19 to 73 years, mean, 45.6 years) were found to have H pylori —associated gastritis. The first 30 consecutive patients received monotherapy with rifaximin 600 mg three times a day (TID) for 14 days. The 41 patients enrolled thereafter were allocated in an open, randomized fashion to four different treatment groups for 14 days: (1) rifaximin 600 mg TID and colloidal bismuth subcitrate 240 mg twice a day (BID) (n = 10); (2) rifaximin 600 mg TID and omeprazole 20 mg BID (n = 10); (3) rifaximin 600 mg TID and amoxicillin 1 g BID (n = 10); or (4) rifaximin 1800 mg TID and metronidazole 500 mg TID (n = 11). Upper gastrointestinal symptoms (pyrosis, bloating, epigastric pain, and nausea) were recorded and assessed before and 4 weeks after treatment. Patients were assessed by endoscopy, histology, CP test, culture, and serology (immunoglobulin G [IgG] to H pylori ) at entry. Sixty-seven patients were available for follow-up 4 weeks after the completion of treatment. A statistically significant improvement in symptoms was seen in patients treated with rifaximin and rifaximin plus colloidal bismuth subcitrate. No statistically significant differences in degree of improvement in endoscopic and histologic findings were seen among the five treatment groups. A statistically significant decrease in the mean IgG value after treatment was found for rifaximin, rifaximin plus colloidal bismuth subcitrate, and rifaximin plus omeprazole. The overall eradication rate was 43%. These results suggest that rifaximin may be an effective antibiotic against H pylori infection and is worthy of further study.

Efficacy and tolerability of nicardipine slow release and enalapril in elderly hypertensive patients: Results of a multicenter study

In an open, multicenter, randomized clinical study, the antihypertensive efficacy and tolerability of nicardipine slow release (SR) and enalapril were evaluated in 561 patients aged 60 years and older with mild to moderate essential hypertension. After a 2- to 3-week washout period, the patients were randomly assigned to receive nicardipine SR 40 mg twice daily or enalapril 20 mg once daily for 6 months. After 2 months of treatment, if the patients blood pressure remained elevated, hydrochlorothiazide (HCTZ) 12.5 to 25 mg/day was added to the monotherapy. The results of this study confirmed the antihypertensive efficacy and tolerability of nicardipine SR and enalapril when given as monotherapy or in combination with HCTZ. However, in the nicardipine group, the number of responders to monotherapy and the degree of reduction in systolic and diastolic blood pressures during monotherapy was greater than that in the enalapril group. Thus the need for combined therapy was lower in the nicardipine group. Heart rate did not change significantly in either group. The incidence of side effects was higher in the nicardipine group (ankle edema, headache, facial flushing, and palpitations) when compared with the enalapril group (fatigue, cough, taste disturbance, and dizziness), but the number of drug-related withdrawals was significantly higher in the enalapril group, mainly because of cough. These results support the hypothesis that the antihypertensive efficacy of calcium antagonists is age dependent and related to pretreatment blood pressure values. Thus dihydropyridine calcium antagonists, such as nicardipine SR, appear to be particularly effective and well tolerated in the treatment of elderly hypertensive patients.