Diana Levi

Ciprofloxacin in primary prophylaxis of spontaneous bacterial peritonitis: A randomized, placebo-controlled study

BACKGROUND/AIMS Low protein concentration in ascitic fluid has been identified as a risk factor for spontaneous bacterial peritonitis (SBP). Until now, primary prophylaxis has not been recommended in these patients. The aim was to investigate the efficacy of long-term administration of ciprofloxacin to prevent SBP. METHODS One hundred cirrhotic patients with <1.5 g/dl of total protein in ascitic fluid were randomized prospectively, in a double blind fashion to receive ciprofloxacin 500 mg/day (n=50) or placebo (n=50) for 12 months. RESULTS Baseline data were similar in both groups. In the ciprofloxacin group, SBP occurred almost four times less frequently than in the placebo group but it was not statistically significant. The probability of survival at 12 months was significantly higher in patients receiving ciprofloxacin (86% versus 66%) (p<0.04). SBP and sepsis were the most frequent causes of death in the placebo group whereas gastrointestinal bleeding was responsible for the most deaths in the ciprofloxacin group. The probability of remaining free of bacterial infections was higher in patients receiving ciprofloxacin (80% versus 55%) (p=0.05). CONCLUSIONS Patients with cirrhosis and low protein concentration in ascitic fluid are candidates to receive long-term prophylaxis to reduce the risk of infections and improve survival.

Paracentesis with Dextran 70 vs. paracentesis with albumin in cirrhosis with tense ascites: Results of a randomized study

Forty-one patients with cirrhosis and tense ascites were randomized to receive daily paracentesis of 5 liters associated with Dextran 70 as volume expander (6 g for each 1000 ml of ascites removed) (group I = 20 patients) or paracentesis with albumin (6 g for each 1000 ml of ascites) (group II = 21 patients). The basal clinical features, laboratory data, and plasma renin activity were similar in both groups. The volume of ascites removed was 12.9 +/- 4.4 and 10.9 +/- 3.7 liters in group I and II, respectively (n.s.). No significant changes were observed in liver and renal function tests, KPTT, platelet count, factor VIII, serum electrolytes or plasma renin activity 24 and 96 h after the last paracentesis in both groups, except for a decrease in bilirubin in group I and a transient increase of serum albumin in group II. Four patients developed complications in each group, mainly hyponatremia, while one patient in each group developed renal impairment. One patient from group I died with hepatic encephalopathy. Moreover, the probability of survival and readmission to the hospital because of tense ascites were similar in both groups of patients during the follow-up. The treatment cost with Dextran 70 was 15.50 dollars vs. 364.30 dollars with albumin for each patient treated. These results indicate that repeated large volume paracentesis associated with Dextran 70 is as effective and safe as paracentesis associated with albumin in cirrhotic patients with tense ascites. However, due to its reduced cost, paracentesis with Dextran 70 may be considered the treatment of choice in cirrhotic patients with tense ascites without liver cancer and renal failure.

Effects of oral ciprofloxacin on aerobic gram-negative fecal flora in patients with cirrhosis: results of short- and long-term administration, with daily and weekly dosages

BACKGROUND/AIMS Selective intestinal decontamination has been proposed to prevent spontaneous bacterial peritonitis in cirrhosis. Because of the cost of antibiotics and the development of resistant bacteria, we have evaluated the effect of different schemes and doses of oral ciprofloxacin on aerobic gram-negative fecal flora in cirrhotic patients. METHOD Twenty-nine cirrhotic patients were allocated to four groups to receive: Group 1: 500 mg/day for 2 weeks (six patients); Group 2: 1000 mg twice a week for 2 weeks (six patients); Group 3: 1000 mg once a week for 2 weeks (six patients); and Group 4: 1000 mg once a week for 12 weeks (11 patients). Quantitative analysis of the gram-negative fecal flora was performed before and 1 and 2 weeks after initiation of treatment in patients in Groups 1, 2 and 3 and before and 4, 8 and 12 weeks after initiation of treatment in patients in Group 4. RESULTS Complete eradication of gram-negative bacilli was observed in four of six patients in Group 1. In contrast, only one patient eradicated gram-negative bacilli in Group 2 and Group 3. In long-term administration of ciprofloxacin (Group 4), only two of 11 patients had persistent eradication of gram-negative bacilli. Four patients developed E. coli resistant to ciprofloxacin (one of them associated to resistant Klebsiella). No patient developed bacterial infection during the study period. CONCLUSION Oral ciprofloxacin administered in a weekly dose is ineffective in selective intestinal decontamination. Different mechanisms, including the emergence of ciprofloxacin-resistant organisms, could account for this failure. Therefore, our results suggest that weekly administration of ciprofloxacin is not useful in preventing spontaneous bacterial peritonitis.

Analysis of clinical course and prognosis of culture-positive spontaneous bacterial peritonitis and neutrocytic ascites. Evidence of the same disease.

The clinical significance and prognosis of culture-negative neutrocytic ascites in cirrhotic patients is a controversial topic. In the present study, the clinical and humoral presentation and the short-and long-term prognosis were analyzed in 36 patients with cirrhosis and culture-positive spontaneous bacterial peritonitis and in 28 patients with cirrhosis and ascitic fluid polymorphonuclear count greater than 250/mm3, a negative ascitic fluid culture, and without previous antibiotic therapy. On admission there were no significant differences between groups related to age, sex, alcoholism, fever, abdominal pain, serum albumin, serum urea, serum creatinine, Child-Pugh score, polymorphonuclear count, and total protein concentration in ascitic fluid. A greater frequency of positive blood culture was found in patients with spontaneous bacterial peritonitis (15/21 vs 2/18) (P<0.001). Mortality during the first episode was 36% in patients with spontaneous bacterial peritonitis and 46% in patients with culture-negative neutrocytic ascites (NS). Mortality during follow-up was high and survival probability at 12 months was 32% in spontaneous bacterial peritonitis and 31% in culture-negative neutrocytic ascites. The probability of recurrence at 12 months was 33% in spontaneous bacterial peritonitis and 34% in culture-negative neutrocytic ascites. Our results show that spontaneous bacterial peritonitis and culture-negative neutrocytic ascites are variants of the same disease with a high mortality and poor prognosis.

NONINVASIVE MEASUREMENT OF PORTAL VENOUS BLOOD FLOW IN PATIENTS WITH CIRRHOSIS : EFFECTS OF PHYSIOLOGICAL AND PHARMACOLOGICAL STIMULI

The present study aims to evaluate the usefulness of combined pulse Doppler-real-time ultrasonography as a noninvasive method for the measurement of portal blood flow in man. This measurement technique was performed on 12 healthy subjects and 20 patients with portal hypertension. Ten patients (group 1) were evaluated prior to and after ingestion of a standard meal (Ensure Plus) or placebo. In the remaining 10 patients (group 2), the effects of isosorbide dinitrate (5 mg/SL) administration or placebo were studied. In group 1, food intake caused a significant increase of portal blood flow (from 1038±539 to 1572±759 ml/min,P<0.02); this effect was due to a significant rise in mean blood velocity (from 18.5±3.7 to 23.9±3.9 cm/sec,P<0.02). In group 2, isosorbide dinitrate significantly reduced portal blood flow (from 985±491 to 625±355 ml/min,P<0.05); a significant decline of mean blood velocity (from 18.8 ±4.5 to 14.5±2.5 cm/sec,P<0.02) was observed. Placebo administration had no significant hemodynamic effects in either group. Our results suggest that Doppler measurements gave accurate noninvasive estimations of portal blood flow and that this technique may be used to monitor physiological and pharmological stimuli in patients with portal hypertension.

Splenic hypofunction in cirrhosis is not associated with increased risk for infections.

Background/aim: Pitted cell count has been described as a sensitive marker of splenic function. Recently, pitted cell count was shown to be increased in patients with alcoholic liver disease, and also to be associated with an increased susceptibility to infection. Therefore, our aim in the present study was to assess splenic function in a group of patients with cirrhosis and to determine its possible role in the development of infections. Methods: Splenic function was assessed during hospitalization in 44 patients diagnosed as having cirrhosis, and was compared to 18 healthy subjects. Function was evaluated by counting the number of pitted cells in peripheral blood films. Results were the mean value of two independent counts and were expressed as number of pitted cells/100 erythrocytes. Results: The mean percentage of pitted cells in peripheral blood of cirrhotic patients was significantly greater than that assessed in controls (3.5 ± 3.7% vs. 1.6 ± 0.9%, P<0.01, Mann-Whitney U test). Eighteen patients with cirrhosis (36%) had counts greater than 3.4% (mean+ 2 SD of the control group). There were no significant differences between patients with counts above or below 3.4% in terms of liver tests, platelet and reticulocyte counts, the presence of complications, Child-Pugh score and the prevalence of infections. There was no difference in pitted cell count between alcoholic and non-alcoholic cirrhotic patients (3.8 ± 3.4% vs. 3.1 ± 2.8% respectively, P, NS). Moreover, the mortality rate and the occurrence of infections were similar in patients with normal and increased pitted cell counts during 1-year follow-up. Conclusion: The increased number of pitted cells in patients with cirrhosis is not related to hepatic function and does not represent a risk factor for infections.

Lidocaine and Monoethylglycinexylidide Serum Determinations to Analyze Liver Function of Cirrhotic Patients After Oral Administration

Our aim was to compare standard liver functiontests (serum bilirubin, serum albumin and prothrombinconcentration), with lidocaine andmonoethylglycinexylidide pharmacokinetic parameters,after oral lidocaine administration, to assess hepatic function ofcirrhotic individuals. Twenty-one consecutive cirrhoticpatients, nine consecutive acute hepatitis patients, andnine healthy individuals received oral lidocaine. Lidocaine and monoethylglycinexylidide serumconcentrations were determined by the TDx system.Cirrhotic patients had higher lidocaine and lowermonoethylglycinexylidide serum concentrations anddifferences in its pharmacokinetic variables, compared tocontrol and hepatitis groups (P < 0.05). Sensitivityof lidocaine serum determinations (100%) was greaterthan sensitivity of serum bilirubin (57%), serum albumin (62%), and prothrombin concentrations(43%) and monoethylglycinexylidide serum concentrations(57%) in differentiating cirrhotic individuals fromcontrols. In conclusion, after oral administration, lidocaine and monoethylglycinexylididepharmacokinetic parameters are significantly altered incirrhotic patients compared to normal and acutehepatitis subjects. Lidocaine pharmacokinetic parameterswould be better than those ofmonoethylglycinexylidide and standard liver functiontests in the evaluation of liver function of cirrhoticpatients.