Amoxicillin-clavulanic acid versus cefotaxime in the therapy of bacterial infections in cirrhotic patients.

BACKGROUND/AIM: Cefotaxime is considered the first-choice antibiotic for empirical treatment in cirrhotic patients developing bacterial infections. It has been suggested that amoxicillin-clavulanic acid could be an alternative to cefotaxime, particularly in patients developing bacterial infections while on prophylactic norfloxacin. The aim of the present study was to compare amoxicillin-clavulanic acid with cefotaxime in the treatment of bacterial infections in cirrhosis. METHODS: Ninety-six hospitalized cirrhotic patients with suspicion of bacterial infection were prospectively included and randomized into two groups: one group (n=48) received amoxicillin-clavulanic acid, first intravenously 1 g-0.2 g every 8 h, and then orally 500 mg-125 mg every 8 h, and the other group (n=48) received intravenous cefotaxime 1 g every 6 h. Patients were stratified for previous prophylaxis with norfloxacin and ascitic fluid infection. RESULTS: Sixteen patients were excluded from the analysis because bacterial infection was not demonstrated or because of secondary peritonitis. Therefore, 38 patients from the amoxicillin-clavulanic acid group and 42 from the cefotaxime group were finally analyzed. There were 24 ascitic fluid infections in each group. Infection resolution (86.8% vs 88%, 95% CI: -0.15 to 0.13, p NS), spontaneous bacterial peritonitis resolution (87.5% vs 83.3%, 95% CI: -0.15 to 0.24, p NS), duration of treatment, incidence of complications, time of hospitalization and hospital mortality were similar in both groups. Considering patients on prophylactic norfloxacin, infection resolution was also similar (100% vs 83.3%, 95% CI: -0.04 to 0.37, p NS). No adverse events were observed in either of the two groups. The cost of antibiotics was statistically lower in the amoxicillin-clavulanic acid group (p<0.001). CONCLUSIONS: Amoxicillin-clavulanic acid is as effective as cefotaxime in the treatment of bacterial infections in cirrhotic patients, but is less expensive and can be administered orally. These results suggest that amoxicillin-clavulanic acid is an effective alternative to cefotaxime for the empirical treatment of bacterial infections in cirrhosis.

Risk of a first community-acquired spontaneous bacterial peritonitis in cirrhotics with low ascitic fluid protein levels.

BACKGROUND & AIMS: Long-term primary antibiotic prophylaxis of spontaneous bacterial peritonitis has been suggested to be useful in cirrhotic patients with low ascitic fluid protein levels. However, it is unlikely that all such patients need prophylactic treatment. The aim of this study was to identify the group of cirrhotic patients with low ascitic fluid protein levels at high risk of developing a first episode of spontaneous bacterial peritonitis during outpatient follow-up. METHODS: One hundred nine cirrhotic patients with low ascitic fluid protein levels and without previous episodes of spontaneous bacterial peritonitis were followed up in an outpatient clinic. RESULTS: Twenty-eight patients developed a first spontaneous bacterial peritonitis episode. In the multivariate analysis, serum bilirubin level (>3.2 mg /dL) and platelet count (<98.000/mm(3)) independently correlated with the risk of developing the first spontaneous bacterial peritonitis (P < 0.01 and P < 0.05, respectively). According to the median relative risk coefficient, a low-risk group (relative risk <1.09) and a high-risk group (relative risk >1.09) were established. The probability of developing a first spontaneous bacterial peritonitis episode at 1-year follow-up was significantly higher in the high risk-group (low-risk group, 23.6%; high-risk group, 55%; P < 0.01) as a consequence of a higher probability of the first community-acquired episode (13.7% vs. 47.6%, respectively, P < 0.01). One-year probability of survival was significantly lower in the high-risk group (low-risk group, 57.6%; high-risk group, 38%, P < 0.05). CONCLUSIONS: Cirrhotic patients with low ascitic fluid protein levels (

Infections caused by Escherichia coli resistant to norfloxacin in hospitalized cirrhotic patients.

Selective intestinal decontamination with norfloxacin is useful to prevent bacterial infections in several groups of cirrhotic patients at high risk of infection. However, the emergence of infections caused by Escherichia coli resistant to quinolones has recently been observed in cirrhotic patients undergoing prophylactic norfloxacin. Our aim is to determine the characteristics of the infections caused by E. coli resistant to norfloxacin in hospitalized cirrhotic patients. One hundred and six infections caused by E. coli in 99 hospitalized cirrhotic patients were analyzed and distributed into two groups: group I (n = 67), infections caused by E. coli sensitive to norfloxacin, and group II (n = 39), infections caused by E. coli resistant to norfloxacin. The clinical and analytical characteristics at diagnosis of the infection were similar in both groups. Previous prophylaxis with norfloxacin was more frequent in group II (15/67, 22.4% vs. 32/39, 82%, P <.0001), as a result of a higher number of patients submitted to continuous long-term prophylaxis in this group, whereas previous short-term prophylaxis was similar in both groups. Infections were more frequently nosocomial-acquired in group II than in group I (17/67, 25.3% vs. 20/39, 51.2%, P =.01). The type of infections was similar in both groups: urinary tract infections 38 in group I and 24 in group II, spontaneous bacterial peritonitis 8 and 2, spontaneous bacteremia 4 and 4, and bacterascites 1 and 0, respectively (pNS). Mortality during hospitalization was similar in the two groups (4/67, 5.9% vs. 5/39, 12.8%, pNS). None of the E. coli resistant to norfloxacin were also resistant to cefotaxime and only one of them was resistant to amoxicillin-clavulanic acid. Prophylaxis with norfloxacin, usually continuous long-term prophylaxis, favors the development of infections caused by norfloxacin-resistant E. coli. Long-term antibiotic prophylaxis should therefore be restricted to highly selected groups of cirrhotic patients at high-risk of infection. Infections caused by E. coli resistant to norfloxacin show a severity similar to those caused by sensitive E. coli. No significant associated resistance between norfloxacin and the antibiotics most frequently used in the treatment of bacterial infections in cirrhotic patients has been observed.

Parenteral antibiotic prophylaxis of bacterial infections does not improve cost-efficacy of oral norfloxacin in cirrhotic patients with gastrointestinal bleeding.

OBJECTIVE: Selective intestinal decontamination with norfloxacin is useful in the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding. However, bleeding cirrhotic patients with ascites, encephalopathy, or shock are at high risk to develop bacterial infections in spite of prophylactic norfloxacin. The aim of this study was to assess whether the addition of intravenous ceftriaxone could improve the efficacy of prophylaxis with norfloxacin in these patients. METHODS: Fifty-six cirrhotic patients with gastrointestinal hemorrhage and ascites, encephalopathy, or shock were randomized into two groups: Group 1 (n = 28) received oral norfloxacin 400 mg/12 h for 7 days, and group 2 (n = 28) received norfloxacin plus intravenous ceftriaxone 2 g daily during the first 3 days of admission. RESULTS: Ten patients were excluded because of community-acquired infection, surgery, or death within the first 24 h. The incidence of bacterial infections during hospitalization was 18.1% in group 1 and 12.5% in group 2 (p = NS). The incidence of severe infections (spontaneous bacterial peritonitis, bacteremia, or pneumonia) was also similar in both groups: 9% in group 1 versus 8.3% in group 2 (p = NS). There were no statistical differences between the two groups with respect to duration of hospitalization or mortality. The cost of antibiotic therapy (including prophylaxis and treatment of infections) was significantly higher in group 2. CONCLUSION: These results suggest that the addition of intravenous ceftriaxone during the first 3 days of hospitalization does not improve the cost-efficacy of oral norfloxacin in the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding and high risk of infection.

Effect of subcutaneous administration of octreotide on endogenous vasoactive systems and renal function in cirrhotic patients with ascites.

Splanchnic and systemic arteriolar vasodilation plays an important role in ascites formation in cirrhosis. Octreotide produces splanchnic vasoconstriction, but the effects on systemic hemodynamics and renal function are controversial. This study evaluated the effect of subcutaneous octreotide administration on systemic hemodynamics, endogenous vasoactive systems, and renal function in cirrhotic patients with ascites. Twenty patients were included: 10 received octreotide 250 microg/12 hr subcutaneously (for five days), and 10 did not. No statistically significant changes were found in mean arterial pressure and cardiac rate. Octreotide induced a statistically significant decrease in plasma renin activity (P < 0.01), plasma aldosterone (P = 0.01) and plasma glucagon (P < 0.05). No significant variations were observed in other systemic vasoactive substances (nitric oxide and prostacyclin). Renal function was not modified in either group. In conclusion, in cirrhotic patients with ascites, subcutaneous octreotide administration decreases plasma glucagon, renin activity, and aldosterone without changing in systemic hemodynamics or renal function.

Early microbiologic diagnosis of spontaneous bacterial peritonitis with BacT/ALERT.

BACKGROUND/AIMS: Inoculation of ascitic fluid into conventional blood culture bottles is more sensitive than conventional culture in the diagnosis of spontaneous bacterial peritonitis. BacT/ALERT is an automated colorimetric microbial detection system that has been shown to be faster than conventional blood culture bottles in the diagnosis of bacteremia. The aim of the study was to compare the BacT/ALERT system with the conventional culture and the conventional blood culture bottles method in the diagnosis of spontaneous bacterial peritonitis. METHODS: All the ascitic fluid samples from patients with cirrhosis hospitalized in our Department between September 1992 and May 1994 (n=1032) were prospectively evaluated. In all cases, an aliquot of ascitic fluid was sent for Gram's stain and conventional culture, and 20 ml were inoculated at the bedside into blood culture bottles: 10 ml into conventional blood culture bottles and 10 ml into BacT/ALERT. RESULTS: Thirty ascitic fluid infections (23 spontaneous bacterial peritonitis and 7 neutrocytic ascites) and 20 bacterascites were diagnosed. Conventional culture was positive in 10/30 ascitic fluid infections (33.3%), conventional blood culture bottles in 22/30 (73.3%) (p<0.01 compared to conventional culture) and BacT/ALERT in 20/30 (66.6%) (p<0.05 compared to conventional culture, pNS compared to conventional blood culture bottles). The time elapsed for culture positivity was 43.4+/-34.2 h for conventional blood culture bottles and 13.3+/-9.2 h for BacT/ALERT (p<0.001). Thirteen of the 23 cases of spontaneous bacterial peritonitis (56.5%) were detected within the first 12 h with BacT/ALERT, as compared to only three (13%) with conventional blood culture bottles (p<0.03). CONCLUSION: The automated system BacT/ALERT provides an earlier microbiologic diagnosis of spontaneous bacterial peritonitis than conventional blood culture bottles with similar sensitivity.

Nadolol plus isosorbide mononitrate compared with sclerotherapy for the prevention of variceal rebleeding.

BACKGROUND: Patients who have bleeding from esophageal varices are at high risk for rebleeding and death. We compared the efficacy and safety of endoscopic sclerotherapy with the efficacy and safety of nadolol plus isosorbide mononitrate for the prevention of variceal rebleeding. METHODS: Eighty-six hospitalized patients with cirrhosis and bleeding from esophageal varices diagnosed by endoscopy were randomly assigned to treatment with repeated sclerotherapy (43 patients) or nadolol plus isosorbide-5-mononitrate (43 patients). The primary outcomes were rebleeding, death, and complications. The hepatic venous pressure gradient was measured at base line and after three months. RESULTS: Base-line data were similar in the two groups, and the median follow-up was 18 months in both. Eleven patients in the medication group and 23 in the sclerotherapy group had rebleeding. The actuarial probability of remaining free of rebleeding was higher in the medication group for all episodes related to portal hypertension (P = 0.001) and variceal rebleeding (P = 0.002). Four patients in the medication group and nine in the sclerotherapy group died (P = 0.07 for the difference in the actuarial probability of survival). Seven patients in the medication group and 16 in the sclerotherapy group had treatment-related complications (P = 0.03). Thirty-one patients in the medication group underwent two hemodynamic studies; 1 of the 13 patients with more than a 20 percent decrease in the hepatic venous pressure gradient had rebleeding, as compared with 8 of the 18 with smaller decreases in the pressure gradient (P = 0.04) for the actuarial probability of rebleeding at two years). CONCLUSIONS: As compared with sclerotherapy, nadolol plus isosorbide mononitrate significantly decreased the risk of rebleeding from esophageal varices.

Increased serum nitrite and nitrate levels in patients with cirrhosis: relationship to endotoxemia.

Nitric oxide derived from vascular endothelium is a potent vasodilator that plays a key role in the homeostasis of blood pressure. Because cirrhotic patients tend to have low arterial pressure, we measured in 51 patients and 10 control subjects serum nitrite and nitrate levels as an index of in vivo nitric oxide generation. We also measured plasma endotoxin, a substance frequently increased in cirrhotic patients and known to induce nitric oxide synthesis. Cirrhotic patients showed significant increases in serum nitrite/nitrate and plasma endotoxin compared with controls. Values were particularly increased in patients with decompensated cirrhosis, as manifested by ascites with or without functional kidney failure. High serum nitrite/nitrate levels were associated with high plasma renin activity, high aldosterone and antidiuretic hormone levels and low urinary excretion of sodium. In addition, serum nitrite/nitrate levels significantly correlated with endotoxemia. Oral administration of colistin to 15 cirrhotic patients reduced significantly plasma endotoxin levels (p < 0.01) and serum nitrite/nitrate levels (p < 0.05). Because endotoxin enhances the expression of inducible nitric oxide synthase, our results suggest that circulating endotoxin in cirrhosis is responsible for excessive synthesis and release of nitric oxide by the vasculature. These findings might explain the hemodynamic dysfunction seen in cirrhotic patients.