Switch therapy with ciprofloxacin vs. intravenous ceftazidime in the treatment of spontaneous bacterial peritonitis in patients with cirrhosis: similar efficacy at lower cost. Oral ciprofloxacin versus intravenous cefotaxime and ceftriaxone in the treatment of spontaneous bacterial peritonitis. Ciprofloxacin and long-term prevention of spontaneous bacterial peritonitis: results of a prospective controlled trial. Randomized trial comparing ceftriaxone with cefonicid for treatment of spontaneous bacterial peritonitis in cirrhotic patients. Short-course versus long-course antibiotic treatment of spontaneous bacterial peritonitis. A randomized controlled study of 100 patients. Randomized, comparative study of oral ofloxacin versus intravenous cefotaxime in spontaneous bacterial peritonitis. Selective intestinal decontamination prevents spontaneous bacterial peritonitis. Ciprofloxacin in primary prophylaxis of spontaneous bacterial peritonitis: a randomized, placebo-controlled study. Oral, nonabsorbable antibiotics prevent infection in cirrhotics with gastrointestinal hemorrhage. Primary prophylaxis of spontaneous bacterial peritonitis delays hepatorenal syndrome and improves survival in cirrhosis.
Intravenous administration of a third-generation cephalosporin is optimal antibiotic treatment for spontaneous bacterial peritonitis.
                To compare an intravenous-oral step-down schedule with ciprofloxacin (switch therapy) to intravenous ceftazidime in the treatment of spontaneous bacterial peritonitis, and to evaluate the impact of terlipressin and albumin in the treatment of type 1 hepatorenal syndrome on mortality.
                A total of 116 cirrhotic patients with spontaneous bacterial peritonitis, were randomly given switch therapy with ciprofloxacin (61 patients) or intravenous ceftazidime (55 patients). All patients who developed type 1 hepatorenal syndrome were treated with terlipressin (2-12 mg/day) and albumin (20-40 g/day).
                Resolution of infection was achieved in 46/55 patients treated with ceftazidime (84%) and in 49/61 patients treated with ciprofloxacin (80%, P = N.S.). An intravenous-oral step-down schedule was possible in 50/61 patients (82%) who received ciprofloxacin; 45/61 patients (74%) were discharged before the end of antibiotic treatment and completed it at home. The mean saving per patient due to the reduction of hospital stay in the ciprofloxacin group was 1150 . Type 1 hepatorenal syndrome was treated successfully in 12/19 patients (63%). As a consequence, the in-hospital mortality rate due to infection was 10%.
                Switch therapy with cephalosporin is more cost-effective than intravenous ceftazidime in the treatment of spontaneous bacterial peritonitis in cirrhotic patients who are not on prophylaxis with quinolones. Cefotaxime or ceftriaxone were considered the first-choice antibiotic for empirical treatment in cirrhotic patients developing spontaneous bacterial peritonitis. It has been suggested that ciprofloxacin could be an alternative to cefotaxime or ceftriaxone in cirrhotic patients developing spontaneous bacterial peritonitis. The aim of the present study was to compare oral ciprofloxacin with cefotaxime and ceftriaxone in the treatment of spontaneous bacterial peritonitis in cirrhotic patients.
                Fifty-three hospitalized cirrhotic patients with spontaneous bacterial peritonitis were prospectively included and randomized into three groups: group A (n = 16); received orally 500 mg ciprofloxacin every 12 h, group B (n = 18); received intravenous cefotaxime 2 g every 8 h and group C (n = 19) received intravenous ceftriaxone 2 g every 24 h.
                15 patients from the ciprofloxacin group, 17 from the cefotaxime group and 17 patients from the ceftriaxone group were finally analyzed. Spontaneous bacterial peritonitis resolution in three groups was found to be 80%, 76%, and 83%, respectively (p = NS). Incidence of complications and hospital mortality was similar in the three groups. No adverse events were observed in any of the three groups. The cost of the treatment was statistically lower in the ciprofloxacin group than in the cefotaxime group and ceftriaxone group (p < 0.001).
                These results suggest that orally ciprofloxacin is as effective as cefotaxime and ceftriaxone in the empirical treatment of spontaneous bacterial peritonitis in cirrhotic patients, and is also less expensive and can be administered orally. The aim of this prospective double-blind study was to evaluate the value of long-term antibiotic prophylaxis using ciprofloxacin for the prevention of spontaneous bacterial peritonitis (SBP) in 60 cirrhotic patients with low ascitic fluid protein levels (< 15 g/L). The patients were assigned to two groups: group I (n = 28) ciprofloxacin 750 mg per os once a week for 6 months, group II (n = 32) placebo. The two groups were similar for clinical and laboratory characteristics. Twelve patients developed an intercurrent disorder, and 10 patients died during the trial. There were no adverse effects in the treated group. There was a significant decrease in the incidence of SBP (3.6 vs. 22%) (P < .05) and duration of hospitalization (9.3 +/- 4.5 vs. 17.6 +/- 6.2 days) (P < .05) in the treated group as compared with the placebo group. The bacteriological study showed no acquired resistance to ciprofloxacin after 6 months' treatment. These results suggest that long-term preventive antibiotic prophylaxis based on the weekly administration of 750 mg of ciprofloxacin is effective in the prevention of SBP in cirrhotic patients. We compared cefonicid (2 g every 12 h) and ceftriaxone (2 g every 24 h) for their efficacy and safety in treating spontaneous bacterial peritonitis in cirrhotic patients in an open randomized clinical trial (30 patients in each group). Clinical, laboratory, and bacteriologic characteristics were similar in both groups. Ceftriaxone-susceptible strains were isolated on 44 occasions (94%), and cefonicid-susceptible strains were isolated on 43 occasions (91.5%). The antibiotic concentration in ascitic fluid/MIC ratio for ceftriaxone was > 100 throughout the dose interval (24 h), while it was lower for cefonicid (between 1 and 18). A total of 100% of patients treated with ceftriaxone, and 94% of those treated with cefonicid were cured of their infections (P was not significant). Hospitalization mortality was 37% in the cefonicid group and 30% in the ceftriaxone group (P was not significant). The time that elapsed between the initiation of treatment and the patient's death was shorter in the cefonicid group patients (5.3 +/- 3.90 days) than in the ceftriaxone group patients (11.8 +/- 9.15 days) (P < 0.05). None of the patients presented with superinfections, and only two patients treated with cefonicid and three patients treated with ceftriaxone developed colonizations with Enterococcus faecalis or Candida albicans. Ceftriaxone and cefonicid are safe and useful agents for treating cirrhotic spontaneous bacterial peritonitis, although the pharmacokinetic characteristics of ceftriaxone seem to be more advantageous than those of cefonicid. In an attempt to determine the optimal duration of therapy of spontaneous bacterial peritonitis, 100 patients with neutrocytic ascites and suspected spontaneous bacterial peritonitis were randomized to short-course vs. long-course treatment groups. Empiric therapy was initiated before the results of ascitic fluid culture were available. Of the 90 patients who met strict criteria for spontaneous bacterial peritonitis or culture-negative neutrocytic ascites, 43 were randomized to a group receiving 5 days and 47 to a group receiving 10 days of single-agent cefotaxime, 2 g IV every 8 hours. Infection-related mortality (0% vs. 4.3%), hospitalization mortality (32.6% vs. 42.5%), bacteriologic cure (93.1% vs. 91.2%), and recurrence of ascitic fluid infection (11.6% vs. 12.8%) were not significantly different between the 5- and 10-day treatment groups, respectively. Recurrence rates were comparable to the values reported in the literature. The cost of antibiotic and antibiotic administration were significantly lower in the short-course group. Short-course treatment of spontaneous bacterial peritonitis is as efficacious as long-course therapy and significantly less expensive. Treatment of spontaneous bacterial peritonitis currently involves intravenous antibiotic administration. To test the possibility of treating spontaneous bacterial peritonitis with oral antibiotics, oral ofloxacin was compared with intravenous cefotaxime in this infection.
                One hundred twenty-three cirrhotics with uncomplicated spontaneous bacterial peritonitis (no septic shock, grade II-IV hepatic encephalopathy, serum creatinine level of > 3 mg/dL, and gastrointestinal hemorrhage or ileus) were randomly given oral ofloxacin (64 patients) or intravenous cefotaxime (59 patients).
                Infection resolution rate was 84% in the ofloxacin group and 85% in the cefotaxime group. Peak serum levels and trough serum and ascitic fluid levels of ofloxacin and cefotaxime measured on days 3 (23 patients) and 6 (11 patients) of therapy were greater than the minimal inhibitory concentration of isolated organisms. Hospital survival rate was 81% in each group of patients. Blood urea nitrogen and hepatic encephalopathy at diagnosis were associated with prognosis. None of the 36 nonazotemic patients with community-acquired spontaneous bacterial peritonitis and without hepatic encephalopathy developed complications during hospitalization, and all were alive at time of discharge.
                Oral ofloxacin is as effective as intravenous cefotaxime in uncomplicated spontaneous bacterial peritonitis. Nonazotemic cirrhotic patients with uncomplicated community-acquired spontaneous bacterial peritonitis and without hepatic encephalopathy have an excellent prognosis and may be treated with oral ofloxacin without requiring hospitalization. In a prospective randomized study, selective intestinal decontamination with norfloxacin was performed during hospitalization in 32 cirrhotic patients with low ascitic fluid total protein levels. The incidence of infections was compared with that in a control group of 31 nontreated cirrhotic patients of similar characteristics. We found a significantly lower incidence of infections [1/32 (3.1%) vs. 13/31 (41.9%); P less than 0.005] and spontaneous bacterial peritonitis [0/32 (0%) vs. 7/31 (22.5%); P less than 0.05] in patients receiving norfloxacin. The lower incidence of extraperitoneal infections [1/32 (3.1%) vs. 7/31 (22.5%); P = 0.052] in the treated group did not reach statistical significance. The incidence of infections [1/28 (3.6%) vs. 9/22 (40.9%); P less than 0.01] and spontaneous bacterial peritonitis [0/28 (0%) vs. 5/22 (22.7%); P less than 0.05] in cirrhotic patients admitted because of ascites was also significantly lower in the treated group. The decrease in the rate of mortality observed in the group undergoing selective intestinal decontamination did not reach statistical significance. These data show that selective intestinal decontamination is useful to prevent spontaneous bacterial peritonitis and extraperitoneal infections in hospitalized cirrhotic patients with low ascitic fluid total protein levels. 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.
                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.
                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).
                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. To investigate if oral, nonabsorbable antibiotics prevent bacterial infections in cirrhotics with gastrointestinal hemorrhage, 140 consecutive patients were randomly allocated into two groups: 68 patients (Group I) were given oral, non absorbable antibiotics (gentamicin + vancomycin + nystatin or neomycin + colistin + nystatin) from the inclusion into the trial up to 48 hr after cessation of the hemorrhage, or until emergency surgery or death in those cases who continued bleeding; and 72 patients (Group II) did not receive oral, nonabsorbable antibiotics. Both groups were similar in relation to clinical and laboratory data and characteristics of the hemorrhage. The incidence of infection was significantly lower in Group I than in Group II (11 patients in Group I and 25 in Group II developed proved infections; p less than 0.025). This difference was due to the fact that spontaneous bacteremia and peritonitis and urinary tract infection caused by enteric bacteria occurred almost exclusively in Group II. Two patients of Group I and 10 of Group II developed spontaneous bacteremia and/or peritonitis caused by enteric bacteria (p less than 0.025). These results indicate that prophylactic administration of oral, nonabsorbable antibiotics markedly reduces the incidence of infections caused by enteric bacteria in cirrhotic patients with gastrointestinal hemorrhage. Norfloxacin is highly effective in preventing spontaneous bacterial peritonitis recurrence in cirrhosis, but its role in the primary prevention of this complication is uncertain.
                Patients with cirrhosis and low protein ascitic levels (<15 g/L) with advanced liver failure (Child-Pugh score > or = 9 points with serum bilirubin level > or = 3 mg/dL) or impaired renal function (serum creatinine level > or = 1.2 mg/dL, blood urea nitrogen level > or = 25 mg/dL, or serum sodium level < or = 130 mEq/L) were included in a randomized controlled trial aimed at comparing norfloxacin (35 patients) vs placebo (33 patients) in the primary prophylaxis of spontaneous bacterial peritonitis. The main end points of the trial were 3-month and 1-year probability of survival. Secondary end points were 1-year probability of development of spontaneous bacterial peritonitis and hepatorenal syndrome.
                Norfloxacin administration reduced the 1-year probability of developing spontaneous bacterial peritonitis (7% vs 61%, P < .001) and hepatorenal syndrome (28% vs 41%, P = .02), and improved the 3-month (94% vs 62%, P = .003) and the 1-year (60% vs 48%, P = .05) probability of survival compared with placebo.
                Primary prophylaxis with norfloxacin has a great impact in the clinical course of patients with advanced cirrhosis. It reduces the incidence of spontaneous bacterial peritonitis, delays the development of hepatorenal syndrome, and improves survival.
This review provides no clear evidence for the treatment of cirrhotic patients with spontaneous bacterial peritonitis. In practice, third generation cephalosporins have already been established as the standard treatment of spontaneous bacterial peritonitis, and it is clear, that empirical antibiotic therapy should be provided in any case. However, until large, well-conducted trials provide more information, practice will remain based on impression, not evidence.