GASTROENTEROLOGY
LIVER, PANCREAS,
AND BILIARY
1991;100:477-481
TRACT
Selective Intestinal Decontamination Prevents Spontaneous Bacterial Peritonitis GERMh SORIANO, CARLOS GUARNER, MONTSERRAT JO& SUCH, JO& BARRIOS, JAIME ENRiQUEZ, and FRANCISCO VILARDELL
TEIXID6,
Servicio de Patologia Digestiva, Hospital de la Santa Creu i Sant Pau, Barcelona,
Spain
as has been shown in volunteers (10) and in neutropenic (11) and cirrhotic (12) patients. Moreover, norfloxacin reduces the incidence of infections caused by gram-negative bacilli in neutropenic patients, without overgrowth of resistant bacteria or important side effects (11,13). Because enteric bacteria are the most common causative agents of SBP (14), it has been suggested that SID with norfloxacin could be useful in its prophylaxis (15). It has recently been shown that norfloxacin reduces the recurrence rate of SBP in cirrhotic patients with a previous episode (16). Hitherto, this is the only group of individuals at high risk of developing SBP in whom a prophylactic trial with norfloxacin has been carried out. Oral nonabsorbable antibiotics reduced the incidence of infections caused by enteric bacteria in cirrhotic patients with gastrointestinal hemorrhage in a study performed by Rimola et al. (17). In a previous study we observed a significant increase in C3 and TP levels in AF in cirrhotic patients with low ascitic fluid TP levels undergoing SID with norfloxacin or oral nonabsorbable antibiotics (15), suggesting that norfloxacin may be useful in the prophylaxis of SBP not only because it inhibits the aerobic intestinal flora but also because it may improve the antimicrobial capacity of ascitic fluid. The aim of the present study has been to assess if SID with norfloxacin decreases the incidence of SBP and other pontaneous bacterial peritonitis (SBP) is a freinfections in hospitalized cirrhotic patients with low quent and severe complication of cirrhosis with a current hospitalization mortality rate > 40% (l-6). levels of ascitic fluid TP. Cirrhotic patients with low opsonic activity and low C3 and total protein (TP) levels in ascitic fluid are Abbreviations used in this paper: SBP, spontaneous bacterial more predisposed to develop SBP (7-9). peritonitis; SID, selective intestinal decontamination; TP, total Norfloxacin produces a selective intestinal deconprotein. tamination (SID) because it inhibits aerobic gram8 1991 by the American Gastroenterological Association 0016-5005/91/$3.00 negative intestinal flora and preserves anaerobic flora,
In a prospective randomized study, selective intestinal decontamination with noriloxacin 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 [l/32(3.1%)vs.13/31 (41.9%); P < 0.0051and spontaneous bacterial peritonitis [O/32 (0%) vs. 7/31 (22.5%); P < 0.051in patients receiving norfloxacin. The lower incidence of extraperitoneal infections [l/32 (3.1%) vs. 7/31 (22.5%); P = 0.0521 in the treated group did not reach statistical significance. The incidence of infections [l/28 (3.8%) vs. 9/22 (40.9%); P < 0.011 and spontaneous bacterial peritonitis [O/28 (0%) vs. 5/22 (22.7%); P < 0.051in 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.
S
478
SORIANO
GASTROENTEROLOGY
ET AL.
Results
Patients and Methods Sixty-three cirrhotic patients consecutively admitted to the hospital with ascites and < 1.5 g/dL (15 g/L) of TP concentration in ascitic fluid were included in the study. Patients with community-acquired infections or active gastrointestinal bleeding at admission and patients undergoing antibiotic therapy during the week before admission were excluded. The “cutoff’ of ascitic fluid TP was established at 1.5 g/dL (15 s/L) because in a previous study we found that 1.5 g/dL (15 g/L) was the upper limit of all ascitic fluid TP values in the patients who developed SBP during their hospitalization (mean + 2SD) (8). At the time of admission a diagnostic paracentesis was performed. If the ascitic fluid TP level was < 1.5 g/dL (15 g/L), patients were randomly allocated into two groups: group 1 (n = 32) received oral norfloxacin, 400 mg/day, throughout all the hospitalization period, and group 2 (n = 311, controls, did not. All the patients had negative results of ascitic fluid culture and < 500 neutrophils/kL at the time of admission. Norfloxacin treatment was begun in the first 8 hours after hospitalization. All patients were closely monitored for the detection of bacterial infections and norfloxacin side effects during the hospitalization period. A careful physical examination, complete white blood cell count, chest radiograph, urine sediment and culture, ascitic fluid neutrophil count, Gram’s stain of ascitic fluid, and ascitic fluid and blood cultures were routinely performed whenever patients developed signs of infection. Further paracentesis was performed in two circumstances: (a) when ascitic fluid infection was suspected (i.e., when patients had fever, hypothermia, abdominal pain, acute encephalopathy, unexplainable deterioration of renal function, acidosis, or increased white blood cell count); and (b) to relieve abdominal or respiratory discomfort due to tense ascites. Diagnosis of SBP was made when > 250 neutrophils/kL were found in ascitic fluid through positive culture results. We defined as culture-negative neutrocytic ascites any instance of negative ascitic fluid culture but with an ascitic fluid neutrophil count > 500 neutrophils/pL, and bacterascites any instance of positive culture with
LIVER, PANCREAS,
AND BILIARY
1991;100:477-481
TRACT
Selective Intestinal Decontamination Prevents Spontaneous Bacterial Peritonitis GERMh SORIANO, CARLOS GUARNER, MONTSERRAT JO& SUCH, JO& BARRIOS, JAIME ENRiQUEZ, and FRANCISCO VILARDELL
TEIXID6,
Servicio de Patologia Digestiva, Hospital de la Santa Creu i Sant Pau, Barcelona,
Spain
as has been shown in volunteers (10) and in neutropenic (11) and cirrhotic (12) patients. Moreover, norfloxacin reduces the incidence of infections caused by gram-negative bacilli in neutropenic patients, without overgrowth of resistant bacteria or important side effects (11,13). Because enteric bacteria are the most common causative agents of SBP (14), it has been suggested that SID with norfloxacin could be useful in its prophylaxis (15). It has recently been shown that norfloxacin reduces the recurrence rate of SBP in cirrhotic patients with a previous episode (16). Hitherto, this is the only group of individuals at high risk of developing SBP in whom a prophylactic trial with norfloxacin has been carried out. Oral nonabsorbable antibiotics reduced the incidence of infections caused by enteric bacteria in cirrhotic patients with gastrointestinal hemorrhage in a study performed by Rimola et al. (17). In a previous study we observed a significant increase in C3 and TP levels in AF in cirrhotic patients with low ascitic fluid TP levels undergoing SID with norfloxacin or oral nonabsorbable antibiotics (15), suggesting that norfloxacin may be useful in the prophylaxis of SBP not only because it inhibits the aerobic intestinal flora but also because it may improve the antimicrobial capacity of ascitic fluid. The aim of the present study has been to assess if SID with norfloxacin decreases the incidence of SBP and other pontaneous bacterial peritonitis (SBP) is a freinfections in hospitalized cirrhotic patients with low quent and severe complication of cirrhosis with a current hospitalization mortality rate > 40% (l-6). levels of ascitic fluid TP. Cirrhotic patients with low opsonic activity and low C3 and total protein (TP) levels in ascitic fluid are Abbreviations used in this paper: SBP, spontaneous bacterial more predisposed to develop SBP (7-9). peritonitis; SID, selective intestinal decontamination; TP, total Norfloxacin produces a selective intestinal deconprotein. tamination (SID) because it inhibits aerobic gram8 1991 by the American Gastroenterological Association 0016-5005/91/$3.00 negative intestinal flora and preserves anaerobic flora,
In a prospective randomized study, selective intestinal decontamination with noriloxacin 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 [l/32(3.1%)vs.13/31 (41.9%); P < 0.0051and spontaneous bacterial peritonitis [O/32 (0%) vs. 7/31 (22.5%); P < 0.051in patients receiving norfloxacin. The lower incidence of extraperitoneal infections [l/32 (3.1%) vs. 7/31 (22.5%); P = 0.0521 in the treated group did not reach statistical significance. The incidence of infections [l/28 (3.8%) vs. 9/22 (40.9%); P < 0.011 and spontaneous bacterial peritonitis [O/28 (0%) vs. 5/22 (22.7%); P < 0.051in 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.
S
478
SORIANO
GASTROENTEROLOGY
ET AL.
Results
Patients and Methods Sixty-three cirrhotic patients consecutively admitted to the hospital with ascites and < 1.5 g/dL (15 g/L) of TP concentration in ascitic fluid were included in the study. Patients with community-acquired infections or active gastrointestinal bleeding at admission and patients undergoing antibiotic therapy during the week before admission were excluded. The “cutoff’ of ascitic fluid TP was established at 1.5 g/dL (15 s/L) because in a previous study we found that 1.5 g/dL (15 g/L) was the upper limit of all ascitic fluid TP values in the patients who developed SBP during their hospitalization (mean + 2SD) (8). At the time of admission a diagnostic paracentesis was performed. If the ascitic fluid TP level was < 1.5 g/dL (15 g/L), patients were randomly allocated into two groups: group 1 (n = 32) received oral norfloxacin, 400 mg/day, throughout all the hospitalization period, and group 2 (n = 311, controls, did not. All the patients had negative results of ascitic fluid culture and < 500 neutrophils/kL at the time of admission. Norfloxacin treatment was begun in the first 8 hours after hospitalization. All patients were closely monitored for the detection of bacterial infections and norfloxacin side effects during the hospitalization period. A careful physical examination, complete white blood cell count, chest radiograph, urine sediment and culture, ascitic fluid neutrophil count, Gram’s stain of ascitic fluid, and ascitic fluid and blood cultures were routinely performed whenever patients developed signs of infection. Further paracentesis was performed in two circumstances: (a) when ascitic fluid infection was suspected (i.e., when patients had fever, hypothermia, abdominal pain, acute encephalopathy, unexplainable deterioration of renal function, acidosis, or increased white blood cell count); and (b) to relieve abdominal or respiratory discomfort due to tense ascites. Diagnosis of SBP was made when > 250 neutrophils/kL were found in ascitic fluid through positive culture results. We defined as culture-negative neutrocytic ascites any instance of negative ascitic fluid culture but with an ascitic fluid neutrophil count > 500 neutrophils/pL, and bacterascites any instance of positive culture with
