GASTROENTEROLOGY
LIVER, PANCREAS,
1992;103:1267-1272
AND BILIARY TRACT
Norfloxacin Prevents Bacterial Infection in Cirrhotics With Gastrointestinal Hemorrhage GERMAN SORIANO, CARLOS GUARNER, ALBERT TOM&, CANDID VILLANUEVA, XAVIER TORRAS, DOLORS GONZALEZ, SERGIO SAINZ, ANA ANGUERA, XAVIER CUSSb, JOAQUIM BALANZ6, and FRANCISCO VILARDELL Liver Unit and Gastrointestinal i Sant Pau, Barcelona, Spain
Hemorrhage
Unit, Department
To assess the efficacy of selective intestinal decontamination with norfloxacin in the prevention of bacterial infections in cirrhotic patients with gastrointestinal hemorrhage, 119 patients were included in a prospective randomized study. Group 1 (n = 60) received norfloxacin orally or through a nasogastric tube, 400 mg twice daily for 7 days beginning immediately after emergency gastroscopy; group z (n = 59) was the control group. We found a significantly lower incidence of infections (10% vs. 37.2%; P = O.OOl),bacteremia and/or spontaneous bacterial peritonitis (3.3% vs. 16.9%; P -K0.05), and urinary infections (0% vs. 16.6%; P = 0.001) in patients receiving norfloxacin, as a consequence of decrease in the incidence of infections caused by aerobic gram-negative bacilli. The decrease in mortality observed in the treated group (6.6% vs. 11.6%) did not reach statistical significance. The cost for antibiotic treatment showed a 62% reduction in the treated group compared with the control group. The results show that selective intestinal decontamination with norfloxacin is useful in preventing bacterial infections in cirrhotics with gastrointestinal hemorrhage. acterial infection is a frequent and severe complication of cirrhosis that accounts for 25% of deaths in cirrhotic patients.le5 Patients with gastrointestinal hemorrhage constitute one of the groups of cirrhotics at high risk of infection described during the last decade.s-g Because enteric aerobic gram-negative bacteria are the most common causative agents isolated in infections in cirrhotics,14 it has been suggested that their inhibition by oral antibiotics may be useful for prevention.‘,” In the one reported study of infection prophylaxis in cirrhotics with gastrointestinal hemorrhage, Rimola et al.’ showed a reduction in the
B
of Gastroenterology,
Hospital de la Santa Creu
incidence of infections caused by enteric bacteria during the first 10 days of hospitalization in patients treated with oral nonabsorbable antibiotics. However, combinations of oral nonabsorbable antibiotics have some disadvantages, such as possible overgrowth of potentially pathogenic resistant bacteria and increase of side effects and cost.1’-‘5 Norfloxacin is a quinolone that produces a selective intestinal decontamination (SID) as it inhibits aerobic gram-negative intestinal flora while preserving the anaerobic flora and, therefore, the colonization resistance of the digestive tract.‘s-20 Norfloxacin reduces the incidence of infections caused by gramnegative bacilli in granulocytopenic patients13*” and is useful in the prevention of spontaneous bacterial peritonitis (SBP) recurrencelg and in the prophylaxis of SBP in hospitalized cirrhotics with low ascitic fluid total protein.” In some instances, prophylactic treatment with norfloxacin was performed for >6 months with negligible overgrowth of resistant bacteria and side effects.lg The aim of the present study was to assess the efficacy of SID with norfloxacin in the prevention of bacterial infections in cirrhotic patients with gastrointestinal hemorrhage. Patients and Methods All cirrhotic patients admitted because of gastrointestinal hemorrhage in the Gastrointestinal Hemorrhage Unit of our Department between August 1989 and June 1991 were considered for inclusion in the study. The following patients were excluded from the trial: (a) patients with signs of infection at admission, (b) patients treated with antibiotics during the z weeks before admission, and (c) patients transferred from other hospitals. A total of 128 patients were randomly allocated on admission into the 0 1992 by the American Gastroenterological 0016~5065/92/$3.00
Association
1268 SORIANO ET AL.
following two groups: group 1 (n = 64) received norfloxatin, 400 mg twice daily orally or through a nasogastric tube for 7 days, and group 2 (n = 64), controls, did not. Norfloxatin treatment in group 1 was started immediately after gastroscopy and was repeated when patients had recurrence of hemorrhage after withdrawal of norfloxacin. At admission, at least two intravenous catheters (one suitable to measure central venous pressure and a small intravenous cannula) and a nasogastric tube were placed in all patients. Urinary catheters were only used when necessary. Gastroscopy was performed within the first 4 hours of admission unless there was profound encephalopathy (grade 3-4) severe hemodynamic instability or when the patient refused. Patients bleeding from esophageal or gastric varices were assigned to endoscopic sclerotherapy. If the treatment failed, continuous intravenous infusion of vasopressin plus nitroglycerin or somatostatin was begun. If the bleeding continued, esophageal tamponade (SengstakenBlakemore or Linton-Nachlas balloon) was performed. When esophageal tamponade failed to control bleeding, surgery was performed in patients with Child-Pugh’s class A and B if their status did not prevent surgical intervention. After the initial bleeding was controlled, the patients were transferred to a conventional hospitalization ward and assigned to an elective sclerotherapy program with or without the addition of P-blocking agents.** In patients with peptic ulcer in whom active bleeding, a red clot, or a visible vessel was seen during gastroscopy,23 endoscopic injection was performed. Surgery was performed if bleeding could not be controlled with conservative measures and operation was not contraindicated. All patients were closely monitored with special emphasis on the detection of bacterial infections and norfloxacin side effects throughout the hospitalization period. A careful physical examination, complete white blood cell count, chest radiography, urine sediment and culture and ascitic fluid neutrophil count, Gram’s stain, and culture in blood culture bottles24*25 were routinely performed on admission. Physical examination was performed at least daily during hospitalization, and blood cell count was performed daily in the Gastrointestinal Hemorrhage Unit. The same procedures of admission as well as blood cultures and other diagnostic maneuvers, when indicated, were performed whenever patients showed signs of infection. When an infection was suspected, the initial empiric antibiotic treatment was cefotaxime in patients from group zzfi and amoxicillin plus clavulanic acid or imipenem, according to the severity of the infection, in patients from group 1, because these antibiotics are highly active against the bacteria most frequently isolated in the infections of cirrhotics submitted to SID, mainly gram-positive cocci.” The diagnosis of SBP was made when 2250 neutrophils/pL were found in ascitic fluid through positive culture results. Culture-negative neutrocytic ascites was defined as any instance of negative ascitic fluid culture but with an ascitic fluid neutrophil count 2500 neutrophils/ FL and bacterascites as any instance of positive culture with ascitic fluid neutrophil count 450 neutrophils/pL.” The possibility of gut perforation and/or an intra-abdomi-
GASTROENTEROLOGY
Vol. 103, No. 4
nal source of infection were excluded in all cases. The diagnosis of bacteremia or urinary infection was made when results of blood and urine cultures, respectively, were positive and the clinical picture was consistent with this diagnosis. Respiratory infections were diagnosed by clinical, analytical, and radiological data. Patients who experienced fever and/or leukocytosis with a shift to the left and without any other evidence of infection were considered to have possible infections and were empirically treated with antibiotics. The incidence of infections in patients who underwent surgery was analyzed only during the period between admission and the operation, because parenteral antibiotic prophylaxis and other factors might have interfered with the results of the study. Patients who died or underwent surgery within the first 24 hours after admission were excluded from analysis of results because the time elapsed was considered too short to allow for the action of norfloxacin. Statistical analysis was performed by means of Student’s t test and the x2 test with Yates’ correction and Fisher’s Exact Test. A P value co.05 was considered statistically significant. All values are expressed as mean f SD. The protocol was approved by the ethical committee of the Hospital and by the Ministry of Health. All patients or their families gave oral consent before the study was begun.
Results Eight patients (3 from group 1 and 5 from group 2) died or underwent surgery within the first 24 hours after admission and were excluded from analysis of results. An additional patient from group I was also excluded because he asked for voluntary discharge from the hospital 8 hours after admission. Therefore, 119patients (60 in group 1 and 59 in group 2) were finally analyzed. The diagnosis of cirrhosis was established by histology in 42 patients (22 from group 1 and 20 from group 2) and by clinical, analytical, and ultrasonographic findings in 77 patients (38 from group 1 and 39 from group 2). There were no significant differences between both groups in the clinical and laboratory data of the patients at admission or during the hospitalization (Tables 1 and 2, respectively). Table 3 shows the features of the hemorrhage that were similar in the two groups. Mortality was slightly lower in group 1 (four deaths, 6.6%) than in group 2 (seven deaths, 11.8%), but this difference did not reach statistical significance. There were no statistical differences between the two groups with regard to the cause of death. The incidence of bacterial infections during hospitalization is shown on Table 4. Six infections were diagnosed in 6 patients (10%) from group 1 and 26 infections in 22 patients (37.2%) from group 2 (P = 0.001). Bacteremia and/or SBP developed in 2 pa-
NORFLOXACIN
October 1992
Table I. Clinical and Analytical Characteristics of the Two Groups of Patients at Admission Group 1 (n = 60 Age (yr) Sex (M/F) Etiology (A/O)’ Hepatocarcinoma Previous SBP Diuretics Child-Pugh A/B/C Ascites Encephalopathy Degree l-2/3-4 Bilirubin @mol/L) Albumin (g/L) Prothrombin time (%) Urea (mmol/L) Creatinine @mol/L) White blood cell count (X109/L) AF TPb (g/dL) AF TP < 1.5 g/dL
61.0f 12.6 31/29 33/27 5 1 11 19/30/11 15 11
58.3f 13.5 30/29 34/25 2 2 11 21/25/13 14 10
8/3 41.9 f 48.5 30.4 f 4.2 57.2 i 15.7 12.0 f 6.7 104.9 + 58.2
9/l 35.3+ 26.7 31.2+ 6.4 57.5 + 14.5 10.6 f 7.1 100.8k 60.0
9010 + 4198 0.7 f 0.6 14
8750 + 4180 1.0 + 0.6 10
tients from group 1 (3.3%) and 10 patients from group 2 (16.9%) (P < 0.05). Urinary infections developed in II patients in group 2 (I&M%), whereas none were diagnosed in group 1 (P = 0.001). Respiratory infections developed in 4 patients in each group (7 pneumonias and 1 pyopneumothorax) (6.6% vs. 6.7%; P,
Table 2. Clinical Characteristics of Patients During Hospitalization Group 1 (n = 60)
Group 2 (n = 59)
13.5 + 9.2 41 2.0 + 1.0 1.6 + 0.9 9 0.8 f 0.6 8 13 9/4 4 3/1/O/O
14.4 f 10.9 34 2.0 + 1.0 1.5 + 1.1 9 0.6 f 0.5 8 11 6/5 7 2/2/2/l
NOTE. P, NS between the two groups. “Patients in whom ascites developed during hospitalization. bAF TP, ascitic fluid total protein in patients in whom ascites developed during hospitalization. ‘Patients in whom encephalopathy developed during hospitalization. dH, gastrointestinal hemorrhage; I, infection; LF, liver failure: 0, other.
1269
Table 3. Characteristics of the Hemorrhage in the Two Groups of Patients
Group 2 (n = 59)
NOTE. P, NS between the two groups. “A, alcoholic: 0, other. bAF TP, ascitic fluid total protein in patients with ascites at admission.
Hospitalization (days) Urinary catheters Endoscopies Sclerotherapy sessions Ascites’ AF TPb (g/dL) AF TP < 1.5 g/dL Encephalopathy” Degree l-2/3-4 Deaths Cause H/I/LF/Od
PREVENTS INFECTIONS IN CIRRHOTICS
Etiology EV/GV/PU/O” Hypovolemic shock Persistent hemorrhage Recurrent hemorrhage Duration (h) Hemoglobin (g/dL) Transfusion (UPRBC)b Vasoactive drugs” Esophageal tamponade Surgery
Group 1 (n = 60)
Group 2 (n = 59)
45/4/2/g 8 0 10 26.9 + 28.8 9.5 + 2.2 3.2 + 3.3 15 6 6
46/3/3/7 5 3 9 33.2 f 34.3 9.0 + 2.3 3.7 * 4.3 10 7 5
NOTE. P, NS between the two groups. “EV, esophageal varices; GV, gastric varices; PU, peptic ulcer; 0, other. bUPRBC, units of packed red blood cells. “Vasopressin plus nitroglycerin, or somatostatin.
NS). A perianal abscess developed in 1 patient from group 2. Possible infections were diagnosed in 6 patients from group 1 (10%) and in 6 patients from group 2 (10.1%) (P, NS). The time elapsed between admission and the diagnosis of infections or possible infections was 4.5 -t 3.2 days (range, l-10) in group 1 and 5.7 + 7.6 days (range, l-26) in group 2 (P, NS). During the first 10 days of hospitalization, 100% of infections in group 1 and 80.7% in group 2 were diagnosed. The incidence of infections during the first 10 days was 10% in group 1 and 30.5% in group 2 (P = 0.01). Two of the four late infections diagnosed in group 2 on days 21, 24, 24, and 26 of hospitalization occurred immediately after rebleeding. The bacteria responsible for the infections are listed in Table 5. An aerobic gram-negative bacillus was isolated in 1 patient from group 1 (1.6%) and 13 in 11 patients from group 2 (18.6%) (P < 0.01). The number of other bacteria, mainly aerobic gram-positive cocci, was not significantly different between the two groups (5 in 3 patients from group 1 and 10 in 9 patients from group 2). We did not observe any side effects attributable to norfloxacin. The cost of antibiotic therapy, including norfloxacin prophylaxis in group 1, was $80 per patient in group 1 and $210 per patient in group 2. Discussion The main finding in the present study was the decrease in the incidence of bacterial infections in cirrhotics with gastrointestinal hemorrhage receiving norfloxacin. Furthermore, our results confirm previous data suggesting that cirrhotic patients with gastrointestinal hemorrhage constitute a group at high risk of infection, especially by aerobic gram-negative bacteria of intestinal origin.%’
1270 SORIANO ET AL.
GASTROENTEROLOGY Vol. 103, No. 4
Table 4. Bacterial Infections Diagnosed in the Two Groups
of Patients
Group 1 (n = 60)
Infections Bacteremia or SBP/CNNA” Bacteremia SBP/CNNA Urinary Respiratory Perianal abscess Possible infections
Group 2 (n = 59)
No. of infections
No. of patients
6
6
26
22b
2 0 2 0 4d 0 6
2 0 2 0 4 0 6
10 6 4 11 4 1 6
10 6 4 11 4 1 6
No. of infections
No. of patients
p” 0.001
LIVER, PANCREAS,
1992;103:1267-1272
AND BILIARY TRACT
Norfloxacin Prevents Bacterial Infection in Cirrhotics With Gastrointestinal Hemorrhage GERMAN SORIANO, CARLOS GUARNER, ALBERT TOM&, CANDID VILLANUEVA, XAVIER TORRAS, DOLORS GONZALEZ, SERGIO SAINZ, ANA ANGUERA, XAVIER CUSSb, JOAQUIM BALANZ6, and FRANCISCO VILARDELL Liver Unit and Gastrointestinal i Sant Pau, Barcelona, Spain
Hemorrhage
Unit, Department
To assess the efficacy of selective intestinal decontamination with norfloxacin in the prevention of bacterial infections in cirrhotic patients with gastrointestinal hemorrhage, 119 patients were included in a prospective randomized study. Group 1 (n = 60) received norfloxacin orally or through a nasogastric tube, 400 mg twice daily for 7 days beginning immediately after emergency gastroscopy; group z (n = 59) was the control group. We found a significantly lower incidence of infections (10% vs. 37.2%; P = O.OOl),bacteremia and/or spontaneous bacterial peritonitis (3.3% vs. 16.9%; P -K0.05), and urinary infections (0% vs. 16.6%; P = 0.001) in patients receiving norfloxacin, as a consequence of decrease in the incidence of infections caused by aerobic gram-negative bacilli. The decrease in mortality observed in the treated group (6.6% vs. 11.6%) did not reach statistical significance. The cost for antibiotic treatment showed a 62% reduction in the treated group compared with the control group. The results show that selective intestinal decontamination with norfloxacin is useful in preventing bacterial infections in cirrhotics with gastrointestinal hemorrhage. acterial infection is a frequent and severe complication of cirrhosis that accounts for 25% of deaths in cirrhotic patients.le5 Patients with gastrointestinal hemorrhage constitute one of the groups of cirrhotics at high risk of infection described during the last decade.s-g Because enteric aerobic gram-negative bacteria are the most common causative agents isolated in infections in cirrhotics,14 it has been suggested that their inhibition by oral antibiotics may be useful for prevention.‘,” In the one reported study of infection prophylaxis in cirrhotics with gastrointestinal hemorrhage, Rimola et al.’ showed a reduction in the
B
of Gastroenterology,
Hospital de la Santa Creu
incidence of infections caused by enteric bacteria during the first 10 days of hospitalization in patients treated with oral nonabsorbable antibiotics. However, combinations of oral nonabsorbable antibiotics have some disadvantages, such as possible overgrowth of potentially pathogenic resistant bacteria and increase of side effects and cost.1’-‘5 Norfloxacin is a quinolone that produces a selective intestinal decontamination (SID) as it inhibits aerobic gram-negative intestinal flora while preserving the anaerobic flora and, therefore, the colonization resistance of the digestive tract.‘s-20 Norfloxacin reduces the incidence of infections caused by gramnegative bacilli in granulocytopenic patients13*” and is useful in the prevention of spontaneous bacterial peritonitis (SBP) recurrencelg and in the prophylaxis of SBP in hospitalized cirrhotics with low ascitic fluid total protein.” In some instances, prophylactic treatment with norfloxacin was performed for >6 months with negligible overgrowth of resistant bacteria and side effects.lg The aim of the present study was to assess the efficacy of SID with norfloxacin in the prevention of bacterial infections in cirrhotic patients with gastrointestinal hemorrhage. Patients and Methods All cirrhotic patients admitted because of gastrointestinal hemorrhage in the Gastrointestinal Hemorrhage Unit of our Department between August 1989 and June 1991 were considered for inclusion in the study. The following patients were excluded from the trial: (a) patients with signs of infection at admission, (b) patients treated with antibiotics during the z weeks before admission, and (c) patients transferred from other hospitals. A total of 128 patients were randomly allocated on admission into the 0 1992 by the American Gastroenterological 0016~5065/92/$3.00
Association
1268 SORIANO ET AL.
following two groups: group 1 (n = 64) received norfloxatin, 400 mg twice daily orally or through a nasogastric tube for 7 days, and group 2 (n = 64), controls, did not. Norfloxatin treatment in group 1 was started immediately after gastroscopy and was repeated when patients had recurrence of hemorrhage after withdrawal of norfloxacin. At admission, at least two intravenous catheters (one suitable to measure central venous pressure and a small intravenous cannula) and a nasogastric tube were placed in all patients. Urinary catheters were only used when necessary. Gastroscopy was performed within the first 4 hours of admission unless there was profound encephalopathy (grade 3-4) severe hemodynamic instability or when the patient refused. Patients bleeding from esophageal or gastric varices were assigned to endoscopic sclerotherapy. If the treatment failed, continuous intravenous infusion of vasopressin plus nitroglycerin or somatostatin was begun. If the bleeding continued, esophageal tamponade (SengstakenBlakemore or Linton-Nachlas balloon) was performed. When esophageal tamponade failed to control bleeding, surgery was performed in patients with Child-Pugh’s class A and B if their status did not prevent surgical intervention. After the initial bleeding was controlled, the patients were transferred to a conventional hospitalization ward and assigned to an elective sclerotherapy program with or without the addition of P-blocking agents.** In patients with peptic ulcer in whom active bleeding, a red clot, or a visible vessel was seen during gastroscopy,23 endoscopic injection was performed. Surgery was performed if bleeding could not be controlled with conservative measures and operation was not contraindicated. All patients were closely monitored with special emphasis on the detection of bacterial infections and norfloxacin side effects throughout the hospitalization period. A careful physical examination, complete white blood cell count, chest radiography, urine sediment and culture and ascitic fluid neutrophil count, Gram’s stain, and culture in blood culture bottles24*25 were routinely performed on admission. Physical examination was performed at least daily during hospitalization, and blood cell count was performed daily in the Gastrointestinal Hemorrhage Unit. The same procedures of admission as well as blood cultures and other diagnostic maneuvers, when indicated, were performed whenever patients showed signs of infection. When an infection was suspected, the initial empiric antibiotic treatment was cefotaxime in patients from group zzfi and amoxicillin plus clavulanic acid or imipenem, according to the severity of the infection, in patients from group 1, because these antibiotics are highly active against the bacteria most frequently isolated in the infections of cirrhotics submitted to SID, mainly gram-positive cocci.” The diagnosis of SBP was made when 2250 neutrophils/pL were found in ascitic fluid through positive culture results. Culture-negative neutrocytic ascites was defined as any instance of negative ascitic fluid culture but with an ascitic fluid neutrophil count 2500 neutrophils/ FL and bacterascites as any instance of positive culture with ascitic fluid neutrophil count 450 neutrophils/pL.” The possibility of gut perforation and/or an intra-abdomi-
GASTROENTEROLOGY
Vol. 103, No. 4
nal source of infection were excluded in all cases. The diagnosis of bacteremia or urinary infection was made when results of blood and urine cultures, respectively, were positive and the clinical picture was consistent with this diagnosis. Respiratory infections were diagnosed by clinical, analytical, and radiological data. Patients who experienced fever and/or leukocytosis with a shift to the left and without any other evidence of infection were considered to have possible infections and were empirically treated with antibiotics. The incidence of infections in patients who underwent surgery was analyzed only during the period between admission and the operation, because parenteral antibiotic prophylaxis and other factors might have interfered with the results of the study. Patients who died or underwent surgery within the first 24 hours after admission were excluded from analysis of results because the time elapsed was considered too short to allow for the action of norfloxacin. Statistical analysis was performed by means of Student’s t test and the x2 test with Yates’ correction and Fisher’s Exact Test. A P value co.05 was considered statistically significant. All values are expressed as mean f SD. The protocol was approved by the ethical committee of the Hospital and by the Ministry of Health. All patients or their families gave oral consent before the study was begun.
Results Eight patients (3 from group 1 and 5 from group 2) died or underwent surgery within the first 24 hours after admission and were excluded from analysis of results. An additional patient from group I was also excluded because he asked for voluntary discharge from the hospital 8 hours after admission. Therefore, 119patients (60 in group 1 and 59 in group 2) were finally analyzed. The diagnosis of cirrhosis was established by histology in 42 patients (22 from group 1 and 20 from group 2) and by clinical, analytical, and ultrasonographic findings in 77 patients (38 from group 1 and 39 from group 2). There were no significant differences between both groups in the clinical and laboratory data of the patients at admission or during the hospitalization (Tables 1 and 2, respectively). Table 3 shows the features of the hemorrhage that were similar in the two groups. Mortality was slightly lower in group 1 (four deaths, 6.6%) than in group 2 (seven deaths, 11.8%), but this difference did not reach statistical significance. There were no statistical differences between the two groups with regard to the cause of death. The incidence of bacterial infections during hospitalization is shown on Table 4. Six infections were diagnosed in 6 patients (10%) from group 1 and 26 infections in 22 patients (37.2%) from group 2 (P = 0.001). Bacteremia and/or SBP developed in 2 pa-
NORFLOXACIN
October 1992
Table I. Clinical and Analytical Characteristics of the Two Groups of Patients at Admission Group 1 (n = 60 Age (yr) Sex (M/F) Etiology (A/O)’ Hepatocarcinoma Previous SBP Diuretics Child-Pugh A/B/C Ascites Encephalopathy Degree l-2/3-4 Bilirubin @mol/L) Albumin (g/L) Prothrombin time (%) Urea (mmol/L) Creatinine @mol/L) White blood cell count (X109/L) AF TPb (g/dL) AF TP < 1.5 g/dL
61.0f 12.6 31/29 33/27 5 1 11 19/30/11 15 11
58.3f 13.5 30/29 34/25 2 2 11 21/25/13 14 10
8/3 41.9 f 48.5 30.4 f 4.2 57.2 i 15.7 12.0 f 6.7 104.9 + 58.2
9/l 35.3+ 26.7 31.2+ 6.4 57.5 + 14.5 10.6 f 7.1 100.8k 60.0
9010 + 4198 0.7 f 0.6 14
8750 + 4180 1.0 + 0.6 10
tients from group 1 (3.3%) and 10 patients from group 2 (16.9%) (P < 0.05). Urinary infections developed in II patients in group 2 (I&M%), whereas none were diagnosed in group 1 (P = 0.001). Respiratory infections developed in 4 patients in each group (7 pneumonias and 1 pyopneumothorax) (6.6% vs. 6.7%; P,
Table 2. Clinical Characteristics of Patients During Hospitalization Group 1 (n = 60)
Group 2 (n = 59)
13.5 + 9.2 41 2.0 + 1.0 1.6 + 0.9 9 0.8 f 0.6 8 13 9/4 4 3/1/O/O
14.4 f 10.9 34 2.0 + 1.0 1.5 + 1.1 9 0.6 f 0.5 8 11 6/5 7 2/2/2/l
NOTE. P, NS between the two groups. “Patients in whom ascites developed during hospitalization. bAF TP, ascitic fluid total protein in patients in whom ascites developed during hospitalization. ‘Patients in whom encephalopathy developed during hospitalization. dH, gastrointestinal hemorrhage; I, infection; LF, liver failure: 0, other.
1269
Table 3. Characteristics of the Hemorrhage in the Two Groups of Patients
Group 2 (n = 59)
NOTE. P, NS between the two groups. “A, alcoholic: 0, other. bAF TP, ascitic fluid total protein in patients with ascites at admission.
Hospitalization (days) Urinary catheters Endoscopies Sclerotherapy sessions Ascites’ AF TPb (g/dL) AF TP < 1.5 g/dL Encephalopathy” Degree l-2/3-4 Deaths Cause H/I/LF/Od
PREVENTS INFECTIONS IN CIRRHOTICS
Etiology EV/GV/PU/O” Hypovolemic shock Persistent hemorrhage Recurrent hemorrhage Duration (h) Hemoglobin (g/dL) Transfusion (UPRBC)b Vasoactive drugs” Esophageal tamponade Surgery
Group 1 (n = 60)
Group 2 (n = 59)
45/4/2/g 8 0 10 26.9 + 28.8 9.5 + 2.2 3.2 + 3.3 15 6 6
46/3/3/7 5 3 9 33.2 f 34.3 9.0 + 2.3 3.7 * 4.3 10 7 5
NOTE. P, NS between the two groups. “EV, esophageal varices; GV, gastric varices; PU, peptic ulcer; 0, other. bUPRBC, units of packed red blood cells. “Vasopressin plus nitroglycerin, or somatostatin.
NS). A perianal abscess developed in 1 patient from group 2. Possible infections were diagnosed in 6 patients from group 1 (10%) and in 6 patients from group 2 (10.1%) (P, NS). The time elapsed between admission and the diagnosis of infections or possible infections was 4.5 -t 3.2 days (range, l-10) in group 1 and 5.7 + 7.6 days (range, l-26) in group 2 (P, NS). During the first 10 days of hospitalization, 100% of infections in group 1 and 80.7% in group 2 were diagnosed. The incidence of infections during the first 10 days was 10% in group 1 and 30.5% in group 2 (P = 0.01). Two of the four late infections diagnosed in group 2 on days 21, 24, 24, and 26 of hospitalization occurred immediately after rebleeding. The bacteria responsible for the infections are listed in Table 5. An aerobic gram-negative bacillus was isolated in 1 patient from group 1 (1.6%) and 13 in 11 patients from group 2 (18.6%) (P < 0.01). The number of other bacteria, mainly aerobic gram-positive cocci, was not significantly different between the two groups (5 in 3 patients from group 1 and 10 in 9 patients from group 2). We did not observe any side effects attributable to norfloxacin. The cost of antibiotic therapy, including norfloxacin prophylaxis in group 1, was $80 per patient in group 1 and $210 per patient in group 2. Discussion The main finding in the present study was the decrease in the incidence of bacterial infections in cirrhotics with gastrointestinal hemorrhage receiving norfloxacin. Furthermore, our results confirm previous data suggesting that cirrhotic patients with gastrointestinal hemorrhage constitute a group at high risk of infection, especially by aerobic gram-negative bacteria of intestinal origin.%’
1270 SORIANO ET AL.
GASTROENTEROLOGY Vol. 103, No. 4
Table 4. Bacterial Infections Diagnosed in the Two Groups
of Patients
Group 1 (n = 60)
Infections Bacteremia or SBP/CNNA” Bacteremia SBP/CNNA Urinary Respiratory Perianal abscess Possible infections
Group 2 (n = 59)
No. of infections
No. of patients
6
6
26
22b
2 0 2 0 4d 0 6
2 0 2 0 4 0 6
10 6 4 11 4 1 6
10 6 4 11 4 1 6
No. of infections
No. of patients
p” 0.001
