Bacterial Infections In Cirrhosis Research Articles

Norfloxacin vs Ceftriaxone in the Prophylaxis of Infections in Patients With Advanced Cirrhosis and Hemorrhage

Oral norfloxacin is the standard of therapy in the prophylaxis of bacterial infections in cirrhotic patients with gastrointestinal hemorrhage. However, during the last years, the epidemiology of bacterial infections in cirrhosis has changed, with a higher incidence of infections caused by quinolone-resistant bacteria. This randomized controlled trial was aimed to compare oral norfloxacin vs intravenous ceftriaxone in the prophylaxis of bacterial infection in cirrhotic patients with gastrointestinal bleeding. One hundred eleven patients with advanced cirrhosis (at least 2 of the following: ascites, severe malnutrition, encephalopathy, or bilirubin >3 mg/dL) and gastrointestinal hemorrhage were randomly treated with oral norfloxacin (400 mg twice daily; n = 57) or intravenous ceftriaxone (1 g/day; n = 54) for 7 days. The end point of the trial was the prevention of bacterial infections within 10 days after inclusion. Clinical data were comparable between groups. The probability of developing proved or possible infections, proved infections, and spontaneous bacteremia or spontaneous bacterial peritonitis was significantly higher in patients receiving norfloxacin (33% vs 11%, P = .003; 26% vs 11%, P = .03; and 12% vs 2%, P = .03, respectively). The type of antibiotic used (norfloxacin), transfusion requirements at inclusion, and failure to control bleeding were independent predictors of infection. Seven gram-negative bacilli were isolated in the norfloxacin group, and 6 were quinolone resistant. Non-enterococcal streptococci were only isolated in the norfloxacin group. No difference in hospital mortality was observed between groups. Intravenous ceftriaxone is more effective than oral norfloxacin in the prophylaxis of bacterial infections in patients with advanced cirrhosis and hemorrhage.

Spontaneous bacterial peritonitis: a historical perspective: Kerr DNS, Pearson DT, Read AE. Infection of ascitic fluid in patients with hepatic cirrhosis [Gut 1963; 4: 394–398]; Conn HO. Spontaneous peritonitis and bacteremia in Laennec's cirrhosis caused by enteric organisms. A relatively common but rarely recognized syndrome [Ann Intern Med 1964; 60: 568–580

Spontaneous bacterial peritonitis: a historical perspective: Kerr DNS, Pearson DT, Read AE. Infection of ascitic fluid in patients with hepatic cirrhosis [Gut 1963; 4: 394–398]; Conn HO. Spontaneous peritonitis and bacteremia in Laennec's cirrhosis caused by enteric organisms. A relatively common but rarely recognized syndrome [Ann Intern Med 1964; 60: 568–580

Bacterial infections in cirrhosis.

Spontaneous bacterial peritonitis, urinary tract infections, respiratory infections and bacteremia are the most frequent infective complications in cirrhosis. These infections are due to the concomitant presence of different facilitating mechanisms including changes in the intestinal flora and in the intestinal barrier, depression of activity of the reticuloendothelial system, decreased opsonic activity of the ascitic fluid, neutrophil leukocyte dysfunction and iatrogenic factors among others. The fact, that the probability of having a microorganism responsible for the infection quinolone resistant is higher than 30% should be taken into account when treating any infection in a cirrhotic patient receiving selective intestinal decontamination with quinolones, and therefore, quinolones as empiric treatment are not indicated.

Bacterial Infections in Cirrhosis

Hospitalized patients with cirrhosis are at increased risk of developing bacterial infections, the most common being spontaneous bacterial peritonitis (SBP) and urinary tract infections. Independent predictors of the development of bacterial infections in hospitalized cirrhotic patients are poor liver synthetic function and admission for gastrointestinal hemorrhage. Short term (seven-day) prophylaxis with norfloxacin reduces the rate of infections and improves survival and should therefore be administered to all patients with cirrhosis and variceal hemorrhage. Cirrhotic patients who develop abdominal pain, tenderness, fever, renal failure or hepatic encephalopathy should undergo diagnostic paracentesis, and those who meet the criterion for SBP (eg, an ascites neutrophil count greater than 250/mm3) should receive antibiotics, preferably a third-generation cephalosporin. In addition to antibiotic therapy, albumin infusions have been shown to reduce the risk of renal failure and mortality in patients with SBP, particularly in those with renal dysfunction and hyperbilirubinemia at the time of diagnosis. Patients who recover from an episode of SBP should be given long term prophylaxis with norfloxacin and should be assessed for liver transplantation.

Increased carbon monoxide production in patients with cirrhosis with and without spontaneous bacterial peritonitis

Carbon monoxide, a product of the heme-oxygenase (HO) pathway, is an important endogenous vasoactive substance. Production of CO has not been assessed in human cirrhosis. The aim of this study was to assess production of CO in patients with cirrhosis with and without spontaneous bacterial peritonitis (SBP). CO concentration in the exhaled air and blood carboxyhemoglobin (COHb) levels, as estimates of total HO activity, were determined in 16 healthy subjects, 32 noninfected cirrhotic patients (20 with ascites), and 19 patients with SBP, all nonsmokers. Noninfected cirrhotic patients had a CO concentration in the exhaled air and COHb levels significantly higher compared with values of healthy subjects (2.3 ± 0.2 ppm vs. 0.7 ± 0.1 ppm and 1.0% ± 0.1% vs. 0.6% ± 0.1%, respectively; P < .05 for both). Patients with ascites had the highest values. Both CO concentration in the exhaled air and COHb levels were very high in patients with SBP (5.6 ± 0.6 ppm and 1.9% ± 0.2%; P < .01 vs. the other 2 groups) and decreased slowly after resolution of the infection, reaching values similar to those of noninfected patients 1 month after SBP. In patients with SBP, there was a significantly direct correlation between CO and plasma renin activity (PRA) ( r = 0.71, P < .001). In conclusion, these results support the existence of increased CO production in human cirrhosis, which further increases in the setting of SBP. Increased CO production may participate in the disturbance of circulatory function that occurs during severe bacterial infections in cirrhosis. (H epathology 2003;38:452-459.)

Effect of Lactobacillus-fermented diets on bacterial translocation and intestinal flora in experimental prehepatic portal hypertension.

Spontaneous bacterial infections in cirrhosis and portal hypertension have been attributed to translocation of gut-derived bacteria, a process promoted by intestinal bacterial overgrowth and disruption of the gut mucosal barrier. Bacteriotherapy with Lactobacillus has been reported to correct bacterial overgrowth, stabilize mucosal barrier function, and decrease bacterial translocation in rat models of acute liver injury and failure. In this study we investigated the effect of Lactobacillus-supplemented diets on intestinal flora and on bacterial translocation rate in portal vein ligated rats. Lactobacillus-fermented milk (yogurt) containing at least 2 x 10(9) colony forming units/ml or placebo (water) was adminstrated by gavage twice daily (2 ml) for 9 days. Portal vein ligation was performed on day 7 of treatment. Bacterial translocation to mesenteric lymph nodes and quantification of intestinal flora was assessed by standard bacteriological cultures. Bacterial translocation was not significantly different between animals that received yogurt (82%) and those that received placebo (75%). Yogurt did not induce any significant changes in intestinal flora, whether it was produced with Lactobacillus acidophilus or Lactobacillus GG. In conclusion, in acute prehepatic portal hypertension, bacteriotherapy with Lactobacillus was unable to induce changes in bacterial translocation probably because it was unable to induce changes in bacterial flora.

Effect of Lactobacillus johnsonii La1 and antioxidants on intestinal flora and bacterial translocation in rats with experimental cirrhosis

Background/Aims: Probiotics and antioxidants could be alternatives to antibiotics in the prevention of bacterial infections in cirrhosis. The aim of the present study was to determine the effect of Lactobacillus johnsonii La1 and antioxidants on intestinal flora, endotoxemia, and bacterial translocation in cirrhotic rats. Methods: Twenty-nine Sprague–Dawley rats with cirrhosis induced by CCl 4 and ascites received Lactobacillus johnsonii La1 10 9 cfu/day in vehicle (antioxidants: vitamin C+glutamate) ( n=10), vehicle alone ( n=11), or water ( n=8) by gavage. Another eight non-cirrhotic rats formed the control group. After 10 days of treatment, a laparotomy was performed to determine microbiological study of ileal and cecal feces, bacterial translocation, endotoxemia, and intestinal malondialdehyde (MDA) levels as index of intestinal oxidative damage. Results: Intestinal enterobacteria and enterococci, bacterial translocation (0/11 and 0/10 vs. 5/8, P<0.01), and ileal MDA levels ( P<0.01) were lower in cirrhotic rats treated with antioxidants alone or in combination with Lactobacillus johnsonii La1 compared to cirrhotic rats receiving water. Only rats treated with antioxidants and Lactobacillus johnsonii La1 showed a decrease in endotoxemia with respect to cirrhotic rats receiving water ( P<0.05). Conclusions: Antioxidants alone or in combination with Lactobacillus johnsonii La1 can be useful in preventing bacterial translocation in cirrhosis.

Bacterial infections in cirrhosis: Epidemiological changes with invasive procedures and norfloxacin prophylaxis

The extensive use of invasive procedures and of long-term norfloxacin prophylaxis in the management of cirrhotic patients may have influenced the epidemiology of bacterial infections in cirrhosis. We conducted a prospective evaluation of all bacterial infections diagnosed in patients with cirrhosis in a Liver Unit between April 1998 and April 2000. A total of 405 patients presented 572 bacterial infections in 507 admissions. Spontaneous bacterial peritonitis was the most frequent infection (138 cases). Gram-positive cocci were responsible for 53% of total bacterial infections in the study, being the main bacteria isolated in nosocomial infections (59%). Patients requiring treatment in an intensive care unit and those submitted to invasive procedures presented a higher rate of infections caused by gram-positive cocci (77% vs. 48%, P < .001 and 58% vs. 40%, P < .02, respectively). Fifty percent of culture-positive spontaneous bacterial peritonitis in patients on long-term norfloxacin administration (n = 93) and 16% in patients not receiving this therapy (n = 414) were caused by quinolone-resistant gram-negative bacilli, P = .01. The rate of culture-positive spontaneous bacterial peritonitis caused by trimethoprim-sulfamethoxazole–resistant gram-negative bacilli was also very high in patients on long-term norfloxacin administration (44% vs. 18%, P = .09). In conclusion, infections caused by gram-positive cocci have markedly increased in cirrhosis. This phenomenon may be related to the current high degree of instrumentation of cirrhotic patients. Quinolone-resistant spontaneous bacterial peritonitis constitutes an emergent problem in patients on long-term norfloxacin prophylaxis, with trimethoprim-sulfamethoxazole not being a valid alternative. (H EPATOLOGY 2002;35:140-148.)

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.

Intravenous albumin infusion prevents renal impairment (RI) and improves hospital survival in patients with spontaneous bacterial peritonitis (SBP)

INTRAVENOUS ALBUMIN INFUSION PREVENTS RENAL IMPAIRMENT (RI) AND IMPROVES HOSPITAL SURVIVAL IN PATIENTS WITH SPONTANEOUS BACTERIAL PERITONITIS (SBP). P.Sort*. M. Navasa* and Soanish aroup for the studv of bacterial infections in cirrhosis. *Hosoital Clinic i Provincial. Barcelona. Soain. One third of patients with SBP develop RI in relation with a deterioration of circulatory function, as reflected by an increase in plasma renin activity (PRA). The development of RI is the most important predictor of hospital mortality in SBP. This study assesses whether plasma volume expansion prevents the impairment in circulatory and renal function and improves hospital survival in these patients. 119 patients with SBP were randomized to receive albumin infusion (1.5 g/Kg body wt. on the 1’ day and 1 g/Kg of body wt. on the 3rd day) plus cefotaxime (n=59) or cefotaxime alone (n=60). At diagnosis, hepatic and renal function, PRA and incidence of hepatocarcinoma were similar in both groups. The incidence of circulatory dysfunction (increase of 50% in PRA above baseline levels at the sixth day of inclusion) (4% vs 30%, p<O.OOl) and of RI (8.5% vs 35%, p<O.OOl), and the hospital mortality rate (10% vs 33%, p<O.O02) were significantly lower in patients who received albumin. Among 31 variables obtained at inclusion, treatment modality, prothrombin time, bilirubin and BUN were the only independent predictors of hospital survival. In conclusion, albumin infusion prevents the deterioration in circulatory function and RI, and reduces hospital mortality in patients with SBP. EVIDENCE OF REDUCED EFFECTIVENESS OF AN OTHERWISE INCREASED ENDGGENOUS DGPAMINERGIC ACTMTY IN COMPENSATED CIRRHOSIS. G Sansot?. A Fenwi. E. Liamldi*. CN Castellana**, G Termnova, M Ghidoni. E Villa, F Manenti. Chairs of Gastmenterologv, ‘Endocrinology and **Clinical Pharmacolqy, Universi@ of Modena, Imly. Endogenous dopamine exerts a combined adrenal and renal mediation of the natriuretic response to central fluid volume expansion. Plasma dopamine levels rise in association with the natriuretic response to volume expansion produced by head-out water immersion. Aldosterone secretion both in rat and in man is inhibited by dopamine. Dopamine inhibits Na’-K’ATPase activity in proximal convoluted and straight tubule segments. In this manner dopamine increases sodium delivery to the distal nephron and natriuresis. We studied 12 patients with Child-Pugh class A cirrhosis without history of previous ascites or diuretic consumption (after an equilibration period of five days on a normocaloric diet with a daily sodium intake of 120 mEq) and compared them to 9 control subjects, on the basis of the evaluation of a) the degree of dopaminergic activity, as measured by the incremental aldosterone responses 30 and 60 min min atler metoclopramide (h4TC) 10 mg i.v. administration; b) basal morning levels of active renin and aldosterone while reclining ; c) 4 h renal clearances of lithium (C-Li) (an index of fluid and sodium delivery to the distal tubule) and creatinine (C-Cr), d) 4 h urinary excretion parameters of sodium and potassium. With respect to controls, patients showed signiticantly greater incremental aldosterone responses both 30 and 60 min atler MTC (respectively, +30 mitt: 160.2 f 68.8 v. 83.6 f 35.2 pg/ml, ~4.01; +60 min: 140.5 f 80.3 v 36.8 i 39.0 pg/ml, p<o.Ol). hi spite of this, patients and controls showed not significantly different values of basal morning aldosterone (respectively, 80.36 f 53.22 v. 111.70 f 54.56, p=O.14), distal delivery of sodium (respectively, 4.25 * 1.30 v. 3.97 f 1.64 mEq/min, H.13) and urinary excretion of sodium (respectively, 0.14 f 0.08 v. 0.20 f 0.05 mEq/min, ~4.76). Remarkably, we observed a significant correlation between basal aldosterone plasma values and the aldosterone response 30’ after MTC among cirrhotic patients (r: 0.81, p<o.Ol) but not controls (r: 0.07, e.05). These data suggest, in patients with compensated cirrhosis, a state of partial resistance to the renal and adrenal effects of dopaminergic activity which is actually increased with respect to normal subjects. The known dependence of dopaminergic function on the degree of central fluid volume replenishment and the correlation observed only in patients between this parameter and a main determinan t of central fluid volume (i.e. plasma aldosterone levels) could imply the concept of a state of central hypervolaemia in compensated cirrhosis.

Spontaneous bacterial peritonitis in patients with cirrhosis undergoing selective intestinal decontamination: A retrospective study of 229 spontaneous bacterial peritonitis episodes

Background/Aims: Selective intestinal decontamination with norfloxacin is widely used to prevent spontaneous bacterial infections in cirrhosis. The study was performed to compared the spontaneous bacterial peritonitis occurring in patients with and without prophylactic norfloxacin. Methods: Two hundred and twenty-nine consecutive episodes of spontaneous bacterial peritonitis, (193 patients without (Group A) and 36 in patients with norfloxacin prophylaxis (Group B)), were retorspectively analyzed. In 100 episodes (86 and 14, respectively), the responsible organism was isolated in ascitic fluid. Results: Clinical and laboratory data at diagnosis were comparable in both groups. There were marked differences ( p<0.001) between group A and B in the frequency of peritonitis caused by gram-negative (67.4% vs. 14.3%) and gram-positive (30.2% vs. 78.6%) bacteria. There were three polymicrobial episodes. Bacteria resistant to cefotaxime and gram-negative bacilli resistant to quinolones were isolated in ascitic fluid in nine (seven in Group A and two in Group B) and three episodes (all in Group A), respectively. No differences in the course of infection and patient survival were observed between groups. Conclusions: Spontaneous bacterial peritonitis in patients with and without prophylaxis with norfloxacin are not different in clinical features, response to treatment and prognosis. Spontaneous bacterial peritonitis caused by gram-negative organisms resistant to quinolones is extremely uncommon in patients with cirrhosis receiving prophylatic norfloxacin.