Effect of long-term acid gastric inhibition on bacterial translocation in cirrhotic rats.

BACKGROUND: Bacterial translocation (BT) related to intestinal bacterial overgrowth (IBO) plays an important role in the pathogenesis of bacterial infections in cirrhosis. Inhibition of acid gastric secretion promotes IBO and might favor BT. We evaluated the effect of long-term inhibition of acid gastric secretion on BT in cirrhotic rats. METHODS: Cirrhotic rats with and without ascites induced by oral CCl4 and controls were randomized to treatment with a daily subcutaneous injection of placebo, ranitidine (50 mg/kg), or pantoprazole (8 mg/kg) during 2 weeks. Continuous pH-metry was performed for 2 h before and at the end of treatment; thereafter, a laparotomy to obtain samples of blood, mesenteric lymph nodes, ascites, spleen, liver, and cecal stools was performed. RESULTS: Ranitidine and pantoprazole increased gastric pH as compared with placebo (P<0.001). However, antisecretory drugs increased the incidence of BT only in ascitic rats treated with ranitidine (P<0.05) or pantoprazole (P=0.07) when compared with placebo-treated ascitic rats or cirrhotic rats without ascites treated with the same drug. Cirrhotic ascitic rats treated with pantoprazole showed a trend toward an increased incidence of IBO (P=0.08), a higher ileal malondialdehyde level (P<0.01), and an increased production of tumor necrosis factor-α (P<0.05). CONCLUSION: Although inhibition of acid gastric secretion increased gastric pH in all animals, the incidence of BT increased only in ascitic rats, and it was associated with a trend toward an increase in IBO incidence, a higher ileal malondialdehyde level, and an increased production of serum tumor necrosis factor-α. Therefore, antisecretory drugs should be carefully administered to cirrhotic ascitic patients.

VSL#3 probiotic treatment decreases bacterial translocation in rats with carbon tetrachloride-induced cirrhosis.

BACKGROUND & AIMS: Probiotics can prevent pathological bacterial translocation in cirrhosis by modulating intestinal microbiota and improving gut barrier and immune disturbances. To evaluate the effect of probiotic VSL#3 on bacterial translocation, intestinal microbiota, gut barrier and inflammatory response in rats with experimental cirrhosis. METHODS: Forty-six Sprague-Dawley rats with CCl4 -induced cirrhosis were randomized into two groups: VSL#3 group (n = 22) that received VSL#3 in drinking water, and water group (n = 24) that received water only. Treatment began at week 6 of cirrhosis induction and continued until laparotomy, performed 1 week after development of ascites or at week 20. A control group included 11 healthy rats. At this study end, we evaluated bacterial translocation, intestinal flora, intestinal barrier (ileal claudin-2 and 4, ß-defensin-1, occludin and malondialdehyde as index of oxidative damage) and serum cytokines. RESULTS: Mortality during this study was similar in the VSL#3 group (10/22, 45%) and the water group (10/24, 42%) (P = 1). The incidence of bacterial translocation was 1/12 (8%) in the VSL#3 group, 7/14 (50%) in the water group (P = 0.03 vs. VSL#3 group) and 0/11 in the control group (P = 0.008 vs. water group). The concentration of ileal and caecal enterobacteria and enterococci was similar in the two groups of cirrhotic rats. The ileal occludin concentration was higher and ileal malondialdehyde and serum levels of TNF-α were lower in the VSL#3 group than in the water group (P < 0.05). CONCLUSIONS: VSL#3 decreases bacterial translocation, the pro-inflammatory state and ileal oxidative damage and increases ileal occludin expression in rats with experimental cirrhosis.

Modulation of inflammatory response in a cirrhotic rat model with induced bacterial peritonitis.

Bacterial peritonitis is a severe complication in patients with cirrhosis and ascites and despite antibiotic treatment, the inflammatory response to infection may induce renal dysfunction leading to death. This investigation evaluated the effect of TNF-α blockade on the inflammatory response and mortality in cirrhotic rats with induced bacterial peritonitis treated or not with antibiotics. Sprague-Dawley rats with carbon-tetrachloride-induced cirrhosis were treated with an intraperitoneal injection of 10(9) CFU of Escherichia coli diluted in 20 mL of sterile water to induce bacterial peritonitis and randomized to receive subcutaneously-administered placebo, ceftriaxone, anti-TNF-α mAb and ceftriaxone, or anti-TNF-α mAb alone. No differences were observed between groups at baseline in respect to renal function, liver hepatic tests, serum levels of nitrite/nitrate and TNF-α. Treatment with ceftriaxone reduced mortality (73.3%) but differences did not reach statistical significance as compared to placebo. Mortality in rats treated with ceftriaxone and anti-TNF-α mAb was significantly lower than in animals receiving placebo (53% vs. 100%, p<0.01). Serum TNF-α decreased significantly in surviving rats treated with ceftriaxone plus anti-TNF-α mAb but not in treated with antibiotics alone. Additional studies including more animals are required to assess if the association of antibiotic therapy and TNF-α blockade might be a possible approach to reduce mortality in cirrhotic patients with bacterial peritonitis.

Community infections caused by extended-spectrum beta-lactamase-producing Escherichia coli.

BACKGROUND: Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli is an increasingly important group of community pathogens worldwide. These organisms are frequently resistant to many of the antimicrobial agents usually recommended for the treatment of infections caused by E coli, such as penicillins, cephalosporins, fluoroquinolones, and trimethoprim-sulfamethoxazole. Data concerning risk factors, clinical features, and therapeutic options for such infections are scarce. METHODS: A case-control study was performed to investigate the risk factors for all types of community-acquired infections caused by ESBL-producing E coli in 11 Spanish hospitals from February 2002 to May 2003. Controls were randomly chosen from among outpatients with a clinical sample not yielding ESBL-producing E coli. The clinical features of these infections were investigated in the case patients. The efficacy of fosfomycin tromethamine and amoxicillin-clavulanate potassium was observationally studied in patients with cystitis. RESULTS: A total of 122 cases were included. Risk factors selected by multivariate analysis included the following: age older than 60 years; female sex; diabetes mellitus; recurrent urinary tract infections (UTIs); previous invasive procedures of the urinary tract; follow-up in outpatient clinic; and previous receipt of aminopenicillins, cephalosporins, and fluoroquinolones. Urinary tract infections accounted for 93% of the cases; 6% of the patients were bacteremic and 10% needed hospitalization. The cure rate of patients with cystitis was 93% with fosfomycin therapy (all isolates were susceptible); among patients treated with amoxicillin-clavulanate, cure rates were 93% for those with susceptible isolates (minimum inhibitory concentration < or =8 microg/mL) and 56% for those with intermediate or resistant isolates (minimum inhibitory concentration > or =16 microg/mL) (P = .02). CONCLUSIONS: In predisposed patients, ESBL-producing E coli is a notable cause of community-acquired infection, and particularly UTI. Fosfomycin and amoxicillin-clavulanate appear to be effective for cystitis caused by susceptible isolates.

A simple phenotypic method for differentiation between acquired and chromosomal AmpC beta-lactamases in Escherichia coli.

BACKGROUND: Screening methods for the detection of plasmid-mediated AmpC beta-lactamases are technically demanding. The purpose of this study was to assess screening methods for the detection of these enzymes in clinical isolates of Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis. METHODS: Isolates were selected according to a resistance phenotype consistent with production of an AmpC-type beta-lactamase. Detection of acquired ampC genes was done with a multiplex ampC-PCR and sequencing. The phenotypic detection methods evaluated included visual examination of antibiogram plates to identify the presence of scattered colonies located near the edge of the inhibition halo of cefoxitin, cefotaxime, ceftazidime and aztreonam, and a double-disc synergy test using cloxacillin (500 mg) to inhibit AmpC enzymes. RESULTS: Seventy-seven isolates were selected from among 6,209 isolates recovered. Acquired ampC genes (blaCMY-2, blaDHA-1, blaCMY-4 and blaACC-1) were found in 19 (24.7%) of these isolates, including 14 E. coli, two K. pneumoniae and three P. mirabilis isolates. The differential trait for the presence of colonies in the inhibition halo was 100% sensitive and specific. Similar results were obtained for the cloxacillin test, except for the E. coli isolates in which specificity was 10.3%. CONCLUSION: The phenotypic trait described here can be considered useful for suspecting the presence of these enzymes. The cloxacillin test was only useful in isolates lacking a natural AmpC beta-lactamase.