Selective Bowel Decontamination Research Articles

Selective bowel decontamination of recipients for prevention against liver injury following orthotopic liver transplantation: evaluation with rat models.

Gut-derived substances can activate Kupffer cells to provoke hepatic necrosis after partial hepatectomy in rats. A similar situation may occur during orthotopic liver transplantation (OLT), as congestion in the intestinal wall, caused by portal vein occlusion, is inevitable during the operation. The contribution of such substances to liver injury following OLT was investigated in rats. Oral administration of polymyxin B sulfate for 7 days significantly altered intestinal bacterial flora in rats; Enterobacteriaceae diminished and anaerobes such as Bifidobacterium , Lactobacillus, Bacteroides, and Eubacterium increased in number, compared with the control rats. Also, this treatment significantly reduced endotoxin concentration in the portal blood 30 minutes after blood reflow following portal vein occlusion. When OLT was performed in rats using the liver preserved in cold University of Wisconsin solution for 18 hours, tissue factor activity in Kupffer cells (KC) isolated from the transplanted liver 1 hour after the operation was significantly higher than in that of normal rats. This increase was significantly reduced by pretreatment of the recipients with polymyxin B sulfate. In these recipients, serum alanine aminotransferase activity, tumor necrosis factor alpha (TNF alpha) concentration, and histological extent of liver necrosis were significantly attenuated at 24 hours after the operation compared with those of control rats. We conclude that the substances derived from bacilli sensitive to polymyxin B sulfate in the gut may be a contributing factor to liver injury following OLT in rats; we feel that this probably occurs by entering of the substances into the portal blood during the ahepatic phase of the operation to activate KC. Selective bowel decontamination of recipients with polymyxin B sulfate would be a candidate for protection against early graft failure following OLT.

Selective bowel decontamination in hospitalized patients awaiting liver transplantation

Infection remains a major contributor to morbidity and mortality following orthotopic liver transplantation (OLT). Selective bowel decontamination (SBD) in hospitalized patients is one strategy for prophylaxis. A retrospective case-control study was performed using 18 consecutive hospitalized patients receiving SBD prior to OLT during the period September 1995 to September 1996. Eighteen consecutive hospitalized patients without SBD transplanted during the period March 1995 to September 1995 served as a historical control group. Selective bowel decontamination was associated with a significantly decreased prevalence of positive cultures for gram-negative bacteria and fungi and reduced overall hospital charges. In hospitalized patients awaiting OLT, SBD is an effective prophylactic measure against infectious morbidity associated with gram-negative bacteria and fungi.

Early bacterial and fungal infections in liver transplantation after oral selective bowel decontamination

Early bacterial and fungal infections in liver transplantation after oral selective bowel decontamination

Prevention of infection in children with acute leukaemia. No major difference between total and selective bowel decontamination.

To evaluate the effect of total bowel decontamination (TD) and selective bowel decontamination (SD) in a non-protective environment clinical and laboratory data of children treated for acute leukaemia between 1983 and 1991 were analysed retrospectively. From 1983 until 1989 34 patients [18 acute non-lymphoblastic leukaemia (ANLL) patients, 16 acute lymphoblastic leukaemia (ALL) patients] received TD and 31 patients (8 ANLL patients, 23 ALL patients) received SD from 1987 until 1991. TD consisted of colistin sulphate, neomycin, cephaloridine and amphotericin B orally as well as Orabase and sterilized food, while the patients were nursed in a single room. SD consisted of oral colistin sulphate, neomycin and amphotericin B. Those patients with ANLL were nursed in a single room; patients with ALL were nursed in a single room during remission induction therapy only. All patients except those with ANLL receiving TD received Pneumocystis carinii pneumonia prophylaxis with cotrimoxazole. Because the two groups were heterogeneous for diagnosis and chemotherapy the occurrence of fever (central body temperature at least 38.5 degrees C) and major infections (septicaemia of infections of the deep tissues or organs) were registered during periods of neutropenia (neutrophilic granulocytes < or = 500/mm3 for at least 8 days). Patients on TD had 55 periods of neutropenia, patients on SD 80. Patients on TD had 89.1 periods of fever/100 periods of neutropenia whereas patients on SD had 56.3. Also patients on TD had 27.3 major infections/100 periods of neutropenia whereas patients on SD had 11.3. Major infections predominantly consisted of septicaemia caused by gram-positive bacteria. We conclude that, in this study, TD in a non-protective environment does not offer better protection against major infections that SD in patients with ALL or ANLL.

Relevance and risk factors of enterococcal bacteremia following liver transplantation.

To analyze the clinical characteristics of and identify specific risk factors for enterococcal bacteremia following liver transplantation, we performed a study in 405 consecutive liver transplantation recipients prophylaxed with a selective bowel decontamination regimen. Seventy enterococcal bacteremias in 52 patients were identified. Enterococcus faecalis (50) outnumbered Enterococcus faecium isolates (18), and 49% of enterococcal bacteremias were polymicrobial. Biliary tree complications were present in 34% of enterococcal bacteremias. Of the 15 deaths (29%) among the patients with enterococcal bacteremia, 4 were directly associated with enterococcal bacteremia. In a multivariate analysis, Roux-en-Y choledochojejunostomy (P=0.005), a cytomegalovirus-seropositive donor (P=0.013), prolonged transplantation time (P=0.02), and biliary stricturing (P=0.016) were identified as significant risk factors. Other risk factors identified in a univariate analysis included primary sclerosing cholangitis (P=0.009) and symptomatic cytomegalovirus infection (P=0.008). Enterococcal bacteremia is a frequent infectious complication in liver transplantation recipients receiving selective bowel decontamination. Its association with cytomegalovirus and biliary tree abnormalities suggest specific areas for prophylactic intervention.

Effect of selective bowel decontamination with norfloxacin on spontaneous bacterial peritonitis, translocation, and survival in an animal model of cirrhosis

Selective bowel decontamination with the orally administered quinolone antibiotic, norfloxacin, has been shown to suppress gut gram-negative bacteria and help prevent gram-negative infections in cirrhotic patients who are at high risk of bacterial infection. Because this drug does not eradicate gram-positive organisms, it is conceivable that gram-positives could replace the suppressed gram-negatives in the gut and lead to subsequent infection. Also the effect of norfloxacin on translocation (as defined by culture positivity of mesenteric lymph nodes) has received little attention. In this study, the effect of oral norfloxacin on translocation, bacterial peritonitis, and survival was investigated in an animal model of carbon tetrachloride—induced cirrhosis and ascites. Treated rats received daily doses of orally administered norfloxacin from the onset of cirrhosis until they died or were killed. Controls received no antibiotic. Norfloxacin led to a reduction in bacterial peritonitis from 70% in untreated cirrhotic controls to 28% in treated cirrhotic rats; these data were statistically significant (P = 0.012). There was no effect on overall translocation rate (28% with norfloxacin vs. 50% without norfloxacin) (P &gt; 0.1). Gram-positives were isolated in 100% of the bacterial peritonitis episodes and in 71.4% of culture-positive mesenteric lymph nodes in treated animals compared with only 25% of peritonitis episodes and 10% of culture-positive mesenteric lymph nodes of untreated cirrhotic controls (P &lt; 0.01 for peritonitis and P &lt; 0.05 for translocation). The survival rate was not different between groups (P &gt; 0.1). Although norfloxacin was associated with a 60% reduction in the overall rate of peritonitis, this drug increased the risk of gram-positive translocation and gram-positive peritonitis, and did not prolong survival in this animal model.

Effect of selective bowel decontamination with norfloxacin on spontaneous bacterial peritonitis, translocation, and survival in an animal model of cirrhosis

Selective bowel decontamination with the orally administered quinolone antibiotic, norfloxacin, has been shown to suppress gut gram-negative bacteria and help prevent gram-negative infections in cirrhotic patients who are at high risk of bacterial infection. Because this drug does not eradicate gram-positive organisms, it is conceivable that gram-positives could replace the suppressed gram-negatives in the gut and lead to subsequent infection. Also the effect of norfloxacin on translocation (as defined by culture positivity of mesenteric lymph nodes) has received little attention. In this study, the effect of oral norfloxacin on translocation, bacterial peritonitis, and survival was investigated in an animal model of carbon tetrachloride—induced cirrhosis and ascites. Treated rats received daily doses of orally administered norfloxacin from the onset of cirrhosis until they died or were killed. Controls received no antibiotic. Norfloxacin led to a reduction in bacterial peritonitis from 70% in untreated cirrhotic controls to 28% in treated cirrhotic rats; these data were statistically significant ( P = .012). There was no effect on overall translocation rate (28% with norfloxacin vs. 50% without norfloxacin) ( P > .1). Gram-positives were isolated in 100% of the bacterial peritonitis episodes and in 71.4% of culture-positive mesenteric lymph nodes in treated animals compared with only 25% of peritonitis episodes and 10% of culture-positive mesenteric lymph nodes of untreated cirrhotic controls ( P < .01 for peritonitis and P < .05 for translocation). The survival rate was not different between groups ( P > .1). Although norfloxacin was associated with a 60% reduction in the overall rate of peritonitis, this drug increased the risk of gram-positive translocation and gram-positive peritonitis, and did not prolong survival in this animal model.

Postoperative Selective Bowel Decontamination Prevents Gram-Negative Bacterial Translocation in Small-Bowel Graft Recipients

Gram-negative septic episodes are a potential risk of small-bowel transplantation; bacterial translocation through the graft is considered the mechanism. As a measure to prevent this complication, we evaluated postoperative selective bowel decontamination (SBD) in the rat model of orthotopic small-bowel transplantation [Lewis (LEW) and Brown-Norway (BN) rats as donors and recipients]. For 4 days after transplantation we gave FK 506, 2 mg/kg, which prevents rejection and results in indefinite recipient survival. For SBD, 24 mg/kg/day polymyxin E and 20 mg/kg/day tobramycin were administered via orogastric gavage to allograft recipients, both with and without FK 506 therapy. On Day 9, all rats were sacrificed, the peritoneal cavity was swabbed, and mesenteric lymph nodes (MLN), spleen, liver, and ileum were harvested for microbial qualitative and quantitative analysis. Animals with positive peritoneal swab cultures were excluded. SBD resulted in a significant reduction of the quantitative gram-negative bacterial flora in the ileum and cecum and of bacterial translocation to the MLN [0% versus 50% (no FK 506 therapy) and 8% versus 50% (FK 506 treated)]. In the allograft groups not treated with FK 506, SBD failed to significantly prolong survival, suggesting that acute rejection is not hastened by infection (bacterial translocation). We conclude that SBD in small-bowel-graft recipients prevents bacterial translocation by reducing intestinal gram-negative bacterial flora; this may reduce local and systemic infections by gut-derived organisms.

Bacterial and fungal colonization and infections using oral selective bowel decontamination in orthotopic liver transplantations.

Bacterial and fungal infections are a major cause of morbidity and mortality after orthotopic liver transplantation. In the immunocompromised host, infections are thought to arise from the gut, which is almost always colonized with potential pathogens. Using oral selective bowel decontamination (SBD), potential pathogens can be eradicated from the gut and infections prevented. In this catamnestic study we have reviewed gastrointestinal colonization, bacterial and fungal infections, and bacterial resistance to standard antibiotics in our first 206 liver transplant patients while under SBD. With few exceptions, gram-negatives were eradicated from the gastrointestinal tract and secondary colonization was inhibited. In spite of unsatisfactory elimination of Candida, probably because nystatin doses were too low, Candida infections were rare (n = 4) and none was fatal. One and two-year survival rates were 93% and 92%, respectively. The bacterial and fungal infection rate was 27.8% with an infection-related mortality of 1.95%. Infections with aerobic gram-positive bacteria prevailed and only 11 gram-negative and 11 fungal infections occurred; among the latter, Aspergillus and Mucor were the most serious and responsible for three of the six deaths in this series. With regard to the development of resistance, we found an increasing number of enterococci and coagulase-negative staphylococci resistant to ciprofloxacin and imipenem, respectively, but unlikely as a consequence of SBD.

Bacterial and fungal colonization and infections using oral selective bowel decontamination in orthotopic liver transplantations

Abstract Bacterial and fungal infections are a major cause of morbidity and mortality after orthotopic liver transplantation. In the immunocom-promised host, infections are thought to arise from the gul, which is almost always colonized with potential pathogens. Using oral selective bowel decontamination (SBD), potential pathogens can be eradicated from the gut and infections prevented. In this catamnestic study we have reviewed gastrointestinal colonization, bacterial and fungal infections, and bacterial resistance to standard antibiotics in our first 206 liver transplant patients while under SBD. With few exceptions, gram-negatives were eradicated from the gastrointestinal tract and secondary colonization was inhibited. In spite of unsatisfactory elimination of Candida, probably because nystatin doses were too low, Candida infections were rare (n= 4) and none was fatal. One and two-year survival rates were 93% and 92%, respectively. The bacterial and fungal infection rate was 27.8% with an infection-related mortality of 1.95%. Infections with acrobic gram-positive bacteria prevailed and only 11 gram-negative and 11 fungal infections occurred; among the latter, Aspergillus and Mucor were the most serious and responsible for three of the six deaths in this series. With regard to the development of resistance, we found an increasing number of enterococci and coagulase-negative staphylococci resistant to ciprofloxacin and imipenem, respectively, but unlikely as a consequence of SBD.

Clinical significance of extended-spectrum beta-lactamases.

Extended-spectrum beta-lactamases (ESBLs) have now been described in many hospitals worldwide. While they have been detected in many pathogenic gram-negative bacteria, they are particularly prevalent in Klebsiella isolates. Known risk factors for colonization and/or infection with organisms harboring these enzymes include admission to an intensive care unit, recent surgery, instrumentation, prolonged hospital stay and antibiotic exposure, especially exposure to extended-spectrum beta-lactam agents. In this report three recent epidemics from the USA will be described in which the role of selective antibiotic pressure seems clear. Data from two hospital epidemics, one from New York and another from Stanford, California, will be reviewed briefly. In addition, recent studies describing the spread of extended-spectrum beta-lactamases among nursing home patients in Chicago, Illinois, will be outlined. The limited data available on treatment options for patients infected with ESBL-containing strains will be reviewed, focusing on the activity of piperacillin/tazobactam and imipenem against these otherwise broadly resistant strains. Lastly, attempts to control these organisms, including infection control measures and selective bowel decontamination, will be reviewed.

Selective bowel decontamination, nutritional therapy and bacterial translocation after burn injury

We studied the influence of selective bowel decontamination (SBD) with neomycin, on bacterial translocation (BT) in rats treated with early post-burn parenteral nutrition (TPN) or enteral nutrition (TEN). Male Wistar rats were randomly assigned to receive either TPN (groups 1, 2) or an isonitrogenous, isocaloric polymeric diet (TEN, groups 3, 4) or a standard rat chow ad libitum (group 5), for 5 days after burn injury (30% b. s. area). In addition, groups 1 and 3 received a daily oral dose of neomycin (30 mg/kg) during the same period. At the end of the study, animals were killed and the mesenteric lymph nodes (MLN), liver (L) and spleen (S) were removed for microbiological cultures. The overall incidence of BT was MLN: 67%, L: 58% and S: 42% with a mortality rate of 12.2% In MLN and L, group 5 showed significantly less BT than groups 1 and 2 (30% vs 84%, p < 0.02) and groups 3 and 4 (38% vs 76%, p < 0.05), respectively. No differences were found between TPN and TEN groups. SBD (groups 1 and 3) resulted in a significantly lower mortality rate (26% vs 0%, p < 0.05) and BT in the liver (38% vs 100%, p < 0.001) than rats without antibiotic treatment (groups 2 and 4). It is concluded that early post-injury TPN or TEN promote BT to a greater extent than a standard chow. In addition, SBD with neomycin prevents mortality and BT after burn injury.

Selective bowel decontamination with quinolones and nystatin reduces gram-negative and fungal infections in orthotopic liver transplant recipients.

Gram-negative and fungal infections are the most important cause of morbidity and mortality after liver transplantation, especially in the first postoperative month. From February 1989 to February 1990, all liver transplant recipients at The Cleveland Clinic Foundation, Cleveland, Ohio, were placed on a selective bowel decontamination regimen employing oral quinolones and nystatin beginning at the time they were put on the active waiting list for transplantation and continuing until the fourth postoperative week. The incidence of gram-negative and fungal infections for these patients was compared against a historical control group. Selective bowel decontamination was well tolerated and highly effective in reducing early serious gram-negative and fungal infections. This regimen may also reduce mortality.

Antifungal prophylaxis in immunocompromised hosts.

To review the literature on the efficacy and safety of antifungal agents for prophylaxis of fungal infections in populations of immunocompromised hosts (key words: hematology-oncology, surgical, solid organ transplant, HIV infection), and to develop guidelines and recommendations regarding safe and effective drug regimens for antifungal prophylaxis in this patient population. Comprehensive review of clinical trials of antifungal prophylaxis published in the English literature, with an emphasis on controlled trials, and discussion of key clinical trials illustrating efficacy and safety of agents for antifungal prophylaxis in immunocompromised patients. Much of the clinical data evaluating the efficacy and safety of antifungal prophylaxis has been generated in cancer patients. The choice of antifungal agent for prophylaxis in this population remains controversial. However, azole compounds such as clotrimazole, ketoconazole and fluconazole appear to be more effective and better tolerated than nystatin suspension. Although ketoconazole has been shown to reduce fungal colonization in surgical patients, current data do not support the routine use of antifungal prophylaxis in this population. In renal transplant recipients, clotrimazole troches have been shown to be more effective than placebo or nystatin suspension. Selective bowel decontamination with nonabsorbable antibiotics and nystatin may be useful in reducing Candida colonization in liver transplant patients but no definitive recommendations may be made at this time regarding optimal antifungal prophylaxis in these patients. In patients with advanced HIV disease or history of prior fungal disease prophylaxis for oropharyngeal candidiasis is indicated, although the agent of choice remains controversial. Fluconazole is the drug of choice for prevention of relapse of cryptococcal meningitis in patients with AIDS. Finally, only limited data exist assessing the relationship between local colonization and systemic fungal infection. Adverse effects associated with antifungal prophylaxis, generally limited to nausea and vomiting and transient elevations in hepatic transaminases, occur with similar frequency among available oral or topical agents. However, the incidence of nausea and vomiting with resultant poor patient tolerance and compliance is usually higher with nystatin. Based on available data from controlled clinical trials, azole agents are currently the most effective and best-tolerated drugs for antifungal prophylaxis in immunocompromised hosts. Choice of one agent in this group over another may be dictated by cost. As new antifungal treatments are released onto the market, these drugs should be compared with existing agents in controlled clinical trials. Future studies should be designed to evaluate the relationship between local colonization and disseminated infection.

Risk factors for cytomegalovirus and severe bacterial infections following liver transplantation: a prospective multivariate time-dependent analysis

Risk factors for cytomegalovirus and severe bacterial infections were studied prospectively by univariate, multivariate and time-dependent Cox model analysis in 79 consecutive liver transplant patients treated with selective bowel decontamination. Cytomegalovirus infection occurred in 39 patients (49%) and was symptomatic in 22 patients. Twenty-six patients (33%) developed at least one of 43 documented severe bacterial infections. In a multivariate analysis of risk factors for all cytomegalovirus infections, the cytomegalovirus seronegative recipient-cytomegalovirus seropositive donor group was the highest risk group (P < 0.001). Using the same analysis for risk factors for symptomatic cytomegalovirus infections, a prolonged prothrombin time (P < 0.005), a diagnosis of acute fulminant hepatitis as the underlying liver disease (P < 0.01) and a cytomegalovirus seronegative patient receiving a liver from a seropositive donor (P < 0.001) were significant. The treatment with OKT3 therapy (P < 0.008) and hepatic artery thrombosis (P < 0.02) were found to be significant risk factors in a time-dependent univariate analysis but were not independent risk factors when multivariate analysis was utilized. Significant risk factors for major bacterial infections (P < 0.03) using univariate analysis included a prolonged anesthesia, anhepatic and surgical times, as well as the transfusion of large amounts of fresh frozen plasma or autologous blood. In a multivariate analysis, only the transfusion of large amounts of fresh frozen plasma (P < 0.04) was a significant independent risk factor. Cytomegalovirus infection was a risk factor for the development of severe bacterial infections (P < 0.03) in a multivariate time-dependent analysis.

Antibiotics may predispose to lactobacillemia in liver transplant patients

Lactobacilli are ubiquitous inhabitants of the human oral cavity, vagina, and gastrointestinal tract, that are generally considered non-pathogenic. We retrospectively reviewed all positive blood cultures for Lactobacillus species (sp.) from liver transplant recipients at our institution. Eight cases of lactobacillus bacteremia were identified. Selective bowel decontamination with non-absorbable oral antibiotics was administered to all patients. Additionally, all patients received intravenous vancomycin; most isolates exhibited either in vitro or in vivo vancomycin resistance. The biliary anastomosis in each patient was a Roux-Y choledochojejunostomy. The underlying clinical conditions included perihepatic abscesses in two patients, biliary strictures with either hepatic abscesses or infected bile in four, and heaptic infarctions with necrosis and infection of the liver in two. The use of selective bowel deontamination, intravenous vancomycin and Roux-Y choledochojejunostomy in liver transplantation patients may predispose to lactobacillemia.

Selective bowel decontamination does not alter hepatic regeneration in rats

The purpose of the present study was to determine whether changes to the gut flora that occur following norfloxacin-induced selective bowel decontamination alter hepatic regenerative activity. Adult rats (n = 6 per group) were treated with norfloxacin (10 mg/day) or vehicle for 10 days before 70% partial hepatectomy. Hepatic regenerative activity was determined 24 hours after surgery by documenting restitution of liver mass, [3H]thymidine incorporation into DNA, and ornithine decarboxylase activity in the liver. The results of the study revealed that hepatic regeneration was unaffected by norfloxacin therapy. Thus, selective bowel decontamination with norfloxacin does not alter hepatic regenerative activity following partial hepatectomy in the rat. (Gastroenterology 1992 Apr;102(4 Pt 1):1403-5)

Selective bowel decontamination does not alter hepatic regeneration in rats

The purpose of the present study was to determine whether changes to the gut flora that occur following norfloxacin-induced selective bowel decontamination alter hepatic regenerative activity. Adult rats (n = 6 per group) were treated with norfloxacin (10 mg/day) or vehicle for 10 days before 70% partial hepatectomy. Hepatic regenerative activity was determined 24 hours after surgery by documenting restitution of liver mass, [3H]thymidine incorporation into DNA, and ornithine decarboxylase activity in the liver. The results of the study revealed that hepatic regeneration was unaffected by norfloxacin therapy. Thus, selective bowel decontamination with norfloxacin does not alter hepatic regenerative activity following partial hepatectomy in the rat.

Selective bowel decontamination (SBD), nutritional therapy (NT) and bacterial translocation (BT) after burn injury

Selective bowel decontamination (SBD), nutritional therapy (NT) and bacterial translocation (BT) after burn injury

Infections following orthotopic liver transplantation.

The epidemiology of infections associated with orthotopic liver transplantation is summarized herein, and approaches to prophylaxis are outlined. Infection is a major complication following orthotopic liver transplantation, and more than half of transplant recipients develop at least one infection. The risk of infection is highest in the first month after transplantation, and the most common pathogens are bacteria and cytomegalovirus (CMV). Bacterial infections usually occur in the first month, arise in the abdomen, and are caused by aerobes. The peak incidence of CMV infection is late in the first month and early in the second month after transplantationn. CMV syndromes include fever and neutropenia, hepatitis, pneumonitis, gut ulceration, and disseminated infection. Other significant problems are Candida intraabdominal infection, Herpes simplex mucocutaneous infection or hepatitis, adenovirus hepatitis, and Pneumocystis carinii pneumonia. Prophylaxis of infection in liver transplant recipients has not been well-studied. Several different regimens of parenteral, oral absorbable, and/or oral non-absorbable antibiotics active against bacteria and yeast have been used at various centers, but no randomized controlled trials have been conducted. Selective bowel decontamination appears to be a promising approach to the prevention of bacterial and Candida infections, while oral acyclovir may be a relatively convenient and effective agent for CMV prophylaxis.