Endotoxin but not malnutrition promotes bacterial translocation of the gut flora in burned mice

Previously we have shown that under certain conditions, bacteria can pass through the intact epithelial mucosa to the mesenteric lymph nodes (MLN), liver, spleen, and bloodstream to cause infection, a process termed bacterial translocation. To extend these studies, we determined the influence of protein malnutrition and endotoxemia on bacterial translocation in burned (25% TBSA) and unburned mice. The results of these experiments documented that protein malnutrition did not promote bacterial translocation from the gut in either burned or unburned animals, although it did disrupt the normal indigenous gut flora. In contrast, a nonlethal dose of endotoxin (IP) promoted bacterial translocation to the mesenteric lymph nodes in burned and unburned mice, but only in burned mice did the bacteria translocate from the gut to other systemic organs (p less than 0.01). Furthermore, the mortality rate of mice receiving only endotoxin or burn was less than 10%, while the combination of endotoxin plus a thermal injury increased the mortality rate to 100% (p less than 0.01). These studies support the concept that bacteria may translocate from the gut to other organs and be a potential source of lethal infections after thermal injury.     

Effect of stress and trauma on bacterial translocation from the gut

Previously, we established that bacteria contained within the gut can cross the GI mucosal barrier and spread systemically, a process termed bacterial translocation. Three models were used to extend this work: cold exposure (up to 16 hr at 4 degrees C), a nontissue injury stress model; femoral fracture-amputation, a trauma model; and thermal injury (30% third-degree burn), a trauma model with retained necrotic tissue. CD-1 mice either with a normal GI microflora or who were monoassociated with Escherichia coli C-25 were subjected to sham or actual stress or trauma. The animals were sacrificed at various times postinsult and the ceca, mesenteric lymph nodes (MLN), spleens, and livers were quantitatively cultured. Neither the incidence nor the magnitude of bacterial translocation was increased in the cold-exposed animals compared to control mice. The incidence of bacterial translocation to the systemic organs was higher in the animals with a normal flora receiving femoral fracture amputation (11%) (P less than 0.02) than in animals receiving a thermal injury (1%) or sham-injured control mice (0%). In contrast, the incidence of translocation to the liver or spleen was higher in burned mice monoassociated with E. coli C-25 (60%) (P less than 0.01) than in E. coli monoassociated mice sustaining femoral fracture amputation (17%). Stress alone (cold exposure) does not promote bacterial translocation; however, trauma, especially in combination with retained necrotic tissue, promotes bacterial translocation. Thus bacteria colonizing the gut can invade systemic organs after trauma, especially when the normal ecology of the gut flora has been disrupted.     

Thermal injury promotes bacterial translocation from the gastrointestinal tract in mice with impaired T-cell-mediated immunity

We have shown previously that after thermal trauma viable bacteria will cross the intact gastrointestinal mucosa (bacterial translocation) to invade the mesenteric lymph nodes and other organs if the normal indigenous microflora is disrupted, allowing bacterial overgrowth. To determine whether T-cell-mediated immunity (T-CMI) was important in preventing translocation after thermal injury in animals with an intact normal flora, conventional (+/+), athymic (nu/nu), and heterozygous (nu/+) mice receiving a 30% third-degree burn were killed at various intervals after burn and their organs cultured. Bacterial translocation did not occur in control or burned specific pathogen-free mice with intact T-CMI but did occur in athymic mice with deficient T-CMI. Both the incidence of positive organs and the numbers of translocated bacteria per gram of organ were increased after thermal injury. Bacterial overgrowth was not responsible for these findings, since the levels of cecal enteric bacteria were not different between the burned and nonburned groups. Since translocation occurred to a greater extent in athymic burned mice than control athymic mice, it appears that a thermal injury promotes translocation by impairing other host defense systems in addition to the T-CMI.     

一氧化氮与创伤,全肠外营养,免疫及肠道细菌易位关系研究

目的：手术应激能抑制机体免疫功能，手术后辅助ＴＰＮ能否减轻免疫抑制仍有争论，手术应激，ＴＰＮ与肠道细菌易位关系至今仍未完全阐明，且已有最新研究表明一氧化氮（ＮＯ）与免疫、肠道细菌易位关系密切，方法：２４例胃癌病人均行胃癌根治手术（Ｄ２）随机分为且和ＴＰＮ组。测定术前及术后第１、３、５、７天静因细菌种类，ＣＤ３、ＣＤ４、ＣＤ８及ＣＤ４／ＣＤ８比值，ＮＫ细胞，同时测定ＮＯ和ＮＯＳ一，并作统计学处理和分     

Effect of oral antibiotics and bacterial overgrowth on the translocation of the GI tract microflora in burned rats

Infections in burned patients have generally been considered to arise from exogenous organisms. Consequently, the therapy of burned patients has emphasized the use of infection control policies and topical antimicrobial agents to reduce bacterial colonization. Even though enteric bacteria are frequently found in the burn wound little attention has been paid to the patient's own GI tract microflora as a potential source of organisms colonizing the burn wound. The current experiments were carried out to determine if the bacteria present in the GI tract of healthy animals would penetrate (translocate) through the GI mucosa and spread to visceral organs after a moderate or major thermal injury. The results of these experiments indicated that bacteria can translocate across the wall of the GI tract and survive in the mesenteric lymph nodes in healthy rats. Furthermore, when the GI tract microflora is altered, either due to bacterial overgrowth or under the influence of oral antibiotic therapy, not only will bacteria translocate to the mesenteric lymph nodes but bacteria will also spread to other visceral organs. The results of these experiments support the hypothesis that the GI tract can serve as a reservoir for nosocomial infections in the burned patient, since bacteria can translocate across the mucosal barrier of the GI tract after thermal injury and survive in visceral organs before colonization of the burn wound occurs.     

The effect of surgical trauma on the bacterial translocation from the gut.

Bacterial translocation is the passage of viable bacteria from the lumen of the gastrointestinal tract through the intestinal mucosa to other sites. It is believed that bacterial translocation may lead to infection and septicemia. The purpose of this study was to determine what factors in experimental surgical trauma lead to bacterial translocation. Two-month-old Wistar albino rats were divided into five groups: (A) control; (B) anesthesia (ether inhalation); (C) anesthesia and surgery (median laparotomy and transient compression of the intestines); (D) fasting only; and (E) anesthesia, surgery, and fasting. After 48 hours, ileum, mesenteric lymph nodes, and blood were cultured for aerobic and anaerobic organisms. In each group the number of animals with bacteria overgrowth was calculated. The incidence of bacterial translocation to mesenteric lymph nodes and blood in groups B and D were similar to the controls (P greater than .01). There was a significant increase in the number of animals with bacterial translocation in groups C and E (P less than .001). The majority of translocating bacteria were E coli.     

Role of bacterial adherence and the mucus barrier on bacterial translocation: effects of protein malnutrition and endotoxin in rats.

OBJECTIVE: The purpose of the study was to investigate the potential relations between mucosal bacterial adherence, intestinal mucus and mucin content, and bacterial translocation. SUMMARY BACKGROUND DATA: The attachment of bacteria to mucosal surfaces is the initial event in the pathogenesis of most bacterial infections that originate at mucosal surfaces, such as the gut. The intestinal mucus layer appears to function as a defensive barrier limiting micro-organisms present in the intestinal lumen from colonizing enterocytes. Consequently, studies focusing on the biology of bacterial adherence to the intestinal mucosa likely are to be important in clarifying the pathogenesis of gut origin sepsis. METHODS: To explore the relations between intestinal bacterial adherence, mucus bacterial binding, and bacterial translocation, two models were used. One (protein malnutrition) in which profound alterations in intestinal morphology occurs in the absence of significant translocation and one (endotoxin challenge) in which bacterial translocation occurs and intestinal morphology is relatively normal. RESULTS: Protein malnutrition was not associated with bacterial translocation and measurement of enteroadherent, mucosally associated bacterial population levels documented that the total number of gram-negative enteric bacilli adherent to the ileum and cecum was less in the protein-malnourished rats than in the normally nourished animals (p < 0.01). Furthermore, there was an inverse relation between the duration of protein malnutrition and bacterial adherence to the intestinal mucosa (r = 0.62, p < 0.002). In contrast, after endotoxin challenge, the level of enteroadherent bacteria was increased and bacterial translocation was observed. The binding of Escherichia coli to immobilized ileal mucus in vitro was decreased significantly in protein-malnourished rats, whereas E. coli binding to insoluble ileal mucus was increased in the rats receiving endotoxin. CONCLUSIONS: This study indicates that the adherence of bacteria to the intestinal mucosal surface is an important factor in bacterial translocation, that intestinal mucus modulates bacterial adherence, and that increased levels of mucosally associated bacteria are associated with a loss intestinal barrier function to bacteria.     

Effect of oral ciprofloxacin on bacterial flora of perineum, urethra, and lower urinary tract in men with spinal cord injury

A study was performed in 25 men with spinal cord injuries undergoing intermittent catheterization whose urine had > or = 10(5) bacterial colonies/ml to determine efficacy of ciprofloxacin in eradicating susceptible organisms from urine, urethra, and perineum. Cultures were obtained prior to, during, and 5 to 7 days after administration of 500 mg twice daily for 10 days. Organisms in urine were also present in the urethra and/or perineum in 20 cases. Susceptible bacteria disappeared from urine in all subjects; but at follow-up 12 had cultures positive for ciprofloxacin-resistant Gram-positive cocci, including 1 with methicillin-resistant Staphylococcus aureus (MRSA), and 2 with ciprofloxacin-resistant Acinetobacter sp. Treatment significantly reduced Gram-negative bacilli in perinea and urethras, but ciprofloxacin-susceptible organisms were replaced by resistant staphylococci, including MRSA, enterococci, and Acinetobacter sp. We support use of ciprofloxacin for treatment of urinary tract infections in persons with spinal cord injury, but in view of supercolonization with resistant organisms, the drug should be reserved for symptomatic persons not likely to respond to other oral agents.     

肠内营养在胃肠外伤手术后的应用

营养支持是减少术后并发症及降低死亡率的基础,肠内营养(enteral nutrition,EN)与肠外营养(parenteral nuti4tion,PN)相比更符合人体生理需求,并且发症更少,价格更合理[1].人们将营养支持的重点从肠外转向肠内,在危重患者中,EN支持尤其受到重视.早期EN在创伤后的应用非常重要,有诸多益处,例如减少感染、并发症的发生,缩短ICU入住时间及机械通气时间等.     

创伤及休克肠道细菌移位的研究

研究创伤失血性休克肠道细菌移位的发生率。设计兔创伤失血性休克试验模型，实验组３０只兔，腹部皮肤撕脱１００ｍｍ×９０ｍｍ，并行股动脉放血致休克，对照组１０只兔，腹部撕脱同实验组，不放血致休克。对照组术后１小时、３小时、５小时取标本均未发现肠道细菌移位，实验组术后１小时采标本已有肠道细菌移位，３小时、５小时组细菌移位达３０％。认为创伤失血性休克早期即有肠道细菌移位，并讨论了其临床意义     

Effect of chlorhexidine 0.5% on the hand bacterial flora

The effects of cleaning the dorsal hand with chlorhexidine 0.5% in spirit was evaluated by bacteriological study in 45 adult patients. In the absence of cleaning it was found that the prevalent microorganisms were Staphylococcus epidermidis, Staphylococcus aureus, Streptococcus viridans and Enterobacteriaceae. Cleaning the hand with chlorhexidine 0.5% eliminated all bacteria except S. epidermidis and S. aureus. In both instances, the culture results showed that the microorganisms were present in very low growth density.     

消化道重建术后肠道细菌移位的临床研究

目的：探讨消化道重建术后肠黏膜屏障损伤与肠道细菌移位（BT）及BT与术后全身炎症反应综合征（SIRS）的关系。方法：选择60例择期行消化道重建术的患者,于术前和术后1、3、5 d采集外周血,进行血浆二胺氧化酶及全血细菌DNA检测。全血DNA提取后进行PCR扩增,采用的靶基因为大肠杆菌特异性β半乳糖苷酶基因和16SrRNA基因。观察患者至术后10 d以监测SIRS情况。结果：术前PCR检测全血细菌DNA均为阴性,术后共有14例阳性。23例患者术后发生SIRS,其中12例患者PCR阳性。PCR阳性组SIRS发生率为85.7%（12/14）,阴性组为23.9%（11/46）（P〈0.01）。术后出现SIRS的患者PCR阳性率为52.2%（12/23）,无SIRS组为5.4%（2/37）（P〈0.01）。PCR阳性的患者血浆二胺氧化酶浓度较PCR阴性者明显升高（P〈0.01）,有SIRS的患者血浆二胺氧化酶较无SIRS患者明显升高（P〈0.01）。结论：消化道重建术后BT与肠黏膜屏障损伤密切相关,术后SIRS与BT密切相关。PCR技术可早期诊断细菌移位,对术后SIRS有较好的早期预警价值。     

Long-term antibiotic treatment of chronic bacterial prostatitis. Effect on bacterial flora

The bacterial flora in patients referred with chronic bacterial prostatitis were studied. Only 13% had Gram-negative bacteria in significant numbers but 43% had Gram-positives using the same criteria. Half of the patients were symptom-free by the end of a 12-week course of antibiotics and remained so after 6 months; in one-third the symptoms were unchanged 6 months after completing treatment. The relief of symptoms correlated with the disappearance of white blood cells in the expressed prostatic secretion (EPS) and with a lowered pH in the EPS. Thus only 1 of the 14 patients without symptoms at 6 months had a significant growth of bacteria at the prostatic level, whereas 7 of 10 patients with unchanged symptoms had a significant bacterial colonisation. Although the initially infecting organism was eliminated in about half of the patients, new Gram-positive bacteria were isolated after treatment in 13 of 29 patients; 12 of these resolved spontaneously within 6 months. Five patients with Gram-positive bacteria were colonised with new Gram-negatives at the end of treatment. Two healed spontaneously but 3 remained colonised with Gram-negatives at the end of the follow-up period. These findings make it likely that many patients infected with Gram-positive bacteria benefit from antibiotic treatment. However, disturbances in the bacterial flora by antibiotic treatment may facilitate invasion by new types of bacteria.     

Intra-abdominal gastrointestinal tract injuries following blunt trauma: the experience of an Australian trauma centre

AIMS: The aim of the study was to use the extensive experience of an Australian Level I trauma centre to develop guidelines for diagnosis and management of significant gastrointestinal tract injuries (GITIs). METHODS: This was a retrospective study of 74 patients admitted to Westmead Hospital between 1985 and 1996 who had sustained major gastrointestinal tract (GIT) injuries following blunt trauma. The patients were identified from the trauma unit database. Clinical information was retrieved from the database and augmented by a review of the medical records. RESULTS: Motor vehicle accidents were responsible for 55 (92%) admissions. Laparotomy was performed as a result of a positive diagnostic peritoneal lavage in 26 (35.1%) patients, abdominal signs in 20 (27%), diagnostic findings on computed tomography in 19 (25.7%), haemodynamic instability in eight (10.8%) and a positive contrast study in one (1.4%) patient. There was a total of 95 injuries: one gastric (1.1%), eight duodenal (8.4%), 64 small bowel (67.3%), two appendiceal (2.1%), 19 colonic (20%) and one rectal (1.1%). Thirty day mortality was 23% (17 patients). Seven (9.5%) patients died within 24h of injury, three (4.1%) of which were directly related to the GIT. Ten (13.5%) patients died within 2 weeks of admission, three (4.1%) of which were attributable to the GIT. Thirty day GIT morbidity was 29.7% (22 patients). The development of GIT morbidity was significantly related to a delay to laparotomy of more than 24h (P=0.036) and tachycardia on presentation (P=0.023). Associated injuries, injury severity scores (ISS) and age did not significantly impact on GITI related morbidity and mortality. DISCUSSION: Major GITIs are associated with a high mortality due to the severity and complexity of associated injuries. Morbidity from GITIs correlates to delays in diagnosis and management.     

Effect of amoxicillin or clindamycin on the adenoids bacterial flora.

OBJECTIVE: We sought to compare the effect on the adenoid bacterial flora of patients with recurrent otitis media of antimicrobial therapy with amoxicillin (Am) or clindamycin (C).Patients and methods Forty-five children scheduled for elective adenoidectomy participated in a prospective randomized study. They were divided into 3 groups of 15 each to receive either no therapy (control) or 10 days of therapy with Am or C. Core adenoid tissues was quantitatively cultured for aerobic and anaerobic bacteria. RESULTS: Polymicrobial aerobic-anaerobic flora were present in all instances. The predominant aerobes in all groups were alpha-hemolytic and gamma-hemolytic streptococci, Haemophilus influenzae, Staphylococcus aureus, group A beta-hemolytic streptococci, and Moraxella catarrhalis. The prominent anaerobes were Peptostreptococcus, Prevotella, and Fusobacterium spp. The number of isolates was significantly reduced in those treated with Am (n = 110, P < 0.05) or C (n = 58, P < 0.001) compared with control (n = 148). The number of bacteria per gram/tissue was lower in those treated with either antibiotics. The number of potential pathogens was lower in those treated with C compared with the other 2 groups (P < 0.001). The number of beta-lactamase-producing bacteria was lower in those treated with C than in those treated with Am (P < 0.025) or control (P < 0.001). CONCLUSIONS: These data illustrate the ability of C and, to a lesser degree, of Am to reduce the bacterial load as well as potential pathogens and beta-lactamase-producing bacteria from the adenoids of children with recurrent otitis media.