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Standardized intraabdominal abscess formation with generalized sepsis: pathophysiology in the rat.

Gelatine capsules containing Escherichia coli and Bacteroides fragilis in a standardized mixture with rat colonic content and barium sulfate were implanted intraabdominally into rats. Capsules of 0.75 g gave approximately 50% mortality whereas 0.35 and 1.10 g caused no or 100% mortality, respectively. In subsequent experiments, using the 0.75 g capsule, all animals became ill with signs of tachypnea, piloerection, low physical activity and hypersecretion of saliva 6-8 h after the implantation. The animals reduced their water and food intake substantially and the body weight decreased. A significant reduction in blood pressure, glucose and leukocyte and platelet counts was found 12 h after challenge. Blood cultures obtained at 12, 24, 48 and 60 h all grew E. coli but none B. fragilis. Succumbed animals revealed diffuse peritonitis with growth of E. coli and B. fragilis at autopsy, whereas surviving animals showed abscess formation at investigation on day 8 after challenge. It was concluded that the model closely resembled intraabdominal abscess formation with sepsis in man.

Abdomen↗

Subperiosteal and Bezold's abscesses complicating cholesteatoma: a case report.

A case of subperiosteal and Bezold's abscesses that occurred in a 60-year-old man with cholesteatoma has been described and the literature reviewed. Bezold's abscess is rarely seen in the current era of antibiotics. The simultaneous occurrence of a subperiosteal abscess in association with cholesteatoma, particularly in an adult, makes this case even more unusual. Although antibiotics have reduced the complications associated with acute otitis media, rare complications still occur and should be recognized by the otolaryngologist.

Abscess↗

[Complications of non-clostridial anaerobic peritonitis].

Under observation there were 71 patients with non-clostridial anaerobic peritonitis, 37 of them having complications--suppurations of operation wounds, phlegmons of the abdominal wall, abscesses of the abdominal cavity, postoperative non-clostridial peritonitis. Fourteen patients died (37.8%).

Abdominal Muscles↗

Immune-enhancing diet and cytokine expression during chronic sepsis: an immune-enhancing diet containing L-arginine, fish oil, and RNA fragments promotes intestinal cytokine expression during chronic sepsis in rats.

Chronic feeding with enteral immune-enhancing diets (IEDs) provides benefits based on composition of the diet, route of feeding, and timing of feeding in relation to timing of trauma or surgery. Our prior studies of acute feeding in naïve rats demonstrated that IED promotes blood flow and proinflammatory cytokines in the ileum. We hypothesized that chronic feeding with IED would shift gut immune status to an anti-inflammatory state during chronic sepsis, resulting in an altered state of cytokine expression in the gut. Five days prior to feeding, gauze was implanted subcutaneously in the backs of male Sprague-Dawley rats, which were fed for 3 days with either control diet (CD, Boost; Mead-Johnson, Evansville, IL) or IED (Impact; Novartis) and randomly assigned to one of four groups: saline control (NS) + control diet (CD), sepsis (EC) + CD, NS + IED, or EC + IED. EC rats were inoculated with 10(9) CFU Escherichia coli and 10(9) CFU Bacteroides fragilis in 2 ml normal saline into the back sponge while NS rats received 2 mL normal saline alone. After 3 days, animals were anesthetized and gut tissue samples were harvested and frozen at -80 degrees C. Tissue protein was extracted and ELISA was performed for interleukin (IL-1beta, IL-5, IL-6, IL-10, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma. In saline controls, IED feeding decreased IL-1beta, IL-5, IL-6, TNF-alpha, and IFN-gamma and increased IL-10 compared with CD-fed animals. In septic animals, IED feeding increased IL-5 and IL-6, while decreasing IFN-gamma and IL-10 in the distal third of the small intestine compared with CD-fed septic rats, whereas IL-1beta and TNF-alpha levels were unchanged. Chronic IED feeding produced a anti-inflammatory state via decreased IFN-gamma and increased IL-5 and IL-6, which both promote gut IgA class switching, suggesting that the gut is shifted toward humoral immunity during chronic IED feeding in septic rats.

Animals↗

Experimental anaerobic liver abscess: observations on treatment.

Various treatment modalities for solitary anaerobic liver abscesses were evaluated in a recently-described rabbit model. In the first phase of the experiment, 35 rabbits with liver abscesses induced with Bacteroides fragilis and Fusobacterium necrophorum were randomized into four groups: surgical drainage alone, drainage plus clindamycin 150 mg IM 8-hourly, clindamycin alone, and untreated controls. Serum clindamycin concentrations in rabbits were similar to those achieved in humans. The survival of rabbits receiving antibiotic chemotherapy alone was significantly better than controls, whereas the survival of those having surgical drainage with or without chemotherapy was not. However, successful surgical drainage was followed by weight gain in surviving rabbits. In the second phase of the experiment 18 rabbits with abscesses were randomized into the same groups. Aspirates of pus from all rabbits receiving clindamycin were sterile by day 7 of treatment, but high bacterial counts were still present in the abscess cavities of control rabbits and of those undergoing drainage alone. These findings illustrate the application of a new model for pyogenic liver abscess in laboratory investigation. Their relevance to management of human pyogenic liver abscesses remains to be assessed.

Animals↗

[Extensive Fournier's gangrene: a case report].

We report a case of extensive Fournier's gangrene that could not be rescued despite emergent debridement. A 51-year-old man presented at another hospital with cough, diarrhea and abdominal pain. He was diagnosed with acute enteritis and hospitalized. The next morning, he became severely hypotensive and his scrotum was swollen and black. The perineal skin also was black. Septic shock and disseminated intravascular coagulation were suspected. He was transferred to our emergency room, and was immediately diagnosed with Fournier's gangrene and acute peritonitis. Computed tomographic scan revealed soft-tissue gas in the scrotum, the retroperitoneal cavity and the abdominal wall. Emergent debridement and laparotomy was performed. Gangrene was also seen at the intestinal wall and the peritoneum, however, resection of intestine was not done because of his poor performance status. Although potent antibiotics and catecholamine were administered, he died of multiple organ failure 29 hours after the operation. This is the first case of Fournier's gangrene extending into the abdominal cavity reported in the Japanese literature.

Acute Disease↗

Aztreonam vs. gentamicin in experimental peritonitis and intra-abdominal abscess formation.

The activity of gentamicin is known to be decreased in acidic environments, and both the peritoneum during peritonitis and the interior of abscesses have been shown to be acidic and hypoxic. The activity of beta-lactam antibiotics is felt to be relatively less diminished under the same circumstances. We determined that the minimum inhibitory concentration of gentamicin against one pathogenic strain of Escherichia coli increased eight-fold, to 8 mugm/mL, when testing conditions were changed from normoxic and neutral to hypoxic and acidic, whereas the MIC of aztreonam doubled under the same conditions, to 0.25 mugm/mL. In further experiments in a murine model of mixed Escherichia coli/Bacteroides fragilis intra-abdominal abscesses, we demonstrated that a combination of aztreonam and clindamycin was superior to a combination of gentamicin and clindamycin in terms of completely preventing abscess formation (33% vs. 0%) and eliminating Escherichia coli from abscesses that did form (100% vs. 61%).

Abdominal Abscess↗

Reduction of bacterial indicators and bacteriophages infecting faecal bacteria in primary and secondary wastewater treatments.

AIMS: To compare the suitability of various bacterial and viral indicators to assess the removal of faecal micro-organisms by primary and secondary wastewater treatment processes. METHODS AND RESULTS: The numbers of several bacterial indicators [faecal coliforms (FC), enterococci (ENT) and sulphite-reducing clostridia (SRC)] and bacteriophages (somatic coliphages, F-specific RNA phages and bacteriophages infecting Bacteroides fragilis strain RYC2056) were determined in incoming raw sewage and effluents from various primary and secondary wastewater treatment processes in several geographical areas. Reductions in the numbers of indicators were calculated as log10 reductions. Processes based on removal and mild disinfection, showed no significant differences in the elimination of any of the indicators tested or between geographical areas. In contrast, treatment processes that include strong microbial inactivation, such as lime-aided flocculation and lagooning, showed significant differences between the log10 reductions of the various micro-organisms studied, FC showing the highest reduction and spores of SRC and phages infecting B. fragilis the lowest. CONCLUSIONS: The microbial elimination performance of treatment processes based principally on removal and mild disinfection can be evaluated with a single indicator. In contrast, processes with additional disinfecting capabilities require more than one indicator for accurate evaluation of the treatment; bacteriophages are good candidates for use as second indicators. SIGNIFICANCE AND IMPACT OF THE STUDY: Bacteriophages provide additional information for the evaluation of microbial elimination in some treatment plants. The easy, fast and cheap methods available for phage determination are feasible both in industrialized and developing countries.

Bacteria↗

The in-vitro activity of linezolid (U-100766) and tentative breakpoints.

The in-vitro activity of linezolid, a novel oxazolidinone, was investigated in comparison with those of amoxycillin, cefuroxime, quinupristin/dalfopristin, trovafloxacin and vancomycin against 420 recent Gram-positive and anaerobic clinical isolates. Linezolid was equally active (MIC90 1 mg/L) against methicillin-susceptible and -resistant Staphylococcus aureus. It demonstrated uniform activity against streptococci and enterococci and no cross-resistance with other agents. The time-kill kinetic data demonstrated that the in-vitro activity of linezolid was predominantly bacteriostatic; slow bactericidal activity was only observed at the higher concentration with streptococci. An increase in inoculum from 10(4) to 10(6) cfu on selected strains had little effect on the MICs (MIC90 within one dilution step) of linezolid and an increase in inoculum from 10(5) to 10(7) cfu/mL had no notable effect on the in-vitro bactericidal activity. A tentative linezolid breakpoint of 2 mg/L was chosen after analysis of distribution of susceptibilities.

Acetamides↗

Chronic hyperdynamic sepsis in the rat: I. Characterization of the animal model.

We describe a new rat model of chronic hyperdynamic sepsis. After control values for weight gain, and food and water intake of each animal were obtained over a 5-day period, male Sprague-Dawley rats weighing 370-425 g were anesthetized, catheterized to allow chronic cardiac-output measurements, and a sterile subcutaneous cavity was formed over the flank area. The animals were allowed a 3-4 day postoperative recovery period. Body weight, food and water intake, and cardiac output were measured daily. Frequent blood samples were withdrawn for bacterial cultures and white cell counts (WBC). On the third and, in some cases, the fourth postoperative day, the subcutaneous cavity was inoculated with 10(9) colony-forming units of Escherichia coli and Bacteroides fragilis. The resulting sepsis was characterized by loss of body weight in spite of normal food and water intake, increased cardiac output, increased WBC, intermittent bacteremia, decreased muscle mass, and decreased cross-sectional area of skeletal muscle myofibrils. Two levels of septic response emerged--moderate and severe. Based on the above-mentioned measurements, it was possible to categorize all long-term septic animals into these two groups. Both groups exhibited cardiac-output, body-weight, and WBC data significantly different from sham controls. Repeated inoculations of the subcutaneous abscess initiated on the third postoperative day resulted in moderate sepsis with no long-term mortality, severe sepsis with 23% mortality over a 3-week period, or a 100% mortality within 4 days, depending on the virulence of the E. coli organisms used. The new model is ideally suited for pathophysiologic studies of sustained, hyperdynamic sepsis.

Animals↗

Effects of live Escherichia coli and Bacteroides fragilis on metabolism and hepatic pO2.

Rats were infused intraaterially with 10(9) live E coli, or 10(10) live B fragilis, or 0.9% NaCl solution. Within 6 hr or sooner E coli-treated rats extensive hepatic hypoxia (mean hepatic pO2 less than 5 mm Hg), hypoglycemia, lactacidemia, and microscopic evidence of sinusoidal damage and hepatocyte hypoxia. Mortality was 100% within 24 hr. Rats which received B fragilis showed significantly less hepatic hypoxia (mean hepatic pO2 13.8 mm Hg) and lactacidemia and were euglycemic at 6 hr. Hepatic tissue showed congested sinusoids and depletion of glycogen. Mortality was 0% in 24 hr. NaCl-treated rats were stable over 6 hr of observation; mean hepatic pO2 was 20.6 mm Hg. We suggest that the events associated with acute lethal E coli bacteremia are related in part to strutural interference of the hepatic microcirculation. Although the effects of B fragilis bacteremia were appreciably less pronounced, the ability to establish hypoxic foci may have important implications.

Animals↗

[Synergistic effect of thiamphenicol and cephalothin on Bacterioides fragilis (author's transl)].

Synergistic effect of thiamphenicol (TP) and cephalothin (CET) on Bacteroides fragilis was proved in vitro. Especially its effect was much clear on B. fragilis which is possible to produce beta-lactamase. Synergistic bactericidal effect of TP and CET was proved. Chemotherapeutic effect of TP and CET against experimental mixed infectious mouse due to E. coli (beta-lactamase -) and B. fragilis (beta-lactamase +) was proved.

Animals↗

Experimental sinusitis in rabbits induced by aerobic and anaerobic bacteria: models for research in sinusitis.

Experimental acute sinusitis can be induced in New Zealand white rabbits by Streptococcus pneumoniae serotype 3, or the anaerobe Bacteroides fragilis, after blocking of the sinus ostium. Histological examination of the sinus mucosa in both models reveals edema, dilated venules, leukocytic infiltration, goblet cell formation, as well as localized epithelial lesions. In comparison the bacteroides sinusitis enhances a more pronounced and long-lasting tissue reaction, including periosteal thickening and new bone formation. The sinus mucosal blood flow as measured with microspheres Sn113 is increased as compared to control side in pneumococcal sinusitis. An increased lactate concentration of sinus secretions as well as in the pathological sinus mucosa indicates an anaerobic metabolism. Furthermore, a decreased ATP-content of the sinus mucosa suggests an energy depletion which could impair epithelial function. The anaerobic milieu of the sinus secretion is probably created by the leukocytes as analyzed by the separation of the D- and L-form of lactate.

Animals↗

Transforming growth factor-beta negatively modulates T-cell responses in sepsis.

Sepsis is associated with depressed T-cell functions and increased circulating levels of immunosuppressive agents. TGF-beta is a potential anti-inflammatory cytokine that can modify T-cell growth and differentiation. The up-regulation of TGF-beta and the mechanism of its action on the T-cells during septic injury have not been resolved. We hypothesized that in sepsis TGF-beta produced by macrophages acts on T-cells in a paracrine manner to suppress interleukin (IL)-2 production and proliferation. In this study, we examined the circulating TGF-beta levels in a rat model of Gram-negative bacterial sepsis, and compared the abilities of adherent and non-adherent splenocytes to produce TGF-beta. Additionally, we investigated the causal relationships of hrTGF-beta to concanavalin A (ConA)-induced T-cell responses and the intracellular mechanism of the generation of these responses in normal splenic rat T-cells. Sepsis was induced in rats by intraabdominally implanting fecal pellets containing Escherichia coli (150 CFU) and Bacteroides fragilis (10000 CFU). Adherent and non-adherent splenocytes were isolated by differential adherence using Ficoll gradient centrifugation. T-cells were purified by use of Nylon wool columns. We observed a 3-6-fold increase in the circulating levels of TGF-beta in sepsis. Western blots and ELISA determinations revealed a 2.5-3-fold increase in cell-associated TGF-beta protein levels in adherent splenic cells. Northern analyses also showed a marked increase in TGF-beta mRNA expression in adherent cells during sepsis. On the other hand, a significant change was not observed in the TGF-beta protein and mRNA expression in non-adherent splenocytes. Pretreatment of control rat T-cells with hrTGF-beta decreased both ConA-induced proliferation (by 35-40%) and IL-2 mRNA expression (by > 50%). Further, whereas incubation of control rat T-cells with either ConA or TGF-beta for 24 h resulted in a 10-15-fold increase in cAMP generation, the addition of hrTGF-beta along with ConA resulted in a 50-60-fold increase in cAMP. These results suggest that in sepsis, TGF-beta produced by splenic macrophages can act in a paracrine manner on T-cells to depress their IL-2 mRNA expression, IL-2 production and proliferation after up-regulation of cAMP which can interfere with T-cell signaling for proliferation.

Animals↗