This study demonstrated no statistically significant difference between the treatment groups for pancreatic or peripancreatic infection, mortality, or requirement for surgical intervention, and did not support early prophylactic antimicrobial use in patients with severe acute necrotizing pancreatitis.
Bacterial infections are frequent, life-threatening complications in cirrhotic patients. This study investigated in vivo neutrophil migration and phagocytic activity in cirrhotic patients with advanced liver disease, in liver transplant recipients, and in healthy volunteers, by use of the skin window technique. Complement receptor type III (CR3) expression was also measured in blood and elicited neutrophils. Neutrophil migration to skin windows and neutrophil in vivo phagocytosis of heat-killed Escherichia coli were significantly decreased in cirrhotic patients compared with healthy controls. Neutrophil migration and phagocytosis were decreased in cirrhotic patients with previous episodes of bacterial infection compared with noninfected patients. Expression of CR3 in circulating neutrophils was significantly higher in cirrhotic patients, whereas it was significantly reduced in elicited neutrophils of cirrhotic patients with previous bacterial infection. These data suggest that deficient neutrophil recruitment to the infection site and impaired phagocytic activity may contribute to bacterial infections in cirrhotic patients with advanced liver disease.
In this study, the efficacy of ertapenem 1 g once a day was equivalent to piperacillin/tazobactam 3.375 g every 6 hours in the treatment of a range of intraabdominal infections. Ertapenem was generally well tolerated and had a similar safety and tolerability profile to piperacillin/tazobactam. A formal process for review of adequacy of source control was found to be of benefit. The results of this trial suggest that ertapenem may be a useful option that could eliminate the need for combination and/or multidosed antibiotic regimens for the empiric treatment of intraabdominal infections.
The IL-6 immunostrip test identified two distinct sepsis populations with significantly different mortality rates. A small (3.7%) absolute reduction in mortality rate was found in the afelimomab-treated patients. The treatment difference did not reach statistical significance.
The peritoneal cavity contains resident and migratory cell populations, which play crucial roles in the local defensive response against bacterial invasion. Although mononuclear phagocytes predominate in the peritoneal cavity of healthy subjects, recent attention has been focused on mesothelial and dendritic cells. Kinetic analysis of inflammatory mediators has derived from experimental models of peritonitis, but advances in the understanding of the roles of molecules such as lipocortins, PAF, leukotriene B4, PPAR gamma agonists, and chemokines has also been made. Little is known about the peritoneal response to physical trauma in the context of the abdominal compartment syndrome. Studies on the cellular and molecular pathology of intra-abdominal abscesses, peritoneal sclerosis, and other less frequent clinical entities (e.g., tertiary peritonitis) are needed. Biological therapy may contribute to improved clinical management of such diseases.
Bacterial infections are frequent complications in patients with liver cirrhosis. Cirrhotic patients present abnormalities in both innate and adaptive immune responses, including a deficient neutrophil recruitment to infected sites. The purpose of this study was to assess neutrophil-endothelium interactions in cirrhotic patients and evaluate the effects of G-CSF on this process. We studied neutrophil adhesion and transendothelial migration in 14 cirrhotic patients and 14 healthy controls. We also analyzed neutrophil expression of the adhesion molecules CD62L and CD11b in whole blood by flow cytometry. Cirrhotic patients expressed higher levels of CD11b than healthy controls, whereas CD62L expression was significantly lower, suggesting exposure of neutrophils to activating agents within the bloodstream. Neutrophils from cirrhotic patients showed increased adhesion to both resting and tumor necrosis factor alpha-stimulated microvascular endothelial cells and decreased transendothelial migration. Granulocyte colony-stimulating factor (G-CSF) (100 ng/ml) significantly enhanced neutrophil adhesion to microvascular endothelial cells in healthy controls but not in cirrhotic patients. G-CSF also significantly improved neutrophil transmigration in cirrhotic patients and healthy controls. In conclusion, cirrhotic patients exhibit increased neutrophil adhesion to microvascular endothelium and deficient transendothelial migration. G-CSF enhances neutrophil transendothelial migration in cirrhotic patients despite having no effect on neutrophil adhesion. Therefore, G-CSF may be able to increase neutrophil recruitment into infected sites in these patients
Antibiotic therapy for complicated intra-abdominal infections (cIAIs) should provide broad-spectrum coverage both Gram-positive and Gram-negative microorganisms. The PROMISE study compared the clinical and bacteriological efficacy and safety of moxifloxacin versus ertapenem for the treatment of cIAIs. This randomised, prospective, double-dummy, double-blind, multicentre trial was designed as a non-inferiority study. The safety and efficacy of 5-14 days of daily intravenous moxifloxacin (400mg) or ertapenem (1g) were compared in patients with cIAIs requiring surgery and parenteral antibiotic therapy. The primary and secondary endpoints included clinical and bacteriological responses at 21-28 days after the end of treatment (TOC), respectively. Of 830 enrolled patients, 699 were efficacy valid. Moxifloxacin was non-inferior to ertapenem regarding clinical success [89.5% (315/352) versus 93.4% (324/347); 95% confidence interval (CI) -7.9%, 0.4%]. There were no significant differences between groups for any of the primary causes or types of cIAI regarding clinical response. Bacteriological success was achieved in 86.5% (257/297) of moxifloxacin-treated patients and 90.2% (249/276) of ertapenem-treated patients (95% CI -9.0%, 1.5%). There were no major differences between groups regarding the frequency or types of organisms eradicated. The incidence of adverse events (AEs) was higher with moxifloxacin than ertapenem (P=0.039), however a similar number of drug-related AEs was seen in each group (P=1.000). Wound infections, nausea and increased lipase were the most commonly reported AEs with both agents. The results show that moxifloxacin is a valuable treatment option for a range of community-acquired cIAIs with mild-to-moderate severity.
The role of the Nae/Ke ratio (the ratio of exchangeable sodium to exchangeable potassium) was examined as a nutritional marker in surgical patients in relation to anthropometrical and biochemical indexes by its ability to identify patients at risk for mortality after hospitalization. In 73 patients with sepsis and malnutrition (Training Group, Madrid) the following were determined: percentage of recent weight loss, triceps skin fold, midarm muscle circumference, serum albumin, serum transferrin, delayed hypersensitivity skin test response, total lymphocytes, and Nae/Ke ratio by multiple isotope dilution. The predictive power of Nae/Ke ratio was so strong (F = 105.1; p less than 0.00001) that it displaced anthropometric, biochemical, and immunologic variables from the linear equation derived from stepwise discriminant analysis using hospital mortality as the dependent variable. A theoretical curve of expected deaths was developed, based on an equation obtained by logistic regression analysis: Pr/death/ = 1/(1 + e[11.8-5.2 Nae/Ke]). Pre- and post-test probabilities on that curve allowed us to determine two cut-off values, Nae/Ke ratios of 1.5 and 2.5, which were markers for nonrisk and mortality, respectively. The model was tested in a heterogeneous data base of surgical patients (n = 417) in another hospital (Validation Group, Montreal). For patients exhibiting an abnormal Nae/Ke ratio (greater than 1.2) and a greater than 10% of probability of death, 54 deaths were expected and 53 observed (X2 = 1.8 NS). Two tests confirmed the basic agreement between the model and its performance, a G statistic of -0.704 and the area beneath the "receiver-operating-characteristic" (ROC) curve (Az = 0.904 + 0.0516 for the Madrid group vs. Az = 0.915 + 0.0349 for the Montreal group, NS). It was concluded from this analysis that, compared with the usual anthropometric measurements, the Nae/Ke ratio, if available, is the best method for identifying malnourished patients at risk of dying.
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