Impact of Enterococcal Bacteremia in Liver Transplant Recipients.

BACKGROUND: Enterococcus species are a common cause of bacteremia in liver transplant recipients. Vancomycin-resistant enterococci (VRE) have become an important cause of nosocomial infection. In this study, we analyzed the incidence, antibiotic resistance, and outcomes of enterococcal bacteremia in living donor liver transplant recipients and the risk factors for VRE. PATIENTS AND METHODS: This single-center, retrospective review included 536 patients who underwent liver transplant between January 2008 and December 2017. RESULTS: Among 536 patients, 42 (7.8%) experienced a total of 58 enterococcal bacteremic episodes (37 Enterococcus faecium, 17 Enterococcus faecalis, 2 Enterococcus casseliflavus, 1 Enterococcus. avium, and 1 Enterococcus raffinosus). Most cases of enterococcal bacteremia (46/58, 79.3%) occurred within 6 months after transplant; among the 26 cases of VRE bacteremia, 50% occurred within 1 month after transplant. E. faecium isolates had the highest rate of vancomycin resistance (25/37, 67.5%), whereas all E. faecalis isolates were susceptible to vancomycin. According to multivariate analysis, post-transplant dialysis (odds ratio, 3.95; 95% CI, 1.51-10.34; P = .005) and length of post-transplant hospital stay (odds ratio, 1.03; 95% CI, 1.009-1.04; P = .004) were significantly associated with VRE bacteremia. One-year mortality was 31% (13/42) among recipients with enterococcal bacteremia, 5.0% (20/384) among nonbacteremic patients, and 11.1% (10/90) among patients with nonenterococcal bacteremia (P < .001). CONCLUSION: In this study, enterococcal bacteremia showed high incidence in liver transplant recipients, especially with vancomycin resistance, occurred in early period after transplant, and was associated with increased mortality. High rates of resistance to vancomycin warrant further efforts to manage enterococcal infection in liver transplant recipients at our center.

Treatment potential of pathogen-reactive antibodies sequentially purified from pooled human immunoglobulin.

OBJECTIVE: Intravenous immune globulin (IVIG), pooled from human blood, is a polyspecific antibody preparation that inhibits the super-antigenic proteins associated with streptococcal and staphylococcal toxic shock, and the Shiga toxin. In addition to this toxin-neutralising activity, IVIG contains other pathogen-reactive antibodies that may confer additional therapeutic benefits. We sought to determine if pathogen-reactive antibodies that promote opsonophagocytosis of different organisms can be sequentially affinity-purified from one IVIG preparation. RESULTS: Antibodies that recognise cell wall antigens of Streptococcus pyogenes, Staphylococcus aureus, and vancomycin-resistant enterococcus (VRE) were sequentially affinity-purified from a single preparation of commercial IVIG and opsonophagocytic activity was assessed using a flow cytometry assay of neutrophil uptake. Non-specific IgG-binding proteins were removed from the S. aureus preparations using an immobilised Fc fragment column, produced using IVIG cleaved with the Immunoglobulin G-degrading enzyme of S. pyogenes (IdeS). Affinity-purified anti-S. aureus and anti-VRE immunoglobulin promoted significantly higher levels of opsonophagocytic uptake by human neutrophils than IVIG when identical total antibody concentrations were compared, confirming activity previously shown for affinity-purified anti-S. pyogenes immunoglobulin. The opsonophagocytic activities of anti-S. pyogenes, anti-S. aureus, and anti-VRE antibodies that were sequentially purified from a single IVIG preparation were undiminished compared to antibodies purified from previously unused IVIG.

Lactobacillus-derived extracellular vesicles enhance host immune responses against vancomycin-resistant enterococci.

BACKGROUND: Probiotic bacteria are known to modulate host immune responses against various pathogens. Recently, extracellular vesicles (EVs) have emerged as potentially important mediators of host-pathogen interactions. In this study, we explored the role of L. plantarum derived EVs in modulating host responses to vancomycin-resistant Enterococcus faecium (VRE) using both Caenorhabditis elegans and human cells. RESULTS: Our previous work has shown that probiotic conditioning C. elegans with L. acidophilus NCFM prolongs the survival of nematodes exposed to VRE. Similarly, L. plantarum WCFS1 derived extracellular vesicles (LDEVs) also significantly protected the worms against VRE infection. To dissect the molecular mechanisms of this EV-induced protection, we found that treatment of C. elegans with LDEVs significantly increased the transcription of host defense genes, cpr-1 and clec-60. Both cpr-1 and clec-60 have been previously reported to have protective roles against bacterial infections. Incubating human colon-derived Caco-2 cells with fluorescent dye-labeled LDEVs confirmed that LDEVs could be transported into the mammalian cells. Furthermore, LDEV uptake was associated with significant upregulation of CTSB, a human homologous gene of cpr-1, and REG3G, a human gene that has similar functions to clec-60. CONCLUSIONS: We have found that EVs produced from L. plantarum WCFS1 up-regulate the expression of host defense genes and provide protective effects on hosts. Using probiotic-derived EVs instead of probiotic bacteria themselves, this study provides a new direction to treat antimicrobial resistant pathogens, such as VRE.

Methods to Prevent or Treat Refractory Diseases by Focusing on Intestinal Microbes Using LPS and Macrophages.

Intestinal microbes are known to influence host homeostasis by producing various substances. Recently, the presence of a diverse range of intestinal microbiota has been shown to play a key role in the maintenance of health, along with influencing the host's innate immunity towards various diseases. For example, fecal microbiota transplantation (FMT) from healthy individuals was remarkably effective in cases of refractory Clostridium difficile colitis. Conversely, decreased number of intestinal microbes resulting from the oral administration of antibiotics reportedly suppressed the antitumor effects of immunotherapy or anticancer drugs. Furthermore, it has been shown that a change in the intestinal environment triggered by oral administration of antibiotics resulted in increased number of drug-resistant microbes causing nosocomial infections. Intestinal microbes are also shown to be effective in cancer treatment as they activate macrophages at the site of cancer. One of the effects of intestinal microbes on hosts that has been gaining increasing attention is the biological regulation caused by the lipopolysaccharides (LPS) produced by Gram-negative bacteria. Among the intestinal microbiota present in the host, Gram-negative bacteria form the most dominant flora. The administration of antibiotics leads to a decreased number of intestinal microbes, as well as to suppression of cancer immunotherapy effects or anticancer drug effects, and this deterioration has been shown to be improved by oral administration of LPS. In this article, we discuss the functions of intestinal microbiota, that is currently undergoing a paradigm shift in relation to maintenance of health and the validity of LPS as a possible target for bio-treatment in the future.