Increased Antibiotic Susceptibility of Gram-Positive Bacteria in Cerebrospinal Fluid Compared to Broth.

In hospital- and community-acquired central nervous system infections, resistant Gram-positive bacteria are an increasing therapeutic challenge. The present approach does not attempt to identify rapidly bactericidal therapies for susceptible pathogens but aims to improve methods to find antibiotic regimens for multi-resistant pathogens that are effective in vivo in spite of reduced in vitro susceptibility in culture media. Antibiotic susceptibility was tested in cerebrospinal fluid (CSF) and Mueller-Hinton broth (, methicillin-resistant , ) or brain-heart infusion ().

Optimization of antiviral dosing in Herpesviridae encephalitis: a promising approach to improve outcome?

Background: Despite established antiviral therapy for herpes simplex virus, varicella zoster and cytomegalovirus encephalitis, the outcome remains poor.

Objectives: To assess pharmacokinetic (PK) and pharmacodynamic (PD) data of antiviral drugs in the central nervous system (CNS) to optimize the treatment of Herpesviridae encephalitis.

Sources: PUBMED search 1950 to September 2024, terms (1) "encephalitis" and ("HSV" or "VZV" or "CMV") or (2) cerebrospinal and ("(val)acyclovir" or "(val)ganciclovir" or "foscarnet" or "cidofovir").

Decreased Phagocytosis and Intracellular Killing of Bacteria in Leukocytes of Geriatric Patients with Clostridioides difficile Infections.

Introduction: Patients suffering from a Clostridioides difficile infection have a higher overall mortality than patients with similar comorbidities.

Methods: Whole blood samples of 15 patients with C. difficile enteritis and 15 control patients matched for age and sex were used to analyze the capacity of blood phagocytes to internalize and kill encapsulated Escherichia (E.

Gum Arabic Increases Phagocytosis of by Blood Leukocytes of Young and Old Healthy Volunteers.

Background: Gum arabic, a polysaccharide exudate from (L.) Willdenow trees, has already been used by African native people in natural medicine.

Methods: Using whole-blood samples from young (20-35 years) and older (>80 years) healthy volunteers (each group n = 10), the effect of an aqueous solution of GA on phagocytosis of was examined with a gentamicin protection assay.

Hydrogen peroxide is responsible for the cytotoxic effects of Streptococcus pneumoniae on primary microglia in the absence of pneumolysin.

Introduction: Streptococcus pneumoniae is the most common cause of bacterial meningitis and meningoencephalitis in humans. The bacterium produces numerous virulence determinants, among them hydrogen peroxide (H2O2) and pneumolysin (Ply), which contribute to bacterial cytotoxicity. Microglia, the resident phagocytes in the brain, are distinct from other macrophages, and we thus compared their susceptibility to pneumococcal toxicity and their ability to phagocytose pneumococci with those of bone marrow-derived macrophages (BMDM).

New Antibiotics for the Treatment of Nosocomial Central Nervous System Infections.

Nosocomial central nervous system (CNS) infections with carbapenem- and colistin-resistant Gram-negative and vancomycin-resistant Gram-positive bacteria are an increasing therapeutic challenge. Here, we review pharmacokinetic and pharmacodynamic data and clinical experiences with new antibiotics administered intravenously for the treatment of CNS infections by multi-resistant bacteria. Cefiderocol, a new siderophore extended-spectrum cephalosporin, pharmacokinetically behaves similar to established cephalosporins and at high doses will probably be a valuable addition in our therapeutic armamentarium for CNS infections.

Serological testing for syphilis in the differential diagnosis of cognitive decline and polyneuropathy in geriatric patients.

Background: In the 19th century, neurosyphilis was the most frequent cause of dementia in Western Europe. Now dementia caused by syphilis has become rare in Germany. We studied whether routine testing of patients with cognitive abnormalities or neuropathy for antibodies against Treponema pallidum has therapeutic consequences in geriatric patients.

Intracerebral Infection with Impairs Spatial Learning and Induces Necrosis of Hippocampal Neurons in the Tg2576 Mouse Model of Alzheimer's Disease.

Background: In patients with Alzheimer's disease (AD), bacterial infections are often associated with a cognitive decline. Animal models of genuine acute infections with viable bacteria which induce deterioration of neurodegenerative diseases are missing.

Objective: We assessed the effect of an intracerebral infection with in a mouse model of AD.

Novel protocol for the isolation of highly purified neonatal murine microglia and astrocytes.

Background: The crosstalk and reactivity of the cell type glia, especially microglia and astrocytes, have progressively gathered research attention in understanding proper brain function regulated by the innate immune response. Therefore, methods to isolate highly viable and pure glia for the analysis on a cell-specific level are indispensable.

New Method: We modified previously established techniques: Animal numbers were reduced by multiple microglial harvests from the same mixed glial culture, thereby maximizing microglial yields following the principles of the 3Rs (replacement, reduction, and refinement).

Neural Injury and Repair in a Novel Neonatal Mouse Model of Listeria Monocytogenes Meningoencephalitis.

To improve the therapy of neonatal central nervous system infections, well-characterized animal models are urgently needed. The present study analyzes neuropathological alterations with particular focus on neural injury and repair in brains of neonatal mice with Listeria monocytogenes (LM) meningitis/meningoencephalitis using a novel nasal infection model. The hippocampal formation and frontal cortex of 14 neonatal mice with LM meningitis/meningoencephalitis and 14 uninfected controls were analyzed by histology, immunohistochemistry, and in situ tailing for morphological alterations.

Reduced Clostridioides difficile infections in hospitalised older people through multiple quality improvement strategies.

Objectives: To reduce infections with Clostridioides difficile (CDI) in geriatric patients by interventions easily implementable in standard clinical care.

Methods: Prevalence and incidence of CDI between January 2015 and February 2020 were analysed (n = 25,311 patients). Pre-intervention status was assessed from April 2016 to March 2017 (n = 4,922).

HIF-1α is involved in blood-brain barrier dysfunction and paracellular migration of bacteria in pneumococcal meningitis.

Bacterial meningitis is a deadly disease most commonly caused by Streptococcus pneumoniae, leading to severe neurological sequelae including cerebral edema, seizures, stroke, and mortality when untreated. Meningitis is initiated by the transfer of S. pneumoniae from blood to the brain across the blood-cerebrospinal fluid barrier or the blood-brain barrier (BBB).

Searching for Antipneumococcal Targets: Choline-Binding Modules as Phagocytosis Enhancers.

Choline-binding proteins (CBPs) from comprise a family of modular polypeptides involved in essential events of this pathogen. They recognize the choline residues present in the teichoic and lipoteichoic acids of the cell wall using the so-called choline-binding modules (CBMs). The importance of CBPs in pneumococcal physiology points to them as novel targets to combat antimicrobial resistances shown by this organism.

Antimicrobial and Immunomodulatory Effect of Gum Arabic on Human and Bovine Granulocytes Against and .

Gum arabic (GA) is a traditional herbal medicine from (L.) Willdenow trees, which consist of a complex mixture of polysaccharides and glycoproteins. It is used in daily applications for several diseases and is considered to protect against bacterial infections.

Comparing Cathelicidin Susceptibility of the Meningitis Pathogens and in Culture Medium in Contrast to Porcine or Human Cerebrospinal Fluid.

Host defense peptides or antimicrobial peptides (AMPs), e.g., cathelicidins, have recently been discussed as a potential new treatment option against bacterial infections.

Prophylactic Palmitoylethanolamide Prolongs Survival and Decreases Detrimental Inflammation in Aged Mice With Bacterial Meningitis.

Easy-to-achieve interventions to promote healthy longevity are desired to diminish the incidence and severity of infections, as well as associated disability upon recovery. The dietary supplement palmitoylethanolamide (PEA) exerts anti-inflammatory and neuroprotective properties. Here, we investigated the effect of prophylactic PEA on the early immune response, clinical course, and survival of old mice after intracerebral K1 infection.

Cisterno-lumbar gradient of complement fractions in geriatric patients with suspected normal pressure hydrocephalus.

Background: The complement system is a functional link between the innate and adaptive immune system and present in all compartments of the body. The composition of the cerebrospinal fluid (CSF) differs between the ventricular, cisternal and lumbar space. Usually, concentrations of blood-derived CSF proteins increase from ventricular to lumbar fractions.

IgM cleavage by Streptococcus suis reduces IgM bound to the bacterial surface and is a novel complement evasion mechanism.

Streptococcus suis (S. suis) causes meningitis, arthritis and endocarditis in piglets. The aim of this study was to characterize the IgM degrading enzyme of S.

The inflammatory response and neuronal injury in Streptococcus suis meningitis.

Background: Many of the currently used models of bacterial meningitis have limitations due to direct inoculation of pathogens into the cerebrospinal fluid or brain and a relatively insensitive assessment of long-term sequelae. The present study evaluates the utility of a Streptococcus (S.) suis intranasal infection model for the investigation of experimental therapies in meningitis.

Activin A increases phagocytosis of Escherichia coli K1 by primary murine microglial cells activated by toll-like receptor agonists.

Background: Bacterial meningitis is associated with high mortality and long-term neurological sequelae. Increasing the phagocytic activity of microglia could improve the resistance of the CNS against infections. We studied the influence of activin A, a member of the TGF-β family with known immunoregulatory and neuroprotective effects, on the functions of microglial cells in vitro.

Pharmacokinetics and pharmacodynamics of antibiotics in central nervous system infections.

Purpose Of Review: The barriers surrounding the central nervous system (CNS) together with the emergence of multiresistant pathogens pose a therapeutic challenge for the effective treatment of CNS infections.

Recent Findings: In addition to vancomycin, colistin and aminoglycosides, classically used for intrathecal injection, drug concentrations in cerebrospinal fluid after intrathecal injection of daptomycin and tigecyclin were recently studied.

Summary: The entry of antiinfectives into the CNS compartments is determined by the physicochemical properties of the drug and by conditions in the host.

Magnesium therapy improves outcome in Streptococcus pneumoniae meningitis by altering pneumolysin pore formation.

Background And Purpose: Streptococcus pneumoniae is the most common cause of bacterial meningitis in adults and is characterized by high lethality and substantial cognitive disabilities in survivors. Here, we have studied the capacity of an established therapeutic agent, magnesium, to improve survival in pneumococcal meningitis by modulating the neurological effects of the major pneumococcal pathogenic factor, pneumolysin.

Experimental Approach: We used mixed primary glial and acute brain slice cultures, pneumolysin injection in infant rats, a mouse meningitis model and complementary approaches such as Western blot, a black lipid bilayer conductance assay and live imaging of primary glial cells.

Identification of a novel host-specific IgG protease in Streptococcus phocae subsp. phocae.

Streptococcus (S.) phocae subsp. phocae causes bronchopneumonia and septicemia in a variety of marine mammals.

Astrocytes Enhance Streptococcus suis-Glial Cell Interaction in Primary Astrocyte-Microglial Cell Co-Cultures.

Streptococcus (S.) suis infections are the most common cause of meningitis in pigs. Moreover, S.