Biochemically assisted antibiotic treatment of lethal murine Staphylococcus aureus septic shock

Abstract

Evidence has been sought for life-prolonging effects of a variety of chemicals given subcutaneously 1 hr after intraperitoneal challenge of mice with 10(9) Staphylococcus aureus cells. The chemicals were chosen to replace chemicals found to be missing in the blood or carcass at death or to treat biochemical or visible abnormalities in sick mice near death from infection. Nafcillin given subcutaneously in adequate amounts cure S. aureus infection. In these experiments nafcillin treatment was delayed until 40% of the time from challenge to death in the controls. Chemicals were given in addition to nafcillin subcutaneously 20% of the time from challenge to death. Cortisol, Dilantic, epsilon-aminocaproic acid, glucose, nicotinamide, olive oil, phentolamine-propanalol, sodium bicarbonate, sodium lactate, and reserpine each prolonged life compared to saline treatment. When nafcillin was added, only cortisol, Dilantin, nicotinamide and reserpine were found to prolong life significantly compared to nafcillin-saline treatment Fatality rates were significantly reduced with cortisol and Dilantin when they were given in association with nafcillin compared to nafcillin-saline treatment.

C/EBPε mediates nicotinamide-enhanced clearance of Staphylococcus aureus in mice

“…For example, NAM is prescribed topically for treatment of a number of inflammatory skin conditions, including acne vulgaris and atopic dermatitis (32). In experimental murine models of Gram-positive and Gram-negative sepsis, NAM has been shown to improve survival (33,34). The mechanism contributing to immune modulation is not well-defined, but NAM has also been shown to suppress secretion of a number of cytokines and chemokines, including IL-1β, TNF-α, IL-6, and iNOS (35,36).…”

Increased Mortality in Mice following Immunoprophylaxis Therapy with High Dosage of Nicotinamide in Burkholderia Persistent Infections

“…In previous studies, NA was shown to significantly relieve disease symptoms in mouse models of Parkinson’s and Huntington’s diseases (32, 33). NA has been used as an immunomodulation agent to suppress secretion of proinflammatory cytokines and chemokines (34–36) and to improve host survival during murine models of sepsis (35, 37). Furthermore, NA has been tested as an antimicrobial therapeutic agent in murine models of infection caused by opportunistic pathogens, including Staphylococcus aureus and Citrobacter rodentium, and was found to stimulate host neutrophil cells to release microbicidal peptides by direct activation of the myeloid-specific transcription factor CCAAT/enhancer-binding protein ε (C/EBPε) (13, 14).…”

Mechanistic Insights into the Multiple Functions of Niacinamide: Therapeutic Implications and Cosmeceutical Applications in Functional Skincare Products

“…Niacinamide was shown to possess antibacterial, antifungal, and antiviral activity, with the literature focusing mainly on its antibacterial activity. The latter was demonstrated in murine Gram-positive and Gram-negative sepsis models, as well as against Escherichia coli and Staphylococcus aureus [67,68]. Niacinamide's antimicrobial activity was also shown to effectively prevent biofilm formation in several clinical studies [69][70][71].…”

“…Importantly, AMPs are part of the skin's innate immune system, having broad antibacterial activity against Gram-positive and negative bacteria and also showing antifungal and antiviral activity [67,76,77]. In fact, an increase in AMPs upon niacinamide application has been shown to protect gut epithelial cells from infection [78].…”