Conclusion
Addition of PTX to antibiotics in murine neonatal E. coli sepsis promoted an anti-inflammatory milieu through inhibition of plasma TNF and enhancement of IL-10 production in plasma and organs without increasing bacterial growth, supporting its utility as a potential adjunctive agent for newborn sepsis.
Methods
Newborn C57BL/6J mice (< 24 h old) were injected intravenously with 105 colony forming units (CFUs)/g weight of a bioluminescent derivative of the encapsulated clinical isolate Escherichia coli O18:K1. Adequacy of intravenous injections was validated using in vivo bioluminescence imaging and Evans blue. Pups were treated with gentamicin (GENT), PTX, (GENT + PTX) or saline at 0, 1.5, or 4 h after sepsis initiation, and euthanized after an additional 4 h. CFUs and cytokines were measured from blood and homogenized organ tissues.
Results
GENT alone inhibited bacterial growth, IL-1β, and IL-6 production in blood and organs. Addition of PTX to GENT profoundly inhibited E. coli-induced TNF and enhanced IL-10 in blood of newborn mice at all timepoints, whereas it primarily upregulated IL-10 production in peripheral organs (lung, spleen, brain). PTX, whether alone or adjunctive to GENT, did not increase microbial colony counts in blood and organs.