COMPLEMENT COMPONENT C9 (C9) POTENTIATES THE PROTECTIVE EFFECT OF CEFOTAXIME IN NEONATAL RATS SEPTIC WITH E. COLI. |[bull]| 1759

C9 is required for rapid complement-mediated killing of E. coli by serum. Previous studies revealed that a diminished C9 concentration restricts the bactericidal capacity of serum from neonatal humans and neonatal rats. Also, significant morbidity and mortality from E. coli sepsis persist in neonates despite the use of bactericidal antibiotics, such as cefotaxime (CEF). Therefore, in vitro and in vivo experiments were designed to determine whether supplemental C9 potentiates the bactericidal and protective effects of CEF in neonatal rats. Undegraded and hemolytically active human C9 was purified from Cohn fraction III paste. First, the survival of E. coli (5 × 104 cfu/ml) was quantitated in vitro during 60 min of incubation with 20% serum pooled from neonatal rats (NeoRS). The bacteria proliferated in NeoRS(bacterial survival [x±SEM] = 199±15% of the original inoculum). Similarly, the bacteria proliferated in NeoRS supplemented with 2.5 ng/ml CEF(bacterial survival = 170±26%) or with 20 μg/ml C9 (147±11%). In contrast, only 54±27% of the bacteria survived in serum supplemented with both CEF and C9 (P .11 vs recipients of only PBS). In contrast, 36/45 recipients of both CEF and C9 survived (P<.05 vs only PBS, vs CEF alone, and vs C9 alone). In conclusion, supplemental C9 potentiated the bactericidal activity of CEF against E. coli in NeoRS and potentiated the protective effect of CEF in septic neonatal rats. These observations may contribute to the development of new strategies to reduce the morbidity and mortality associated with E. coli sepsis in human neonates. Funded by the Alliant Community Trust Fund.