title: Complement component C9 enhances the capacity of beta-lactam antibiotics to kill Escherichia coli in vitro and in vivo.
abstract: Complement component C9 is required for rapid complement-mediated killing of Escherichia coli. In this report, the influence of supplemental C9 on the bactericidal and protective effects of beta-lactam antibiotics in neonates was assessed. By rocket immunoelectrophoresis, the intrinsic C9 concentrations of pooled serum from both human and rat neonates was less than 20% of adult levels. Supplemental C9 purified from human plasma enhanced the capacity of ampicillin-treated serum from human neonates to impair the survival of E coli O7:K1:NM (P < 0.02). Similarly, supplemental C9 enhanced the capacity of cefotaxime-treated neonatal rat serum to impair the survival of E coli O1:K1:NM (P < 0.05). Moreover, the intraperitoneal administration of C9 enhanced the survival of cefotaxime-treated neonatal rats that were septic with E coli (P < 0.05). These observations may contribute to the development of new strategies, such as augmentation of complement component serum concentrations, to reduce the morbidity and mortality of neonatal E coli sepsis.
authors.affiliation: Department of Pediatrics, University of Louisville School of Medicine, Kentucky 40202-3830, USA.
authors.forename: E
authors.initials: E
authors.lastname: Jung
authors.forename: R C
authors.initials: RC
authors.lastname: Feldhoff
authors.forename: B M
authors.initials: BM
authors.lastname: Walz
authors.forename: M M
authors.initials: MM
authors.lastname: Drehs
authors.forename: J Q
authors.initials: JQ
authors.lastname: Buchheit
authors.forename: H A
authors.initials: HA
authors.lastname: Lassiter
mesh_terms: D000328:Adult; D000667:Ampicillin / Q000008:administration & dosage; D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D016470:Bacteremia / Q000188:drug therapy / Q000628:therapy; D001770:Blood Bactericidal Activity; D002439:Cefotaxime / Q000008:administration & dosage; D003186:Complement C9 / Q000008:administration & dosage*; D004926:Escherichia coli / Q000187:drug effects*; D004927:Escherichia coli Infections / Q000628:therapy; D005260:Female; D005312:Fetal Blood / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000188:drug therapy / Q000628:therapy
chemical_list: D000900:Anti-Bacterial Agents; D003186:Complement C9; D000667:Ampicillin; D002439:Cefotaxime