title: Prophylaxis with lactoferrin, a novel antimicrobial agent, in a neonatal rat model of coinfection.
abstract: Lactoferrin has broad-spectrum antimicrobial activity, and the authors hypothesized that recombinant human lactoferrin (Talactoferrin alfa [TLF]) would reduce mortality and morbidity in a coinfection model. The MIC 50 (minimum inhibitory concentration required to inhibit the growth of 50% of organisms) of TLF against Candida albicans and Staphylococcus epidermidis was determined. Neonatal Wistar rats were infected with C albicans or S epidermidis or both, at doses of 2 x10(8) colony-forming units (CFUs) given subcutaneously. Rat pups in each group were randomly given TLF intraperitoneally at 40 mg/kg/dose or 300 mg/kg/dose, or saline in 0.2 mL, once a day for 4 d and were monitored for mortality, weight gain, and blood culture positivity. Trough serum levels of TLF were measured at 24, 48, 72, 96, and 144 h. MIC 50 of TLF was 30 microg/mL and 500 microg/mL for C albicans and S epidermidis, respectively. TLF prophylaxis significantly improved survival in the coinfection group at 40 mg/kg/dose (by 16.1%; P=.019) and at 300 mg/kg/dose (by 15.1%; P=.027) and in the S epidermidis group at a dose of 40 mg/kg/dose (by 18.6%; P=.04). Weight gain was not affected by TLF prophylaxis. Serum trough levels of TLF were 1000-fold lower than in vitro MIC 50. The authors conclude that lactoferrin prophylaxis significantly enhanced survival in coinfection and in the subgroup of S epidermidis infection (40 mg/kg/dose) through indirect mechanisms.
authors.affiliation: Baylor College of Medicine and Texas Children's Hospital, Houston, TX 77030, USA. Mohanv@bcm.edu
authors.forename: Mohan Pammi
authors.initials: MP
authors.lastname: Venkatesh
authors.forename: Don
authors.initials: D
authors.lastname: Pham
authors.forename: Lingkun
authors.initials: L
authors.lastname: Kong
authors.forename: Leonard E
authors.initials: LE
authors.lastname: Weisman
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007781:Lactoferrin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008826:Microbial Sensitivity Tests; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013203:Staphylococcal Infections / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D013212:Staphylococcus epidermidis / Q000187:drug effects; D015430:Weight Gain
chemical_list: D000890:Anti-Infective Agents; D011994:Recombinant Proteins; C515276:talactoferrin alfa; D007781:Lactoferrin