Prophylaxis with lactoferrin,a novel antimicrobial agent,in a neonatal rat model of coinfection

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 MIC₅₀ (minimum inhibitory concentration required to inhibit the growth of 50% of organisms) of TLF againstCandida albicans andStaphylococcus epidermidis was determined. Neonatal Wistar rats were infected withCalbicans orS epidermidis or both, at doses of 2 × 10⁸ 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. MIC₅₀ of TLF was 30 μg/mL and 500 μg/mL forC albicans and Sepidermidis, 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 Sepidermidis group at a dose of 40 mg/kg/dose (by 1 8.6%; P=.04). Weight gain was not affected by TLF prophylaxis. Serum trough levels of TLF were 1000-fold lower than in vitro MIC₅₀. The authors conclude that lactoferrin prophylaxis significantly enhanced survival in coinfection and in the subgroupof S epidermidis infection (40 mg/kg/dose) through indirect mechanisms.