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

Advances in Therapy volume 24, pages 941–954 (2007)Cite this article

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 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.

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Affiliations

  1. Baylor College of Medicine, Texas Children’s Hospital, MC: WT 6-1 04 6621 Fannin Street, 77030, Houston, Texas

    Mohan Pammi Venkatesh, Don Pham & Lingkun Kong

  2. Pediatrics and Neonatology Director of Perinatal Health Center, Texas Children’s Hospital Houston, Texas

    Leonard E. Weisman

Authors
  1. Mohan Pammi Venkatesh
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  2. Don Pham
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  3. Lingkun Kong
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  4. Leonard E. Weisman
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Correspondence to Mohan Pammi Venkatesh.

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Venkatesh, M.P., Pham, D., Kong, L. et al. Prophylaxis with lactoferrin, a novel antimicrobial agent, in a neonatal rat model of coinfection. Adv Therapy 24, 941–954 (2007). https://doi.org/10.1007/BF02877698

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Keywords

  • lactoferrin
  • coinfection
  • Staphylococcus
  • Candida
  • neonate