Human recombinant lactoferrin acts synergistically with antimicrobials commonly used in neonatal practice against coagulase-negative staphylococci and Candida albicans causing neonatal sepsis.
Neonatal sepsis causes significant mortality and morbidity. Coagulase-negative staphylococci (CoNS) and Candida frequently cause neonatal sepsis at >72 h of age. Lactoferrin, which is present in human milk, is a component of innate immunity and has broad-spectrum antimicrobial activity. The synergistic effects of lactoferrin with antibiotics against neonatal isolates have not been systematically evaluated. Here, eight clinical strains (seven neonatal) of CoNS and three strains (two neonatal) of Candida albicans were studied. MIC50 and MIC90 values of human recombinant lactoferrin (talactoferrin; TLF), vancomycin (VAN) and nafcillin (NAF) against CoNS, and of TLF, amphotericin B (AMB) and fluconazole (FLC) against C. albicans, were evaluated according to established guidelines. Antimicrobial combinations of TLF with NAF or VAN against CoNS, and TLF with AMB or FLC against C. albicans, were evaluated by a checkerboard method with serial twofold dilutions. Synergy was evaluated by the median effects principle, and combination indices and dose reduction indices were reported at 50, 75 and 90% inhibitory effect at several drug-dose ratios. It was found that TLF acted synergistically with NAF and VAN against CoNS, and with AMB and FLC against C. albicans, at multiple dose effects and drug-dose ratios with few exceptions. In synergistic combinations, drug reduction indices indicated a significant reduction in doses of antibiotics, which may be clinically relevant. Thus TLF acts synergistically with anti-staphylococcal and anti-Candida agents commonly used in neonatal practice and is a promising agent that needs to be evaluated in clinical studies.
Venkatesh
Mohan Pammi
MP
Baylor College of Medicine & Texas Children's Hospital, 6621 Fannin, MC: WT 6-104, Houston, TX 77030, USA.
Rong
Liang
L
Baylor College of Medicine, 1102 Bates Avenue, MC: BCM 320, Houston, TX 77030, USA.
D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy*; D003030:Coagulase / Q000378:metabolism; D004357:Drug Synergism; D006801:Humans; D007231:Infant, Newborn; D007781:Lactoferrin / Q000008:administration & dosage* / Q000627:therapeutic use; D008826:Microbial Sensitivity Tests; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013210:Staphylococcus / Q000201:enzymology / Q000235:genetics
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D003030:Coagulase; D011994:Recombinant Proteins; D007781:Lactoferrin