Bovine Lactoferrin as a Natural Regimen of Selective Decontamination of the Digestive Tract in Patients With Prolonged Mechanical Ventilation

Background Nosocomial infection Nosocomial infection, especially those caused by bacteria resistant to antibiotics, is a major threat to critical care medicine. A systemic review revealed that 10-20% of patients receiving mechanical ventilation (MV) more than 48 hours will develop ventilator associated pneumonia (VAP), patients who develop VAP are twice as likely to die compared with the similar patients without VAP, and patients who develop VAP have in additional hospital costs more than $ 10,019 [1].

The same problem occurs in Respiratory Care Centers (RCCs) which are designed to care the patients with prolonged mechanical ventilation (PMV), MV for more than 21 days, in Taiwan. One report from Taiwan showed that nosocomial infection rate in RCC is about 40% and the patients develop nosocomial infection have lower weaning rate and higher mortality compared with the patients without infection [2]. It has been estimated that 50% to 60% the nosocomial infection occurring each year in the United Sates are caused by antibiotic-resistant bacterial strains [3]. This high rate of resistant strains increases the morbidity, mortality and medical costs of infection. Preventing infection and limiting the emergence of antibiotic-resistant strains are two important issues in critical care medicine.

Selective Decontamination of Digestive Tract (SDD) One of the current hypotheses of nosocomial infection is that colonization of the nasopharynx and oropharynx predisposes patients to the development of nosocomial pneumonia, and the bacterial overgrowth in the intestinal tract increases gut wall permeability, leading to bacterial translocation and sepsis. Selective decontamination of the digestive tract (SDD), which aims to eradicate colonization of potential pathogens from the oropharynx and gastrointestinal tract, is one of the strategies to reduce ventilator associated pneumonia (VAP) and sepsis in critically ill patients. Controversy exists about the effectiveness of SDD in reducing mortality and preventing antibiotic resistance [4-6]. The present SDD regimens may create selective pressure and induce the emergence of methicillin-resistant Staphylococcus aureus (MRSA), Gram-negative bacilli harboring extended-spectrum β-lactamases (ESBL), and even Candida [7, 8]. Therefore, SDD research must aim to find an ideal regimen effective on most pathogens while leaving the anaerobic flora undisturbed.

Lactoferrin Lactoferrin (LF) is an iron-binding glycoprotein found in milk and various external secretions such as saliva, tears, airway secretion, and the granules of neutrophils, implying a important role in innate immunity. This protein has a number of biological functions, including antimicrobial, anti-tumor, antioxidant, and immunomodulatory effects. Partial degradation of LF by pepsin in stomach, may give rise to peptides termed lactoferricin with more potent antimicrobial activity. LF and lactoferricin have been shown to inhibit the growth of a number of pathogenic bacteria including antibiotic-resistant strains, fungi and even viruses in both in vitro and in vivo studies [9,10]. In mouse experiments, oral administration of bovine LF reduced bacterial infections in the gastrointestinal tract [9] while promoting the growth of bacteria with low iron requirements such as Lactobacillus and Bifidobacteria, which are generally believed to be beneficial to the host [11].

Bovine lactoferrin (bLF) and human lactoferrin (hLF) have high (77%) amino acid homology, with bLF exhibiting even higher in vitro antimicrobial activity than hLF.5 Bovine lactoferrin has been granted GRAS (generally recognized as safe) status by the US Food and Drug Administration [12] and on this basis is added to infant formula by many manufacturers with no reported adverse effects. Despite many promising in vitro and animal experimental data, clinical information on bLF is scarce, with no studies investigating the effects of bLF supplementation in patients with prolonged mechanical ventilation.