| ObjectiveWith the development of medical science and the increasing application of invasive diagnostic and treating approaches, nosocomial infection has been a significant factor about medical safety and patient's prognosis. The incidence of nosocomial infection related with catheter introduction is increasing because of the prevalence of its application, which leads to the growing mortality, the prolonged length of stay and the additional treatment expenses. Central venous catheter (CVC) is one of the most popular catheters in clinical medicine, which is invasive. In USA, the incidence of infection related with CVC introduction is 5%-26%, which spend about additional treatment expenses of tens of billions of US dollars. In China, the incidence of CVC-related bloodstream infection is about 4.5%. In order to decrease this kind of nosocomial infection, it is necessary to develop new style of antibacterial catheter.The research aimed at the antibacterial effect in vitro and the safety of silver-containing zirconium phosphate antibacterial agents of nanometer level. The agent with good antibacterial effect and relative lower silver-containing would be selected to add into the material of CVC considering its higher safety and lower effect on mechanical performance of catheter. The antibacterial effects of the CVC with silver-containing zirconium phosphate antibacterial agents of nanometer level (hereafter referred to as "CVC with nanometer silver") were evaluated both in vitro and in vivo.Methods1. Minimum inhibitory concentrations (MICs) measurement of silver-containing antibacterial agents of nanometer level1) MICs of 0%,3.0%,6.0%, and 9.0% silver-containing antibacterial agents of nanometer level were evaluated against the standard strains Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli.2) The MICs of 6.0%silver-containing one against clinical isolates Pseudomonas onion, Pseudomonas aeruginosa, Escherichia coli, Stenotrophomonas maltophilia, and Staphylococcus epidermidis were measured in vitro.2. Safety evaluation of silver-containing antibacterial agent of nanometer levelThe safety of 6.0%silver-containing antibacterial agent of nanometer level was evaluated by acute oral toxicity test in mice, dermal irritation test in rabbits, and release of silver ion test.3. Surface antimicrobial activity assessment of CVC with nanometer silver1) The 6.0% silver-containing antibacterial agent of nanometer level was added to the material of CVC with the contents of 1.0%,2.0%, and 3.0%, respectively. The surface antimicrobial activity against Pseudomonas aeruginosa (standard strain) of the materials with different contents of antibacterial agent was assessed.2) The surface antimicrobial activity of 3.0% antibacterial agent against the standard strains Staphylococcus aureus and Escherichia coli was assessed.4. Antibacterial effect assessment of CVC with nanometer silver in vivo1) Thirty-six male New Zealand white rabbits (2.2-3 kg) were randomly divided into2 groups:CVC with nanometer silver group and Arrow antimicrobial CVC group. Each group was further divided into 3 groups:3 d group,7 d group and 14 d group. The CVCs were intubated in left jugular veins of rabbits and left for a period of time with heparin sealed every day. The local and systematic infection symptoms of rabbits were under observation.2) The rabbits were sacrificed at 3,7, and 14 d post-intubation, respectively. The blood samples from both sides of jugular veins (5 ml each side) and the terminal parts (2 cm) of CVCs were taken for germiculture.3) The statistical approach was Fisher's Exact Test.Results1. MICs measurement of silver-containing antibacterial agents of nanometer level1) The MICs of the 3.0% silver-containing zirconium phosphate antibacterial agent of nanometer level against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa were between 0.0625 to 0.125 mg/mL, while those of 6.0% and 9.0% ones were between 0.039 to 0.078 mg/mL. The three contents of silver all had a good non-specific antibacterial effect, while the effects of the 6.0% and 9.0% ones was better and similar.2) The MICs of 6.0% silver-containing one against the clinical isolates Pseudomonas onion, Pseudomonas aeruginosa, Escherichia coli, Stenotrophomonas maltophilia, and Staphylococcus epidermidis were between 0.039 to 0.078 mg/mL.3) Zirconium phosphate agent of nanometer level without silver-containting had no antibacterial effect.2. Safety evaluation of silver-containing antibacterial agent of nanometer level1) 6.0% silver-containing zirconium phosphate antibacterial agent of nanometer level in oral toxicity test in mice showed LD50> 5000 mg/kg, which was of the actual non-toxic level.2) No erythema or edema was found from the local skin of 6.0% silver-containing zirconium phosphate antibacterial agent of nanometer level. And no systemic toxic signs were found. The average integral data of this kind of agent to rabbits.was zero. It had no full skin irritation..3)The release dose of silver ion was less than 0.03μg/mL.3. Surface antimicrobial activity assessment of CVC with nanometer silver1) The surface antimicrobial activity number against Pseudomonas aeruginosa of the 1.0%,2.0%, and 3.0% silver-containing zirconium phosphate antibacterial agent of nanometer level were 1.5,2.7 and 2.5. It showed that 2.0%, and 3.0% silver-containing zirconium phosphate antibacterial agent of nanometer level had perfect antimicrobial activity.2) The surface antimicrobial activity number against the standard strains Staphylococcus aureus and Escherichia coli of the 3.0% ones were 2.4 and 4.6. It showed that 3.0% silver-containing zirconium phosphate antibacterial agent of nanometer level had perfect antimicrobial activity.4. Antibacterial effect assessment in vivo of CVC with nanometer silver in rabbits1) All the rabbits of the two groups survive during the experiment, without any local or systematic infection symptoms.2) The results of the germiculture of blood samples and tubes from CVC with namometer silver group were all negative.3) Staphylococcus aureus was found in two blood samples (7-day group and 14-day group) and one tube sample (14-day group) of the Arrow antimicrobial CVC. The total positive rate of the germiculture of blood and tube samples were 11.1% and 5.6%, respectively. 4) There were no statistical difference between the two groups in the positive rates of blood samples and CVC germiculture.ConclusionsSilver-containing zirconium phosphate antibacterial agents of nanometer level had antibacterial effect against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa, etc. in the infection of venous catheter in vitro. The 6.0% and 9.0% silver-containing ones both showed good antibacterial effect. The 6.0% silver-containing one was chosen as the good additives to the material of venous catheter.3.0% silver-containing zirconium phosphate antibacterial agent of nanometer level had perfect antimicrobial activity against Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli. The preliminary results of animal experiment showed that CVC with nanometer silver had excellent antibacterial effect in vivo, which was nothing less than Arrow antimicrobial CVC.
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