Capdevila J A, Gavaldà J, Fortea J, López P, Martin M T, Gomis X, Pahissa A
Infectious Diseases Research Laboratory and Infectious Diseases Service, Hospitals Universitaris Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
Clin Microbiol Infect. 2001 Apr;7(4):206-12. doi: 10.1046/j.1469-0691.2001.00233.x.
To elucidate the potential antimicrobial activity of sodium heparin in the treatment of catheter-infection using the antibiotic-lock technique.
We performed in vitro studies of the antibiotic susceptibility, stability and synergy of sodium heparin, vancomycin and ciprofloxacin. Efficacy studies were performed in a new animal model of Staphylococcus aureus catheter-related infection in which infection was produced via the endoluminal route. White New Zealand rabbits were surgically implanted with a sylastic catheter into the inferior cava vein. Immediately afterwards, infection was induced by filling and locking the catheters with 0.7 mL of broth culture containing 108 colony-forming units of S. aureus. Eighteen hours later the antibiotic-lock technique was started. Treatment groups were: control without treatment, sodium heparin at 2500 IU/mL, vancomycin at 2500 mg/L, ciprofloxacin at 1000 mg/L, vancomycin plus heparin and ciprofloxacin plus heparin.
Sodium heparin showed an MIC90 higher than 6000 UI/mL against S. aureus causing catheter infection. Studies of antimicrobial synergy by the time-kill method between vancomycin and ciprofloxacin at MIC with sodium heparin at 2500 IU/mL showed no interactions. Vancomycin (2000 microg/mL) and ciprofloxacin (1000 microg/mL) in a solution containing sodium heparin (2500 IU/mL) were stable at 37 degrees C for a 72-h period. Two sets of in vivo experiments were carried out using differents strains of S. aureus. In both cases, sodium heparin showed no therapeutic efficacy when compared to control group and did not increase the antibiotic efficacy when used in combination with vancomycin or ciprofloxacin.
Sodium heparin lacked antibacterial activity against S. aureus causing catheter-related infections.
运用抗生素封管技术阐明肝素钠在治疗导管感染中的潜在抗菌活性。
我们对肝素钠、万古霉素和环丙沙星进行了抗生素敏感性、稳定性及协同作用的体外研究。在一种新的金黄色葡萄球菌导管相关感染动物模型中进行疗效研究，该模型通过腔内途径引发感染。将白色新西兰兔通过手术植入一根硅橡胶导管至下腔静脉。随后立即用0.7 mL含10⁸个金黄色葡萄球菌菌落形成单位的肉汤培养物充盈并封管以诱导感染。18小时后开始抗生素封管技术。治疗组包括：未治疗的对照组、2500 IU/mL的肝素钠组、2500 mg/L的万古霉素组、1000 mg/L的环丙沙星组、万古霉素加肝素组以及环丙沙星加肝素组。
肝素钠对引起导管感染的金黄色葡萄球菌的MIC90高于6000 UI/mL。采用时间杀菌法对2500 IU/mL肝素钠与MIC浓度的万古霉素和环丙沙星之间的抗菌协同作用研究显示无相互作用。在含2500 IU/mL肝素钠的溶液中，万古霉素（2000 μg/mL）和环丙沙星（1000 μg/mL）在37℃下72小时内稳定。使用不同菌株的金黄色葡萄球菌进行了两组体内实验。在这两种情况下，与对照组相比，肝素钠均未显示出治疗效果，且与万古霉素或环丙沙星联合使用时也未提高抗生素疗效。
肝素钠对引起导管相关感染的金黄色葡萄球菌缺乏抗菌活性。
