Leung J W, Liu Y, Cheung S, Chan R C, Inciardi J F, Cheng A F
CW Law Biofilm Research Laboratory, the Division of Gastroenterology, and Pharmacokinetic Consult Service, University of California, Davis Health System, Sacramento 95817, USA.
Gastrointest Endosc. 2001 Apr;53(4):431-7. doi: 10.1067/mge.2001.113089.
Ciprofloxacin prophylaxis significantly prolonged stent patency in cats, but human studies produced conflicting results, possibly due to varying drug levels in bile. The uptake (charge) and release (discharge) of ciprofloxacin from a hydrophilic stent (HS) in an antibiotic solution and the effect of a ciprofloxacin-loaded stent (CHS) in inhibiting Escherichia coli adherence were tested. The adjuvant effect of ciprofloxacin perfusion (recharge) in the inhibition of E coli adherence was also tested.
Uptake: segments of HS were immersed in 5 mL of ciprofloxacin solutions for 24 hours. Ciprofloxacin remaining in solution was measured to determine the uptake by the HS. Release: CHS were placed in 5 mL water for 24 hours, and released ciprofloxacin was measured. CHS were placed on culture plates with E coli and incubated; diameters of inhibited zones were measured. CHS 0.5 cm in length were incubated in separate 5 mL E coli suspension (10(7) colony forming units [CFU]/mL) in 2% ox bile for 4 hours. E coli adhered on CHS were measured and compared with control HS. An E coli (10(6) CFU/mL) suspension was perfused through a modified Robbins device (MRD)-containing CHS. Stents were removed at regular intervals and processed to determine the adherence of E coli; non-loaded HS served as controls. The experiment was repeated by using CHS together with perfusion of ciprofloxacin solution (0.3 microg/mL) into the MRD for up to 7 days; normal saline solution was used as a control in a second MRD. Stents were removed daily to determine the adherence of E coli.
Uptake and release of ciprofloxacin by HS and CHS, respectively, were related to concentration of ciprofloxacin. Between 50% to 90% of the drug was released in 24 hours. Zonal inhibition of E coli growth was proportional to the concentration of ciprofloxacin on the CHS. There was an initial 10-fold reduction in attached E coli on CHS compared with controls, but this effect diminished after 24 hours. With ciprofloxacin perfusion, there was a 100-fold reduction in adhered E coli on CHS, although there was no change in E coli concentration in bile.
There was a free exchange (uptake and release) of ciprofloxacin along a concentration gradient between the antibiotic solution and HS. CHS reduced the number of adhered E coli, but the effect was short-lived. Perfusion of ciprofloxacin offers an adjuvant benefit by enhancing inhibition of E coli adherence on CHS.
环丙沙星预防措施可显著延长猫体内支架的通畅时间，但人体研究结果相互矛盾，这可能是由于胆汁中药物水平不同所致。测试了亲水性支架（HS）在抗生素溶液中环丙沙星的摄取（充电）和释放（放电）情况，以及载有环丙沙星的支架（CHS）对抑制大肠杆菌黏附的作用。还测试了环丙沙星灌注（再充电）在抑制大肠杆菌黏附方面的辅助作用。
摄取：将HS片段浸入5 mL环丙沙星溶液中24小时。测量溶液中剩余的环丙沙星，以确定HS的摄取量。释放：将CHS置于5 mL水中24小时，测量释放的环丙沙星。将CHS置于含有大肠杆菌的培养板上并孵育；测量抑菌圈直径。将长度为0.5 cm的CHS在含有2%牛胆汁的5 mL单独大肠杆菌悬液（10⁷菌落形成单位[CFU]/mL）中孵育4小时。测量CHS上黏附的大肠杆菌，并与对照HS进行比较。将大肠杆菌（10⁶ CFU/mL）悬液通过含有CHS的改良Robbins装置（MRD）进行灌注。定期取出支架并进行处理，以确定大肠杆菌的黏附情况；未载药的HS作为对照。通过将CHS与环丙沙星溶液（0.3 μg/mL）灌注到MRD中长达7天来重复该实验；在第二个MRD中使用生理盐水作为对照。每天取出支架以确定大肠杆菌的黏附情况。
HS和CHS对环丙沙星的摄取和释放分别与环丙沙星浓度有关。24小时内50%至90%的药物被释放。CHS上大肠杆菌生长的区域抑制与环丙沙星浓度成正比。与对照相比，CHS上附着的大肠杆菌最初减少了10倍，但24小时后这种效果减弱。通过环丙沙星灌注，CHS上黏附的大肠杆菌减少了100倍，尽管胆汁中大肠杆菌浓度没有变化。
环丙沙星在抗生素溶液和HS之间沿浓度梯度进行自由交换（摄取和释放）。CHS减少了黏附的大肠杆菌数量，但效果是短暂的。环丙沙星灌注通过增强对CHS上大肠杆菌黏附的抑制作用提供了辅助益处。
