Effect of antibiotic-loaded hydrophilic stent in the prevention of bacterial adherence: a study of the charge, discharge, and recharge concept using ciprofloxacin.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
CW Law Biofilm Research Laboratory, the Division of Gastroenterology, and Pharmacokinetic Consult Service, University of California, Davis Health System, Sacramento 95817, USA.
J W
JW
Leung
Y
Y
Liu
S
S
Cheung
R C
RC
Chan
J F
JF
Inciardi
A F
AF
Cheng
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000187:drug effects*; D018441:Biofilms / Q000187:drug effects; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000472:pathogenicity; D007700:Kinetics; D010477:Perfusion; D015607:Stents / Q000382:microbiology*
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D002939:Ciprofloxacin