Efficacy of sustained release ciprofloxacin microspheres against device-associated Pseudomonas aeruginosa biofilm infection in a rabbit peritoneal model.
The relative effectiveness of a poly(L-lactic acid) ciprofloxacin hydrochloride (CIP) microsphere formulation (250-425 microns) against peritoneal implanted biofilm of Pseudomonas aeruginosa was investigated in a rabbit model. Correlations between in-vivo CIP pharmacokinetics in peritoneal dialysate and serum after intraperitoneal administration, in-vivo cell counts and rabbit survival rate were obtained. Dialysate and serum concentrations after 12 h (C12h) were greater than those obtained with free drug whereas maximum serum concentrations (Cmax) were lower and the time to reach Cmax(tmax) was longer. A silastic implant device pre-colonised with P. aeruginosa for 2 days was implanted in the rabbit peritoneum, and dialysate with or without drug or microspheres was administered via a catheter. Rabbits receiving no antibiotic and those receiving free drug (10 mg in dialysate) died of peritonitis and septicaemia, whereas all rabbits given CIP microspheres recovered completely from infection. The viable count of P. aeruginosa was markedly reduced or eliminated from the catheter, the device and the peritoneal wall in CIP microsphere-treated rabbits but not in rabbits treated with free drug, as determined from histological and scanning electronmicroscopic evidence. These results demonstrate that sustained release of antibiotics at biofilm eradication concentrations (BEC) is required to treat biofilm infections associated with peritoneal implanted devices.
Owusu-Ababio
G
G
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Rogers
J A
JA
Morck
D W
DW
Olson
M E
ME
D000042:Absorption; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D005260:Female; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010531:Peritoneal Dialysis, Continuous Ambulatory; D019736:Prostheses and Implants / Q000009:adverse effects*; D016459:Prosthesis-Related Infections / Q000188:drug therapy*; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development; D011817:Rabbits
D000890:Anti-Infective Agents; D003692:Delayed-Action Preparations; D002939:Ciprofloxacin