Biofilm eradication with biodegradable modified-release antibiotic pellets: a potential treatment for glue ear.
OBJECTIVE
To develop a biodegradable, modified-release antibiotic pellet capable of eradicating biofilms as a potential novel treatment for biofilm infections.


METHODS
Pellets containing poly(DL-lactic-co-glycolic acid) microparticles, rifampin and clindamycin hydrochloride (3.5%, 7%, or 28% antibiotic by weight), and carrier gel (carboxymethylcellulose or poloxamer 407) were tested in vitro. Drug release was assessed using serial plate transfer testing and high-performance liquid chromatography, and pellets were tested against biofilms in an in vitro model of Staphylococcus aureus biofilm grown on silicone.


RESULTS
Serial plate transfer testing demonstrated continuing bacterial inhibition for up to 21 days for all pellets studied. High-performance liquid chromatography showed high levels of drug release for 2 to 4 days, with greatly reduced levels subsequently; continued measurable clindamycin (but not rifampin) release for up to 21 days was achieved. Pellets made with poloxamer released higher drug levels for a longer period. Irrespective of the carrier gel used, pellets containing 7% and 28% (but not 3.5%) antibiotic eradicated biofilms successfully.


CONCLUSIONS
Antibiotic pellets can release antibiotics for up to 21 days and are able to eradicate biofilms in an in vitro model. Use of modified-release antibiotic formulations in the middle ear as a treatment for biofilms appears to be a potentially promising new therapy for otitis media with effusion.
Department of Otorhinolaryngology–Head and Neck Surgery, The University of Nottingham, Queens Medical Centre, Derby Road, Nottingham NG7 2UH, England. msxmd1@nottingham.ac.uk
Matija
M
Daniel
Robert
R
Chessman
Saif
S
Al-Zahid
Brian
B
Richards
Cheryl
C
Rahman
Waheed
W
Ashraf
Jane
J
McLaren
Helen
H
Cox
Omar
O
Qutachi
Heather
H
Fortnum
Neil
N
Fergie
Kevin
K
Shakesheff
John P
JP
Birchall
Roger R
RR
Bayston
D020341:Absorbable Implants; D000596:Amino Acids; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D018441:Biofilms / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D005782:Gels; D006801:Humans; D019344:Lactic Acid; D008828:Microbiological Techniques; D008855:Microscopy, Electron, Scanning; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013211:Staphylococcus aureus / Q000254:growth & development*; D013400:Sugar Acids
D000596:Amino Acids; D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D005782:Gels; D013400:Sugar Acids; C529752:polyoxamic acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid