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Original Article |

Biofilm Eradication With Biodegradable Modified-Release Antibiotic Pellets:  A Potential Treatment for Glue Ear

Matija Daniel, FRCSEd(ORL-HNS); Robert Chessman, BMedSci(Hons); Saif Al-Zahid, MRCS; Brian Richards, MSc; Cheryl Rahman, PhD; Waheed Ashraf, MSc; Jane McLaren, PhD; Helen Cox, BSc; Omar Qutachi, PhD; Heather Fortnum, DM; Neil Fergie, FRCS, DM; Kevin Shakesheff, PhD; John P. Birchall, FRCS, DM; Roger R. Bayston, PhD
Arch Otolaryngol Head Neck Surg. 2012;138(10):942-949. doi:10.1001/archotol.2013.238.
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Objective  To develop a biodegradable, modified-release antibiotic pellet capable of eradicating biofilms as a potential novel treatment for biofilm infections.

Design  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.

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Figure 1. Scanning electron microscopic (JSM-6060LV; JEOL Ltd) image of the surface of the antibiotic pellet (original magnification ×2000).

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Figure 2. Zone of inhibition around the antibiotic pellets on agar plates after serial plate transfer testing. CMC indicates carboxymethylcellulose; H, L, and M, high, low, and medium antibiotic concentrations, respectively; and PL, poloxamer 407. Error bars represent the standard deviation.

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Grahic Jump Location

Figure 3. Clindamycin hydrochloride levels released from the antibiotic pellets with (A) and without (B) day 2 data. The graph excluding day 2 data (B) has a different scale for ease of interpretation. Error bars represent the standard deviation. CMC indicates carboxymethylcellulose; H, L, and M, high, low, and medium antibiotic concentrations, respectively; and PL, poloxamer 407.

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