Biofilm Eradication With Biodegradable Modified-Release Antibiotic Pellets

Abstract

To develop a biodegradable, modifiedrelease 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

Update on otitis media – prevention and treatment

“…Ventilation tube insertion is associated with a number of risks, which include purulent otorrhea (10%–26%), myringosclerosis (39%–65%), retraction pockets (21%), and persistent tympanic membrane perforations (3%, although with longer-stay T-tubes, up to 24%) 55. In addition, once tubes extrude OME may return, with one trial of short-term tubes noting that 20%–25% of children required a second set of ventilation tubes within 2 years 56. Adenoidectomy is also thought to have a role in preventing recurrent OME,57 but due to associated risks it is typically not recommended as a primary treatment of OME, unless there are frequent or persistent upper respiratory tract infections 53.…”

“…The biofilm mode of growth contributes to persistence through a variety of mechanisms, including phenotypically altered “persister cells” that can repopulate biofilm bacteria;78,79 defense by the exopolysaccharide matrix, which physically blocks host defense mechanisms, leading to an ineffective inflammatory response; and horizontal gene transfer which can increase virulence 79. The high rate of OME reoccurrence, 20%–25% after ventilation tube removal,80 could also be explained by biofilm persistence because ventilation tubes remove the effusion but may not necessarily treat the underlying biofilm 56. Furthermore, biofilms can develop recalcitrance and resistance to antibiotics 81.…”

“…However, the downside is the need to incise or puncture the ear drum in order to achieve drug delivery. A variety of different methods have been proposed, including drug delivery gels87 and antibiotic pellets,56 with the latter strategy shown to eradicate S. aureus biofilms in vitro.…”

Anti-confocal versus confocal assessment of the middle ear simulated by Monte Carlo methods

“…This is a common condition and the surgery is among the commonest performed in the developed world [1]. However, 25 % of treated children have a recurrence requiring further surgery [2]. Our hypothesis is that these cases are remaining in an inflammatory state.…”

Determination of the glycosylation-pattern of the middle ear mucosa in guinea pigs

“…Although specific antibiotics are administered, the overall clinical effectiveness is limited due to low penetration of the drug to the middle ear mucosa (MEM) ( Coates et al, 2008 ), inaccessibility of the bacteria within the grown biofilm ( Post et al, 2004 ) as well as low symptomatic amendment within the first 24 h ( Glasziou et al, 2004; Rovers et al, 2006 ). To increase the therapeutic outcome and to prolong the contact time of the drug with the infected tissue drug loaded formulations such as thermosensitive hydrogels ( Lee et al, 2004; Li et al, 2014; Honeder et al, 2014 ), ototopical drops ( Kutz et al, 2013 ), implants ( Goycoolea et al, 1992; Goycoolea and Muchow, 1994; Nether et al, 2004 ), micropumps ( Lehner et al, 1997 ), intranasal drug delivery systems ( Chandrasekhar and Mautone, 2004 ), coated middle ear prostheses ( Lensing et al, 2013; Ehlert et al, 2013; Hesse et al, 2013 ), and pellets ( Daniel et al, 2012 ) were developed. Although there are many different therapeutic approaches, a local intratympanic therapy seems to be most beneficial for the treatment of OM as a decrease in side effects provoked by systemic therapy as well as an increase in compliance of the young patients will be expected.…”