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JCI Insight. 2018 Oct 4;3(19). pii: 123415. doi: 10.1172/jci.insight.123415.

Treatment of Streptococcus pneumoniae otitis media in a chinchilla model by transtympanic delivery of antibiotics.

Author information

1
Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Children's Hospital Boston, Harvard Medical School, Boston Massachusetts, USA.
2
Division of Pediatric Infectious Diseases, Maxwell Finland Laboratory for Infectious Diseases, Boston Medical Center, Boston, Massachusetts, USA.

Abstract

Otits media (OM) is the most frequent indication for antimicrobial prescription to US children. Streptococcus pneumoniae (S. pneumoniae) remains one of the most common pathogens causing OM. Successful eradication of S. pneumoniae in the middle ear can be achieved by adhering to a 7-10 day regimen of oral antibiotics. However, oral drug administration is challenging for parents. Lack of adherence has been associated with treatment failure or early relapse. To overcome this challenge, we used a noninvasive formulation to achieve high transtympanic antibiotic flux and cured S. pneumoniae OM in chinchillas. The formulation consists of a thermosensitive in situ gelling hydrogel, chemical permeation enhancers, and an antibiotic. The direct transport of drugs into the middle ear produced high concentrations of ciprofloxacin (in the range of hundreds of micrograms per milliliter) within the first 24 hours of administration. Drug concentrations above the minimum inhibitory concentration (MIC) for S. pneumoniae were sustained throughout the 7-day treatment. S. pneumoniae OM in a chinchilla model was successfully eradicated, without causing tissue toxicity. Transtympanic delivery minimized systemic drug exposure, as evidenced by undetectable levels in blood, measured by high-performance liquid chromatography.

KEYWORDS:

Bacterial infections; Infectious disease; Otology; Skin; Translation

PMID:
30282835
PMCID:
PMC6237455
DOI:
10.1172/jci.insight.123415
[Indexed for MEDLINE]
Free PMC Article

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