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Treatment of Streptococcus pneumoniae otitis media in a chinchilla model by transtympanic delivery of antibiotics
Rong Yang, … , Stephen I. Pelton, Daniel S. Kohane
Rong Yang, … , Stephen I. Pelton, Daniel S. Kohane
Published October 4, 2018
Citation Information: JCI Insight. 2018;3(19):e123415. https://doi.org/10.1172/jci.insight.123415.
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Resource and Technical Advance Infectious disease Otology

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

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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.

Authors

Rong Yang, Vishakha Sabharwal, Nadya Shlykova, Obiajulu S. Okonkwo, Stephen I. Pelton, Daniel S. Kohane

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Figure 5

(Representative H&E-stained sections of tympanic membranes (TM).

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(Representative H&E-stained sections of tympanic membranes (TM).
The...
The H&E-stained sections were obtained from healthy TMs and of TMs after 7 days of otitis media (OM), without or after treatment with the formulation containing 4% (w/v) ciprofloxacin, 2% (w/v) limonene, 1% (w/v) sodium dodecyl sulfate, 0.5% (w/v) bupivacaine hydrochloride, and 12% (w/v) poloxamer 407-polybutylphosphoester (4%Cip-3CPE-[P407-PBP]). n = 11 for healthy TM with no treatment; n = 4 for TM with OM with no treatment; n = 4 for healthy TM with treatment; n = 11 for TM with OM with treatment. Scale bar: 12 μm. The average thickness of TMs ( ± SD) for each group is shown above their respective panels.

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