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Transtympanic Delivery of Local Anesthetics for Pain in Acute Otitis Media.

ABSTRACT: Acute otitis media (AOM) commonly causes pain and distress in children. Existing analgesic ototopical drops have limited effectiveness due to the impermeable nature of the tympanic membrane. We developed a local drug delivery system to provide sustained pain relief in patients with AOM, achieved by applying a single dose of a hydrogel formulation onto the tympanic membrane. Successful drug delivery across intact tympanic membranes was demonstrated using the amino-amide anesthetic, bupivacaine, and a highly potent site 1 sodium channel blocker anesthetic, tetrodotoxin. The chemical permeation enhancers incorporated in the delivery system increased the permeability of the tympanic membrane to the anesthetics considerably. The drug levels measured using a previously developed ex vivo model reflect the potential for highly effective local anesthesia.

SUBMITTER: Yang R

PROVIDER: S-EPMC6724207 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Transtympanic Delivery of Local Anesthetics for Pain in Acute Otitis Media.

Yang Rong R Saarinen Riitta R Okonkwo Obiajulu S OS Hao Yi Y Mehta Manisha M Kohane Daniel S DS

Molecular pharmaceutics 20190306 4

Acute otitis media (AOM) commonly causes pain and distress in children. Existing analgesic ototopical drops have limited effectiveness due to the impermeable nature of the tympanic membrane. We developed a local drug delivery system to provide sustained pain relief in patients with AOM, achieved by applying a single dose of a hydrogel formulation onto the tympanic membrane. Successful drug delivery across intact tympanic membranes was demonstrated using the amino-amide anesthetic, bupivacaine, a ...[more]

PMID: 30840478

Similar Datasets

Acute Otitis Media Curriculum.

Project description:IntroductionStudies have shown that clinicians do a poor job of diagnosing middle ear infections, and an inaccurate diagnosis may result in inappropriate treatment, such as overuse of antibiotics. Antibiotic overuse is known to lead to increased bacterial resistance and puts patients at risk of deleterious side effects, including allergic reactions, vomiting, diarrhea, and rash. In this curriculum, we teach three important topics for achieving a successful middle ear exam and diagnosis of pathology.MethodsThe topics covered during the session are middle ear examination techniques, diagnosis of middle ear pathology and criteria for diagnosing acute otitis media, and treatment of acute otitis media. Each topic has a 30-minute lesson plan with broad goals, specific and measurable learning objectives, interactive learning activities, and assessment measures. Teaching activities include a mix of knowledge, skill, and attitude activities. Assessment measures aim at the highest level of Miller's pyramid of assessment when possible. Also included is a scholarship map that relates how this learning activity can fit into the assessment of learners at the program level by linking learning objectives with pediatric developmental milestones.ResultsThe interactive nature of these lessons has been very well received by learners, and pediatric residents have had a self-perceived increase in skills.DiscussionThis curriculum provides a standardized approach to teaching the middle ear exam structured by educational rubrics and allows for accurate assessment of learners.

| S-EPMC6440425 | biostudies-literature

Pain management in acute otitis media: a qualitative study of parents' views and expectations.

Project description:BackgroundFor unclarified reasons, parents tend to be cautious about administering analgesics to their children, potentially leading to suboptimal management of AOM symptoms. We aim to understand parents' views and expectations of pain management in acute otitis media (AOM) in children.MethodsQualitative study alongside a cluster-randomised controlled trial (PIM-POM study) aimed at optimising pain management in childhood AOM. We purposefully sampled 14 parents of children diagnosed with AOM by their GP, who were recruited to the trial between November 2017 and May 2018. Semi-structured interviews were held at home in the first two weeks after trial enrollment. Interviews were audio-recorded, transcribed and analyzed thematically.ResultsParents experienced difficulties in recognising earache and other symptoms of an ear infection. They consulted the GP for a diagnosis, for reassurance and for management advice. Parents shared that, prior to consultation, they had insufficient knowledge of the benefits of correctly dosed pain medication at regularly scheduled intervals. Parents valued the GP's advice on pain management, and were happy to accept pain medication as standalone therapy, provided that the GP explained why antibiotics would not be needed. Parents' views and expectations of pain management in AOM were shaped by previous experiences of AOM within their family; those with a positive experience of pain medication are more likely to use it in subsequent AOM episodes.ConclusionsParents of children with AOM consult the GP to help cope with uncertainties in recognising symptoms of AOM, and to receive management advice. It is important that GPs are aware of parents' lack of understanding of the role of pain medication in managing AOM, and that they address this during the consultation.Trial registrationNetherlands Trial Register, identifier NTR4920 (registration date: 19 December 2014).

| S-EPMC6343236 | biostudies-literature

Nystagmus in adult patients with acute otitis media or otitis media with effusion without dizziness.

Project description:The present study aimed to investigate the incidence and patterns of nystagmus in adult patients with acute otitis media (AOM) or otitis media with effusion (OME) without dizziness or vertigo, and discuss possible mechanisms. From February 2018 to November 2018, 34 consecutive patients with AOM or OME without dizziness were included. Nystagmus was examined with video Frenzel glasses. Of 34 adult AOM or OME patients without dizziness, nystagmus was observed in 28 patients (82%). In unilateral AOM or OME (n = 30), the most commonly observed nystagmus pattern was irritative-type direction-fixed nystagmus (n = 13), followed by paretic-type direction-fixed nystagmus (n = 8), and direction-changing positional nystagmus (n = 4). In bilateral AOM or OME (n = 4), direction-fixed nystagmus and direction-changing positional nystagmus were observed in two and one patients, respectively. Nystagmus was observed in as many as 82% of adult AOM or OME patients even though they did not complain of dizziness, and the pattern of nystagmus was either direction-fixed or direction-changing. Direct effect of inflammatory mediators penetrated from the middle ear and biochemical alteration in the inner ear fluids due to blood-perilymph barrier dysfunction may result in the presence of nystagmus in AOM or OME patients without dizziness.

| S-EPMC8118351 | biostudies-literature

Treatment of otitis media by transtympanic delivery of antibiotics.

Project description:Otitis media is the most common reason U.S. children receive antibiotics. The requisite 7- to 10-day course of oral antibiotics can be challenging to deliver in children, entails potential systemic toxicity, and encourages selection of antimicrobial-resistant bacteria. We developed a drug delivery system that, when applied once to the tympanic membrane through the external auditory canal, delivers an entire course of antimicrobial therapy to the middle ear. A pentablock copolymer poloxamer 407-polybutylphosphoester (P407-PBP) was designed to flow easily during application and then to form a mechanically strong hydrogel on the tympanic membrane. U.S. Food and Drug Administration-approved chemical permeation enhancers within the hydrogel assisted flux of the antibiotic ciprofloxacin across the membrane. This drug delivery system completely eradicated otitis media from nontypable Haemophilus influenzae (NTHi) in 10 of 10 chinchillas, whereas only 62.5% of animals receiving 1% ciprofloxacin alone had cleared the infection by day 7. The hydrogel system was biocompatible in the ear, and ciprofloxacin was undetectable systemically (in blood), confirming local drug delivery and activity. This fast-gelling hydrogel could improve compliance, minimize side effects, and prevent systemic distribution of antibiotics in one of the most common pediatric illnesses, possibly minimizing the development of antibiotic resistance.

| S-EPMC5615819 | biostudies-literature

Microbial profiling does not differentiate between childhood recurrent acute otitis media and chronic otitis media with effusion.

Project description:ObjectivesOtitis media (OM) is one of the most frequent diseases of childhood, with a minority of children suffering from recurrent acute otitis media (rAOM) or chronic otitis media with effusion (COME), both of which are associated with significant morbidity. We investigated whether the microbiological profiling could be used to differentiate between these two conditions.MethodsChildren up to five years of age, with rAOM (n = 45) or COME (n = 129) and scheduled for tympanostomy tube insertion were enrolled in a prospective study between 2008 and 2009. Middle ear fluids (n = 119) and nasopharyngeal samples (n = 173) were collected during surgery for bacterial culture and PCR analysis to identify Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, and to detect 15 distinct respiratory viruses.ResultsThe occurrence of bacterial and viral pathogens in middle ear fluids did not significantly differ between patients suffering from rAOM and COME. In both patient cohorts, H. influenzae and rhinovirus were the predominant pathogens in the middle ear and nasopharynx. Nasopharyngeal carriage with two or three bacterial pathogens was associated with the presence of bacteria in middle ear fluid (P = 0.04). The great majority of the bacteria isolated from middle ear fluid were genetically identical to nasopharyngeal isolates from the same patient.ConclusionsBased on these results, we propose that the common perception that rAOM is associated with recurrent episodes of microbiologically mediated AOM, whereas COME is generally a sterile inflammation, should be reconsidered.

| S-EPMC7132406 | biostudies-literature

Nasopharyngeal microbiota in infants with acute otitis media.

Project description:BACKGROUND:Interspecies interactions of the nasopharyngeal microbiota are likely to be involved in the pathogenesis of acute otitis media (AOM). Capturing the breadth of microbial interactions requires a detailed description of the microbiota during health and AOM. METHODS:The nasopharyngeal microbiota of 163 infants with (n = 153) or without (n = 10) AOM was characterized using nasopharyngeal swabs and multiplexed pyrosequencing of 16S rRNA. Nasopharyngeal swab specimens were collected during 4 winter seasons from 2004 through 2010 for infants with AOM and during 2010 for controls. RESULTS:Fifty-eight bacterial families were identified, of which Moraxellaceae, Streptococcaceae, and Pasteurellaceae were the most frequent. Commensal families were less prevalent in infants with AOM than in controls. In infants with AOM, prior exposure to antimicrobials and administration of the heptavalent conjugated pneumococcal polysaccharide vaccine (PCV7) were also associated with reduced prevalence of distinct commensal families (Streptococcaceae and Corynebacteriaceae). In addition, antimicrobial exposure increased the prevalence of Enterobacteriaceae and the abundance of Pasteurellaceae. Other factors, such as age, sex, day care, and a history of recurrent AOM, did not influence the microbiota. CONCLUSIONS:Infants' nasopharyngeal microbiota undergoes significant changes during AOM and after exposure to antimicrobials and PCV7, which is mainly attributable to reduced prevalence of commensal bacterial families.

| S-EPMC7107284 | biostudies-literature

Window of Susceptibility to Acute Otitis Media Infection.

Project description:BackgroundContemporary, quantitative data are needed to inform recommendations and decision-making regarding referral and surgeon endorsement of tympanostomy tube placement in young children with recurrent acute otitis media (AOM).MethodsA prospective, observational cohort study of 286 children in a primary care pediatric practice setting, who had at least 1 AOM (range 1-8). Children were followed longitudinally from 6 to 36 months old. AOMs were microbiologically confirmed by tympanocentesis for diagnostic accuracy. A window of susceptibility (WOS) was defined as AOMs closely spaced in time with no gap in occurrence >6 months. For prediction of total number of AOMs, we used a quasi-poisson generalized linear model.ResultsEighty percent of AOMs occurred during child age 6 to 21 months old. Seventy two percent of WOS intervals were <5 months and 97% were <10 months. Clinically applicable models were developed to predict which children would benefit most from tympanostomy tubes. Significant predictors were child age at the first AOM (P < .001) and daycare attendance (P = .03). The age of a child when 2, 3, or 4 AOMs had occurred allowed prediction of the number of additional AOMs that might occur. After insertion of tympanostomy tubes, 16 (52%) of 31 children had no additional AOMs.ConclusionsRecurrent AOM occurs in a narrow WOS and number of AOMs can be predicted at time of AOM based on child age and daycare attendance. Insertion of tympanostomy tubes likely occurs in many children after the WOS to recurrent AOM has passed or only 1 more AOM may be prevented at most.

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Probiotics for preventing acute otitis media in children.

Project description: Not available

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Otitis media metagenome

Project description:Impact of narrow-spectrum antibiotics on the oral and fecal microbiome and resistome in a young child treated for otitis media

| PRJEB31957 | ENA

Xylitol syrup for the prevention of acute otitis media.

Project description:Acute otitis media (AOM) is a common childhood illness and the leading indication for antibiotic prescriptions for US children. Xylitol, a naturally occurring sugar alcohol, can reduce AOM when given 5 times per day as a gum or syrup, but a more convenient dosing regimen is needed for widespread adoption.We designed a pragmatic practice-based randomized controlled trial to determine if viscous xylitol solution at a dose of 5 g 3 times per day could reduce the occurrence of clinically diagnosed AOM among otitis-prone children 6 months through 5 years of age.A total of 326 subjects were enrolled, with 160 allocated to xylitol and 166 to placebo. In the primary analysis of time to first clinically diagnosed AOM episode, the hazard ratio for xylitol versus placebo recipients was 0.88 (95% confidence interval [CI] 0.61 to 1.3). In secondary analyses, the incidence of AOM was 0.53 episodes per 90 days in the xylitol group versus 0.59 in the placebo group (difference 0.06; 95% CI -0.25 to 0.13); total antibiotic use was 6.8 days per 90 days in the xylitol group versus 6.4 in the placebo group (difference 0.4; 95% CI -1.8 to 2.7). The lack of effectiveness was not explained by nonadherence to treatment, as the hazard ratio for those taking nearly all assigned xylitol compared with those taking none was 0.93 (95% CI 0.56 to 1.57).Viscous xylitol solution in a dose of 5 g 3 times per day was ineffective in reducing clinically diagnosed AOM among otitis-prone children.

| S-EPMC3904279 | biostudies-literature

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