Cortisporin Otic Suspension Research Articles

Topical otic antibiotics: Clinical cochlear ototoxicity and cost consideration

Determine the incidence of clinical cochlear ototoxicity in routine use of Cortisporin after ventilation tube placement. Cost differential between use of Cortisporin and fluoroquinolone agents was evaluated. A retrospective review of 500 patients was performed. Cortisporin otic suspension was used for 5 days following ventilation tube insertion. Testing following surgery indicated a sensorineural hearing loss (SNHL) in 19 (2.1%) ears. The SNHL existed prior to the surgery and there was no deterioration in the hearing postoperatively. The total cost for our study group who used Cortisporin was $15,500. If Floxin had been prescribed the cost would have been $45,000. Had Ciprodex been prescribed, the cost would have been $49,500. Our study demonstrates no clinical cochlear ototoxicity in children who received Cortisporin following ventilation tube placement. The cost differential for prescribing fluoroquinolone drops is significant. C-4.

Once-daily ofloxacin otic solution versus neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension four times a day: a multicenter, randomized, evaluator-blinded trial to compare the efficacy, safety, and pain relief in pediatric patients with otitis externa

ABSTRACTIntroduction: Otitis externa (OE) is an infection of the external auditory canal affecting children and adults and is associated with symptoms of local pain and tenderness. Twice-daily topical treatment with ofloxacin otic solution (0.3% [Floxin otic solution]) for 10 days has been reported to be as effective and well tolerated as neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension (Cortisporin otic suspension) administered four times daily for 10 days.Objective: This study compared the efficacy, safety, and ear-pain resolution of once-daily ofloxacin otic solution (0.3%) versus neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension administered four times daily, in children with OE.Research design, patients, and methods: This multicenter, randomized, parallel-group, evaluator-blinded study was conducted at 34 centers in 278 pediatric OE patients aged 6 months to 12 years. Patients received five drops of ofloxacin otic solution (0.3%) in the affected ears once daily or three drops of neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension four times daily, for 7–10 days. Patient evaluations were performed at pretherapy (day 1), end of therapy (days 7–9), and test of cure (7–10 days post-treatment) visits. Data for 208 patients were clinically evaluable and those for 90 patients were microbiologically evaluable. Scores were obtained for patient assessments of pain severity.Main outcome measures: The overall clinical response was cure in the clinically evaluable patients, demonstrated by resolution of OE signs and symptoms at the test of cure visit. The overall clinical-microbiological response was cure in the microbiologically evaluable patients demonstrated by both clinical cure and microbiological eradication.Results: For the clinically evaluable patients, equivalent cure rates were obtained between the once-daily ofloxacin-treated and four-times-daily neomycin sulfate/polymyxin B sulfate/hydrocortisone-treated patients (93.8% and 94.7%, respectively). For the clinically and microbiologically evaluable patients, the overall cure rates were 96.4% versus 97.1% for the ofloxacin-treated and neomycin sulfate/polymyxin B sulfate/hydrocortisone-treated patients, respectively. The eradication rates for the prevalent pathogen, Pseudomonas aeruginosa, were 98% versus 100% for ofloxacin-treated and neomycin sulfate/polymyxin B sulfate/hydrocortisone-treated patients, respectively. Decreases in pain severity were similar in both treatment groups. Statistical analyses were limited by the small numbers of patients in each treatment group.Conclusion: In the treatment of OE in children, once-daily ofloxacin otic solution was as effective and safe as neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension given four times daily. The two treatments provide rapid and comparable pain relief; however, ofloxacin otic solution does not have the risk of ototoxicity associated with neomycin and provides effective pain relief without adjunctive steroids.

Early Postoperative Otorrhea after Tympanostomy Tube Placement: A Comparison of Topical Ophthalmic and Otic Drops

In a retrospective review of the incidence of early postoperative otorrhea, we compared cortisporin otic suspension with sulfacetamide/prednisolone ophthalmic drops and found them to be approximately equally effective. The beneficial effect of topical otic and ophthalmic antibiotic drops after tympanoplasty tube placement has already been well documented. It is therefore suggested that the potentially more comfortable and theoretically less ototoxic ophthalmic drop be used to decrease the incidence of early postoperative otorrhea.

Effect of cortisporin otic suspension on cochlear function and efferent activity in the guinea pig.

To predict cochlear receptor cell insult from therapeutic aminoglycoside antibiotics, we sought to determine whether the presence of subtoxic concentrations of Cortisporin otic suspension in the cochlea can be detected by measuring changes in efferent suppression of compound action potentials recorded from the round window. Olivocochlear efferent suppression in an earlier study was reversibly inhibited by injections of gentamicin in guinea pigs. Using that same technique, we found that 2.0 microliter of Cortisporin otic suspension (neomycin, polymyxin B, hydrocortisone) placed on the round window of guinea pigs in varying concentrations causes a rapid, permanent alteration in thresholds. Solutions of Cortisporin otic suspension diluted to a concentration of 1:20 yield a reversible loss of efferent suppression without measurable changes in compound action potential. These data suggest that the presence of Cortisporin otic suspension can be detected functionally in the cochlea at very low concentrations prior to the development of a threshold shift.

Safety of ototopical antibiotics

A prospective randomized study analyzing the safety and efficacy of a single dose of ototopical antibiotics following human middle ear tympanostomy tube insertion was performed. Fifty children undergoing bilateral tympanostomy tube insertion were studied by the placement of 0.5 mL of Cortisporin Otic Suspension (COS; Burroughs Wellcome Co., Research Triangle Park, N.C.) to one middle ear space by random assignment. Preoperative and postoperative audiograms were obtained, and the presence of otorrhea was noted. In one patient sensorineural hearing loss of 6 dB developed bilaterally, which was symmetric in both the treated and the untreated ear. This preliminary study showed no statistical difference in hearing loss or postoperative otorrhea associated with a single application of Cortisporin to the middle ear space.

Round Window Membrane Permeability during Experimental Purulent Otitis Media: Altered Cortisporin Ototoxicity

Round window membrane (RWM) permeability is the most critical factor influencing cochlear function following otitis media. Because otic drops are frequently used during purulent otitis media (POM), we investigated RWM permeability and ototoxicity of Cortisporin otic suspension after inducing experimental POM. Unilateral POM was induced in eight chinchillas by inoculating type 7F Streptococcus pneumoniae into the right ears. Left ears were inoculated with phosphate-buffered saline (control). When POM resolved, the animals were divided into two groups. The round window niches of group 1 were covered with Cortisporin otic suspension. Compound action potentials were measured before and after drug application. The RWM permeability was measured in group 2 by use of tetraethylammonium (TEA) ions as tracers, and the arrival time of TEA and the slope of the potassium-selective microelectrode response were measured. Animals with otitis media exhibited less susceptibility to ototoxicity of Cortisporin otic suspension and reduced RWM permeability to the medium-sized molecule TEA.

Toxicity of Ototopical Drugs: Animal Modeling

It is important to be aware of the potential ototoxicity of any drug, vehicle, or antiseptic that is used in the middle ear. Frequently used ear drops (Cortisporin otic suspension, Coly-Mycin S Otic, and VoSoL otic solution) were studied for their ototoxicity. Compound action potentials were measured before and at 1, 2, and 24 hours following drug application on the round window membranes of chinchillas. Each drug was applied for 10 minutes and then was removed by rinsing. The sound pressure in decibels sound pressure level that produced a compound action potential amplitude of 10 microV was defined as the threshold. The change in threshold was interpreted as hearing loss. On the basis of the short-term results at 24 hours following drug application, the ototoxicity of Coly-Mycin was calculated to be twice that of Cortisporin, and the ototoxicity of VoSoL four times that of Cortisporin.

Effects of Otic Drops on Chinchilla Tympanic Membrane

Experimental studies have shown that if antibiotic otic drops reach the middle ear cavity they produce severe inflammation. However, the effects of these preparations on the tympanic membrane have not been thoroughly investigated. This study was designed to assess morphological changes in the chinchilla tympanic membrane two to 21 days after a single 0.2-mL application of an antibiotic otic preparation (Cortisporin Otic Suspension) to the middle ear cavity. At two days, the epidermal and the mucosal layers were destroyed. By four days, reepithelialization had occurred and all layers of the tympanic membrane subsequently became markedly hyperplastic. Disruption of the fibrous layer, invasion of keratinizing epidermis to the medial surface, and perforation were observed at three weeks. These findings indicate that tympanic membrane damage is a potentially significant aspect of the ototoxic properties of topical otic preparations.

Inflammatory effects of topical antibiotic suspensions containing propylene glycol in chinchilla middle ears

This study examines the occurrence of inflammatory changes and cholesteatoma in the middle ears of seven chinchillas after the application of topical antibiotic suspensions containing two different concentrations of propylene glycol. The preparations used were Cortisporin otic suspension, which contains neomycin, polymyxin B, hydrocortisone, and 10.5% propylene glycol, and Cortisporin ophthalmic suspension, containing the same ingredients, but only a 2% concentration of propylene glycol. Six weeks after the administration of the Cortisporin preparations, applied to the middle ear through a transbulla approach, no cholesteatomas were found in the seven ears treated with the ophthalmic suspension. Evidence of mild inflammation was present in only two of these ears. In the seven contralateral ears treated with the otic suspension, middle ear adhesions were found in six, cholesteatoma was present in four, serous effusions were found in three, and one had a large tympanic membrane perforation. The ears that showed cholesteatomas also had histologic evidence of squamous metaplasia, granulation tissue, and erosion of the underlying bone. We submit that the pathologic responses of the middle ear mucosa treated with the otic suspension, were due to an inflammatory response to the higher concentration of propylene glycol compared to that of the ophthalmic suspension.

Middle ear cholesteatoma: An animal model

Topical otic preparations now in clinical use contain a variety of antibiotics and solvents that may produce severe inflammation if they reach the middle ear cavity. This report describes the response of the chinchilla middle ear to direct application of one such preparation that appears to act as a nonspecific irritant. Cortisporin otic suspension (containing neomycin, polymyxin B, hydrocortisone, and propylene glycol) was introduced into the bullae of 32 chinchillas that were kept alive for four days to five months before histologic examination of their temporal bones. All the experimental animals had tissue damage and inflammation within the middle ear. The changes observed included proliferation of ciliated and secretory columnar cells, formation of granulation tissue, bone erosion, and osteoneogenesis. Some areas of the mucosa underwent metaplasia to stratified squamous epithelium; this metaplastic epithelium, however, did not produce keratin. In the majority of animals kept for two months or more, cholesteatoma was identified in the middle ear. The cholesteatomas appeared to develop as a result of penetration of external canal epidermis through intact tympanic membranes or as the result of migration of epidermis through perforations. The experimental cholesteatomas behaved like those seen clinically in humans, with extensive erosion of bony structures within the middle ear.

Inflammatory effects of otic drops on the middle ear.

Combination topical otic preparations are used to treat many infections of the external and middle ears. Despite the presence of ototoxic drugs in a number of these drops and convincing evidence of sensorineural hearing loss in humans and animal studies (Meyerhoff et al., presented at Southern Section Triological Meeting, Jan. 1983) following use of these medications, otic drops remain the cornerstone of treatment for many infectious disorders of the ear. Twelve chinchillas underwent bilateral tympanostomy tube placement and daily instillation of Cortisporin Otic Suspension (polymyxin B, neomycin, hydrocortisone, propylene glycol) in the right external auditory canal for 7 consecutive days. The animals were sacrificed 3 days later, 10 days following initiation of the Cortisporin Otic Suspension treatment. Following routine preparation of the temporal bones for light microscopy, the tissue was evaluated for evidence of inflammatory changes. All 12 animals demonstrated granulation tissue, effusion and focal hemorrhage in the ears subjected to the Cortisporin Otic Suspension. All of the contralateral control ears were normal. The present data suggest that this inflammatory response is due to a topical irritant effect of the otic preparation.

Ototoxicity of otic drops applied to the middle ear in the chinchilla

Previous studies have shown that the application of topical otic drops to the external ear canals of animals with patent tympanostomy tubes may result in hearing impairment and cochlear hair cell loss. Otic drops are used in patients with tympanostomy tubes or tympanic membrane perforations and could have deleterious effects on the human membranous labyrinth. This report describes the inner ear damage that occurred after direct application of aminoglycoside-containing otic drops to the middle ears of experimental animals. The membranous labyrinths of 25 chinchillas were studied two days to five months after application of Cortisporin otic suspension (which contains neomycin, polymyxin B, hydrocortisone, and propylene glycol) to the middle ear cavity. Application of 0.5 ml of Cortisporin resulted in degeneration of all inner and outer hair cells throughout the cochlea, as well as severe damage to the stria vascularis. Moderate to severe degeneration of the vestibular receptor organs was also observed. The endolymphatic sacs showed dark-staining endolymph, cellular debris, and macrophages in the sac lumina, as well as increased activity of the epithelial lining.

Tympanostomy tubes and otic drops.

Otic drops have been proposed as a form of prophylaxis against the otitis media which follows middle ear contamination by water in patients with tympanostomy tubes. The potential adverse effects of this form of therapy were studied in chinchillas with tympanostomy tubes; 31 chinchillas underwent bilateral tympanostomy tube insertion. Seven animals had a mixture of green dye and Cortisporin otic suspension placed in both external auditory canals 24 hours following the placement of tympanostomy tubes and were sacrificed 30 minutes later for gross examination; 3 of these animals had previous eustachian tube obstruction with Silastic sponge. Twenty-one animals had Cortisporin otic suspension placed in the right external auditory canal on postoperative days 3, 4, 5, 6 and 7. No otic drops were placed in the left ear. Ten of these 20 animals had VIIIth nerve action potentials measured on postoperative day 17 and the other 11 animals had VIIIth nerve action potentials measured on postoperative day 42 followed by immediate sacrifice for histological examination and scanning electronmicroscopy. The remaining 3 animals had VIIIth nerve action potentials measured 21 days following tympanostomy tube insertion and served as electrophysiological controls. The 8 ears receiving Cortisporin otic drops mixed with green dye from animals with normal eustachian tubes showed staining of the round window membrane at sacrifice, while the 6 ears receiving Cortisporin otic suspension and green dye from animals with eustachian tube obstruction demonstrated no dye in the middle ear. All animals receiving Cortisporin otic drops in the right ear showed an intra-aural difference in action potentials with the right ear being attenuated by an average of 10.3 dB at 2,000 Hz, 12 dB at 4,000 Hz, 21 dB and 8,000 Hz, and 26 dB at 12,000 Hz. Morphological study revealed hair cell loss in the hook portion of the cochlea in those animals receiving Cortisporin otic drops. It was concluded from this study that, in patients with patent tympanostomy tubes in place, potentially ototoxic topical agents should be used with caution.