Ciprofloxacin/dexamethasone precipitate formation in the ear canal of a paediatric patient

Abstract

This case report describes a paediatric patient diagnosed with otitis externa and treated with topical ciprofloxacin/dexamethasone. The patient completed the course of therapy and then developed precipitate formation from the pharmacological treatment. Laboratory testing of the precipitate confirmed the presence of a large quantity of ciprofloxacin. Removal of the precipitate required the use of an elephant ear washer system and removal with surgical tweezers. This case report investigated a probable topical ciprofloxacin/dexamethasone-induced ear precipitate formation in the ear canal, which, subsequently, was successfully removed from the patient’s ear canal.

Background

Otitis externa involves diffuse inflammation of the external ear canal that may extend distally to the pinna and beyond.¹ Most cases of otitis externa are caused by a bacterial infection. The two most common isolates are Pseudomonas aeruginosa and Staphylococcus aureus, necessitating the use of topical antimicrobials with or without topical corticosteroids.¹ Ciprofloxacin/dexamethasone is a commonly prescribed otic suspension in the USA for the treatment of bacterial infections of the outer ear. Ear precipitate formation has been reported in ciprofloxacin/dexamethasone, ciprofloxacin and ofloxacin otic suspensions in children with acute otitis externa.^2–4

Case presentation

A 13-year-old otherwise healthy girl attended a 2-week summer camp, where she participated in various water sports. On returning home, she reported significant ear discomfort. A visit to her paediatrician revealed inflammation of the external ear canal characterised by redness and swelling leading to the diagnosis of otitis externa.

The paediatrician prescribed topical ciprofloxacin/dexamethasone 0.3%–0.1% otic suspension with the directions to instil four drops into the affected ear two times per day for 7 days. The pharmacist instructed the patient’s mother to shake the medication bottle prior to each use. The patient was not taking any other medications and had no significant prior medical history.

The pain and discomfort from the infection resolved following a 7-day course of treatment; however, the patient began complaining of new symptoms almost immediately after cessation of the ear medication. According to the patient, ‘she could not hear well out of that ear, felt something was crawling in her ear, and it was itching.’ No additional medication was used to alleviate the patient’s symptoms. A return visit to the paediatrician revealed the otitis externa resolved; however, the eardrum appeared to be covered in a ‘white sandy’ substance. The paediatrician rinsed the patient’s ear using an elephant ear washer system which removed a significant amount of white particles. Inspection of the ear canal revealed additional white particles adhering to the patient’s tympanic membrane. The particles were not attributed to debris from the patient’s recent visit to camp. After rinsing, the paediatrician decided the patient should be referred to an ear nose and throat (ENT) physician. On examination the next morning, the ENT physician used a microscope to identify the offending agent and removed it with surgical tweezers. Visual examination revealed a cast of the tympanic membrane due to precipitate (measuring approximately 1.2 cm in length) being stuck to the cerumen inside the patient’s ear (figure 1).

Figure 1.

Precipitate removed from patient’s ear.

Investigations

To confirm if the substance was the result of ciprofloxacin/dexamethasone precipitation, the offending agent removed from the patient’s ear was analysed using liquid chromatography with tandem mass spectrometry at the Infectious Disease Pharmacokinetics Laboratory at the University of Florida. 4.62 mg of the sample (approximately half) was dissolved overnight in 100% acetonitrile. The sample was then analysed for fluoroquinolones. The sample’s calculated concentration was approximately 600 µg/mL, which was an imprecise extrapolation due to the concentration testing well above the highest calibrator.

Treatment

The child remained well following the removal of the precipitate and no further treatment was required.

Outcome and follow-up

Both the irritation and hearing loss were resolved following removal of the precipitate. The child was considered discharged from care, and no audiometry was considered necessary.

Discussion

Otitis externa is a common condition treated with topical medications such as ciprofloxacin/dexamethasone 0.3%–0.1%. The mechanism of ciprofloxacin/dexamethasone induced ear precipitation is unknown. We hypothesise that ciprofloxacin may chelate with multivalent cations found in cerumen, causing the precipitate to adhere to the cerumen, resulting in a cast on the patient’s eardrum. Patients being treated with this medication should be warned of this possibility. A follow-up visit should be scheduled in an effort to ensure any precipitate is addressed, or if an alternative treatment should be considered.

A Naranjo score of 8 indicates an adverse drug reaction due to ciprofloxacin/dexamethasone as probable.⁵ Because the mechanism of ear precipitate formation is unclear, clinicians should be alert to the possibility of the substantial aggregate formation when unexpected events occur following the use of otic preparations containing ciprofloxacin/dexamethasone, ciprofloxacin or ofloxacin.^2–4

Effective alternative pharmacological treatment options for uncomplicated otitis externa include topical aluminium acetate or topical antibacterial agents. For example, topical aminoglycoside/steroid preparations may be used which is associated with less precipitate accumulation but would need to be used with caution in patients with suspected perforations or ventilation tubes in situ due to the potential risk of ototoxicity with these agents.¹ One topical antibacterial regimen has not demonstrated superiority over another. Systemic antibiotics have not been shown to be beneficial in uncomplicated cases.¹ A lack of evidence exists for topical corticosteroids when used alone; however, they are likely to be beneficial when used in combination with antibacterials.¹ In conclusion, this case report highlights the management and awareness of ciprofloxacin/dexamethasone-induced precipitate aggregation. Referral to an ENT physician is encouraged if further ear precipitation removal is necessary.

Patient’s perspective.

Having the ear infection was a very unpleasant experience because of the pain. This was worse. I felt like there was something crawling inside of my ear and the itching was driving me crazy. In addition, I could not hear out of my ear. The only time it wasn’t bothering me was when I was asleep but as soon as I would get up in the morning it would start again. The crawling and itching was constant and my hearing was muffled. I was very afraid that a bug had crawled into my ear. Fortunately, once the doctor removed the precipitant from my ear, the crawling and itching went away and my hearing was immediately restored.

Learning points.

• Most cases of otitis externa are caused by a bacterial infection.

• Instruct patients to shake the ciprofloxacin/dexamethasone container.

• The formation of a precipitate can be large enough to produce unpleasant symptoms for the patient, necessitating a referral to an ear, nose and throa specialist for careful removal under an operating microscope.