Moxifloxacin-induced tinnitus in an older adult

Abstract

An increased risk of bacterial resistance toward fluoroquinolones and the increased risk of disabling and serious adverse effects prompted the US Food and Drug Administration to recommend limiting fluoroquinolone use to the treatment of community-acquired pneumonia, skin and skin-structure infections, bacterial sinusitis, plague, chronic bronchitis exacerbations, and complicated intra-abdominal infections. We report a case of moxifloxacin-induced tinnitus in an older adult prescribed oral moxifloxacin 400 mg for 5 days for the treatment of acute diverticulitis, due to allergies to nonfluoroquinolone preferred agents. A thorough literature review provided few other reported incidents of this rare and serious adverse event.

Introduction

Moxifloxacin is a broad-spectrum fluoroquinolone antibiotic used to treat ophthalmic and systemic bacterial infections. Oral moxifloxacin is approved by the US Food and Drug Administration (FDA) to treat community-acquired pneumonia, skin and skin-structure infections, bacterial sinusitis, plague, chronic bronchitis exacerbations, and complicated intra-abdominal infections.¹ An increase in microbial resistance and increased risk of potentially permanent disabling side effects involving tendons, muscles, joints, nerves, and the central nervous system has prompted the FDA to recommend limiting the use of oral fluoroquinolone antibiotics.² Commonly reported adverse drug reactions (ADRs) associated with moxifloxacin or other fluoroquinolones include gastrointestinal upset (e.g. nausea, vomiting, and diarrhea), central nervous system toxicities (e.g. seizures, dizziness, and headache), and rash. Rare ADRs associated with fluoroquinolone use include tendon rupture or tendonitis, QTc prolongation, and peripheral neuropathy.¹ Moxifloxacin or other fluoroquinolone- associated tinnitus is reported in less than 1% of patients, per the product label, and a literature review of fluoroquinolone-associated tinnitus revealed very few reports.^1,4 This report discusses a further case of moxifloxacin-induced tinnitus that occurred during a 5-day course for the treatment of acute uncomplicated diverticulitis. Ethics approval is not required at the institution for case reports. In addition, verbal consent from the patient was obtained and documented within the electronic medical record. Written consent was unable to be obtained since the interaction took place over the telephone and the patient was unable to drive to the clinic.

Case report

A 76-year-old woman was admitted to the hospital due to acute uncomplicated diverticulitis. Her past medical history included dyslipidemia, hypertension, coronary artery disease, and gastroesophageal reflux disease. The patient reported allergies to metronidazole (shortness of breath and hives), penicillin (rash), and sulfonamide antibiotics (rash). Although not listed as an allergy, a review of the patient’s medical history revealed a prior incident of shortness of breath when levofloxacin 750 mg daily was used to treat a flare of her acute diverticulitis 5 years earlier. Medications on admission and continued after discharge included calcium, vitamin D, vitamin B complex, clopidogrel, carvedilol, pantoprazole, simvastatin, and low-dose aspirin.

Despite her allergy to penicillin, a single empiric dose of ertapenem 1000 mg was given intravenously (IV) on admission to treat her diverticulitis. After consulting with the infectious disease team, the patient was transitioned to moxifloxacin 400 mg IV daily on day 2 of her hospitalization and then transitioned to oral moxifloxacin 400 mg daily on day 3. The patient received two doses of moxifloxacin during her hospital stay, on days 3 and 4, and was later discharged home with a 5-day course to complete therapy. Based on the 2010 Surgical Infection Society and Infectious Disease Society of America guidelines on the management of intra-abdominal infections, metronidazole in combination with ciprofloxacin, sulfamethoxazole/trimethoprim, or amoxicillin/clavulanate are the preferred treatment regimens.³ However, our patient had allergies to the nonfluoroquinolone agents, thus moxifloxacin was an appropriate alternative.

After the third dose of moxifloxacin (day 3 of oral therapy), during a discharge follow-up phone call, it was discovered that the patient had mild ringing/buzzing in both ears, starting approximately 2–3 h after her dose and continuing consistently for several hours. The ringing reoccurred with each dose at home and continued throughout her 5-day outpatient moxifloxacin course. The patient stated the ringing stopped approximately 8 h after her last oral moxifloxacin dose. Since completion of therapy, the patient has reported no further tinnitus and denied any episodes of deafness.

Using the Naranjo Adverse Drug Reaction Probability Scale, a score of 5 was calculated for our patient indicating a probable chance that moxifloxacin contributed to her adverse reaction. The score was calculated based on the following factors: previous conclusive reports of this reaction, the ADR appeared after the drug was administered, the ADR ceased when the drug was discontinued, and there were no alternative causes for the ADR.⁵

Discussion/implications for clinical care

Since the 1990s there have been rare reports of tinnitus occurring during fluoroquinolone therapy. A 1995 British Medical Journal article reported an occurrence of tinnitus in a 57-year-old man after he was given ciprofloxacin 750 mg twice daily.⁴ The patient reported that the tinnitus started 10–30 min after administration of ciprofloxacin and continued for several hours after each dose. For unknown reasons the patient did not report the tinnitus to medical staff until day 8 of therapy and also admitted to experiencing buzzing and deafness after 3 days of therapy. Ciprofloxacin was stopped on day 9 of therapy, after the patient reported tinnitus following his morning dose. The reported tinnitus resolved within 6 h upon discontinuation of ciprofloxacin.⁴ The authors noted the patient had no pre-existing neurological abnormalities, normal renal function, and was taking aspirin, amiodarone, diclofenac sodium, and bumetanide for months without side effects.⁴ In addition, the patient’s ciprofloxacin concentrations were not elevated.

Our patient reported tinnitus occurring daily with each moxifloxacin dose at home and her tinnitus resolved upon discontinuation of the moxifloxacin. The patient’s tinnitus was self-reported and not confirmed by an audiologist. Tinnitus has been associated with the use of nonsteroidal anti-inflammatory drugs, particularly aspirin.⁶ Aspirin-induced tinnitus is typically caused by large consumptions (> 3.6 g/day) of aspirin, or serum concentrations greater than 0.2 mg/L, and reversible upon discontinuation, typically within 1–3 days.^7–10 We were unable to find any reports of low-dose aspirin-induced tinnitus. There was a case report of aspirin-induced tinnitus in a 25-year-old woman who had been taking high-dose aspirin, 80 mg/kg/day, for 3 years for severe arthritis.⁹ Authors attributed her tinnitus to increases in unbound salicylate, caused by the patient’s hypoalbuminemia. A urinalysis revealed the patient had severe albuminuria (+4 protein) and a serum albumin of 1.74 µmol/L.⁹ Our patient had been taking low-dose aspirin daily for 9 years when she reported tinnitus with moxifloxacin and her albumin level was normal. We excluded aspirin as contributing to her tinnitus based on her 9-year history with no prior reports of tinnitus, either before or after, her moxifloxacin use. In addition, a urinalysis performed during her hospital stay was negative for protein and laboratory results did not show hypoalbuminemia.

During a review of our patient’s medical record, it appears the patient received a 10-day supply of levofloxacin for treatment of Helicobacter pylori, 5 years prior to moxifloxacin exposure, and did not experience tinnitus. Due to her previous exposure to fluoroquinolones, a prior history of tinnitus was excluded. Based on the onset and discontinuation of reported tinnitus from our patient, the exclusion of other possible contributory factors (medications, age association, prior history of or chronic tinnitus) and a Naranjo score of 5, it is probable that the reported case of tinnitus was induced by moxifloxacin. In addition, moxifloxacin is widely distributed, specifically in sinus tissues.¹ Due to the proximity of sinus tissues to the ear this may increase the likelihood of experiencing tinnitus.

Conclusion

Tinnitus and hearing loss may be overlooked as a potential drug-induced side effect, especially in older adults, where declining age and increasing frailty can be blamed for new symptoms. Even though the association of tinnitus and/or hearing loss with administration of a fluoroquinolone is rare, it is important that patients presenting with ringing in the ears or deafness during fluoroquinolone use be evaluated to determine if the fluoroquinolone is contributing.