Prospective cohort study of ototoxicity in persons with cystic fibrosis following a single course of intravenous tobramycin.

INTRODUCTION: Aminoglycoside (AG) antibiotics, such as tobramycin, are known to be ototoxic but important clinically due to their bactericidal efficacy. Persons with cystic fibrosis (CF) are at risk for AG-induced ototoxicity due to the repeated use of intravenous (IV) tobramycin for the treatment of pulmonary exacerbations. While it is well-established that ototoxic hearing loss is highly prevalent in this clinical population, the progression of hearing loss over time remains unclear. Cumulative IV-AG dosing has been associated with a higher risk of ototoxic hearing loss, yet some individuals lose substantial hearing after a single IV-AG treatment, while others never seem to lose hearing. METHODS: 31 persons with CF (18 on IV tobramycin, 13 controls) were enrolled in an observational study. Pure-tone hearing thresholds (0.25-16 kHz) were measured at baseline (pre-treatment) and at follow-up for each subject. A hearing shift was determined using various metrics, and outcomes were compared to characterize changes in hearing bilaterally for both study groups. RESULTS: Comparison of pure-tone threshold shifts between baseline and follow-up audiograms following either a course of IV tobramycin (n = 18) or no intervening therapy (n = 13) demonstrated significant (p < 0.05) threshold shifts in all continuous metrics tested. CONCLUSION: A single course of IV tobramycin causes ototoxic hearing loss in some people with CF, which supports the need for routine ototoxicity monitoring and management in this clinical population. These findings also suggest that people with CF are a suitable population for clinical trials examining ototherapeutics in single IV-tobramycin treatment episodes.

Negative hearing effects of a single course of IV aminoglycoside therapy in cystic fibrosis patients.

OBJECTIVE: Identify hearing effects of a single course of intravenous (IV) aminoglycoside antibiotics (AGs) therapy in adult cystic fibrosis (CF) patients. Determine whether the change is large enough to enable a proof-of-concept study of a new drug preventing AG-associated hearing loss. DESIGN: Retrospective case review of CF patients with sequential audiograms ± an intervening course of IV AG therapy. STUDY SAMPLE: 84 patients with no intervening IV AG treatment, 38 patients undergoing a single course of IV AGs. RESULTS: Using ASHA ototoxicity metrics, 45% of adult CF patients in the Single-IV group met the criteria for ototoxicity compared to 23% of the No-IV patients. Other hearing metrics including the average maximal threshold shift (TS) and average high frequency TS showed highly significant differences between groups. Testing only participants with mild or greater pre-therapy high frequency hearing loss further increased the differences between the two groups by every metric tested. CONCLUSION: Adult CF patients exposed to a single course of IV AGs have significantly greater TS than patients without IV AG exposure. Patients with mild to moderate hearing loss prior to AG-IVs are at increased risk of developing ototoxicity from subsequent parenteral AG therapy.

Progressive Hearing Loss among Patients with Cystic Fibrosis and Parenteral Aminoglycoside Treatment.

OBJECTIVE: Hearing loss is a significant and growing problem as patients with cystic fibrosis (CF) live longer and experience frequent courses of intravenous aminoglycoside antibiotics (hereafter, "IVs"). This study seeks to document that risk in a large adult population with CF, accounting for age and aminoglycoside exposure. STUDY DESIGN: Retrospective case review of patients with CF who had multiple audiograms over years. SETTING: Tertiary care cystic fibrosis setting. SUBJECT AND METHODS: The first and last audiograms recorded over a 10-year period were compared for 165 adult patients with CF. Patients were divided into 3 study groups: 34 patients with no intervening aminoglycoside IVs (0 IVs), 103 patients with 1 to 9 IVs, and 28 patients with ≥10 IVs. Threshold shift (TS) between the audiograms were examined for the 3 groups before and after age/sex adjustments. Two new hearing loss metrics were tested. RESULTS: At first examination, 48% of patients (average age, 30.0 years) already had hearing loss. At last examination (average, 4.4 years later), 64% of the patients had hearing loss even with age/sex adjustment. Use of the age/sex hearing threshold adjustment eliminated the TS in the 0 IVs group. Two new metrics calculated for each patient demonstrated that 48% of patients who had 1 to 9 IVs had ototoxic scores, while almost 80% of the ≥10 IV group had ototoxic scores. CONCLUSION: The majority of adult patients with CF are (often repeatedly) exposed to parenteral aminoglycosides and lose hearing at a rate that far exceeds that predicted from aging alone.