Clinical Considerations for Routine Auditory and Vestibular Monitoring in Patients With Cystic Fibrosis.

Purpose Specific classes of antibiotics, such as aminoglycosides, have well-established adverse events producing permanent hearing loss, tinnitus, and balance and/or vestibular problems (i.e., ototoxicity). Although these antibiotics are frequently used to treat pseudomonas and other bacterial infections in patients with cystic fibrosis (CF), there are no formalized recommendations describing approaches to implementation of guideline adherent ototoxicity monitoring as part of CF clinical care. Method This consensus statement was developed by the International Ototoxicity Management Working Group (IOMG) Ad Hoc Committee on Aminoglycoside Antibiotics to address the clinical need for ototoxicity management in CF patients treated with known ototoxic medications. These clinical protocol considerations were created using consensus opinion from a community of international experts and available evidence specific to patients with CF, as well as published national and international guidelines on ototoxicity monitoring. Results The IOMG advocates four clinical recommendations for implementing routine and guideline adherent ototoxicity management in patients with CF. These are (a) including questions about hearing, tinnitus, and balance/vestibular problems as part of the routine CF case history for all patients; (b) utilizing timely point-of-care measures; (c) establishing a baseline and conducting posttreatment evaluations for each course of intravenous ototoxic drug treatment; and (d) repeating annual hearing and vestibular evaluations for all patients with a history of ototoxic antibiotic exposure. Conclusion Increased efforts for implementation of an ototoxicity management program in the CF care team model will improve identification of ototoxicity signs and symptoms, allow for timely therapeutic follow-up, and provide the clinician and patient an opportunity to make an informed decision about potential treatment modifications to minimize adverse events. Supplemental Material https://doi.org/10.23641/asha.16624366.

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.

Frequency of mitochondrial 12S ribosomal RNA variants in an adult cystic fibrosis population.

In adult cystic fibrosis patient populations, gram-negative bacteria, particularly Pseudomonas aeruginosa, frequently require aggressive therapy including systemic antibiotics, bronchodilators and airway clearance techniques. Aminoglycosides including tobramycin are used frequently to control these chronic airway infections. They, however, cause important nephrotoxic and ototoxic effects that can significantly alter the quality of life. We investigated the genetic predisposition to aminoglycoside ototoxicity in a typical unscreened North American cystic fibrosis population by screening for variants in mitochondrial 12S ribosomal RNA and noted several polymorphisms occurred at higher frequencies than expected and were associated with clinically significant cases of hearing loss. In the population studied, both patients possessing the 1555A>G transition exhibited profound ototoxicity after nontoxic dosing of tobramycin. We also identified new homoplasmic genetic variations in the mitochondrial 12S ribosomal RNA, several of which occurred in highly conserved regions of the gene and were present in patients with moderate-to-severe ototoxicity after exposure to aminoglycosides.

Transient emission suppression tuning curve attributes in relation to psychoacoustic threshold.

Ipsilateral suppression characteristics of transiently evoked otoacoustic emissions (TEOAEs) are described in relation to psychoacoustic threshold at 4000 Hz and the presence or absence of spontaneous otoacoustic emissions in 41 adults with normal hearing. TEOAE amplitudes were measured in response to 4000-Hz tonebursts presented in linear blocks at 40 and 50 dB SPL while puretone suppressors were introduced at a variety of frequencies and levels ipsilateral to and simultaneously with the tonebursts. Suppressors close to the toneburst frequency were most effective in decreasing the amplitude of the TEOAEs, while those more remote in frequency required significantly greater intensity for a similar amount of suppression. Consequently, characteristic tuning curve shapes were obtained. Tuning-curve tip levels were closely associated with the level of the toneburst and tip frequencies occurred at or above the toneburst frequency. Tuning-curve widths (Q10), however, varied significantly across subjects with similar psychoacoustic thresholds in quiet determined by a two-alternative forced-choice method. The results suggest that a portion of that variability may be explained by the presence or absence of spontaneous otoacoustic emissions in an individual ear.