The cumulative effects of intravenous antibiotic treatments on hearing in patients with cystic fibrosis

Abstract

Background: Aminoglycosides (AGs) and glycopeptides are antibiotics essential for treating life-threatening respiratory infections in patients with cystic fibrosis (CF). The goal of this study was to examine the effects of cumulative intravenous (IV)-AG (amikacin and/or tobramycin) and/or glycopeptide (vancomycin) dosing on hearing status in patients with CF.

Methods: Hearing thresholds were measured from 0.25 to 16.0kHz, in 81 participants with CF. Participants were categorized into two groups: normal hearing in both ears (≤25dB HL for all frequency bands) or hearing loss (>25dB HL for any frequency band in either ear). Participants were also characterized into quartiles by their cumulative IV-AG (with or without vancomycin) exposure. Dosing was calculated using two strategies: (i) total number of lifetime doses, and (ii) total number of lifetime doses while accounting for the total doses per day. This was referred to as the "weighted" method.

Results: Participants in the hearing loss group were significantly older than those in the normal-hearing group. After adjusting for gender and age at the time of hearing test, participants in the two highest-quartile exposure groups were almost 5 X more likely to have permanent sensorineural hearing loss than those in the two lowest-quartile exposure groups. There was a small group of CF patients who had normal hearing despite high exposure to IV-antibiotics.

Conclusions: Cumulative IV-antibiotic dosing has a significant negative effect on hearing sensitivity in patients with CF, when controlling for age and gender effects. A trend for increasing odds of hearing loss was associated with increasing cumulative IV-antibiotic dosing.

Figure 1

Audiometric profiles ears in the lowest dosing group (Q1) up to the highest dosing group (Q4). Age (median and range) is also displayed for individual ears within each dosing quartile. Individual hearing thresholds across the conventional (0.25 to 8.0 kHz) and extended high frequency (9.0 to 16.0 kHz) ranges for participants in the lowest dosing group (Q1) up to the highest dosing group (Q4). The ear with the greatest degree of hearing loss for each participant is displayed. Participants who were older than the median age for each quartile are displayed in colored lines.

Figure 2. Odds ratios for association of cumulative IV dose for AG (± vancomycin) exposure

(Q1 = Referent; horizontal line at 1) Odds ratios for association of cumulative IV antibiotic dosing. There was a significant trend of increased odds of SNHL with increased dosing quartiles (p for trend = 0.01) when Q1 was used as the referent group.