| Absence of Cochleotoxicity measured by standard and high-frequency pure tone audiometry in a trial of once- vs. three times-daily tobramycin in cystic fibrosis patients (Mulheran et al., 2006) |
Experimental study: randomized controlled trial. Web of Science, PubMed - indexed for MedLine |
244 patients with Cystic Fibrosis (CF) were included, of which 219 (125 children and 94 adults) underwent audiometry. Results were obtained for 168 of the total number of patients who completed treatment. |
Pure tone audiometry was performed throughout the frequency range of 0.25-8 kHz. High-frequency audiometry of 10-16 kHz. Audiometric tests were performed at the beginning of the treatment with tobramycin, at the end of a 14-day treatment, and 6-8 weeks later. |
No significant differences were detected in the auditory thresholds between treatment regimens. There was loss of hearing thresholds at high frequencies in both groups of treatment regimens. |
No cumulative cochleotoxicity risk was demonstrated in patients with CF due to repeated therapy with aminoglycosides, requiring a better characterization. |
| Aminoglycoside antibiotics cochleotoxicity in pediatric Cystic Fibrosis (CF) patients (Al-Malky et al., 2011) |
Observational cohort study: Web of Science, PubMed-indexed for MedLine |
45 children with cystic fibrosis (CF). 39/45 participants had received aminoglycosides (AGs), through intravenous (IV) route, 23 of them having received it repeatedly every 3 months. |
Audiometric tests and distortion-product otoacoustic emissions (DPOAE) were performed during routine visits to the CF outpatient clinic or when patients were hospitalized. Participants were grouped according to their prior history of AG exposure intravenously. |
In the high-exposure group, 8 (21%) had clear signs of ototoxicity; thresholds at 8-20 kHz were elevated by ∼50 dB. DPOAE amplitudes were >10 dB lower in f2 3.2-6.3 kHz. The remaining 31/39 (79%) patients exposed to treatment with AGs maintained normal hearing threshold. |
A significant number of children with CF had ototoxicity due to repeated courses of treatment with AGs intravenously. It is recommended to perform auditory tests in all CF patients with high exposure to AG. The occurrence of hearing loss (HL) was associated with high exposure; however, high exposure only resulted in HL in a minority of patients. Genetic analysis may help explain the dichotomy found in response to AGs. |
| Aminoglycoside ototoxicity in cystic fibrosis. Evaluation by high-frequency audiometry (McRorie, Bosso, Randolph, 1989) |
Observational study: paired case-control. Web of Science, PubMed - indexed for MedLine |
22 patients with Cystic Fibrosis (CF) treated with aminoglycosides (AGs). 13 of them were paired and compared to 38 individuals without CF, who had never received treatment with AGs. |
Audiometric tests were performed to measure hearing thresholds of 250-20,000 Hz. |
In patients with CF that were treated with AGs (younger than 20 years), there were statistically significant differences in frequencies > 16 kHz. CF patients who were treated with AG older than 20 years had elevated thresholds at all tested frequencies. CF patients who were not treated with AG did not differ statistically. |
The high-frequency audiometry can be a useful measure of the increase in hearing thresholds preceding the noticeable loss of hearing acuity in CF patients who are treated with long-term AGs. |
| Assessment of ultra-high frequency audiometry use in patients receiving ototoxic drugs (Weigert et al., 2013) |
Observational, cross-sectional study with unpaired control group. LILACS |
69 individuals aged 7-20 years of age. 35 patients regularly submitted to therapy with potentially ototoxic medication that were part of the study group (SG) and 34 healthy subjects that were the control group (CG). |
Conventional audiometry (250-8000 Hz) and audiometry at ultra-high frequencies (9000-16,000 Hz) were performed. |
There was one altered case in the conventional audiometry (2.9%) and 6 altered cases in the audiometry at ultra-high frequencies (17.1%) ( p = 0.063). The SG had statistically higher thresholds in relation to the CG in the conventional audiometry at the frequencies of 2 kHz and 8 kHz and, in the audiometry with ultra-high frequencies, at 10 kHz ( p = 0.004) and 16 kHz ( p < 0.001). |
The study suggested that the audiometry in ultra-high frequencies is useful for hearing monitoring in patients at risk for ototoxicity. |
| Cumulative and acute toxicity of repeated high-dose tobramycin treatment in cystic fibrosis (Pedersen et al., 1987) |
Observational, cross-sectional study. Web of Science, PubMed indexed for MedLine |
46 patients with Cystic Fibrosis (CF), mean age of 15.7 years and chronic bronchopulmonary infection by Pseudomonas aeruginosa . |
Patients were studied before and at the end of a two-week course of treatment with tobramycin (10-20 mg/kg per day) to discriminate between acute and chronic toxicity using audiometry and electronystagmography tests. |
Two patients (5%) had hearing loss at high frequency (above 8 kHz), but only one related to tobramycin. No chronic vestibular toxicity was observed. After 2 weeks of treatment, 32% had a slightly reduced hearing threshold (15-30 dB) at two or more high frequencies and 28% had a decrease in the superior vestibular response at 25% of the initial value, but remained within normal limits. |
The acute and chronic toxicity during treatment with high doses of tobramycin in CF patients seems to be very mild. |
| Hearing loss in cystic fibrosis (Martins et al., 2010) |
Observational, cross-sectional, descriptive study. Web of Science, PubMed indexed for MedLine |
120 patients with Cystic Fibrosis (CF) aged 5 months to 18 years. |
The study was carried out through questionnaires, audiometric testing and analysis of distortion-product otoacoustic emissions (DPOAE). The evaluation of prior use of aminoglycoside antibiotics (AGs) was performed by collecting data from medical records. |
Audiometric tests showed a 4-11% prevalence of sensorineural hearing loss. There was no statistically significant association between the use of AGs and hearing loss ( p = 0.48). |
Analysis of audiometric tests and DPOAE showed that there was a high prevalence of hearing loss, which makes CF patients a group of high risk that requires periodic hearing assessment. The comparison of the groups with and without use of AGs showed no statistically significant difference, suggesting that the use of AGs is not the only causal factor for hearing loss in CF. |
| High-frequency audiometry reveals high prevalence of aminoglycoside ototoxicity in children with cystic fibrosis (Al-Malky et al., 2015) |
Observational, cross-sectional, prospective study. Web of Science, PubMed - in process |
70 children with Cystic Fibrosis (CF). Mean age of 10.7 years. |
Hearing assessment was performed in children with CF using standard pure tone audiometry (PTA) and high frequency audiometry (HFA), as well as distortion-product otoacoustic emissions (DPOAE). |
Of the 63 children who received intravenous (IV) AGs, 15 (24%) had ototoxicity detected by HFA and DPOAE. PTA detected ototoxicity in 5 children (only at the frequency of 8 kHz, with hearing loss >20 dB HL) and 13 children with some non-significant change. A hearing loss of 25-85 dB HL at all high frequencies and a significant decrease in DPOAE amplitude at frequencies of 4-8 kHz were detected. There was a statistically significant difference ( p < 0.05) in the hearing threshold between the groups at high frequencies (8-16 kHz). |
Children with CF who received at least 10 AG courses through IV route had a higher risk of ototoxicity. HFA identified 2 children with ototoxicity more than PTA. Depending on the available facilities, HFA must be the test of choice for the detection of ototoxicity in children with CF who received treatment with AGs. |
| High frequency hearing thresholds and product distortion otoacoustic emissions in cystic fibrosis patients (Geyer, Barreto, Weigert, Teixeira, 2015) |
Observational cross-sectional, retrospective and prospective study with a control group.
MedLine PubMed-in process |
Children and adolescents from adult and pediatric Cystic Fibrosis (CF) outpatient clinics. The sample consisted of 75 individuals, 39 in the Study Group (SG) and 36 in the control group (CG). |
Existing data were used, from a database created earlier. Further tests were added to this database, by conducting pure tone audiometry (PTA), High-Frequency Audiometry (HFA) and distortion product otoacoustic emissions (DPOAE) in more patients from the Cystic Fibrosis Outpatient Clinic (SG) and Control Group (CG). |
The SG had significantly higher thresholds at 250, 1000, 8000, 9000, 10,000, 12,500 and 16,000 Hz; ( p = 0.004).
There was a significant association between changes in hearing thresholds in the HFA with the number of courses of aminoglycosides (AGs) that were carried out ( p = 0.005). 83% of patients who had more than 10 courses of AGs had hearing loss in the HFA. |
A significant number of CF patients who received repeated AGs courses showed changes in the HFA and DPOAE. Receiving 10 or more AG courses was associated with changes in the HFA. |
| Occurrence and risk of cochleotoxicity in cystic fibrosis patients receiving repeated high-dose aminoglycoside therapy (Mulheran et al., 2001) |
Observational cross-sectional, retrospective study with a control group. Web of Science, PubMed - indexed for MedLine |
70 patients with CF subdivided into groups; 27 pediatric patients (10-18 years) and 43 adults (19-37 years). Results were compared with the results of 91 individuals from the control group. |
Standard pure tone audiometry (0.25-8 kHz) and high-frequency audiometry (10-16 kHz) were performed. |
Of 70 patients with CF, 12 (one pediatric patient) had hearing loss considered to be caused by repeated exposure to aminoglycosides (AGs).
There was a nonlinear association between the therapy courses received and the incidence of hearing loss. Loss severity does not seem to be associated with the number of courses received. Preliminary risk estimates of hearing loss per AG course were less than 2%. |
After comparison with previous clinical studies and experimental work, these findings suggest that the incidence of cochleotoxicity in CF patients is considerably lower than expected, suggesting that the CF condition can confer protection against cochleotoxicity. |
