Cumulative and acute toxicity of repeated high-dose tobramycin treatment in cystic fibrosis

Pedersen, S S; Jensen, Tim; Osterhammel, Dorrit; Osterhammel, P.

doi:10.1128/aac.31.4.594

Cited by 66 publications

(59 citation statements)

References 39 publications

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“…These data show that in comparison with non-CF patient groups, the per-course exposure to tobramycin is greater by a factor of between 2 and 4. The results presented here are in line with those of previous reports of lower-than-expected acute and chronic cochleotoxicity in CF patients (18,20). The observations reported here may be explained either by the more rapid clearance of aminoglycosides in CF or, possibly, by the fact that the CF condition actually confers some protection against aminoglycosideinduced cochleotoxicity (18).…”

Section: Discussionsupporting

confidence: 82%

Absence of Cochleotoxicity Measured by Standard and High-Frequency Pure Tone Audiometry in a Trial of Once- versus Three-Times-Daily Tobramycin in Cystic Fibrosis Patients

Mulheran

Hyman‐Taylor

Tan

et al. 2006

Antimicrob Agents Chemother

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We undertook assessment of hearing in patients with cystic fibrosis who were taking part in a large randomized controlled trial of once-versus three-times-daily tobramycin for pulmonary exacerbations of cystic fibrosis (the TOPIC study). All patients were eligible to have standard pure tone audiometry performed across the frequency range of 0.25 to 8 kHz. High-frequency pure tone audiometry over 10 to 16 kHz was also performed with a subset of patients. Audiometry was undertaken at the start of tobramycin treatment, at the end of a 14-day course of treatment, and at follow-up 6 to 8 weeks later. We enrolled 244 patients, of whom 219 (125 children and 94 adults) completed treatment. Nineteen patients were excluded from analysis due to abnormal baseline audiometry. Complete pre-and posttreatment standard audiological data were obtained for 168/219 patients. We found no significant differences in hearing thresholds when they were assessed at the baseline, at the end of treatment, and at follow-up 6 to 8 weeks later were compared. In addition, no significant differences in hearing thresholds were detected between treatment regimens. Similar results were obtained for the subset of 63/168 patients who underwent high-frequency audiometry. We conclude that for a single 14-day course of tobramycin treatment in patients with cystic fibrosis with no preexisiting auditory deficit, no measurable effect on hearing was apparent with either once-or three-times-daily treatment. Estimation of the cumulative cochleotoxic risk in cystic fibrosis patients due to repeated aminoglycoside therapy, as evidenced by the patients excluded from this study due to hearing loss, also requires further characterization.

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Section: Discussionsupporting

confidence: 82%

Absence of Cochleotoxicity Measured by Standard and High-Frequency Pure Tone Audiometry in a Trial of Once- versus Three-Times-Daily Tobramycin in Cystic Fibrosis Patients

Mulheran

Hyman‐Taylor

Tan

et al. 2006

Antimicrob Agents Chemother

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“…Previous studies have found an increased risk of renal dysfunction after IV aminoglycoside exposure (3,5,20). IV aminoglycosides are directly toxic to the kidneys but the precise mechanism leading to nephrotoxicity remains uncertain (21).…”

Section: Discussionmentioning

confidence: 99%

Risk Factors for Chronic Kidney Disease in Adults with Cystic Fibrosis

Quon

Mayer-Hamblett

Aitken

et al. 2011

Am J Respir Crit Care Med

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Rationale: Adults with cystic fibrosis (CF) possess multiple potential risk factors for chronic kidney disease, including CF-related diabetes (CFRD) and lifetime nephrotoxic drug exposure. Objectives: To determine whether cumulative intravenous (IV) aminoglycoside exposure and CFRD increase the risk of chronic kidney disease in adults with CF. Methods: This was a cohort study using adults (> 18 yr) in the CF Foundation registry from [2001][2002][2003][2004][2005][2006][2007][2008]. Chronic kidney disease (stage 3 or greater) was defined by an estimated glomerular filtration rate of less than 60 ml/min/1.73 m 2 . Time-dependent multivariable Cox proportional hazards models were used to determine whether cumulative number of acute pulmonary exacerbations (surrogate for IV aminoglycoside exposure) and CFRD requiring insulin increase the risk of chronic kidney disease, adjusting for confounders. Measurements and Main Results: The study cohort included 11,912 adults with a median follow-up of 4 years. During the study period, 204 subjects had chronic kidney disease, with an annual disease prevalence of 2.3%. Disease prevalence doubled with every 10-year increase in age. CFRD requiring insulin therapy substantially increased the risk of chronic kidney disease (1-4 yr of CFRD requiring insulin vs. no CFRD, hazard ratio [HR] ¼ 2.40, 95% confidence interval [CI] 1.74-3.32; > 5 yr, HR ¼ 4.56, 95% CI 2.84-7.31). Pulmonary exacerbations did not significantly increase the risk of chronic kidney disease (one to five exacerbations vs. none, HR ¼ 0.79, 95% CI 0.56-1.11; six to nine exacerbations, HR ¼ 0.92, 95% CI 0.58-1.46; > 10 exacerbations, HR ¼ 1.16, 95% CI 0.75-1.81). Conclusions: CF-related diabetes is a significant risk factor for chronic kidney disease in adults with CF, but additional studies examining IV aminoglycoside exposure directly are required.

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“…day -1 of tobramycin [102] and netilmicin [120] has been associated with symptoms of dizziness after the antibiotic infusion. However, surprisingly few side-effects have been reported in high dose aminoglycoside therapy [89,121,122]. Nevertheless, it is necessary to monitor ototoxicity and renal function and adjust the dosage interval accordingly, early in therapy [64].…”

Section: Intravenous Antipseudomonal Antibiotic Therapy In Cystic Fibmentioning

confidence: 99%

Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus

Döring¹,

Conway²,

Heijerman³

et al. 2000

Eur Respir J

556

478

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Cystic fibrosis (CF) is the most common lethal hereditary disorder with autosomal recessive heredity in caucasians. The majority of CF patients suffer from chronic respiratory infection with the opportunistic bacterial pathogen Pseudomonas aeruginosa. No consensus among clinicians has been reached so far concerning antibiotic treatment against P. aeruginosa in CF patients.Consensus answers to 24 important questions in this context, based on current evidence, are presented, given by a panel of 34 European experts. Questions addressed and answered are: The diagnosis of P. aeruginosa lung colonization in CF; The impact of P. aeruginosa on the clinical state of CF patients; The assessment of P. aeruginosa susceptibility against antibiotics and the importance of these results for the clinician; The use of monotherapy versus combination therapy; The development of microbial resistance; The achievement of optimal airway concentrations; The effects of subinhibitory concentrations of antibiotics on P. aeruginosa; Statements on the pharmacokinetics of antibiotics in CF patients; Recommendations for doses and dosing intervals and length of treatment regimens; and Toxic side effects due to repeated antibiotic therapy was addressed.The expert panel answered further questions on the use of fluoroquinolones in children with CF, on the administration of nebulized antibiotics and whether prevention of P. aeruginosa lung colonization is possible in CF using antibiotic therapy.Problems of antibiotic therapy at home and in the hospital were addressed, a consensus statement on regular maintenance treatment, or treatment on demand, was given and different routes of administration of antibiotics were recommended for different clinical situations.Finally, the factors which determine the choice of the antibiotic, the dosage, and the duration of the treatment in cystic fibrosis patients were addressed and the design of future antibiotic studies in the context of Pseudomonas aeruginosa lung infection in cystic fibrosis patients were recommended. Eur Respir J 2000; 16: 749±767.

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Cumulative and acute toxicity of repeated high-dose tobramycin treatment in cystic fibrosis

Cited by 66 publications

References 39 publications

Absence of Cochleotoxicity Measured by Standard and High-Frequency Pure Tone Audiometry in a Trial of Once- versus Three-Times-Daily Tobramycin in Cystic Fibrosis Patients

Absence of Cochleotoxicity Measured by Standard and High-Frequency Pure Tone Audiometry in a Trial of Once- versus Three-Times-Daily Tobramycin in Cystic Fibrosis Patients

Risk Factors for Chronic Kidney Disease in Adults with Cystic Fibrosis

Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus

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