Glomerular and Tubular Renal Function after Repeated Once-Daily Tobramycin Courses in Cystic Fibrosis Patients

Abstract

Introduction. Antibiotic treatment regimens against Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) patients often include aminoglycoside antibiotics that may cause chronic renal failure after repeated courses. Aminoaciduria is an early marker of acute aminoglycoside-induced renal tubular dysfunction. We hypothesized that urinary amino acid reabsorption is decreased after repeated once-daily tobramycin therapies. Methods. In this prospective cross-sectional study creatinine clearance was estimated by the Schwartz and the Cockcroft-Gault formula. Tubular amino acid reabsorption was determined by ion exchange chromatography in 46 patients with CF who received multiple tobramycin courses (6.3 ± 10.1 (1–57)) in a once-daily dosing regimen and 10 who did not. Results. Estimated creatinine clearance employing the Cockcroft-Gault was mildly reduced in 17/46 (37%) of the patients who received tobramycin and 5/10 (50%) of the patients who did not but in none using the Schwartz formula. No association with lifetime tobramycin courses was found. Tubular amino acid reabsorption was not influenced by the amount of once-daily tobramycin courses. Conclusion. Clinically not significant reduction of eCCL occurred in a minority of CF patients. However, chronic tubular dysfunction was not present in patients with CF repeatedly treated with tobramycin in the once-daily dosing scheme.

Exposure to an Extended-Interval, High-Dose Gentamicin Regimen in the Neonatal Period Is Not Associated With Long-Term Nephrotoxicity

“…In line with some others ( 43 ), we found no signs of chronic tubular dysfunction after prior therapy with aminoglycosides. In contrast, in a retrospective study of children who developed nephrotoxin-induced AKI (after ≥3 days of aminoglycosides or ≥3 nephrotoxins simultaneously for 1 day), the relative risk of developing signs of CKD 6 months later was 3.84 (95% CI 1.57–9.40) compared to nephrotoxin-exposed controls who did not develop AKI ( 9 ).…”

Free and Nanoencapsulated Tobramycin: Effects on Planktonic and Biofilm Forms of Pseudomonas

“…Like other aminoglycosides, tobramycin targets the bacterial ribosome, such that bacterial resistance, although rare, mainly involves impermeability and the acquisition of aminoglycoside-modifying enzymes, encoded either on a plasmid or within the genome by transposable elements [ 7 ]. However—despite their chemical stability, fast bactericidal effect, synergy with ß-lactam antibiotics, and low incidence of resistance—aminoglycosides are of limited utility because of their nephrotoxicity [ 8 , 9 ]. While tobramycin is less nephrotoxic than gentamicin and other aminoglycosides and has been successfully used against P. aeruginosa [ 10 ], planktonic bacteria are much more sensitive than bacteria in biofilms, the growth form occurring in the lower respiratory tract of CF patients.…”

A randomised controlled trial of rosuvastatin for the prevention of aminoglycoside-induced kidney toxicity in children with cystic fibrosis

“…In one cohort of adults with CF, between 31% and 42% had evidence of chronic renal impairment which was significantly associated with cumulative aminoglycoside exposure 7 . However, this has not been replicated in other cohorts 8,9 . Strategies such as therapeutic drug monitoring and extended-interval dosing 10 are only partially effective in preventing aminoglycoside-induced nephrotoxicity.…”