MINIMIZATION OF AMINOGLYCOSIDE TOXICITY IN PATIENTS WITH CYSTIC-FIBROSIS

Background - There is evidence that administration of higher doses of aminoglycosides given less frequently improves the bactericidal effect and reduces the potential to cause side effects. To investigate this, a prospectively randomised open label therapeutic trial was undertake n in stratified groups of patients with cystic fibrosis to examine the efficacy and toxic potential of an aminoglycoside dosing regimen desi gned to generate high peak drug concentrations at 12 hourly intervals compared with conventional dosing at eight hourly intervals. Methods - Patients in group A received tobramycin eight hourly using a dose aim ed at generating a peak concentration of 10 mg/l with trough concentra tions below 2 mg/l, and those in group B received the total daily dose required to achieve eight hourly target concentrations administered a s two equal 12 hourly doses. Clinical outcomes measured and assessed i ncluded vestibular symptoms, hearing and renal function, length of hos pital stay, readmission rate, and mortality. Results - Twenty nine pat ients were recruited during a six month period, 20 to group A and nine to group B. The average peak tobramycin level was higher in group (12 .5 (2.2) mg/l) than in group A (7.9 (1.9) mg/l), whilst the average tr ough level was higher in group A (0.8 (0.3) mg/l) than in group B (0.5 (0.2) mg/l). There was a difference in the number of ototoxic events between patients in group A (seven of 18, 38.9%) and group B (none of eight), but no difference was found in other outcome measures assessed . Conclusions - These results suggest that 12 hourly high peak aminogl ycoside dosing may be less toxic than equivalent eight hourly dosing, without any apparent difference in efficacy.