Once-daily tobramycin in cystic fibrosis: better for clinical outcome than thrice-daily tobramycin but more resistance development?

Olaf Burkhardt, Christine Lehmann, Rajanikanth Madabushi, Vipul Kumar, Hartmut Derendorf, Tobias Welte
Journal of Antimicrobial Chemotherapy 2006, 58 (4): 822-9

OBJECTIVES: Once-daily administration of aminoglycosides in cystic fibrosis (CF) patients is considered equally efficacious and potentially less nephrotoxic than dosing three times a day. However, the choice of the most suitable PK/PD index (C(max)/MIC versus AUC(24)/MIC) to ensure optimum clinical outcome in this patient population is not clear.

PATIENTS AND METHODS: In a single-centre, open, randomized, controlled, non-blinded study 33 adult CF patients (20 females, 19-37 years) were treated with intravenous tobramycin (10 mg/kg/day) for 14 days given either as single dose once a day (Q24; 17 patients) or divided into three equal doses every 8 h (Q8; 16 patients). Tobramycin serum concentrations and MICs for Pseudomonas aeruginosa were determined on days 1 and 14. The clinical outcome parameter, correlated to PK/PD indices, was the percentage predicted forced expiratory volume in 1 s (FEV(1)% pred.).

RESULTS: FEV(1)% pred. improved significantly for both treatments. There was a log-linear relationship between C(max)/MIC and FEV(1)% pred. and AUC/MIC and FEV(1)% pred. for both treatments. For equal values of AUC24/MIC, however, Q24 treatment provided better improvement in lung function than Q8 dosing, whereas C(max)/MIC did not show any dosing interval dependence. A statistically significant increase was observed for MIC (day 1) versus MIC (day 14) for Q24 treatment, however, no such difference was observed for Q8 treatment.

CONCLUSIONS: The most important PK/PD parameter for clinical outcome in CF patients was C(max)/MIC. Outcome prediction of AUC(24)/MIC was dependent on the regimen. The increase of P. aeruginosa resistance after once-daily administration is linked to a long dosing interval. More and larger studies are needed to optimize the dosing regimen for maximum clinical outcome with minimum resistance development.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"