Evaluation of high-dose tobramycin-carbenicillin therapy in pseudomonal infections in cystic fibrosis

Fourteen episodes of acute pseudomonal pulmonary exacerbations of cystic fibrosis were treated with high-dose tobramycin (10.1-17.1 mg/kg/d) and carbenicillin (600 mg/kg/d). The Sawchuck-Zaske method of dosing tobramycin was used and resulted in good agreement between the desired and measured peak (8.1 +/- 0.5 vs. 8.2 +/- 1.5 micrograms/ml) and trough (0.5 +/- 0.2 vs. 1.0 +/- 0.4 micrograms/ml) concentrations. Ninety-three percent of cases improved clinically. Forced expiratory volume in one second and forced vital capacity increased significantly (39.3 +/- 24.8, p less than 0.001 and 24.1 +/- 22.8 percent, p less than 0.05, respectively) after treatment. Pseudomonas aeruginosa was eradicated from the sputa of 69 percent of the cases, with recolonization occurring within three months. Significant nephrotoxicity and ototoxicity were not seen. Liver enzymes, however, were elevated in 29 percent of those treated. Combination high-dose carbenicillin and tobramycin satisfies the treatment goals of bacteriological and clinical cure with a minimal degree of toxicity.