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Keith A Rodvold

Publications and source records attributed to Keith A Rodvold.

21 records · Page 2Linked to original sources
PubMed2003

Steady-state plasma and bronchopulmonary concentrations of intravenous levofloxacin and azithromycin in healthy adults.

The purpose of this study was to compare the concentrations of levofloxacin and azithromycin in steady-state plasma, epithelial lining fluid (ELF), and alveolar macrophage (AM) after intravenous administration. Thirty-six healthy, nonsmoking adult subjects were randomized to either intravenous levofloxacin (500 or 750 mg) or azithromycin (500 mg) once daily for five doses. Venipuncture and bronchoscopy with bronchoalveolar lavage were performed in each subject at either 4, 12, or 24 h after the start of the last antibiotic infusion. The mean concentrations of levofloxacin and azithromycin in plasma were similar to those previously published. The dosing regimens of levofloxacin achieved significantly (P < 0.05) higher concentrations in steady-state plasma than azithromycin during the 24 h after drug administration. The respective mean (+/- standard deviation) concentrations at 4, 12, and 24 h in ELF for 500 mg of levofloxacin were 11.01 +/- 4.52, 2.50 +/- 0.97, and 1.24 +/- 0.55 micro g/ml; those for 750 mg of levofloxacin were 12.94 +/- 1.21, 6.04 +/- 0.39, and 1.73 +/- 0.78 micro g/ml; and those for azithromycin were 1.70 +/- 0.74, 1.27 +/- 0.47, and 2.86 +/- 1.75 micro g/ml. The differences in concentrations in ELF among the two levofloxacin groups and azithromycin were significantly (P < 0.05) higher at the 4- and 12-h sampling times. The respective concentrations in AM for 500 mg of levofloxacin were 83.9 +/- 53.2, 18.3 +/- 6.7, and 5.6 +/- 3.2 micro g/ml; those for 750 mg of levofloxacin were 81.7 +/- 37.0, 78.2 +/- 55.4, and 13.3 +/- 6.5 micro g/ml; and those for azithromycin were 650 +/- 259, 669 +/- 311, and 734 +/- 770 micro g/ml. Azithromycin achieved significantly (P < 0.05) higher concentrations in AM than levofloxacin at all sampling times. The concentrations in ELF and AM following intravenous administration of levofloxacin and azithromycin were higher than concentrations in plasma. Further studies are needed to determine the clinical significance of such high intrapulmonary concentrations in patients with respiratory tract infections.

Adult↗
PubMed2002

Efficacy and tolerability of extended-interval aminoglycoside administration in pediatric patients.

Aminoglycosides are commonly used to treat serious Gram-negative infections in pediatric patients. An effort to improve the efficacy and tolerability of this antibiotic class has led to evaluation of extended-interval aminoglycoside administration (EIAA). EIAA is designed to achieve higher peak plasma aminoglycoside concentrations, with relatively undetectable trough concentrations, when compared with conventional aminoglycoside administration (CAA), and is therefore expected to be markedly effective and to reduce drug accumulation and prevent nephrotoxicity and ototoxicity. Clinical trials evaluating EIAA in neonates included patients with suspected Gram-negative infections requiring short courses of aminoglycoside therapy. Consequently, comparative efficacy of EIAA versus CAA could not be assessed. In addition, ototoxicity was often not assessed, and nephrotoxicity was virtually undetectable. Similarly, trials evaluating EIAA versus CAA in infants and children have not demonstrated a difference in outcomes. The use of EIAA in children with febrile neutropenia has been evaluated primarily with amikacin. The incidences of nephrotoxicity and ototoxicity were low, and were similar between EIAA and CAA. No deaths were reported in any of these studies; however, this could be related to the inclusion of patients with undocumented bacteremia. Further investigation of EIAA is necessary in patients with documented bacteremia, since plasma aminoglycoside concentrations were undetectable for most of the dosage interval in children with febrile neutropenia who were treated once daily. Overall, clinical studies suggest that EIAA has similar efficacy to, and no higher risk of toxicity than, CAA in neonates, infants, and children. A few evaluations have also demonstrated that EIAA is cost-effective in neonates and in children with febrile neutropenia. Future studies evaluating the efficacy and tolerability of EIAA in pediatric patients with documented systemic infections should be prospective, randomized, controlled trials with sample sizes sufficient to detect differences between administration methods. Further evaluations should also address the optimal dosage and cost-effectiveness of EIAA in infants and children.

Aminoglycosides↗