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Biomedical subjects

G L Fraser

Publications and source records attributed to G L Fraser.

39 records · Page 3Linked to original sources

Antibiotic optimization. An evaluation of patient safety and economic outcomes.

BACKGROUND: Although numerous reports have described interventions designed to influence antibiotic utilization, to our knowledge none have been evaluated in a randomized study. METHODS: Adult inpatients receiving 1 or more of 10 designated parenteral antibiotics for 3 or more days during a 3-month period were randomized to an intervention (n = 141) and a control (n = 111) group using an unblocked, computer-generated random number table. Obstetric patients and those seen in infectious disease consultation were excluded. The intervention group received antibiotic-related suggestions from a team consisting of an infectious disease fellow and a clinical pharmacist. Both groups were evaluated for clinical and microbiological outcomes as well as antibiotic utilization via prospective chart reviews and analysis of the hospital's administrative database. RESULTS: Sixty-two (49%) of the intervention group patients received a total of 74 suggestions. Sixty-three (84%) of these suggestions were implemented; the majority involved changes in antibiotic choice, dosing regimen, or route of administration. Per patient antibiotic charges were nearly $400 less in the intervention group vs controls (P = .05). Almost all the savings were related to lower intravenous antibiotic charges. Clinical and microbiological response, antibiotic-associated toxic effects, in-hospital mortality, and readmission rates were similar for both groups. Multiple linear regression analysis identified randomization to the intervention group and female sex as the sole predictors of lower antibiotic charges. There was a trend toward a shorter length of stay for the intervention group (20 vs 24.7 days, P = .11). CONCLUSIONS: This is the first randomized study to evaluate whether antibiotic choices can be influenced in a cost-effective fashion without sacrificing patient safety. We demonstrate that 50% of patients initially treated with expensive parenteral antibiotics can have their regimens refined after 3 days of therapy and that these modifications result in good clinical outcomes with a substantial reduction in antibiotic expense.

Administration, Oral↗

Valproic acid pharmacokinetics in children: III. Very high dosage requirements.

Nine children were studied who required very high doses of valproic acid (VPA) (63.6-105 mg/kg/day) in order to achieve VPA serum concentrations between 50-100 micrograms/ml. These nine children had poorly controlled seizures and were receiving other antiepileptic drugs at the time of this study. The children with very high dose requirements were significantly lighter, shorter, and had less body surface area than the control group. Of the pharmacokinetic parameters studied, total and intrinsic clearance, distribution volume, and valproic acid free fraction were significantly increased in the very high dose group. In three patients who were investigated after co-medications were eliminated, clearances and dosage requirements decreased by more than 50%. We concluded that very high VPA dosages are sometimes required to achieve therapeutic serum drug concentrations and that this therapy occasionally improves seizure control. There were no adverse effects of very high dose therapy that required dosage reduction.

Adolescent↗

Treatment of Nongonococcal bacterial septic arthritis.

Septic arthritis carries significant morbidity and mortality, necessitating prompt, appropriate therapy with joint fluid aspiration, intravenous antibiotics, and occasionally, surgical intervention. The initial choice of antimicrobial agent is guided by the results of synovial fluid gram stain, by identification of the pathogenesis of the primary focus, or by epidemiologic factors. Adequacy of therapy is assessed by serial synovial fluid white blood cell counts and by determining antimicrobial concentrations in the joint space. The goal of treatment is a clinically normal and sterile joint. Factors that may affect antimicrobial joint penetration include the degree of joint tissue inflammation, the degree of drug protein binding, and the chemical characteristics of the drug. Perhaps most important in determining the extent of joint penetration are factors that may affect serum antibiotic concentrations, for example, dose, route of administration, volume of distribution, but rate of elimination.

Anti-Bacterial Agents↗