Increased dosing requirements for amikacin in burned children.

Pharmacokinetic analysis was performed on 38 thermally injured children ranging from 3 months to 18 years of age with per cent total body surface area burns (%TBSA) of 17-87%. All patients needed increased dosing requirements for amikacin to maintain therapeutic serum levels. There was a wide variation in the volumes of distribution and an inverse relationship with age, i.e., the volume of distribution tended to be lower in the older children. The results indicate the manufacturer's recommended dose will result in subtherapeutic serum levels and we recommended initial doses of at least 10 mg/kg administered every 6 h. Dosage adjustments using individualized pharmacokinetics should then be performed within 24 h of initiation of therapy. The study documents the importance of dosage individualization for amikacin in the burned child.

Inability to justify a part-time clinical pharmacist in a community hospital intensive-care unit.

The potential for justifying the cost of a part-time clinical pharmacist position was evaluated. Patients in the medical and surgical intensive-care units of a community hospital were monitored two hours per day for 32 weekdays by a part-time staff pharmacist. The pharmacist completed an initial review of the charts of all patients newly admitted to the units and further evaluated each medical record for at least five minutes each day to determine the need for drug therapy interventions. The pharmacist contacted physicians to make any recommendations for changes in therapy. At the end of the study, the pharmacist calculated the difference in the costs of the original and recommended drug regimens for all recommendations accepted by physicians. A total of 147 patients were monitored during the 32-day period. There were 122 recommended interventions for 60 patients, and 101 (83%) of these recommendations were accepted. Estimated drug cost savings totaled $1651.35, but the cost of the pharmacist, $2599.35, resulted in a net cost to the hospital of $948. There was no significant difference in drug cost savings with respect to the day of the week when the monitoring was performed, the time of day, or the interaction of day with time. A part-time clinical pharmacist in the intensive-care unit of a community hospital reduced the costs associated with drug therapy, but the savings realized were not sufficient to offset the cost of the position.

Selecting patients for monoclonal antibody therapy.

The role of the pharmacist in defining and implementing criteria for selection of patients who are most likely to benefit from monoclonal antibody therapy is discussed. The introduction of new biotechnology products has raised concerns about rationing of health-care services, particularly in view of the costs of drug research and development. Traditional antimicrobial therapy has not reduced morbidity and mortality from gram-negative sepsis. Early clinical trials indicate that immunotherapy with new agents that supplement the host immunological response to these infections may be effective. Criteria must be developed to identify patients who will obtain maximum benefits from these newer interventions. Severity-stratification systems (e.g., the APACHE II scoring system) have been used to classify disease and monitor treatment outcome. These techniques have been applied in clinical trials assessing E5 monoclonal antibody therapy in patients with gram-negative sepsis and in others evaluating the use of imipenem versus tobramycin and clindamycin in the treatment of intraabdominal infection. Pharmacists with a knowledge of infectious-disease processes and pharmacotherapeutics can play a major role in developing criteria for identifying patients who are most likely to benefit from the products of biotechnology and thereby ensuring the cost-effective use of these products.

Fat emulsion effects on prothrombin time in warfarin anticoagulated patients: an in vitro study.

The effect of lipid emulsions on prothrombin time in blood from anticoagulated patients was determined. Blood samples were obtained from 23 patients therapeutically anticoagulated with warfarin (prothrombin time 1.3-2.0 x control). Varying amounts of an intravenous lipid emulsion (Intra-lipid) were added to the blood to simulate concentrations seen in vivo with a constant lipid infusion. The prothrombin time was measured on the plasma from these samples and compared to the prothrombin time of the plasma samples without lipid. The mean decrease in prothrombin times were: 0.29 sec at 50 micrograms/ml, 0.23 sec at 100 micrograms/ml, and 0.29 sec at 200 micrograms/ml. All concentrations showed a statistically significant decrease (p less than 0.05) when compared to the control by the Scheffe test. Lipid emulsions appear to decrease the prothrombin times in anti-coagulated patients. The differences however, were small and not of clinical significance at the concentrations tested.

The effect of "superactive" charcoal and magnesium citrate solution on blood ethanol concentrations and area under the curve in humans.

Eleven healthy males between 21 and 37 years of age were enrolled into a non-randomized crossover study comparing superactive charcoal (SAC) given after ethanol administration. After receiving 0.6 gm/kg ethanol orally (95% V/V diluted in orange juice), blood was sampled at 0, 0.5, 1.0, 1.5, 2.0, 3.0, and 4.0 hours. Area under the curve (AUC) was calculated and the highest ethanol level was recorded. After a minimum of 1 week washout, the volunteers ingested an identical ethanol dose but in addition received 60 grams of SAC and 300 ml of 5.8% magnesium citrate solution 1 and 3 hours post ingestion. The data was compared using the paired t-test with p less than 0.05 considered significant. Nine volunteers completed the study. Volunteers had difficulty ingesting the full second 60 gram SAC dose. The AUC (mean 1184 mcg x hr/ml) and highest ethanol concentrations (mean 46.3 mg/dl) for the control group were not significantly greater than in the SAC group (mean AUC 1167 mcg x hr/ml and highest ethanol concentration of 49.0 mg/dl). The ethanol concentration in the SAC group was significantly less than control only at 2.0 hours (31.6 mg/dl vs 36.6 mg/dl, p less than 0.01). The peak ethanol concentration in the SAC group occurred at 1.0 hours in 7 of 9 volunteers, while in the control group, peak concentration occurred randomly between 0.5 and 2.0 hours. We conclude SAC in the dose used is not effective in decreasing AUC, highest ethanol concentration, and blood ethanol levels when given 1 and 3 hours after ethanol ingestion.

Cefuroxime axetil.

Cefuroxime axetil is a orally active prodrug formulation of cefuroxime, which upon absorption undergoes immediate deesterification to free cefuroxime. Cefuroxime axetil offers an in vitro antibacterial spectrum against many gram-positive and some gram-negative organisms. Its beta-lactamase stability makes it useful in treating a variety of infections caused by beta-lactamase-producing strains of Haemophilus influenzae, Branhamella catarrhalis, and Staphylococcus aureus. Cefuroxime axetil has good activity against the Enterobacteriaceae and moderate activity against non-Bacteroides fragilis anaerobes. Clinical studies suggest it is at least as effective as ampicillin, amoxicillin, amoxicillin/clavulanic acid, penicillin V, or cefaclor in the treatment of uncomplicated urinary tract infections, acute otitis media, upper respiratory infections, skin and soft tissue infections, and uncomplicated gonorrhea.

Controversies in antimicrobial therapy: pitfalls in monitoring aminoglycoside therapy.

Efficacy, safety, and cost factors related to aminoglycoside therapy, which is the treatment of choice for mixed infections of the skin, respiratory tract, and abdominal cavity, are reviewed. The cost of therapy must include all measurable costs of drug preparation, administration, monitoring, and potential toxicity or treatment failure. These costs are often difficult to quantify, as are potential differences in efficacy. Aminoglycosides are usually given by injection and are excreted unchanged by the kidneys. They are concentrated in the renal cortex, leading some investigators to assess the correlation of this uptake with renal toxicity. An increase in serum aminoglycoside concentrations serves as a retrospective, nonspecific marker of the renal toxicity that occurs in up to 35% of patients receiving these drugs. Pharmacokinetic monitoring of aminoglycoside therapy is used to assure therapeutic drug concentrations. Blood samples for aminoglycoside assays must be drawn, stored, separated, and assayed correctly, and the timing and labeling of the sample is of utmost importance. Nomograms and pharmacokinetic models, which can be used with computers and hand-held calculators, are useful for predicting initial doses and modifying subsequent doses. Aminoglycoside therapy is important in selected patients, but the comparative efficacy and safety of these drugs remains insufficiently assessed. Pharmacokinetic monitoring is helpful in assuring safe and effective dosing of aminoglycosides.

Cost-effectiveness analysis as a tool to compare two methods of preparing and administering intravenous heparin solutions.

Thirty-six patients who received heparin infusions were prospectively monitored to determine costs involved in preparation and administration of heparin solutions and to determine the most cost-effective heparin concentration. Thirty-five courses of therapy were evaluated. All patients were treated with intravenous (IV) heparin in variable concentrations to allow for delivery of 20 ml/hour of solution (Standard Rate Method). Changes in dosing required preparation of a new solution. The average cost of a course of therapy was $36.62 +/- $23.98. Using a microcomputer, data for these courses of heparin were fitted to ten standard heparin concentration models. The solutions represented standard concentration models obtained from the pharmacy literature. Standard concentrations would allow for decreased preparation time and potential use of discontinued solutions. Of ten different standard concentrations evaluated, three (30,000 units/500 ml, 25,000 units/500 ml, and 25,000 units/250 ml) were found to be cost-effective when compared to the hospital's standard rate method. The potential cost savings of a standard heparin concentration in our institution is approximately $2000 each year.

Randomized trial of imipenem/cilastatin versus gentamicin and clindamycin in mixed flora infections.

Results of a randomized trial comparing imipenem/cilastatin versus the combination of gentamicin plus clindamycin for mixed flora surgical sepsis are reported herein. Seventy-four patients were evaluable, 50 of whom had intra-abdominal sepsis. No imipenem-resistant initially infecting isolates were encountered. When outcome was evaluated on the basis of severity scoring (APACHE II), no difference in mortality was noted. However, therapy in two patients with Pseudomonas emerging from a polymicrobial flora failed with gentamicin, whereas no Pseudomonas failures were noted with imipenem/cilastatin. The major difference noted was in toxicity. There was a 20 percent incidence of nephrotoxicity in gentamicin-treated patients despite serum level monitoring and multiple dose adjustments. The degree of efficacy and the relative tolerability of imipenem/cilastatin in seriously ill surgical patients is demonstrated.

Prediction of steady-state nortriptyline plasma levels by the repeated one-point method.

10 psychiatric inpatients with a diagnosis of depression were entered into a prospective study to investigate the repeated one-point method as a method of predicting steady-state concentrations for nortriptyline. Four males and 4 females completed all requirements of the protocol. Single plasma concentrations obtained after the first and second daily doses were found to be accurate predictors of the steady-state minimum plasma concentrations. The difference between the measured and the predicted steady-state minimum values ranged from 2.10 to 32.7 micrograms/L with a standard deviation 10.4 and a mean of 10.5 micrograms/L, assuming a normal distribution. The correlation coefficient of predicted versus measured concentrations was 0.946 with 90% confidence limits, ranging from 0.800 to 0.990. The repeated one-point method was found to be an accurate predictor of steady-state minimum plasma concentrations in patients receiving nortriptyline. This method should allow for individual adjustment of dose while minimising the time required to achieve therapeutic, non-toxic plasma concentrations.