Serum concentrations of cefuroxime after continuous infusion in coronary bypass graft patients.

OBJECTIVE: To describe the serum concentrations of continuous infusion of cefuroxime for postsurgical prophylaxis of sternal wound infection in patients undergoing coronary artery bypass graft (CABG), and to assess the incidence of sternal wound infection in this population. METHODS: This was a prospective, noncomparative trial involving 54 patients undergoing elective CABG surgery. All patients enrolled in the study received cefuroxime 1.5 g as a single intravenous dose 30 minutes preoperatively, followed by a continuous infusion of 3 g every 24 hours until removal of all central venous catheters. RESULTS: Of the 53 evaluable patients, the mean steady-state cefuroxime serum concentration was 21.6 +/- 14.2 microg/mL (range 6.56-59.5). No patient developed a sternal wound infection. The mean treatment duration was 2.58 +/- 2.13 days (range 1-13). The median hospital and intensive care unit lengths of stay were six days and 46 hours, respectively. The average antibiotic cost per day was $32.76. CONCLUSIONS: These preliminary results of continuous infusion of cefuroxime 3 g/d for prophylaxis of sternal wound infections in CABG patients indicate that serum concentrations are highly variable, but reliably above the minimum inhibitory concentration for the common anticipated pathogens in this setting. Further comparative trials in a larger number of patients are necessary before this mode of administration can be routinely advocated for prophylaxis.

Paralyzation and sedation of the ventilated patient.

The selection of pharmacologic agents for the sedation and paralysis of critically ill patients should be based on clinical and pharmacoeconomic trials in this patient population. There is a need for the design and evaluation of cost-effective regimens, especially with the continued development and release of newer agents. Additionally, clinicians must continue to be sensitive to the monitoring techniques of sedation and paralysis to ensure maximal clinical benefit while minimizing the adverse effect profile of pharmacologic agents.

Pharmacokinetics of once-daily dosing of gentamicin in surgical intensive care unit patients with open fractures.

OBJECTIVE: To compare the first-dose pharmacokinetic parameters of gentamicin 6 mg/kg and 2 mg/kg in stable, nonobese surgical intensive care unit patients with open extremity fractures receiving gentamicin prophylactically. METHODS: Serial blood samples were obtained over 8 or 24 hours following the first dose of gentamicin. Serum concentrations of gentamicin were measured using fluorescence polarization immunoassay and analyzed by noncompartmental means. RESULTS: Eleven patients were enrolled, 7 in the 6 mg/kg group and 4 in the 2 mg/kg group. The median (6 vs. 2 mg/kg) age was 29 versus 28 years; serum creatinine 80 versus 88 mumol/L; and APACHE II score 13 versus 10. The mean +/- SD (micrograms/mL) of concentration at the end of the 30-minute infusion (Cmax), concentration 30 minutes after the end of the infusion (Cpk), and concentration at the end of the dosing interval for 6 versus 2 mg/kg were: 35.0 +/- 19.0 versus 10.1 +/- 1.77; 17.0 +/- 2.7 versus 5.4 +/- 0.4, and 0.45 +/- 0.31 versus 0.69 +/- 0.11, respectively. Area under the curve0-infinity (AUC0-infinity), apparent volume of distribution, and half-life were: 89.0 +/- 28.9 versus 26.1 +/- 1.2 mg.h/L, 0.40 +/- 0.10 versus 0.47 +/- 0.14 L/kg, and 4.0 +/- 1.1 versus 4.3 +/- 1.5 h, respectively. CONCLUSIONS: The first-dose pharmacokinetics of gentamicin 6 mg/kg resulted in a proportional rise in Cmax, Cpk, and AUC0-infinity compared with gentamicin 2 mg/kg in patients with open fractures, but with greater variability.

Principles of antibiotic therapy.

The primary development in the area of antibiotic treatment for surgical infections in the last 5 years has been the expanded clinical importance of beta-lactamases in the protection of Gram-negative organisms from previously active drugs. To counter this problem, a series of new antibiotic agents has been developed, including new cephalosporins, carbapenems, quinolones, and beta-lactamase inhibitors. This article describes the various beta-lactamases and their mechanisms of action, and details the activity of new antibiotic agents against resistant Gram-negative organisms. Recent information on the importance of combination therapy for patients with severe Gram-negative infections is reviewed. The use of optimized aminoglycoside dosing regimens, including once-a-day dosing, provides an additional strategy for treating serious Gram-negative infections.

Aminoglycosides in the intensive care unit: an old drug in a dynamic environment.

Aminoglycosides have historically been the mainstay of antibiotic therapy in the ICU. Despite the availability of numerous less toxic antibiotics, the clinical and microbiologic attributes of these agents have ensured their continued use in the management of infections in the critically ill patient. Innovative dosing regimens may replace traditional dosing methods if they are shown to provide improved clinical response with less toxicity potential.

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.

Microbiology of adult cellulitis.

Needle aspiration of cellulitis sites is commonly advocated to assist in the identification of causative organisms. Twenty-five nondiabetic, adult patients with a clinical diagnosis of cellulitis had site aspirations and blood cultures obtained before antibiotic therapy was initiated. Site cultures were positive in 6 of 25 patients. Blood cultures were positive in 4 of 25 patients. All organisms except one (Enterobacter agglomerans) were staphylococci or streptococci. The gram-negative bacilli were not believed to be a pathogen based on the patient's prompt response to nafcillin. In adult patients who do not have complications, the use of needle aspiration was not supported. Empiric treatment of cellulitis aimed at gram-positive cocci appears to be sufficient.

Effect of pharmacist interventions on drug therapy costs in a surgical intensive-care unit.

The effect of interventions by a clinical pharmacist on the cost of drug therapy in a 14-bed surgical intensive-care unit (SICU) was evaluated. The SICU pharmacist provides both distributive and clinical services from a modified satellite pharmacy five days each week. During a 13-week study period that comprised 65 days, the pharmacist documented all interventions that resulted in a discontinuation of or change in drug therapy, all nonformulary-drug requests, the detection and avoidance of problems related to drug therapy, and the enrollment of patients in investigational drug studies (for which the pharmacy department received monetary remuneration). The effect of these interventions on the costs of drug therapy was calculated using drug acquisition costs and, for i.v. preparations, the cost of the i.v. fluid and the cost of preparing and checking the product. A total of 332 interventions during the study period represented $18,030 in potential cost avoidance, which would extrapolate to an annual cost avoidance of $72,122. The majority of interventions involved discontinuations of or changes in drug therapy, most often involving antimicrobials. This pharmacist had a positive impact on the cost of drug therapy in the SICU.

The pharmacologic management of the syndrome of inappropriate secretion of antidiuretic hormone.

There have been numerous treatment modalities reported in the literature concerning the acute and chronic treatment of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Water restriction remains the mainstay of therapy. However, patient noncompliance for this regimen often makes additional treatment modalities necessary. In the long-term treatment of chronic SIADH, lithium, demeclocycline, loop diuretics, and urea are helpful, regardless of the origin of the SIADH. The use of lithium is not recommended due to the incidence of digestive, cardiac, thyroid, and central nervous system side effects, as well as the demonstrated superiority of demeclocycline. Urea and loop diuretics, although shown to be effective, have not been used clinically to the extent as demeclocyline, and are not free of adverse effects. Phenytoin is limited in its use to the treatment of SIADH secondary to abnormalities of the hypothalamic-pituitary axis, and plays no role in the treatment of tumor-induced SIADH. Demeclocyline has been shown to be effective in all types of SIADH. The lack of comparative studies of long-term treatment regimens makes the selection of a regimen of choice difficult. At this point loop diuretics or demeclocycline appear to be the regimens of choice based primarily upon case reports and relatively small comparative study patient populations. Further comparative studies are needed in an attempt to identify the most efficacious regimen with the minimal incidence of adverse effects.