Influence of the British Columbia reference drug program on hospital formularies: a survey of hospital pharmacy managers.

OBJECTIVES: To assess the impact of the British Columbia Reference Drug (RD) Program on the management of hospital formularies in the province. MATERIALS AND METHODS: A survey of pharmacy managers in British Columbia hospitals with more than 100 beds was conducted in November, 1997. The survey instrument contained questions regarding hospital characteristics, drugs listed on the formulary before and after implementation of RD policies for four drug classes, the hospitals' responses to RD policies and the respondents' opinions of the RD Program. RESULTS: Thirty-two (86%) hospitals returned the survey by the stated deadline. Before the RD Program was implemented, significantly more hospitals listed cimetidine (P=0.03), felodipine (P<0.001), quinapril (P<0.001) and ramipril (P<0.001) on the hospital drug formulary. The main reasons given for changes to hospital drug formularies were community prescribing patterns (25% to 38%) and the RD Program (23% to 44%) depending on the drug category. Twenty-seven (84%) hospitals did not automatically adopt RD policies; 22 (69%) hospitals reviewed the policies at Pharmacy and Therapeutics Committee meetings. Sixteen (50%) respondents thought that hospitals should change their drug formularies to match the policies. Median satisfaction with the RD Program on a 10-point rating scale (1 = unsatisfied, 10 = satisfied) was 7 (range 2 to 10). CONCLUSIONS: Respondents appeared to be neutral when asked their opinion of the RD initiative. The RD policies resulted in drug category-dependent changes in the hospital formulary listings. H2 receptor antagonists and antihypertensives were the most significantly influenced drug categories. RD status does not automatically confer formulary status of a drug; however, it does appear to be a criterion in most hospitals when considering a drug for inclusion in the formulary.

A new ciprofloxacin stepdown program in the treatment of high-risk febrile neutropenia: a clinical and economic analysis.

STUDY OBJECTIVE: To determine treatment outcomes and economic impact of a ciprofloxacin stepdown program for high-risk febrile neutropenic adults from the hospital's perspective. DESIGN: Unblinded, two-phase, single-center study. SETTING: Adult leukemia and stem cell transplant unit. PATIENTS: High-risk adults with febrile neutropenia. INTERVENTION: Two conditions were analyzed: a multidisciplinary ciprofloxacin stepdown program involving a reduction in parenteral ciprofloxacin dose from 400 to 200 mg (i.v.-i.v.) and conversion to oral ciprofloxacin (i.v.-p.o.) when criteria were met; and no i.v.-i.v. stepdown program. MEASUREMENTS AND MAIN RESULTS: Forty-six sequential treatment courses were compared with 42 treatment course from 6-month periods in preintervention (P1) and postintervention (P2) phases. Assessed parameters were clinical and microbiologic outcomes, adverse drug reactions (ADRs), and direct medical resource use and costs (1998 $Canadian) for the episode of febrile neutropenia. A decision analytic model was used to map probabilities and costs and to conduct sensitivity analyses. To supplement standard statistical testing, 1,000 bootstrap samples were created, and the mean cost difference was calculated between phases for each sample. Patient demographics, percentage i.v.-p.o. stepdown, and duration of therapy were similar between phases. Clinical success (83% P1, 81% P2), microbiologic eradication (15% P1, 24% P2), and possible ADRs (6% P1, 9% P2) did not differ. Intravenous-to-intravenous dose stepdown occurred in 33% of P2 and no P1 treatment courses (p<0.001). Resource use and costs were similar between phases, although a reduction was seen in the drug's mean total cost/day ($58 P1, $52 P2, p=0.04). There was also a trend toward a decrease in mean total treatment costs ($4,843 P1, $3,493 P2, p=0.08). In 1,000 bootstrap samples, 99.8% showed a cost advantage for P2. The model was robust to sensitivity analyses. CONCLUSION: This intervention influenced administration of ciprofloxacin without apparent compromise of patient outcomes and resulted in a reduction in total costs of treating febrile neutropenia.

Economic impact of standardized orders for antimicrobial prophylaxis program.

OBJECTIVE: To assess the effect and economic impact of an intervention aimed at standardizing the timing of preoperative antimicrobial prophylaxis from the perspective of a major teaching hospital. DESIGN: A pre/post study design in which a random sample of 60 procedures from a 12-month period in the preintervention phase were reviewed. A comparative sample of 60 procedures during a seven-month postintervention phase was selected. For each prophylactic course, preoperative dose administration details were classified as early (>2 h prior to incision), on time (0-2 h prior), delayed (0-3 h after), or late (>3 after). To determine the economic impact of this intervention, we used a predictive decision analytic model using institutional costs and the published probabilities of inpatient surgical wound infections (SWIs) following administration of antimicrobials timed according to the above criteria. Two conditions were analyzed: (1) an interdisciplinary two-stage therapeutic interchange program involving staff education and modification of preoperative antimicrobial orders to ensure timely administration and (2) no intervention. SETTING: An 1100-bed tertiary care, university-affiliated institution. PATIENTS: 120 randomly selected procedures involving inpatients who received a preoperative antibiotic. OUTCOME MEASURES: Differences in preoperative antimicrobial timing and cost avoidance associated with the intervention. RESULTS: In the preintervention phase, 68% of prophylactic courses were on time, 22% were early, and the balance were delayed or late. The incidence of on-time prophylaxis increased to 97% during the postintervention phase (p = 0.001). Operating room staff involvement in antimicrobial administration increased from 57% to 92% (p = 0.001). Based on a setup and annual intervention cost of $9100 CAN ($1 CAN = $0.68 US), an annual inpatient SWI avoidance of 51 cases, an average infection-associated extended hospital stay of four days, and an average treatment cost of $1957 CAN per inpatient SWI, we estimated that 153 hospital days were avoided and there was an annual cost avoidance of $90 707 CAN ($1779 CAN saved per inpatient infection avoided) due to this intervention. Using sensitivity analyses, no plausible changes in the base case estimates altered the results of the economic model. CONCLUSIONS: An interdisciplinary approach to optimizing the timing of preoperative antimicrobial doses can impact positively on practice patterns and result in substantial cost avoidance. Costs incurred to implement such an intervention are small when compared with the annual cost avoidance to the institution.

Continuous intrathecal pump infusion of baclofen with antibiotic drugs for treatment of pump-associated meningitis. Case report.

Intrathecal baclofen administered by means of an implantable pump is being increasingly used for successful treatment of spasticity. Meningitis following intrathecally administered baclofen is a rare but serious complication that is difficult to treat without removal of the pump. Because success rates with intravenously administered antibiotic drugs for the treatment of meningitis have been low, intrathecal administration of antibiotic agents is often required to eradicate the pathogen. The authors report the case of a patient in whom Staphylococcus epidermidis meningitis developed after insertion of an intrathecal baclofen pump. The patient was successfully treated by intrathecal coadministration of vancomycin and baclofen.

Cost analysis of an adult outpatient parenteral antibiotic therapy (OPAT) programme. A Canadian teaching hospital and Ministry of Health perspective.

BACKGROUND: Outpatient parenteral antibiotic therapy (OPAT) programmes have become prevalent over the past 2 decades. From the US perspective, these programmes have been shown to reduce healthcare costs. No comprehensive analysis has been published from the Canadian perspective. OBJECTIVE: To describe a Canadian OPAT programme for the 3-year period since its inception and to conduct a treatment cost analysis. DESIGN AND METHODS: Demographics and resource utilisation data (health professional labour, laboratory and diagnostic tests, antimicrobials, delivery, home nursing care, catheters and catheter placement) were prospectively collected for enrollees in the OPAT programme over the evaluation period. Avoided hospital resource utilisation was estimated via retrospective chart review by the investigators. Costs were retrospectively assigned to each resource and total cost avoidance by the OPAT programme was determined from each perspective. PERSPECTIVE: A teaching hospital and a provincial Ministry of Health (MOH). MAIN OUTCOME MEASURES AND RESULTS: 140 treatment courses were initiated for 117 adult patients (mean age 54 years) who were enrolled into the programme. Mean pre-OPAT length of hospital stay was 12 days, and mean OPAT duration was 22.5 days. Bone/joint (39%), skin and soft tissue (16%), cardiac (13%) and respiratory tract (12%) infections were the most common infections managed. The most commonly used antimicrobials were vancomycin (29%), cloxacillin +/- gentamicin (22%) and ceftriaxone +/- gentamicin (11%) 85% of enrollees successfully completed their planned antimicrobial treatment regimens. Premature discontinuation of antimicrobial therapy for various reasons occurred in the remaining 15% of courses. The mean cost per treatment course of OPAT was 1910 Canadian dollars ($Can) from the hospital perspective and $Can6326 from the MOH perspective. Assuming that patients would have otherwise completed their antimicrobial therapy in hospital, the mean cost per treatment course was estimated to be $Can14,271. The overall cost avoidance of the OPAT programme was $Can1,730,520 (hospital perspective) and $Can1,009,450 (MOH perspective) over the 3-year assessment period. Sensitivity analyses revealed the results to be robust to plausible changes. CONCLUSIONS: This analysis supports the premise that an adult OPAT programme can substantially reduce healthcare costs in the Canadian healthcare setting.

Experience with ceftazidime parenteral-to-parenteral dosage stepdown in the empiric treatment of febrile neutropenia.

We assessed the clinical and economic impact of a new parenteral-toparenteral stepdown program involving ceftazidime for the treatment of febrile neutropenia. This was a two-phase (before and after), 12-month, single-center, prospective study with a historical control. Ninety-eight ceftazidime treatment courses (47 preintervention, 51 postintervention) were administered for management of febrile neutropenia in 85 adults with hematologic malignancies. Multidisciplinary creation and promotion of parenteral-to-parenteral ceftazidime stepdown criteria were applied at the discretion of the health care team. Patient demographics between phases were similar. Only 2 (4%) treatment courses before the intervention involved parenteral-to-parenteral dosage stepdown, compared with 34 (67%) after the intervention (p<0.00001). Mean number of total ceftazidime doses/treatment course and mean duration of therapy did not change between phases. Clinical cure or improvement was identified in 74% and 80% of treatment courses before and after the intervention, respectively. The two main reasons for discontinuing the drug before the intervention were recovery of neutrophil count (60%) and adverse reactions (19%). Neutrophil count recovery (59%) and hospital discharge (14%) were the two most common reasons for discontinuation after the intervention. Of 34 stepdown treatment courses after the intervention, 3 (9%) failed to meet established stepdown criteria, and 2 of these required stepdown reversal. Ancillary antibacterial drugs and treatment course outcomes were similar between phases. Total ceftazidime acquisition cost for 704 treatment days in the preintervention phase was $52,473 CAN compared with $54,778 CAN for 907 days of therapy in the postintervention phase. The mean acquisition cost/ceftazidime treatment course was $1100 CAN and did not differ between phases. The mean daily cost of ceftazidime therapy was lower after the intervention ($60.39 vs $74.54 CAN) as a result of a greater frequency of stepdown (p<0.001). Assuming an equivalent number of treatment days, the projected annual acquisition cost avoidance associated with this stepdown program was $19,900 CAN.

Cost-minimization analysis of piperacillin/tazobactam versus imipenem/cilastatin for the treatment of serious infections: a Canadian hospital perspective.

BACKGROUND: In 1998 we reported the first Canadian double-blind, randomized, clinical trial involving a comparison of piperacillin/tazobactam (P/T) with imipenem/cilastatin (I/C). The present study was conducted to determine the feasibility of replacing I/C at our institution. OBJECTIVE: To describe the outcome of a pharmacoeconomic analysis of the clinical trial from the perspective of a tertiary acute-care institution. METHODS: A total of 150 consenting adults originally prescribed I/C were randomly assigned to receive either P/T 4.5 g i.v. (n = 75) or I/C 500 mg i.v. (n = 75) every six hours. Actual direct medical resources used in relation to the treatment of bacterial infections were prospectively assessed during a clinical trial; these included cost of study and ancillary antibiotics, hospitalization, diagnostic testing (radiology, laboratory assessments), and labor, as well as treatment of adverse drug reactions, antibiotic failures, and superinfections. RESULTS: While costs for successful treatment courses were similar across treatment arms, hospitalization costs for treatment course failures were higher for P/T recipients. Direct medical costs for treatment courses associated with a superinfection were also higher in the P/T arm. Overall costs for treatment failures with either study drug were at least twofold those observed for successful treatment courses. Mean total management cost per patient in the P/T group was $15,211 ($ CDN throughout) (95% CI $11,429 to $18,993), compared with $14,232 (95% CI $11,421 to $17,043) in the I/C group (p = 0.32), resulting in a mean cost difference of $979. Sensitivity analyses revealed that the superiority of I/C over P/T for successful treatment of serious infections was sensitive to changes in the cost of hospitalization and drug efficacy for either drug. CONCLUSIONS: Based on the results of the clinical trial, P/T and I/C offer similar clinical, microbiologic, and toxicity outcomes in hospitalized patients with serious infections. Under base-case conditions, our pharmacoeconomic analysis showed that I/C was a cost-effective alternative to P/T at the dosage regimens studied. However, this finding was sensitive to plausible changes in both clinical and economic parameters.

Piperacillin/tazobactam versus imipenem: a double-blind, randomized formulary feasibility study at a major teaching hospital.

With the introduction of piperacillin/tazobactam to the North American market, hospitals have been faced with the task of making a decision regarding its formulary role. In view of its broad spectrum of activity, piperacillin/tazobactam could be considered as a formulary alternative to imipenem. To evaluate the formulary feasibility of substituting piperacillin/tazobactam for imipenem, a comparative assessment of these agents in the empiric treatment of serious bacterial infections was undertaken at this tertiary care hospital. This trial was conducted as a randomized, double-blind, single-center study. Consenting adult patients (>16 years of age) who were prescribed imipenem were randomized to receive either 4 g of i.v. piperacillin/tazobactam or imipenem 500 mg of i.v. Q6H with or without concurrent antibiotics. Doses were adjusted according to renal function. There were no restrictions regarding the use of nonstudy antibiotics before and during the study period. Patients with beta-lactam allergies or meningitis or who had received greater than 72 h of previous imipenem therapy were excluded. Patients were evaluated at the end of treatment, at discharge, and at 30 days postdischarge. Endpoints included both clinical and microbiologic efficacy as well as drug toxicity. Over the 433-day study period, 360 imipenem treatment courses were initiated. Of these, 150 treatment courses (75 piperacillin/tazobactam courses and 75 imipenem courses) met study criteria and were subsequently randomized. The distribution of prescriber services for enrolled patients was similar to that for all patients receiving imipenem during the study period (p = 0.15). Also, there were no statistically significant differences in demographic parameters between enrolled and excluded patients. For those patients enrolled in the study, demographic characteristics, treatment course indication(s), and accompanying antibiotics were similar across treatment arms. The mean duration of study drug therapy was 7.7 days (SD, 6.2) for imipenem and 7.5 days (SD, 6.7)for piperacillin/tazobactam (p = 0.84). In the majority of cases, treatment discontinuation occurred as a result of a favorable treatment course outcome, stepdown to a narrower spectrum parenteral agent, or stepdown to an oral agent and did not differ between study drugs (p = 0.73). Clinical and microbiologic treatment course outcomes were also similar across treatment arms. Clinical outcome was deemed successful or improved for 68% of imipenem and 70% of the piperacillin/tazobactam treatment courses (p = 0.54). Fifty-three percent of treatment courses were microbiologically confirmed. Of the 58 courses that were assessed for microbiological outcome, 93% demonstrated successful eradication of the causative pathogens. There was no difference between study drugs (96% imipenem; 90% piperacillin/tazobactam; p = 0.61). The proportion of treatment courses with at least one adverse event was similar between the study drugs (p = 1.0). Nausea and/or vomiting were/was observed more commonly in the imipenem arm (p = 0.03). Discontinuation of therapy due to drug toxicity occurred in 16% of imipenem and 5% of piperacillin/tazobactam treatment courses (p = 0.06). There was no statistically significant difference between the mean treatment course cost for imipenem ($762; range, $55-$3192) versus piperacillin/tazobactam ($696; range, $79-$2967; p = 0.59). In summary, piperacillin/tazobactam seems to represent a suitable alternative to imipenem for several clinical indications including intraabdominal infections, pneumonia, febrile neutropenia, and skin/soft tissue infections in which the causative pathogens are susceptible. However, in view of the prevalence of multiresistant Gram-negative aerobic pathogens at this institution, we do not believe that imipenem can be removed from the drug formulary. In addition, at the currently studied dosing regimen, there seems to be no evidence of a direct cost advantage associated with

A double-blind, randomized study of three antimicrobial regimens in the prevention of infections after elective colorectal surgery.

The objective of this study was to assess the prophylactic efficacy of cefoxitin, ceftizoxime, and metronidazole-gentamicin in colorectal surgery. A double-blind, randomized prospective clinical trial design was used in a Canadian tertiary care teaching hospital. Patients were randomized to one of three treatment groups and received three doses of a study drug (30 min preoperative and 2 postoperative doses at 12 and 24 h). Cefoxitin and ceftizoxime were given as 1000-mg doses. Metronidazole-gentamicin was given as 500 mg of metronidazole plus 120 mg of gentamicin in a minibag. High-risk patients (bowel ischemia, diabetic, current steroid use, etc.) received 10 postoperative doses. Patients with infections, prior antibiotics, or study drug allergies were excluded. Over 30 months, 153 patients were enrolled. Thirty-one patients were excluded for protocol violations. Of the 122 evaluable patients (38 ceftizoxime, 45 metronidazole-gentamicin, 39 cefoxitin), there was no difference across groups regarding sex, age, weight, preoperative Apache II score, and prior history of bowel surgery. Groups were equivalent regarding surgeon, nursing unit, high-risk status (six ceftizoxime, seven metronidazole-gentamicin, seven cefoxitin), bowel preparation, and procedure (including blood loss, drains, organ injury, intraoperative complications). Clinically significant infection requiring systemic antibiotics (7-day hospital and 30-day follow-up) was identified in 0% of ceftizoxime, 15% of metronidazole-gentamicin, and 26% of cefoxitin receiving patients (p = 0.005). Mean ASEPSIS scores for each group were 2.3 (range 0-15) for ceftizoxime, 9.2 (range 0-45) for metronidazole-gentamicin, and 10.4 (range 0-75) for cefoxitin (p = 0.01). Ceftizoxime patients tended to have a shorter total hospital stay (12.2 days versus 19.7 days for cefoxitin versus 13.9 days for metronidazole-gentamicin; p = 0.04), although the procedure to discharge interval was not significantly different (p = 0.09). There was no difference in clinical outcome according to risk status. Anaerobic bacteria were observed more commonly in the ceftizoxime and cefoxitin groups, whereas enteric Gram-negative aerobes were observed most often in the metronidazole-gentamicin group. The study regimens were generally well tolerated. Drug costs were equivalent between ceftizoxime and cefoxitin and lowest with the metronidazole-gentamicin regimen. Ceftizoxime appears to be more effective for the prevention of infection in colorectal surgery than either cefoxitin or metronidazole-gentamicin in the dosage regimens studied.

Aminoglycoside administration as a single daily dose. An improvement to current practice or a repeat of previous errors?

Despite the availability of newer and safer antibacterials, aminoglycosides continue to play a major role in the management of infections in hospitalised patients. The concept of single daily dose (SDD) regimens was introduced many years ago and is now receiving much attention as an alternative regimen for this class of drugs. To evaluate the rationale and clinical support for SDD schemes, we conducted a 'MEDLINE' search to locate relevant preclinical and clinical literature pertaining to this issue. The results of animal model and noncomparative clinical data tended to be variable and inconclusive. We were able to identify 28 prospective comparative clinical trials; however, only one was randomised, double-blind and of sufficient sample size to detect differences in efficacy between treatment arms, should any exist. Despite these flaws, our review suggests that SDD schemes appear to be no more efficacious and no less toxic, but may be less costly, than traditional multiple daily dose schemes. We also assessed the predicted disposition of tobramycin/gentamicin in 415 patients with known pharmacokinetic parameters. With doses of 7 mg/kg at intervals of between 24 and 60 hours (depending upon renal function), the maximum serum concentration at steady-state (Cmaxss) varied from 8.5 to 55.6 mg/L, while the Cminss was < 2.0 mg/L in the majority of patients. Mid-interval serum aminoglycoside concentrations were < 0.5 mg/L in up to 23% of patients, suggesting possible underdosage in certain patients with this scheme. More conclusive clinical evidence is necessary before SDD schemes should be adopted as standard clinical practice. Empirical weight-based dosage schemes appear to yield widely variable serum aminoglycoside concentrations which could be considered therapeutically inadequate or toxic.

Evaluation of the use of cefuroxime and cefuroxime axetil in an intravenous-oral stepdown program.

OBJECTIVE: To characterize cefuroxime and cefuroxime axetil use under the influence of a parenteral-to-oral (iv-po) stepdown program. DESIGN: Open single-center retrospective review. SETTING: Tertiary care teaching and referral Canadian hospital with 1100 beds. PATIENTS: A random sample of 78 patients receiving cefuroxime was compared with a random sample of 50 patients receiving iv-po cefuroxime stepdown. RESULTS: During the first 6 months following formulary introduction, 1535 patients received cefuroxime. Stepdown to any oral antibiotic occurred in 22% of patients. Cefuroxime axetil was used as the stepdown agent in 64% of these cases. In a comparison of nonstepdown courses with stepdown courses, some differences were apparent. Nonstepdown treatment courses were primarily prophylactic, whereas stepdown courses were typically initiated as primary therapy for the 10-day management of respiratory tract infections (p < 0.001). Conversion to oral therapy typically occurred on day 5 of parenteral therapy and continued for 5 days. Stepdown was considered possible in 46% of treatment courses in which this process did not happen. When stepdown did occur, it was considered timely in 64% of cases, unnecessarily delayed in 32%, and premature in 4% of treatment courses. Stepdown did not appear to be associated with a negative impact on patient outcome. Mean +/- SD cost of drug therapy per day was less for the stepdown group (US $15.78 +/- $5.97) than the nonstepdown group (US $25.47 +/- $7.87; p < 0.001). CONCLUSIONS: As a result of this study we intend to maintain cefuroxime and cefuroxime axetil on the formulary and continue to judiciously promote the timely conversion to oral therapy.

Double-blind comparison of cefazolin and ceftizoxime for prophylaxis against infections following elective biliary tract surgery.

Antibiotics have been shown to reduce the incidence of wound infections after elective biliary tract procedures. Cefazolin and cefoxitin are among the agents most commonly promoted for this purpose. Cefoxitin has been substituted with ceftizoxime in many institutions; however, the role of ceftizoxime as a prophylactic agent in this setting has not been determined. To assess the comparative prophylactic efficacies of cefazolin and ceftizoxime in biliary tract surgery, we conducted a double-blind, randomized prospective clinical trial in a tertiary-care teaching hospital. Adult patients were randomized to one of two treatment groups and received a 30-min preoperative dose of study drug and as many as two postoperative doses at 12 and 24 h, depending on hospitalization status. Cefazolin and ceftizoxime were given as 1,000-mg doses. Patients with infections, those receiving prior antibiotics, or those with beta-lactam allergies were excluded. Over the 19-month study tenure, 167 patients were enrolled. Seventeen patients were excluded from analysis because of protocol violations. Of the 150 evaluable patients (72 and 78 receiving cefazolin and ceftizoxime doses, respectively), there was no significant difference among groups regarding sex, age, weight, preoperative Apache II score, baseline chemistry, and hematological parameters. Groups were also equivalent regarding the surgeon, type of procedure, characteristics (blood loss, drains, organ injury, and complications), and duration of hospital stay (mean, 5.6 versus 4.3 days [P = 0.31]). No clinical evidence of infection (7-day hospital stay and 30-day follow-up) was identified in 93% of cefazolin and 92% of ceftizoxime patients (P = 1.0). Microbiological confirmation was found in only 18% of primary-site infections. In conclusion, cefazolin and ceftizoxime appear to be equivalent for the prevention of infection in biliary tract surgery with the dosage regimens studied.

Vancomycin Serum Concentration Monitoring : The Middle Ground is Best.

The recent increase in the use of vancomycin has led to renewed interest in its pharmacokinetics, and, in particular, the importance of monitoring serum drug concentrations. A review of the literature and evaluation of pharmacokinetic data from Vancouver Hospital and Health Sciences Centre demonstrated that vancomycin meets the criteria necessary for serum drug concentration monitoring. These include the availability of a sensitive and specific assay, substantial interpatient and intrapatient variability in drug disposition, and evidence suggesting a correlation between vancomycin serum concentration and both efficacy and toxicity. A review of vancomycin disposition data for 371 consecutive treatment courses at this hospital revealed significant interpatient variability in drug clearance and volume of distribution. Accordingly, it would be difficult to accurately predict the change in serum concentration resulting from a given vancomycin dose. There appears to be less intrapatient variability in volume of distribution; however, serum elimination half-life tends to increase during treatment, necessitating an alteration in dose interval. Although convenient, physiological parameters to monitor serum creatinine concentration and bodyweight are not accurate predictors of drug clearance and volume of distribution. Serum concentration monitoring is also necessary to ensure that vancomycin concentrations are in excess of the minimum inhibitory concentration of the organism at all times during treatment. Although a causal relationship between vancomycin and toxicity has been difficult to prove, there is some evidence in the literature to support a relationship between high troughs and nephrotoxicity. In view of the available evidence, we do not believe that serum concentration monitoring should be totally abandoned. We have created empiric dosage guidelines and a decision-making algorithm for serum drug concentration monitoring that have streamlined the process of drug prescribing and monitoring at this institution.

A prospective survey of knowledge and perceptions of ondansetron: what do health care workers know about this drug?

Ondansetron is a relatively new drug whose optimal use is dependent on an understanding of its characteristics and role relative to traditional antiemetics. To assess perceptions and knowledge regarding ondansetron, we conducted a prospective written survey involving 56 physicians, pharmacists, and nurses at this hospital. Pharmacists claimed to be exposed to ondansetron promotion by industry more than the other groups. Apart from industry, pharmacists were considered to be the most common source of drug information. Nurses were less aware of dosage form equivalence than the other groups (p = 0.042). Physicians were more aware of twice daily dosing efficacy than other respondents (p = 0.0006). Nurses were able to better identify the relative duration of antiemetic benefit over metoclopramide (p = 0.008); however, most participants tended to be misinformed on this issue. Pharmacists were more familiar with the side effect profile while physicians were more cognizant of oral (p = 0.001) and parenteral (p = 0.018) drug costs than other groups. Overall, survey scores for physicians and pharmacists were higher than those for nurses (p = 0.007). There is an apparent difference across health care profession disciplines in the perceptions and knowledge about ondansetron. Specific misconceptions could lead to suboptimal drug use and warrant efforts to ensure a good understanding of the attributes and relative role of this agent.

Amphotericin B infusion-related toxicity: comparison of two- and four-hour infusions.

OBJECTIVE: To investigate the influence of infusion duration on infusion-related adverse effects (IRAEs) associated with prophylactic or treatment regimens of amphotericin B in patients with leukemia/bone marrow transplant (BMT). DESIGN: Randomized, double-blind, 2-arm, complete crossover, prospective clinical trial. SETTING: A university-affiliated tertiary care teaching hospital. PARTICIPANTS: The study population consisted of 25 consecutive patients with leukemia/BMT who received 162 prophylactic regimen infusions and 169 treatment regimen infusions of amphotericin B via a central line. Prior to each infusion all patients received a parenteral IRAE prophylaxis regimen of diphenhydramine 25 mg and hydrocortisone 25 mg. No test doses or incremental amphotericin B doses were administered. Patients were monitored closely for IRAEs, which were documented by using a standardized data collection form. MAIN OUTCOME MEASURES: The incidence and nature of IRAEs during a 6-hour monitoring period following the initiation of each infusion was measured. Patients served as their own controls. IRAEs were compared according to infusion duration and therapeutic indication. RESULTS: Three hundred and thirty-one 2- and 4-hour amphotericin B infusions were administered. We found no difference between 2- and 4-hour infusions in the incidence and severity of IRAEs, including overall events (29% of 166 2-hour infusions vs. 25% of 165 4-hour infusions), chill scores (8% of 166 2-hour infusions vs. 7% of 165 4-hour infusions; highest score 7 vs. 6), nausea and vomiting (7% vs. 12%; highest score 4 in both groups), fever (3% vs. 2%), highest temperature increase (2.4 vs. 1.6 degrees C), systolic hypotension (6% vs. 2%), greatest decrease from baseline (40 vs. 62 mm Hg), diastolic hypotension (5% vs. 3%), and greatest decrease (30 vs. 28 mm Hg) (p > 0.05). Overall, IRAEs were less common in prophylactic treatment regimens (35 events [22%] in 162 infusions) than in treatment regimens (55 events [32%] in 169 infusions) (p < 0.05). CONCLUSIONS: This study demonstrates that patients with leukemia/BMT without myocardial or renal dysfunction who receive hydrocortisone and diphenhydramine as premedications can tolerate 2-hour central line infusions of prophylactic or treatment regimens of amphotericin B as well as 4-hour infusions.

Aprotinin reduces the need for blood products during liver transplantation.

BACKGROUND: Bleeding complications and blood product consumption have been a major concern during liver transplantation. Prevention of plasminogen activation and fibrinolysis by aprotinin administration has been shown to reduce perioperative bleeding during operations associated with high blood-product consumption. PATIENTS AND METHODS: Use of blood-products (packed red cells, frozen plasma, platelets, and cryoprecipitate) was analyzed both during the three stages of orthotopic liver transplantation and during total hospitalization of the 26 patients transplanted without aprotinin and the subsequent 40 patients with aprotinin. A similar analysis was performed for 15 patients immediately before and after the introduction of aprotinin to eliminate the "learning curve" effect for liver transplantation. The effect of epsilon-amino-caproic acid was analyzed as 13 patients received neither epsilon-aminocaproic acid nor aprotinin and 13 patients received epsilon-aminocaproic acid but not aprotinin. RESULTS: There was a significant reduction in total hospital use of cryoprecipitate, frozen plasma, platelets, and red cells in the aprotinin-treated patients. This reduction was seen during the anhepatic and reperfusion stages of liver transplantation. There was no difference in blood product consumption between the groups who were or were not treated with epsilon-aminocaproic acid. CONCLUSION: Aprotinin significantly reduces the need for red cell, frozen plasma, platelet, and cryoprecipitate transfusion use during orthotopic liver transplantation, and appears to be more efficacious than epsilon-aminocaproic acid.

Streptomycin-loaded bone cement in the treatment of tuberculous osteomyelitis: an adjunct to conventional therapy.

Streptomycin-loaded bone-cement (7 g of streptomycin in 40 g of bone cement) beads were used in the treatment of tuberculous bursitis and osteomyelitis of the greater trochanter in a 76-year-old woman. Wound drainage, serum and urine concentrations of streptomycin were measured. For the first 96 hours, the streptomycin levels in the wound drainage ranged from 2932 mg/L to 414.4 mg/L, and in the serum, streptomycin levels ranged from 1.7 mg/L to 13.7 mg/L. The patient recovered without complication and at follow-up 2 years later was free of infection and walking without pain. The authors conclude that the use of streptomycin-loaded bone cement can safely and effectively eradicate mycobacterial tuberculosis osteomyelitis.

Antibiotic therapeutic interchange program: six years of experience.

To assess the long-term impact of a therapeutic interchange program on the use of target antimicrobial drugs, we conducted a retrospective study of target drug utilization at our institution--a 1,000-bed Canadian tertiary care teaching hospital. Data were assessed to determine target drug utilization, incidence of therapeutic interchanges, and patient-target drug exposures. Results showed that the incidence of therapeutic interchanges per patient-target drug exposure decreased from a mean of 23% to 2%, resulting in a total net savings for the target drugs of approximately $1.07 million (Canadian) over 6 years. Prescriber acceptance and low manpower requirements combine to make this a useful method of altering prescribing patterns and reducing drug and drug delivery costs.