Adherence to, and outcomes of, a galactomannan screening protocol in high-risk hematology patients.

Background: A twice-weekly galactomannan (gm) screening protocol was implemented in high-risk hematology inpatients. Study objectives were to determine adherence to the protocol, use of selected resources, and patient outcomes. Methods: This retrospective cohort study compared outcomes of interest before and after implementation of gm screening. Adults undergoing matched related allogeneic hematopoietic stem-cell transplantation or induction chemotherapy for acute leukemia were eligible. Patients could be enrolled more than once and were evaluated as episodes. Adherence to the gm protocol was assessed in post-implementation episodes. Use of broad-spectrum antifungals (bsafs), consultations (infectious diseases, respirology), and diagnostic procedures (computed tomography imaging, bronchoalveolar lavage) were compared between phases, as were the patient outcomes of all-cause mortality and clinical success (alive and not taking a bsaf). Results: Of 182 episodes consecutively screened, 70 per phase were enrolled. Clinical characteristics and duration of assessment were similar for the phases. Full or partial adherence to the protocol was observed in 61 post-implementation episodes (87%), with full adherence in 40 episodes (57%). More episodes in the pre-implementation phase than in the post-implementation phase involved receipt of bsafs, consultations, and diagnostics (27% vs. 7%, p = 0.02; 46% vs. 26%, p = 0.014; and 46% vs. 31%, p = 0.083 respectively). Although mortality was similar in the two phases, clinical success at the final assessment was observed in fewer pre-implementation than post-implementation episodes (79% vs. 98%, p < 0.001). Conclusions: Implementation of a gm screening protocol was feasible and associated with significantly fewer episodes involving receipt of bsafs and consultations, and with significantly more episodes showing clinical success.

Imipenem pharmacokinetics in patients with burns.

The pharmacokinetics of imipenem were studied in 11 adult patients with severe burns who were receiving a therapeutic regimen of imipenem-cilastatin 500 mg intravenously every 6 hours. Serial blood samples for measuring imipenem and 24-hour urine collections for creatinine clearance (CrCl) were obtained after the initial dose and after multiple dosing. Plasma was assayed for imipenem by use of HPLC. A two-compartment model provided a superior fit to the data compared with a one-compartment model in 9 of the 11 patients. There was no significant difference in any pharmacokinetic parameter between the initial dose and after multiple dosing (p greater than 0.05). Combined mean (+/- SD) parameter estimates for the two dosing periods were as follows: VC, 0.11 +/- 0.06 L/kg; Vss, 0.22 +/- 0.06 L/kg; CL, 12.5 +/- 3.6 L/hr/1.73 m2; t1/2 alpha, 0.18 +/- 0.13 hr; t1/2 beta, 1.12 +/- 0.44 hr. Mean clearance in two patients with creatinine clearance values greater than 150 ml/min/1.73 m2 was 17.7 L/hr/1.73 m2. Mean clearance in two patients with creatinine clearance values less than 50 ml/min/1.73 m2 was 8.5 L/hr/1.73 m2. No pharmacokinetic parameter was significantly different from previously reported parameters in normal volunteers (p greater than 0.05). Creatinine clearance ranged from 17 to 218 ml/min/1.73 m2. Imipenem clearance was significantly related to creatinine clearance (CL = 63 + 0.059 CLCR; r2 = 0.60, p = 0.001). No significant association was found between total body surface area burns and imipenem clearance (p greater than 0.05). Our data suggest imipenem pharmacokinetics in patients with burns are comparable to those in normal volunteers although substantial intersubject variability exists.(ABSTRACT TRUNCATED AT 250 WORDS)

Oral absorption of clarithromycin in acute illness and during convalescence in patients with community-acquired pneumonia.

STUDY OBJECTIVE: To compare the extent of oral clarithromycin absorption in patients during an illness and in health. DESIGN: Sequential two-phase prospective study including an acutely ill pneumonia phase (PP) and a subsequent convalescent phase (CP). STUDY POPULATION: Patients >/= 18 years old with radiographically confirmed community-acquired pneumonia (CAP) who were admitted to the hospital. METHODS: During both study phases, patients received one single 500-mg dose of oral clarithromycin. Serial blood samples were drawn over a 24-h period in order to characterize the plasma concentration-time curves. Area under the curve from zero to 24 h (AUC(0-24)), maximum plasma concentration (Cmax), and time to maximum concentration (Tmax) were determined for both clarithromycin and its metabolite, 14-hydroxyclarithromycin, and compared between the two phases. RESULTS: Twelve patients completed both phases of the study. For clarithromycin, there was a significant increase AUC(0-24) (47.37 +/- 8.51 microg/h/mL vs 36.22 +/- 6.09 microg/h/mL) in favor of the PP. There were no significant differences detected with respect to Cmax (4.32 +/- 0.63 microg/mL vs 3.57 +/- 0.46 microg/mL), or Tmax (3.50 +/- 0.50 h vs 2.83 +/- 0.59 h) between PP and CP. For 14-hydroxyclarithromycin, the AUC(0-24) and Cmax were significantly higher (5.84 +/- 1.08 microg/h/mL vs 8.84 +/- 1.92 microg/h/mL; 0.42 +/- 0.08 microg/mL vs 0.76 +/- 0.23 microg/mL) in the CP as compared to the PP. Tmax remained unchanged. CONCLUSION: The extent of absorption of oral clarithromycin was not diminished during an acute illness with CAP.

Pharmacist's management of drug-related problems: a tool for teaching and providing pharmaceutical care.

During the development of education and practice models based on the philosophy of pharmaceutical care (PC), six pharmacists worked with the University of Toronto Faculty of Pharmacy to implement the PC model in their practice sites. These pharmacists found it necessary to modify existing tools to create one that explicitly guided them through the PC process, including the phase of monitoring patients for desired outcomes. This resulted in the development of the Pharmacist's Management of Drug Related Problems. This tool requires pharmacists to collect patient drug and medical data and write responses to specific questions about the data to interpret their significance. As proficiency in providing PC is attained, the questions and space for written responses can be eliminated, leaving a comprehensive documentation system of patient outcomes and the data collected, recommendations made, and monitoring completed by the pharmacist. This tool has been adopted by the University of Toronto Faculty of Pharmacy and is being used in various continuing education programs and by practicing pharmacists across Canada.

Phenytoin prodrug 3-phosphoryloxymethyl phenytoin (ACC-9653): pharmacokinetics in patients following intravenous and intramuscular administration.

A phenytoin prodrug, 3-phosphoryloxymethyl phenytoin (ACC-9653; 1), has been developed with more favorable physicochemical properties than phenytoin for parenteral administration. The purpose of this study was to evaluate the pharmacokinetic profile of 1 following iv and im administration in adult patients receiving chronic oral phenytoin monotherapy. Each patient (9 males, 1 female) received a single iv dose of undiluted 1 equivalent to their twice daily phenytoin dose (100-200 mg). An equivalent dose of im 1 was administered in the gluteus maximus muscle one week later. Serial blood samples were obtained after each dose. Phenytoin and 1 concentrations were measured using HPLC. Compartmental analysis using weighted nonlinear least squares, and noncompartmental pharmacokinetic analysis were performed on each patient's concentration-time data. Data following iv 1 in eight of ten patients were best described using a two-compartment model. Mean pharmacokinetic parameter estimates for iv 1 in these patients were central volume of distribution (Vdc) of 0.040 +/- 0.0084 L/kg and plasma disappearance half-life (t1/2 alpha) of 8.0 +/- 2.9 min ("conversion" t1/2). Overall mean clearance (CL) was 0.24 +/- 0.080 L/kg/h in the 10 patients. Mean pharmacokinetic parameter estimates for im 1 were a rate constant (ka) of 2.47 +/- 1.41 h-1 and an absolute bioavailability (F) of 100.5 +/- 20.3%. Mean observed tmax values for phenytoin were 0.57 +/- 0.26 and 1.46 +/- 0.76 h following iv and im 1, respectively. Model-independent estimates of clearance agreed well with the compartmental analyses. Steady-state predose phenytoin concentrations did not significantly vary from the comparable concentrations following iv 1 administration (p = 0.22).(ABSTRACT TRUNCATED AT 250 WORDS)

Pseudomonas aeruginosa blepharitis in a patient with vancomycin induced neutropenia.

A patient who developed a necrotizing pseudomonas blepharitis as a complication of drug induced neutropenia is reported. Although the patient's neutrophil count recovered and he survived his infection, radical reconstructive surgery of his eyelids was required. Clinicians should keep in mind that in patients with predisposing risk factors, even commonly encountered infections such as blepharoconjunctivitis may be caused by atypical pathogens.

Clostridium difficile colitis following antibiotic prophylaxis for dental procedures.

Clostridium difficile-induced diarrhea and colitis are common complications of therapeutic courses of antibiotics in the hospital setting. We report a case of Clostridium difficile colitis following antibiotic prophylaxis for endocarditis prior to dental procedures in the community setting. The infection necessitated hospital admission and a prolonged hospital stay. Dental practitioners must be aware of the significance of the disease and the risk associated with antibiotics, whether they are used for prophylaxis or treatment.

Conformity with guidelines for antimicrobial prophylaxis against bacterial endocarditis.

The extent to which prescribed antimicrobial prophylaxis against bacterial endocarditis conformed with American Heart Association (AHA) guidelines was determined and the frequency of nonconformity with specific elements of the guidelines was evaluated. Patients with conditions defined by AHA as placing them at risk for developing endocarditis were identified through medical records for a four-year period at an 850-bed hospital. Data about the procedures they underwent and prophylaxis prescribed were compared with the AHA guidelines. Conformity with the guidelines was evaluated according to whether prophylaxis was recommended, optional, or unnecessary; nonconformity with specific elements of the guidelines (indication, choice of antimicrobial, dose, dosage interval, timing, and duration) was also evaluated. The following variables were evaluated for possible association with nonconformity to the guidelines: patient's age and sex, penicillin allergy, use of a consultant, and whether the procedure was the first performed in the patient after identification of the cardiac condition. Of the 131 cases analyzed, 29 (22%) involved prophylaxis that conformed with the AHA guidelines. Conformity with the guidelines was significantly lower when prophylaxis was recommended or optional than when it was unnecessary. Nonconformity was most common with the following elements: indication, choice of antimicrobial, and dose. Recommended prophylaxis was given more often in children than in adults and more often before first procedures than before subsequent procedures. More of the regimens prescribed for children exceeded the recommended duration than those prescribed for adults. Unnecessary prophylaxis was given more often when a consultant was involved than when no consultant was involved. In hospitalized patients, conformity with AHA guidelines for antimicrobial prophylaxis against endocarditis was low.

Standardized gentamicin dosing enhances peak serum concentrations.

The objectives of this study were to determine if a standardized gentamicin dosing protocol would improve clinical effectiveness, yield higher peak serum concentrations, and improve the success rate of attaining peaks in the desired range when compared with empiric dosing practices used by prescribers. The study was conducted as a before-after program effectiveness evaluation in non-critically ill patients, aged 16-65 y with stable renal function, who were prescribed gentamicin. A standardized dose of 2 mg/kg (ideal or adjusted weight) was administered intravenously every 12 h in the intervention phase. Response to therapy (time to defervescence, white cell count, reinstitution of antibiotic therapy), serum concentrations (peaks > 10 mumol/L (5.6 mg/L) and troughs < 4 mumol/L (2.2 mg/L)), and toxicity were monitored in both groups. Thirty-four consecutive patients were enrolled into the control phase and an equal number into the intervention phase. Surgical patients comprised the majority of the study population. Desired peak concentrations were attained in 97% of intervention vs. 59% of control patients (p < 0.001). Mean peak serum concentrations were higher in the intervention phase than in the control phase, 16.1 mumol/L vs. 11.2 mumol/L (p < 0.001), respectively. Median time to become afebrile trended toward a statistical decrease in the intervention as compared to the control group, 3 vs. 5 d (p = 0.076), respectively. There was no significant difference in clinical effectiveness nor in the occurrence of nephro- or ototoxicity. Continued evaluation of this dosing protocol is warranted.