Outcomes associated with a thrice-weekly antimicrobial stewardship programme in a 253-bed community hospital.

WHAT IS KNOWN AND OBJECTIVES: Antimicrobial stewardship programmes (ASPs) have been shown to decrease antimicrobial resistance, reduce hospital-acquired infections and decrease overall antimicrobial expenditures. At St. Joseph Medical Center in Bellingham, WA, a thrice-weekly ASP was initiated in 2010 with the goals of decreasing carbapenem, fluoroquinolone and vancomycin use and tailoring duration of therapy. METHODS: Antibiotic use per 1000 patient-days and carbapenem, fluoroquinolone and vancomycin use were evaluated pre- and post-implementation of the ASP. Total antimicrobial expenditures were evaluated for the 3 years prior to ASP implementation and three years following implementation. RESULTS AND DISCUSSION: Antimicrobial days of therapy per 1000 patient-days declined by 6·4% after implementation of our ASP. There was a 37% reduction in total antimicrobial expenditures after implementation. Carbapenems, vancomycin and levofloxacin use decreased considerably. Ciprofloxacin use increased during the same time period. WHAT IS NEW AND CONCLUSION: A thrice-weekly, pharmacist-driven ASP can decrease antimicrobial expenditure, shorten duration of therapy and decrease the utilization of carbapenems, vancomycin and levofloxacin.

Variability of tobramycin pharmacokinetics in cystic fibrosis.

This study determined the extent and impact of tobramycin pharmacokinetic variability in cystic fibrosis patients. Twenty patients were hospitalized twice and the tobramycin half-life, volume of distribution and clearance were determined during Weeks 1 and 2 of both admissions. A difference (P less than 0.05) existed between Weeks 1 and 2 of each admission, but not between admissions, for the clearance and half-life. No difference existed between weeks or admissions for the volume of distribution. No significant correlations existed between weeks within an admission for the half-life and clearance. There was a significant correlation for the volume of distribution between Weeks 1 and 2 of the second admission but not for the first admission. The percents of coefficient of variation and ranges were large. With dosing regimens derived from previously determined factors, "within admission" predicted peaks and troughs would result in 60 and 35% of patients outside the therapeutic range for Admissions 1 and 2, respectively. "Between admission" predictions would result in 65 and 75% of patients outside the therapeutic range. We conclude that considerable variability exists and recommend weekly determinations of serum concentrations and dosing adjustments.

The use of a rapid theophylline assay in the ambulatory setting.

The Seralyzer reflectance photometer was evaluated in three ambulatory settings. Of the total 99 assays in the pediatric general medicine clinic, 47 were below the therapeutic range, and 20 patients were noncompliant. There were 13 low and nine high levels along with 22 noncompliant patients detected from a total of 109 in the allergy clinic. The physician's office documented 43 low and four high levels along with 10 noncompliant patients from 105 assays. The mean time required for Seralyzer results in both the allergy and pediatric general medicine clinic was 13 minutes. Regression analysis of both finger-stick and venipuncture split samples indicated a strong correlation between Seralyzer results and traditional methods of assay (r = 0.94 and 0.99, respectively). The Seralyzer proved accurate, timely, and simple to operate.

Predictive models for mortality and length of hospital stay in an Egyptian burns centre.

Our aim was to obtain a statistical profile of survivors and deaths among burn victims and to develop predictive models for mortality and length of hospital stay. All patients admitted to the Burns Unit of Alexandria Main University Hospital over a 1-year period were included. Of 533 cases, mean length of hospital stay was 15.5 +/- 21.6 days and the mortality rate was 33%. Total surface area burnt, inhalation burns, age, sex, depth and degree of burn wounds were the significant independent predictors of mortality in multiple logistic regression analysis. The significant independent predictors of the length of hospital stay were clothing ignition, total surface area burnt, sex, degree and depth of burn and inhalation burns.

Update on the treatment of bacterial urinary tract infections.

The treatment of urinary tract infections (UTIs) has become a complex problem for the clinical practitioner. An understanding of the pharmacology, pharmacokinetics, and in vivo biological activity of antimicrobial agents is needed, as is an understanding of the variables that may influence patient compliance with medication regimens. Although UTIs are usually treated for 10 to 14 days, shorter treatment schedules of seven to ten days or even single-dose regimens are possible. Guidelines for the treatment of UTIs are presented along with suggestions for increased patient compliance.

The utilization of a clinical pharmacist--a way of decreasing medications in a community hospital.

This article summarizes the results of a study designed to evaluate clinical pharmacy services as a means of reducing drug usage in a 170-bed community hospital. A total of 591 medication orders for 93 hospitalized patients were evaluated. A pharmacy resident made recommendations regarding the appropriateness of the medication order to the attending physicians. A team of reviewing physicians later evaluated these recommendations. The resident's suggestions were also monitored by a university-affiliated and experienced clinical pharmacist. The number of medications ordered which the pharmacy resident would have prescribed during consultation with physicians was 312 (53 percent), while the overseeing clinical pharmacist would have prescribed 352 (60 percent). Two hundred and fifteen therapeutic recommendations were provided by the pharmacy resident, of which 38 (17.6 percent) were carried out by the attending physician. The reviewing physicians did not agree with 37 of these recommendations. Twenty-two drug interactions were detected, of which eleven were thought to be of definite clinical significance by the pharmacy resident. The study demonstrated that a 40 percent reduction in medication utilization could result in a community hospital, while the same level of therapeutic effectiveness was maintained, by using the services of a properly trained clinical pharmacist. The patient care appraisal committee which was appointed to evaluate the study reviewed the results and agreed that, based on the cost factor and improvement of patient care, clinical pharmacy services would be beneficial.

Oral 5-aminosalicyclic acid in children with colonic chronic inflammatory bowel disease: clinical and pharmacokinetic experience.

Five children between the ages of 10 and 17 years with chronic inflammatory bowel disease with involvement of colon had intolerance to sulfasalazine, and desensitization trials had failed in them. In addition, they were steroid dependent. Therefore treatment was tried with an oral 5-aminosalicylic acid (5-ASA) preparation coated with the pH sensitive polymer Asacol. Three of these patients responded to the new drug and were weaned off the steroids. However, the other two patients developed repeated side effects from the medication. Plasma levels and urinary excretion of 5-ASA and its major metabolite in four of these patients were determined and were noted to be similar to those in the adults. Range of variable steady state plasma level of 5-ASA was 0.1-5 mg/L and of its acetyl-metabolite (Ac-5-ASA) was 1-8 mg/L.

Comparison of the Seralyzer and EMIT systems for determination of theophylline concentrations.

A reflectance photometry assay for measurement of serum theophylline concentration was evaluated by comparison with an enzyme-multiplied immunoassay technique (EMIT). The concentration of theophylline in blood samples obtained from patients receiving intravenous theophylline therapy in the pediatric intensive-care unit was measured by both the Seralyzer and the EMIT systems. The interday and intraday variability of each method were also determined by means of calibrators of known concentration (5 to 40 micrograms/mL). There was significant correlation between the serum theophylline concentrations determined by the Seralyzer system and the EMIT system. The overall standard error of the estimate was 2.3 micrograms/mL, but with operator experience this improved to 1.3 micrograms/mL. Intraday variability was 1.2 micrograms/mL for the Seralyzer and 0.7 micrograms/mL for EMIT; the respective values for interday variability were 1.4 micrograms/mL and 0.8 micrograms/mL. The Seralyzer method measures theophylline concentrations with reliability, convenience, and speed. It could be potentially useful in a satellite, clinic, or acute-care pharmacy area.

Pharmacokinetics of gentamicin in neonatal patients supported with extracorporeal membrane oxygenation.

This analysis of gentamicin pharmacokinetics involved 15 neonates supported by extracorporeal membrane oxygenation (ECMO). Two sets of blood samples were obtained from each neonate while supported by ECMO. The mean volume of distribution, elimination half-life, and clearance calculated from the first set of samples were 0.62 liters/kg, 7.6 hours, and 1.17 ml/kg/minute, respectively. Mean values from the second set of samples were 0.61 liters/kg, 7.9 hours and 0.99 ml/kg/minute, respectively. There were no statistical differences (p greater than 0.05) between the pharmacokinetics calculated from the first and second set of samples. A comparison of our results with those of others involving neonates not supported by ECMO failed to demonstrate any major impact of ECMO on the pharmacokinetics of gentamicin.

Factors influencing prices offered to pharmaceutical purchasing groups.

Purchasing-group characteristics that influence pharmaceutical-vendor pricing are discussed. A questionnaire about pricing practices and a self-addressed stamped envelope were mailed to bid managers of vendors in November 1985. The bid managers' attitudes toward the effect of various characteristics of purchasing groups on prices was determined by calculating the mean response to each of a group of four questions about pricing practices. Of the 269 questionnaires distributed, 161 (59.8%) were returned. Of these, 115 were usable. Three vendor groups were established from demographic information: Pharmaceutical Manufacturers Association members (44.3%), generic manufacturers (13.9%), and wholesalers (41.7%). Bid managers agreed that the following characteristics would influence lower prices: single group membership, market conditions, group size, adherence to contracts, and volume commitment; they disagreed that the time of year during which bid solicitations are conducted would affect prices. Further studies are needed to correlate actual pricing practices and the opinions of vendors regarding factors influencing pricing.

Compatibility of cefazolin and gentamicin in peritoneal dialysis solutions.

The compatibility of cefazolin and gentamicin in fluid commonly used for continuous ambulatory peritoneal dialysis (CAPD) was studied. Five admixtures containing cefazolin (75 mg/L and 150 mg/L) and gentamicin (8 mg/L), alone and in combination, were prepared in 1.5% dextrose peritoneal dialysis solution. Solutions were stored for 48 hours at 4 degrees C, 26 degrees C, and 37 degrees C; aliquots for drug assay were obtained at 0, 4, 8, 24, and 48 hours. HPLC and immunofluorescent assays were used to determine cefazolin and gentamicin concentrations, respectively. The cefazolin and gentamicin concentration changes over the study period did not reach statistical significance. Maximal cefazolin and gentamicin losses (12 and 7 percent of the initial concentrations, respectively) were observed at 48 hours in solutions stored at 37 degrees C. No significant differences in concentration changes were observed between combination solutions and solutions containing either cefazolin or gentamicin alone. Cefazolin and gentamicin, alone or in combination, are compatible for at least 48 hours in CAPD solutions.

A clinical comparison of terbutaline with albuterol administered by metered-dose inhaler.

The effects of albuterol and terbutaline administered by metered-dose inhaler were compared via a randomized crossover design. For 20 previously diagnosed asthmatics, spirometric measurements were determined prior to and at nine times post-dose up to six hours. Patients used each drug for a 7-day test period and recorded the occurrence of side effects. As measured by FEV1 and FEF25-75, both drugs caused a rapid and significant bronchodilation of approximately 4-hour duration. For both drugs, there was little effect on blood pressure and heart rate and reported side effects were minimal. There was no statistically significant difference between drugs in pulmonary response nor in any reported side effect.

Decreased binding of verapamil to plasma proteins in patients with liver disease.

The binding of verapamil to proteins in plasma of patients with liver disease was studied using equilibrium dialysis. Compared with an age- and sex-matched control group, the fraction unbound of verapamil was significantly greater in patients with liver disease (p less than 0.01). The mean +/- SD fraction unbound in the patients was 0.16 +/- 0.05 compared with 0.099 +/- 0.015 in the control group (p less than 0.01). The higher fraction unbound in the liver disease patients appeared to be largely due to lower concentrations of binding proteins in plasma. A substantial effect of pH on the binding of verapamil to plasma proteins was observed. The increase in fraction unbound is consistent with previous findings of an increased apparent volume of distribution in patients with liver disease. Because of the pharmacokinetic characteristics of verapamil, the observed altered binding to plasma proteins would be expected to result in higher steady-state plasma concentrations of unbound drug after intravenous but not oral administration. For clinical monitoring, at any given total concentration, the unbound concentration would be approximately 60% higher in patients with liver disease. This study, together with previous studies in the literature, suggests that caution should be exercised in the administration of verapamil to patients with liver disease.

Evaluation of Ames Seralyzer for the therapeutic drug monitoring of phenobarbital and phenytoin.

Comparison of a reflective photometry assay (Ames Seralyzer) and a fluorescence polarization immunoassay (Abbott TDx) for measuring phenobarbital and phenytoin serum concentration was performed. Routine phenobarbital and phenytoin plasma levels drawn from patients in the pediatric neurology clinic and pediatric intensive care unit were determined in duplicate by the Abbott TDx and Ames Seralyzer systems. A total of 40 samples were assayed. The interday and intraday variability of the Ames system was determined using calibrators of known concentrations (5-25 micrograms/ml). There was significant correlation between the serum phenobarbital or phenytoin concentrations when determined by the Seralyzer and TDx systems. The intraday variability for the measurement of phenytoin when determined by the Seralyzer had coefficients of variation ranging from 2.2 to 8.9%. The interday variability for phenytoin when measured by both the TDx and the Seralyzer correlated well with known calibrators. The utility of the Ames Seralyzer for acute-care facilities, physician offices, and pharmacy satellites is apparent. Based on statistical analysis, the Seralyzer provides accurate phenobarbital and phenytoin serum measurements for clinical use in therapeutic drug monitoring.