Tom A. Larson

Assessment of effects of protein binding on daptomycin and vancomycin killing of Staphylococcus aureus by using an in vitro pharmacodynamic model.

Initial clinical trials with daptomycin (2 mg/kg per day) were prematurely suspended because of unexplained treatment failures in patients with bacteremia who were treated with daptomycin, despite in vitro data indicating that the gram-positive cocci causing the infection were susceptible to daptomycin. One explanation for these clinical failures may relate to the relatively high degree of daptomycin protein binding (94%). To evaluate the impact of protein on daptomycin activity, a two-chamber in vitro pharmacodynamic model was used to study and compare the interaction between Staphylococcus aureus (clinical isolate) and either daptomycin or vancomycin, each in the presence and absence of physiologic human albumin concentrations. Low-dose (2 mg/kg) daptomycin, high-dose (6 mg/kg) daptomycin, and 10 mg of vancomycin per kg beta-phase elimination serum-concentration-versus-time curves were simulated by using this in vitro pharmacodynamic model. The bacterial kill rates by all three regimens were decreased in the presence of albumin (P less than 0.0002). The average times required for a 99% kill of the initial S. aureus inocula (approximately 5 x 10(7) CFU/ml) without albumin were 0.81 (low-dose daptomycin), 0.33 (high-dose daptomycin), and 6.18 (vancomycin) h. The average times required for a 99% kill of S. aureus with albumin were 7.66 (low-dose daptomycin), 0.95 (high-dose daptomycin), and 10.52 (vancomycin) h. These data demonstrate that, depending on the concentration of daptomycin, the presence of albumin can profoundly diminish the bactericidal activity of daptomycin.

Pharmacokinetics of fluconazole in immune-compromised children with leukemia or other hematologic disease

Study Objective. To describe the pharmacokinetics of fluconazole in immune‐compromised children with leukemia or other hematologic disease.

Resistance surveillance programs and the incidence of gram-negative bacillary resistance to amikacin from 1967 to 1985

Data relating to amikacin resistance among gram-negative bacilli were obtained by means of a review of published literature and resistance surveillance studies. Data from the first several years of amikacin use are difficult to interpret because the 10-micrograms disk used for Kirby-Bauer susceptibility testing resulted in apparent greater resistance than the present 30-micrograms disk. A large United States susceptibility surveillance program that monitors antibiotic use has shown a trend since 1977 of greater susceptibility of Serratia species and greater resistance among Pseudomonas aeruginosa for all the aminoglycosides. Pseudomonas resistance to amikacin has shown the smallest increase of any aminoglycoside. Several hospitals (Strong Memorial Hospital, University of Maryland Cancer Center, and Minneapolis Veterans Administration Medical Center) have reported either no significant change or a decrease in resistance to amikacin when it was the most frequently used aminoglycoside. In a large, 14-center, prospective study, high-level use of amikacin resulted in a significant decrease in resistance to gentamicin and tobramycin (p less than 0.01) and a marginal increase (p less than 0.05) in amikacin resistance. Significantly increased amikacin resistance has been reported from two institutions, neither of which used amikacin as the predominant aminoglycoside. Overall, the high-level use of amikacin in large multi-center surveillance programs for as long as five years has not resulted in a significant increase in amikacin resistance rates at any of the individual institutions surveyed.

Investigation of the early killing of Staphylococcus aureus by daptomycin by using an in vitro pharmacodynamic model

The purpose of this study was to develop a pharmacodynamic model to describe the dependency of the rate of Staphylococcus aureus killing upon the concentration of daptomycin. A range of free (unbound) daptomycin concentrations ranging from 0.12 to 27 times the MIC were simulated in the peripheral compartment of a two-compartment pharmacokinetic model. Log-linear regression of free daptomycin concentrations versus growth or kill rate constants showed a significant correlation (r = -0.90; P less than 0.001). A Lineweaver-Burk plot of the reciprocal transformation of these data yielded a poor fit (r = -0.38; P greater than 0.05). When a Lineweaver-Burk-type regression analysis was performed on the reciprocal of the change in the rate constant rather than the rate constant itself, the result demonstrated good correlation (r = 0.90; P less than 0.0001). The observations were also well described by a sigmoidal maximum plateau pharmacologic effect model, in which the pharmacologic effect of daptomycin is a reduction in the bacterial exponential growth rate constant from the baseline in the absence of antibiotic to a lower (positive) growth or (negative) death rate constant observed in the presence of antibiotic. These data confirm that daptomycin exhibits concentration-dependent killing over a wide range of free daptomycin concentrations relative to the MIC and suggest that this is a saturable process similar to the Michaelis-Menten pharmacokinetic elimination of certain drugs.

Rural interprofessional service-learning: the Minnesota experience.

The Minnesota Rural Health School (MRHS), which operated from 1996 to 2003, was the University of Minnesotas first initiative that provided rural, community-based, interdisciplinary health professions education. The newly funded Minnesota Area Health Education Center (AHEC) is now coordinating interprofessional rural clinical education at the Academic Health Center level for the university. The service-learning curricular component is one of the most lasting legacies of the MRHS. This article provides a descriptive summary of the initial 61 service-learning projects completed by students from various health professions who participated in the MRHS and indicates the type of projects that have continuing effects. The seven community site coordinators affiliated with the MRHS completed a survey analyzing service-learning projects performed in their communities. Student interest was predominant in selecting 28% of the 61 projects, community interest was paramount in selecting 10%, and a mixture of both student and community interest contributed to 62% of project selection. Thirty of the projects were designed as single interventions, and the remaining 31 projects have ongoing impact. Students demonstrated interprofessional group synergy and significant creativity in addressing multiple community health care issues and needs, within time constraints of only ten to 12 days in which to develop and implement a service-learning project. Two project examples are described in detail to illustrate the challenges and successes of this type of civic engagement.

Integrating a pharmacist into a home healthcare agency care model: impact on hospitalizations and emergency visits.

Medication regimens can be complicated during the transition from hospital to home for a variety of reasons. The primary purpose of this retrospective study was to measure the impact of integrating a pharmacist into a model of care at a Medicare-certified home healthcare agency for clients recently discharged from the hospital. The secondary purpose was to describe the medication-related problems among clients receiving services from the model of care involving a pharmacist. Integrating a pharmacist within the model of care demonstrated a positive clinical impact on clients.

Interprofessional Collaboration to Improve Discharge from Skilled Nursing Facility to Home: Preliminary Data on Postdischarge Hospitalizations and Emergency Department Visits

An interprofessional collaborative practice model was established at Hennepin County Medical Center to improve discharge management from the transitional care unit of the skilled nursing facility (SNF) to home. The practice model involves a geriatrician, nurse practitioner, and pharmacist who care for individuals at a community‐based SNF. Before SNF discharge, the pharmacist conducts a chart and in‐person medication review and collaborates with the nurse practitioner to determine the discharge medication regimen. The pharmacists review focuses on assessing the indication, safety, effectiveness, and convenience of medications. The pharmacist provides follow‐up in‐home or over the telephone 1 week after SNF discharge, focusing on reviewing medications and assessing adherence. Hospitalizations and emergency department (ED) visits 30 days after SNF discharge of individuals who received care from this model was compared with those of individuals who received usual care from a nurse practitioner and geriatrician. From October 2012 through December 2013, the intervention was delivered to 87 individuals, with 189 individuals serving as the control group. After adjusting for age, sex, race, and payor, those receiving the intervention had a lower risk of ED visits (odds ratio (OR) = 0.46, 95% confidence interval (CI) = 0.22–0.97), although there was no significant difference in hospitalizations (OR = 0.47, 95% CI = 0.21–1.08). The study suggests that an interprofessional approach involving a pharmacist may be beneficial in reducing ED visits 30 days after SNF discharge.

PDP or MA-PD? Medicare part D enrollment decisions in CMS Region 25

BACKGROUND The Medicare Prescription Drug Improvement and Modernization Act of 2003 provides outpatient prescription drug coverage for Medicare beneficiaries through private insurers. This coverage is available through 2 primary venues: stand-alone prescription drug plans (PDPs) and integrated managed care (or Medicare Advantage) plans that also provide prescription drug coverage (MA-PDs). OBJECTIVES The first objective was to describe factors associated with Medicare beneficiaries choosing to enroll in any Medicare part D PDP. The second objective was to describe factors associated with the choice of an MA-PD, given enrollment in the part D program. METHODS The study used a cross-sectional, survey design. Data were collected from a stratified random sample of 5000 community-dwelling adults, aged 65 years and older in the Center for Medicaid and Medicare Services Region 25. Data were collected by means of a mailed questionnaire. Data analyses included univariate and bivariate descriptive statistics and multivariate probit modeling. RESULTS The overall adjusted response rate was 50.2% (2309 of 4603). Data from 1490 respondents (32.4% of those attempted) were analyzed in this study. Nearly 75% of sample members elected to enroll in one of the Medicare part D coverage options in 2007, with more than 3 times as many choosing a PDP compared with a MA-PD option (57.2% vs 17.8%). A variety of variables including rurality, plan price, perceived future need for medications, and preferences emerged as important predictors of choosing to enroll in any Medicare part D drug plan, whereas rurality, state of residence, and number of diagnosed medical conditions were associated with the decision to enroll in a MA-PD. CONCLUSIONS Models of health insurance demand and plan choice applied in this context appear to be modestly effective. Rurality and state of residence were particularly important contributors to both of these decisions, as were a variety of individual characteristics.

An in Vitro Pharmacodynamic Model to Simulate Antibiotic Behavior of Acute Otitis Media with Effusion

The purpose of this investigation was to develop an in vitro pharmacodynamic model (IVPM) that would simultaneously simulate in vivo serum and middle ear amoxicillin pharmacokinetic characteristics of acute (purulent) otitis media and then utilize the IVPM to assess amoxicillin-mediated killing of a type 7F Streptococcus pneu-moniae (MIC = 0.002 mg/L). The IVPM consisted of a sterile central compartment and a membrane-bound “infected” peripheral compartment. Peak peripheral compartment amoxicillin concentrations occurred within 2 hr after its introduction into the central compartment and were approximately 30% of peak central compartment concentrations. Amoxicillin elimination from the central compartment was designed to provide a 1-hr t1/2. Amoxicillin elimination from the peripheral compartment was slower than from the central compartment, with an average half-life of 2.3 hr. Significant concentration-related differences in maximal bacterial kill rates were not detected over the range of amoxicillin concentrations studied (0.26 to 14.6 mg/L). However, at peak central compartment amoxicillin concentrations of ≤2 mg/L, a lag phase in killing was observed. In general, the in vitro pharmacokinetic data derived from this model compare well with published in vivo data.

The role of a pharmacist on the home care team: a collaborative model between a college of pharmacy and a visiting nurse agency.

Medication-related problems are common among home care clients who take many medications and have complex medical histories and health problems. Helping clients manage medications can be a challenge for all home care clinicians. By partnering with a college of pharmacy at a large university in the community, the agency successfully included a pharmacist as a member of their home care team.