Population Pharmacokinetics and Pharmacodynamics of Extended-Infusion Piperacillin and Tazobactam in Critically Ill Children.

The study objective was to evaluate the population pharmacokinetics and pharmacodynamics of extended-infusion piperacillin-tazobactam in children hospitalized in an intensive care unit. Seventy-two serum samples were collected at steady state from 12 patients who received piperacillin-tazobactam at 100/12.5 mg/kg of body weight every 8 h infused over 4 h. Population pharmacokinetic analyses were performed using NONMEM, and Monte Carlo simulations were performed to estimate the piperacillin pharmacokinetic profiles for dosing regimens of 80 to 100 mg/kg of the piperacillin component given every 6 to 8 h and infused over 0.5, 3, or 4 h. The probability of target attainment (PTA) for a cumulative percentage of the dosing interval that the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (TMIC) of ≥50% was calculated at MICs ranging from 0.25 to 64 mg/liter. The mean ± standard deviation (SD) age, weight, and estimated glomerular filtration rate were 5 ± 3 years, 17 ± 6.2 kg, and 118 ± 41 ml/min/1.73 m(2), respectively. A one-compartment model with zero-order input and first-order elimination best fit the pharmacokinetic data for both drugs. Weight was significantly associated with piperacillin clearance, and weight and sex were significantly associated with tazobactam clearance. Pharmacokinetic parameters (mean ± SD) for piperacillin and tazobactam were as follows: clearance, 0.22 ± 0.07 and 0.19 ± 0.07 liter/h/kg, respectively; volume of distribution, 0.43 ± 0.16 and 0.37 ± 0.14 liter/kg, respectively. All extended-infusion regimens achieved PTAs of >90% at MICs of ≤16 mg/liter. Only the 3-h infusion regimens given every 6 h achieved PTAs of >90% at an MIC of 32 mg/liter. For susceptible bacterial pathogens, piperacillin-tazobactam doses of ≥80/10 mg/kg given every 8 h and infused over 4 h achieve adequate pharmacodynamic exposures in critically ill children.

Understanding pharmacist success in practice: A scoping review.

OBJECTIVES: The objective was to identify literature providing a description of characteristics contributing to pharmacists' individual level success in providing advanced patient care. DESIGN: An interpretive scoping review was conducted to synthesize knowledge and address the study objective. SETTING: Searches were undertaken in Ovid MEDLINE (1946-2015), EMBASE (1974-2015), and International Pharmaceutical Abstracts (1970-2015). PARTICIPANTS: Not applicable. MAIN OUTCOME MEASURES: Specific keywords used in the search included: motivation, attitude, career, clinical competence, certification, pursuit of an expanded scope of practice, pharmacist, and success. This was not intended to be an exhaustive list, and every effort was made to be inclusive as the search revealed additional words and phrases of interest. RESULTS: A total of 93 articles were initially identified, 10 articles met inclusion criteria and were retained for full-text analysis. Most of the included articles were published in the United States (70%). One-third of the articles conducted semi-structured interviews, one-third of the articles were editorials or commentaries, and the remaining articles collected data using surveys, knowledge assessments, and observation. Content analysis of the extracted definitions of success yielded 2 themes; "what successful pharmacists do" and "what successful pharmacists should be." CONCLUSION: Professional organizations representing pharmacy have made significant strides in advocating for pharmacists' provision of advanced patient care. If pharmacists are to successfully provide advanced patient care a more specific and practically-oriented understanding that accounts for individual and environmental factors of how to achieve individual-level success is needed.

Influence of the Fear of Missing Out in Student Pharmacists' Decision to Pursue Residency Training.

Objective. To examine the influence of the fear of missing out (FOMO) on student pharmacists' postgraduate career decisions, specifically on whether to pursue a residency. Methods. A 14-item FOMO scale was designed to examine the influence of this factor on student pharmacists' residency decision. A survey was distributed to second-, third-, and fourth-year student pharmacists at four participating universities. Average FOMO scores were compared based on residency intentions. Logistic regression analysis was used to predict residency intentions based on students' average FOMO scores. Results. The survey response rate was 74%. Of the 833 respondents, 42% indicated an intention to pursue residency training. Students indicated the FOMO items were "slightly" true of them, as evidenced by the overall FOMO mean score of 2.0 on a 5-point scale. Comparison among classes revealed a higher mean FOMO score among students in the second year of the pharmacy curriculum than among students in the third and fourth years. Logistic regression analysis indicated that FOMO score can reliably distinguish between students with residency intentions and those without. Conclusion. This study supports the existence of FOMO in the decision to pursue a pharmacy residency, although more research and scale refinement is needed to better identify its impact.

Patient centered research to improve community involvement (PaRTICIpate) in diabetes self-management: a conference series for developing collaborations between researchers, stakeholders, and patients.

BACKGROUND: A patient-centered approach to research development is important to the creation of research evidence that is meaningful and beneficial to patients. Collaboration between patients, stakeholders, and researchers, where patients serve an integral role in all aspects of the research development process, is integral to achieving these twin objectives. RESULTS: This paper presents a unique approach to engaging patients and stakeholders in research by describing a conference series focused on meaningfully integrating patients in each phase of the project. Through three meeting phases, patients were not only introduced to patient-centered research (PCR) concepts, but they also led discussions about diabetes self-management and developed PCR questions. A total of 17 questions were developed represented by four main themes: communication, patient knowledge and perceptions, diabetes prevention, and diabetes management. Through patient feedback, three research questions were each identified as immediate priorities for development into research project proposals. CONCLUSION: To our knowledge, the use of a conference series designed to teach patients about research, encourage collaboration across stakeholder groups, and write research questions has not been described in the literature. Moreover, this approach has proven successful in recruiting and retaining patient participation through the life of the project. This project has also identified a number of issues for consideration by future researchers looking to meaningfully engage patients in the development of research proposals.

Balancing vancomycin efficacy and nephrotoxicity: should we be aiming for trough or AUC/MIC?

Sixty years later, the question that still remains is how to appropriately utilize vancomycin in the pediatric population. The Infectious Diseases Society of America published guidelines in 2011 that provide guidance for dosing and monitoring of vancomycin in adults and pediatrics. However, goal vancomycin trough concentrations of 15-20 µg/mL for invasive infections caused by methicillin-resistant Staphylococcus aureus were based primarily on adult pharmacokinetic and pharmacodynamic data that achieved an area under the curve to minimum inhibitory concentration ratio (AUC/MIC) of ≥400. Recent pediatric literature shows that vancomycin trough concentrations needed to achieve the target AUC/MIC are different than the adult goal troughs cited in the guidelines. This paper addresses several thoughts, including the role of vancomycin AUC/MIC in dosing strategies and safety monitoring, consistency in laboratory reporting, and future directions for calculating AUC/MIC in pediatrics.

Acid-Suppressing Agents and Risk for Clostridium difficile Infection in Pediatric Patients.

BACKGROUND: Acid-suppressing agents have been associated with increased Clostridium difficile infection (CDI) in adults. The objective of this study was to evaluate the association of acid-suppressing therapy with the development of CDI in the pediatric population. METHODS: This was a retrospective case-control study. Children aged 1 through 17 years with a positive C difficile polymerase chain reaction (PCR) result obtained between June 1, 2008, and June 1, 2012, were randomly matched to a control population selected from patients with negative PCR. RESULTS: A total of 458 children were included. No difference was observed in acid-suppressive therapy prior to PCR in CDI-positive versus -negative patients (n = 131 [57.2%] vs n = 121 [52.8%], P = .348). Among patients receiving acid-suppressing therapy prior to obtaining a PCR, no difference was observed in proton pump inhibitor use (45% vs 46.3%, P = .843), but histamine-2 receptor antagonist (H2RA) use was greater in the CDI-positive patients (32.8% vs 14.9%, P = .001). Logistic regression analysis demonstrated that H2RA therapy at home (odds ratio = 4.6; 95% confidence interval = 1.5-14.5) was an independent CDI predictor. CONCLUSION: In this pediatric population, CDI risk in children receiving home acid-suppressive therapy with H2RAs is nearly 4.5 times greater than that of children not receiving H2RA therapy. These results suggest the need for continued monitoring and study of H2RA therapy in children.