Administration of Extended Infusion Piperacillin-TazobactamWith the Use of Smart Pump Technology

Background:

For beta-lactams, the parameter that best predicts bacterial killing is the length of time the antibiotic concentration exceeds the minimum inhibitory concentration (MIC). Studies have demonstrated improved outcomes with extended infusion (4-hour) piperacillin-tazobactam (P-TZ) compared with traditional immediate infusions.

Objectives:

To describe how one institution made the conversion from immediate infusion of P-TZ to a 4-hour extended infusion utilizing an approved automatic therapeutic substitution, staff education, and smart pump technology, and to examine the impact of this conversion on patient length of stay and pharmacy costs.

Methods:

With approval from the Pharmacy and Therapeutics (P&T), Antimicrobial Stewardship, and Medical Executive Committees, the decision was made to automatically convert all P-TZ orders to a standardized 4-hour infusion given every 8 to 12 hours depending on renal function. The medical records of all adult patients receiving P-TZ during 12 months pre implementation and 24 months post implementation of a 4-hour extended infusion of P-TZ were retrospectively analyzed for length of stay and mortality. The cost of P-TZ was also assessed during these time periods.

Results:

With the help of smart pump technology, our institution successfully completed a conversion to 4-hour extended infusion P-TZ. Through this conversion, pharmacy expenditure of P-TZ was reduced by 38%; the total cost savings was $387,980.62 for the 24-month postintervention phase. Extended infusion P-TZ reduced hospital length of stay by 0.6 days (P < .05), resulting in an additional cost savings of $1,689,480 for the 24-month postintervention phase. A conservative estimate of total cost savings to the hospital in the first 24 months, including the reduction in P-TZ expenditures, was $2,077,460.Key Words: antibiotics, length of stay, piperacillin-tazobactam, smart pump technologyInfections caused by antibiotic-resistant bacteria are a great concern to public health, as growing resistance among both gram-positive and gram-negative pathogens is observed.¹ Data from the Centers for Disease Control and Prevention (CDC) show rapidly rising rates of infection due to methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE), and fluoroquinolone-resistant Pseudomonas aeruginosa.² Even more concerning is the fact that the number of new antibacterial drugs approved for marketing in the United States is dramatically decreasing.³The increase in resistance of organisms and the availability of fewer effective antibiotics have led infectious disease specialists to reevaluate optimal methods of administering intravenous (IV) antibiotics.^4,5The relationship between the pharmacokinetics and pharmacodynamic activity of beta-lactam antibiotics influences their dose and effectiveness in eradicating pathogens, and the time above the minimum inhibitory concentration (MIC) is an important marker for efficacy.^6–10 Studies have shown that bactericidal effects of penicillins are maximized when the drug concentrations are higher than the MIC for greater than 50% of the dosing interval.¹¹     

Amplification of low-frequency antiviral CD8 T cell responses using autologous dendritic cells.

OBJECTIVE: To utilize the potent antigen-presenting capacity of mature dendritic cells (MDC) in order to develop a rapid, sensitive method for quantifying antigen-specific CD8 T cells present at low frequency in peripheral blood. DESIGN: Peripheral blood mononuclear cells (PBMC) were obtained from seven HIV-1-positive individuals with low to moderate CD8 T cell responses, including five on highly active antiretroviral therapy (HAART). IFN-gamma ELISPOT assays were performed using either monocytes or MDC to present antigens expressed by recombinant vaccinia viruses (r-VV). METHODS: Peripheral blood-derived monocytes were cultured for 5-6 days in the presence of IL-4 and granulocyte macrophage colony-stimulating factor, then matured in monocyte-conditioned medium. MDC were infected with r-VV and co-cultured in an ELISPOT assay with autologous monocyte-depleted PBMC. RESULTS: Relative to autologous monocytes, MDC amplified detection of antigen-specific CD8 T cells by 2-30-fold in response to antigens from HIV-1, Epstein-Barr virus and cytomegalovirus. Furthermore, antigenic specificities were revealed that had not been detected using standard ELISPOT of PBMC. CONCLUSION: This assay will prove useful for the detection of memory T cells present at low frequency, and may be of interest for identifying subdominant cytotoxic T lymphocyte epitopes. This method may have broad applications for the detection of antiviral CD8 T cell responses in patient populations in whom such responses have been difficult to detect, including HIV-1-seropositive individuals with advanced disease or undergoing HAART.     

PEER umbrella systematic review of systematic reviews: Management of osteoarthritis in primary care

ObjectiveTo determine how many patients with chronic osteoarthritis pain respond to various non-surgical treatments.Data sourcesPubMed and the Cochrane Library.Study selection Published systematic reviews of randomized controlled trials (RCTs) that included meta-analysis of responder outcomes for at least 1 of the following interventions were included: acetaminophen, oral nonsteroidal anti-inflammatory drugs (NSAIDs), topical NSAIDs, serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, cannabinoids, counseling, exercise, platelet-rich plasma, viscosupplementation, glucosamine, chondroitin, intra-articular corticosteroids, rubefacients, or opioids.Synthesis In total, 235 systematic reviews were included. Owing to limited reporting of responder meta-analyses, a post hoc decision was made to evaluate individual RCTs with responder analysis within the included systematic reviews. New meta-analyses were performed where possible. A total of 155 RCTs were included. Interventions that led to more patients attaining meaningful pain relief compared with control included exercise (risk ratio [RR] of 2.36; 95% CI 1.79 to 3.12), intra-articular corticosteroids (RR = 1.74; 95% CI 1.15 to 2.62), SNRIs (RR = 1.53; 95% CI 1.25 to 1.87), oral NSAIDs (RR = 1.44; 95% CI 1.36 to 1.52), glucosamine (RR = 1.33; 95% CI 1.02 to 1.74), topical NSAIDs (RR = 1.27; 95% CI 1.16 to 1.38), chondroitin (RR = 1.26; 95% CI 1.13 to 1.41), viscosupplementation (RR = 1.22; 95% CI 1.12 to 1.33), and opioids (RR = 1.16; 95% CI 1.02 to 1.32). Preplanned subgroup analysis demonstrated no effect with glucosamine, chondroitin, or viscosupplementation in studies that were only publicly funded. When trials longer than 4 weeks were analyzed, the benefits of opioids were not statistically significant.ConclusionInterventions that provide meaningful relief for chronic osteoarthritis pain might include exercise, intra-articular corticosteroids, SNRIs, oral and topical NSAIDs, glucosamine, chondroitin, viscosupplementation, and opioids. However, funding of studies and length of treatment are important considerations in interpreting these data.     

Targeting VPAC1 Receptors for Imaging Glioblastoma

Molecular Imaging and Biology - Scintigraphic imaging of malignant glioblastoma (MG) continues to be challenging. We hypothesized that VPAC1 cell surface receptors can be targeted for positron...     

Development of LactaPedia: A lactation glossary for science and medicine

During the last decade, there have been several publications highlighting the need for consistent terminology in breastfeeding research. Standard terms and definitions are essential for the comparison and interpretation of scientific studies that, in turn, support evidence‐based education, consistency of health care, and breastfeeding policy. Inconsistent advice is commonly reported by mothers to contribute to early weaning. A standard language is the fundamental starting point required for the provision of consistent advice. LactaPedia ( www.lactapedia.com ) is a comprehensive lactation glossary of over 500 terms and definitions created during the development of LactaMap ( www.lactamap.com ), an online lactation care support system. This paper describes the development of LactaPedia, a website that is accessible free of charge to anyone with access to the Internet. Multiple methodological frameworks were incorporated in LactaPedia's development in order to meet the needs of a glossary to support both consistent health care and scientific research. The resulting LactaPedia methodology is a six‐stage process that was developed inductively and includes framework to guide vetting and extension of its content using public feedback via discussion forums. The discussion forums support ongoing usability and refinement of the glossary. The development of LactaPedia provides a fundamental first step towards improving breastfeeding outcomes that are currently well below World Health Organisation recommendations globally.