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Introduction: A drug combination that has gained recent attention for an additive risk of nephrotoxicity is vancomycin plus piperacillin-tazobactam. Clinicians need to better understand whether tubular cell stress occurs with piperacillin-tazobactam administration to establish whether renal injury associated with this combination is a valid clinical concern.Objective: An evaluation of the pharmacokinetics of urinary tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding-protein 7 (IGFBP7) for patients receiving vancomycin alone, piperacillin-tazobactam alone, and vancomycin plus piperacillin-tazobactam in combination was conducted to understand the impact on acute kidney cell stress and compare the rates of dialysis or death at 9 months among these three drug exposure types.Methods: A secondary analysis of the prospective, multicenter Sapphire study (ClinicalTrials.gov identifier NCT01209169) including 35 intensive care units (ICUs) in North America and Europe was performed. Critically ill adult patients at risk for acute kidney injury (AKI) were included. Urinary [TIMP-2]∙[IGFBP7] was measured serially. Patients who received vancomycin alone, piperacillin-tazobactam alone, or vancomycin plus piperacillin-tazobactam were grouped according to their maximum AKI stage within 3 days of the first drug dose.Results: Of 723 critically ill adults admitted to the ICU, 46% received either piperacillin-tazobactam (n = 110), vancomycin (n = 156), or both (n = 67). The urinary [TIMP-2]∙[IGFBP7] was highest on day 1 for the combination group. AKI stage 2/3 occurred more frequently in patients receiving the drug combination than in those receiving piperacillin-tazobactam alone (p = 0.03) but not vancomycin alone (p = 0.29). Risk of death or dialysis at 9 months was greatest for vancomycin plus piperacillin-tazobactam (48%) and similar for patients receiving vancomycin alone (29%) or piperacillin-tazobactam alone (35%) (p = 0.03 for unadjusted and p = 0.048 after adjusting for covariates).Conclusion: After exposure to piperacillin-tazobactam and vancomycin in combination, there was a greater release of AKI biomarkers in patients who develop AKI than with piperacillin-tazobactam or vancomycin monotherapy and the combination is associated with possible increased long-term adverse outcomes. [ABSTRACT FROM AUTHOR]

Introduction: There is an increased risk of potential drug-drug interactions (pDDIs) in critically ill patients based on the number of drugs received. The occurrence of pDDIs and clinical significance is not well described.Objective: The aim was to provide insight into important clinical issues and offer guidance on drug-drug interaction (DDI) surveillance through the performance of a systematic review.Methods: Five targeted objectives were developed, a priori, which guided study selection and data abstraction. Two independent reviewers extracted the definition, frequency, type, and clinical significance of pDDIs. A meta-analysis was performed to evaluate the proportion of patients exposed to a pDDI. Three data sources (PubMed, Embase, and Scopus) were utilized for the search to include studies that evaluated pDDIs in adult critically ill patients. Included studies in the systematic review and meta-analysis were required to be full text.Results: A total of 39 studies met inclusion criteria. Definitions of pDDIs were diverse. Frequency of pDDIs varied by study, but was most commonly between one and five pDDIs per patient. Fifty-eight percent of patients were exposed to at least one pDDI during their intensive care unit admission. Types of pDDIs identified were numerous, with aspirin being the most common drug involved. As expected, not all pDDIs were clinically significant. Clinical significance was determined by varied definitions and sources.Conclusions: Improving the understanding of clinically significant pDDIs and alerts that clinicians encounter may guide better development of surveillance through clinical decision support and decrease alert fatigue. [ABSTRACT FROM AUTHOR]

Background: Utilization of telemedicine allows pharmacists to extend the reach of clinical interventions, connecting them with patients and providers, but the overall impact of these services is under-studied.Objective: Identify the impact of clinical pharmacist telemedicine interventions on clinical outcomes, subsequently defined as clinical disease management, patient self-management, and adherence, in outpatient or ambulatory settings.Methods: A literature search was conducted from database inception through May 2016 in Medline, SCOPUS, and EMBASE. Broad terms "telemedicine", "telehealth", and "telephone" were used in combination with "pharmacist" or "pharmacy" and "telepharmacy". The search and extraction process followed PRISMA guidelines. Results were screened for pharmacist interventions and reviewed to identify studies in outpatient our ambulatory settings. Studies of non-clinical outcomes (i.e. dispensing or product preparation) and with no comparator were excluded. The final studies were categorized by types of outcomes reported: clinical disease management, patient self-management, and adherence.Results: Only 34 studies measured clinical outcomes against a comparator, consistent with the research question. The majority utilized scheduled models of care (n = 29). Telephone was the most common communication method (n = 25). The most utilized interventions were pharmacist-led telephonic clinics (n = 10). Most studies focused on chronic disease management in adults including hypertension, diabetes, anticoagulation, depression, hyperlipidemia, asthma, heart failure, HIV, PTSD, CKD, stroke, COPD and smoking cessation. Twenty-three studies had a positive impact with one reporting negative results. Higher positive impact rate was observed for scheduled (72.4%, 21/29) and continuous (100%, 2/2) models compared to responsive/reactive (25%, 1/4).Conclusions: Clinical pharmacy telemedicine interventions in the outpatient or ambulatory setting, primarily via phone, have an overall positive impact on outcomes related to clinical disease management, patient self-management, and adherence in the management of chronic diseases. Commonalities among studies with positive impact included utilization of continuous or scheduled models via telephone, with frequent monitoring and interventions. Studies identified did not evaluate benefits of video capability over telephone or cost-effectiveness, both of which are useful directions for future study. [ABSTRACT FROM AUTHOR]

Aims: To summarize and extend the main conclusions and recommendations relevant to drug management during acute kidney disease (AKD) as agreed at the 16th Acute Disease Quality Initiative (ADQI) consensus conference. Methods: Using a modified Delphi method to achieve consensus, experts attending the 16th ADQI consensus conference reviewed and appraised the existing literature on drug management during AKD and identified recommendations for clinical practice and future research. The group focussed on drugs with one of the following characteristics: (i) predominant renal excretion; (ii) nephrotoxicity; (iii) potential to alter glomerular function; and (iv) presence of metabolites that are modified in AKD and may affect other organs. Results: We recommend that medication reconciliation should occur at admission and discharge, at AKD diagnosis and change in AKD phase, and when the patient's condition changes. Strategies to avoid adverse drug reactions in AKD should seek to minimize adverse events from overdosing and nephrotoxicity and therapeutic failure from under‐dosing or incorrect drug selection. Medication regimen assessment or introduction of medications during the AKD period should consider the nephrotoxic potential, altered renal and nonrenal elimination, the effects of toxic metabolites and drug interactions and altered pharmacodynamics in AKD. A dynamic monitoring plan including repeated serial assessment of clinical features, utilization of renal diagnostic tests and therapeutic drug monitoring should be used to guide medication regimen assessment. Conclusions: Drug management during different phases of AKD requires an individualized approach and frequent re‐assessment. More research is needed to avoid drug associated harm and therapeutic failure. [ABSTRACT FROM AUTHOR]

Nephrotoxin exposure accounts for up to one-fourth of acute kidney injury episodes in hospitalized patients, and the associated consequences are as severe as acute kidney injury due to other etiologies. As the use of nephrotoxic agents represents one of the few modifiable risk factors for acute kidney injury, clinicians must be able to identify patients at high risk for drug-induced kidney injury rapidly. Recently, significant advancements have been made in the field of biomarker utilization for the prediction and detection of acute kidney injury. Such biomarkers may have a role both for detection of drug-induced kidney disease and implementation of preventative and therapeutic strategies designed to mitigate injury. In this article, basic principles of renal biomarker use in practice are summarized, and the existing evidence for six markers specifically used to detect drug-induced kidney injury are outlined, including liver-type fatty acid binding protein, neutrophil gelatinase-associated lipocalin, tissue inhibitor of metalloproteinase-2 times insulin-like growth factor-binding protein 7 ([TIMP-2]·[IGFBP7]), kidney injury molecule-1 and N-acetyl-β-D-glucosaminidase. The results of the literature search for these six kidney damage biomarkers identified 29 unique articles with none detected for liver-type fatty acid binding protein and [TIMP-2]·[IGFBP7]. For three biomarkers, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin and N-acetyl-β-D-glucosaminidase, the majority of the studies suggest utility in clinical practice. While many questions need to be answered to clearly articulate the use of biomarkers to predict drug-induced kidney disease, current data are promising. [ABSTRACT FROM AUTHOR]

Objective: To provide ICU clinicians with evidence-based guidance on safe medication use practices for the critically ill.Data Sources: PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, Scopus, and ISI Web of Science for relevant material to December 2015.Study Selection: Based on three key components: 1) environment and patients, 2) the medication use process, and 3) the patient safety surveillance system. The committee collectively developed Population, Intervention, Comparator, Outcome questions and quality of evidence statements pertaining to medication errors and adverse drug events addressing the key components. A total of 34 Population, Intervention, Comparator, Outcome questions, five quality of evidence statements, and one commentary on disclosure was developed.Data Extraction: Subcommittee members were assigned selected Population, Intervention, Comparator, Outcome questions or quality of evidence statements. Subcommittee members completed their Grading of Recommendations Assessment, Development, and Evaluation of the question with his/her quality of evidence assessment and proposed strength of recommendation, then the draft was reviewed by the relevant subcommittee. The subcommittee collectively reviewed the evidence profiles for each question they developed. After the draft was discussed and approved by the entire committee, then the document was circulated among all members for voting on the quality of evidence and strength of recommendation.Data Synthesis: The committee followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation system to determine quality of evidence and strength of recommendations.Conclusions: This guideline evaluates the ICU environment as a risk for medication-related events and the environmental changes that are possible to improve safe medication use. Prevention strategies for medication-related events are reviewed by medication use process node (prescribing, distribution, administration, monitoring). Detailed considerations to an active surveillance system that includes reporting, identification, and evaluation are discussed. Also, highlighted is the need for future research for safe medication practices that is specific to critically ill patients. [ABSTRACT FROM AUTHOR]