Recommendations to improve the usability of drug-drug interaction clinical decision support alerts.

OBJECTIVE: To establish preferred strategies for presenting drug-drug interaction (DDI) clinical decision support alerts. MATERIALS AND METHODS: A DDI Clinical Decision Support Conference Series included a workgroup consisting of 24 clinical, usability, and informatics experts representing academia, health information technology (IT) vendors, healthcare organizations, and the Office of the National Coordinator for Health IT. Workgroup members met via web-based meetings 12 times from January 2013 to February 2014, and two in-person meetings to reach consensus on recommendations to improve decision support for DDIs. We addressed three key questions: (1) what, how, where, and when do we display DDI decision support? (2) should presentation of DDI decision support vary by clinicians? and (3) how should effectiveness of DDI decision support be measured? RESULTS: Our recommendations include the consistent use of terminology, visual cues, minimal text, formatting, content, and reporting standards to facilitate usability. All clinicians involved in the medication use process should be able to view DDI alerts and actions by other clinicians. Override rates are common but may not be a good measure of effectiveness. DISCUSSION: Seven core elements should be included with DDI decision support. DDI information should be presented to all clinicians. Finally, in their current form, override rates have limited capability to evaluate alert effectiveness. CONCLUSION: DDI clinical decision support alerts need major improvements. We provide recommendations for healthcare organizations and IT vendors to improve the clinician interface of DDI alerts, with the aim of reducing alert fatigue and improving patient safety.

Pharmacokinetics of antibacterial agents in the CSF of children and adolescents.

The adequate management of central nervous system (CNS) infections requires that antimicrobial agents penetrate the blood-brain barrier (BBB) and achieve concentrations in the CNS adequate for eradication of the infecting pathogen. This review details the currently available literature on the pharmacokinetics (PK) of antibacterials in the CNS of children. Clinical trials affirm that the physicochemical properties of a drug remain one of the most important factors dictating penetration of antimicrobial agents into the CNS, irrespective of the population being treated (i.e. small, lipophilic drugs with low protein binding exhibit the best translocation across the BBB). These same physicochemical characteristics determine the primary disposition pathways of the drug, and by extension the magnitude and duration of circulating drug concentrations in the plasma, a second major driving force behind achievable CNS drug concentrations. Notably, these disposition pathways can be expected to change during the normal process of growth and development. Finally, CNS drug penetration is influenced by the nature and extent of the infection (i.e. the presence of meningeal inflammation). Aminoglycosides have poor CNS penetration when administered intravenously. Intrathecal gentamicin has been studied in children with more promising results, often exceeding the minimum inhibitory concentration. There are very limited data with intrathecal tobramycin in children. However, in the few patients that have been studied, the CSF concentrations were highly variable. Penicillins generally have good CNS penetration. Aqueous penicillin G reaches greater concentrations than procaine or benzathine penicillin. Concentrations remain detectable for ≥ 12 h. Of the aminopenicillins, both ampicillin and parenteral amoxicillin reach adequate CNS concentrations; however, orally administered amoxicillin resulted in much lower concentrations. Nafcillin and piperacillin are the final two penicillins with pediatric data: their penetration is erratic at best. Cephalosporins vary greatly in regard to their CSF penetration. Few first- and second-generation cephalosporins are able to reach higher CSF concentrations. Cefuroxime is the only exception and is usually avoided due to its adverse effects and slower sterilization of the CSF than third-generation agents. Ceftriaxone, cefotaxime, ceftazidime, cefixime and cefepime have been studied in children and are all able to adequately penetrate the CSF. As with penicillins, concentrations are greatest in the presence of meningeal inflammation. Meropenem and imipenem are the only carbapenems with pediatric data. Imipenem reaches higher CSF concentrations; however, meropenem is preferred due to its lower incidence of seizures. Aztreonam has also demonstrated favorable penetration but only one study has been completed in children. Both chloramphenicol and sulfamethoxazole/trimethoprim (cotrimoxazole) penetrate into the CNS well; however, significant toxicities limit their use. The small size and minimal protein binding of fosfomycin contribute to its favorable CNS PK. Although rarely used, it achieves higher concentrations in the presence of inflammation and accumulation is possible. Linezolid reaches high CSF concentrations; however, more frequent dosing might be required in infants due to their increased elimination. Metronidazole also has very limited information but it demonstrated favorable results similar to adult data; CSF concentrations even exceeded plasma concentrations at certain time points. Rifampin (rifampicin) demonstrated good CNS penetration after oral administration. Vancomycin demonstrates poor CNS penetration after intravenous administration. When combined with intraventricular therapy, CNS concentrations are much greater. Of the antituberculosis agents, isoniazid, pyrazinamide and streptomycin have been studied in children. Isoniazid and pyrazinamide have favorable CSF penetration. Streptomycin appears to produce unpredictable CSF levels. No pediatric-specific data are available for clindamycin, daptomycin, macrolides, tetracyclines, and fluoroquinolones. Daptomycin, fluoroquinolones, and tetracyclines have demonstrated favorable CNS penetration in adults; however, data are limited due to their potential pediatric-specific toxicities and newness within the marketplace. Macrolides and clindamycin have demonstrated poor CNS penetration in adults and thus have not been studied in pediatrics.

Pediatric Pharmacovigilance: Enhancing Adverse Drug Reaction Reporting in a Tertiary Care Children's Hospital.

BACKGROUND: Adverse drug reactions (ADRs) are notoriously underreported within health care facilities. In 2009-2010, ADRs were detected in only 0.5% of patients at the authors' institution, a pediatric hospital in the Midwestern United States. Additionally, historical ADRs were often inaccurately or incompletely documented in the medical record. An integrative Drug Safety Service (DSS) was implemented to improve the detection and accurate documentation of ADRs. METHODS: The DSS incorporated standardized ADR terminology, computerized triggers to identify ADRs, and a simplified voluntary reporting system within the facility. The DSS staff provided extensive hospital staff education on ADR reporting and the role of the DSS. The primary aim of this report was to assess the impact of the DSS on the number of ADRs reported at the authors' institution. The secondary aims were to evaluate the mechanisms by which patients with ADRs were identified and to assess the accuracy of ADR documentation after implementation of the DSS. RESULTS: A significant increase was observed (slope, 6.01; P < .001) in ADR detection after implementation of the DSS, with a greater than 4-fold increase from 10 cases per 10,000 admissions before initiation to 41 cases per 10,000 admissions after DSS implementation. Computerized triggers, International Classification of Diseases, 9th Edition (ICD-9) codes associated with ADRs, and the DSS identified 33%, 33%, and 24% of ADRs, respectively, while voluntary reporting only detected 9% of ADRs. CONCLUSIONS: Implementation of a multifaceted, interdisciplinary DSS was more effective in detecting ADRs than voluntary reporting alone. A proactive approach to ADR detection resulted in a significant increase in the identification and evaluation of ADRs.