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.

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 bindi...

Purpose The objective of this study was to determine whether the order of implementation of computerized prescriber order entry (CPOE) and electronic medication administration records (eMAR) into a health care facility would impact the medication error rate at an academic medical center. Methods A single academic medical center implemented CPOE first in one of its facilities (CPOE-first facility) and eMAR first in the other facility (eMAR-first facility). We conducted a retrospective chart review of patients admitted during designated data collection time periods (baseline, after the first intervention, and after both CPOE and eMAR). The primary outcome was defined as the change in medication error rate from baseline to the first intervention (either CPOE or eMAR). Secondary aims included evaluating final medication error rate and the severity and origin of detected errors. Results In the eMAR-first facility, the medication error rate decreased by 22.6% from baseline after only eMAR was introduced (odds ratio [OR], 1.4; P < .05). The CPOE-first facility showed a 13.3% reduction in the medication error rate after only CPOE was introduced (OR, 1.18; P = .24). Both hospitals demonstrated a significant decrease in medication error rates from baseline to after both CPOE and eMAR were implemented. Additionally, eMAR seemed to reduce errors reaching the patient to a greater extent than CPOE. Conclusion The integration of eMAR prior to CPOE resulted in a greater reduction in medication errors during the implementation of computerized health care technology. Because eMAR also reduced errors reaching the patient, we recommend initiating health information technology implementation with eMAR prior to CPOE.