The anticancer agent miltefosine and the antifungal drug voriconazole were tested in vitro against Balamuthia mandrillaris, Acanthamoeba spp., and Naegleria fowleri. All three amebas are etiologic agents of chronic (Balamuthia, Acanthamoeba) or fulminant (Naegleria) encephalitides in humans and animals and, in the case of Acanthamoeba, amebic keratitis. Balamuthia exposed to <40 microm concentrations of miltefosine survived, while concentrations of >or=40 microM were generally amebacidal, with variation in sensitivity between strains. At amebastatic drug concentrations, recovery from drug effects could take as long as 2 weeks. Acanthamoeba spp. recovered from exposure to 40 microM, but not 80 microM miltefosin. Attempts to define more narrowly the minimal inhibitory (MIC) and minimal amebacidal concentrations (MAC) for Balamuthia and Acanthamoeba were difficult due to persistence of non-proliferating trophic amebas in the medium. For N. fowleri, 40 and 55 microM were the MIC and MAC, respectively, with no trophic amebas seen at the MAC. Voriconazole had little or no inhibitory effect on Balamuthia at concentrations up to 40 microg/ml, but had a strong inhibitory effect upon Acanthamoeba spp. and N. fowleri at all drug concentrations through 40 microg/ml. Following transfer to drug-free medium, Acanthamoeba polyphaga recovered within a period of 2 weeks; N. fowleri amebas recovered from exposure to 1 microg/ml, but not from higher concentrations. All testing was done on trophic amebas; drug sensitivities of cysts were not examined. Miltefosine and voriconazole are potentially useful drugs for treatment of free-living amebic infections, though sensitivities differ between genera, species, and strains.

No abstract

Vancomycin area under the curve/minimal inhibitory concentration (AUC/MIC) >400 best predicts the outcome when treating invasive methicillin-resistant Staphylococcus aureus infection; however, trough serum concentrations are used clinically to assess the appropriateness of dosing. We used pharmacokinetic modeling and simulation to examine the relationship between vancomycin trough values and AUC/MIC in children receiving vancomycin 15 mg/kg every 6 hours and methicillin-resistant Staphylococcus aureus MIC of 1 μg/mL. A trough of 7-10 μg/mL predicted achievement of AUC/MIC >400 in >90% of children.

All four medication safety assessment techniques-incident report review, chart review, direct observation, and trigger tool-have different strengths and weaknesses. Overlap between different methods in identifying DRPs is minimal. While trigger tool appeared to be the most effective and labor-efficient method, incident report review best identified high-severity DRPs.

This review assessed the effects of computerised physician order entry, automated dispensing machines, bar coding and computerised medication administration records on the likelihood of medication errors and adverse drug events. The authors' conclusion, that there was limited evidence in support of these technologies, is likely to be reliable. Authors' objectives To assess the effect of computerised physician order entry (CPOE), automated dispensing machines (ADMs), bar coding and computerised medication administration records (CMARs) on medication errors and adverse drug events (ADEs). Searching PubMed was searched from 1982 to March 2002 for studies published in peer-reviewed journals; the MeSH terms were stated. The reference lists in identified studies and previous reviews were also checked. Only studies that were published in full were included. Guidelines for implementation, reviews and user-satisfaction surveys were excluded. Study selection Study designs of evaluations included in the review Controlled studies were eligible for inclusion. The included studies were prospective controlled studies (including timeand-motion studies and crossover studies), prospective time series with historical control, prospective and retrospective before-and-after studies, and retrospective time series. Specific interventions included in the review Studies of CPOEs, ADMs, bar coding and CMARs were eligible for inclusion if they were conducted in the USA. Studies of clinical decision support systems were excluded. Most of the included studies of CPOE were conducted in institutions and, in all studies, CPOE systems were developed internally. Participants included in the review The inclusion criteria were not specified in terms of participants. Outcomes assessed in the review Studies that assessed medication errors and ADEs (the primary outcomes in the review) or other outcomes were eligible for inclusion. In the review, medication errors were defined as 'any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the health care professional, patient or consumer'. ADEs were defined as 'any response to a drug which is noxious, unintended, and which occurs at doses normally used in humans for the prophylaxis, diagnosis or therapy of disease'. Some studies in the review reported results for different categories of ADEs (preventable and potential) and medication errors (errors in dosage, missed doses, non missed doses and wrong time). The review also assessed the appropriateness of the use of these interventions, where appropriateness was defined as the 'degree to which the technology was used as intended'. Other outcomes included the use of specific drugs, the time required to carry out various tasks, the number of drugs prescribed, hospital stay and the duration of therapy. How were decisions on the relevance of primary studies made? The authors did not state how the papers were selected for the review, or how many reviewers performed the selection.

While administration of IV haloperidol can be associated with QTP/TdP, this complication most often took place in the setting of concomitant risk factors. Importantly, the available data suggest that a total cumulative dose of IV haloperidol of <2 mg can safely be administered without ongoing electrocardiographic monitoring in patients without concomitant risk factors.

Study Objective To evaluate the pharmacokinetics of gentamicin in neonates with hypoxic ischemic encephalopathy (HIE) receiving hypothermia and to identify an empiric gentamicin dosing strategy in this population that optimizes achievement of target peak and trough concentrations. Design Population pharmacokinetic study using retrospective medical record data. Setting Tertiary neonatal intensive care unit. Patients A total of 29 term neonates diagnosed with HIE treated with hypothermia who received gentamicin and underwent therapeutic drug monitoring. Measurement and Main Results Patient demographics and gentamicin concentration data were retrospectively collected over a 2-year period. A population-based pharmacokinetic model was developed using nonlinear mixed-effects modeling (NONMEM). Using the developed model, Monte Carlo simulations were performed to evaluate the probability of achieving target peak (>6 mg/L) and trough (<2 mg/L) gentamicin concentrations for various potential dosing regimens. A one-compartment model best described the available gentamicin concentration data. Birthweight (BW) and serum creatinine (SCr) significantly influenced gentamicin clearance. For the typical study neonate (BW 3.3 kg; SCr 0.9 mg/dL), clearance was 0.034 L/H/kg and volume was 0.52 L/kg. At a 24-hour dosing interval, Monte Carlo simulations predicted target gentamicin peak and trough concentrations could not be reliably achieved at any dose. At a 36-hour dosing interval, a dose of 4-5 mg/kg is predicted to achieve target gentamicin peak and trough concentrations in >90% of neonates. Conclusions Gentamicin clearance is decreased in neonates with HIE treated with hypothermia compared with previous reports in nonasphyxiated normothermic term neonates. A prolonged 36-hour dosing interval will be needed to achieve target gentamicin trough concentrations in this population. Further prospective evaluation of this dosing recommendation is needed.

Most hospitalized patients with CAP receive antimicrobial therapy consistent with the ATS guidelines. The addition of a macrolide may be associated with improved patient outcomes.