Pharmacodynamic evaluation of meropenem and cefotaxime for pediatric meningitis: a report from the OPTAMA program.

OBJECTIVE: To determine the probability of meropenem (Merrem, AstraZeneca Pharmaceuticals L.P., Wilmington, DE, USA) and cefotaxime (Claforan, Aventis Pharmaceuticals Inc., Bridgewater, NJ, USA) achieving bactericidal exposures in the cerebrospinal fluid against Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. METHODS: A 5,000-patient Monte Carlo simulation in a population of 10-year-old children with meningitis was conducted. Pediatric pharmacokinetic data were derived from the literature. Pathogen minimum inhibitory concentrations (MICs) were obtained from common bacteria that had caused meningitis collected during pediatric clinical trials. Time above the MIC exposures in the cerebrospinal fluid was calculated. Bactericidal exposure or probability of target attainment was defined as 40% and 50% time above the MIC for meropenem and cefotaxime, respectively. High cumulative fractions of responses were defined as >90% probability of target attainment against the populations of bacteria. RESULTS: Meropenem was calculated to achieve 94.7%, 94.3%, and 96.1% cumulative fractions of response against S. pneumoniae, H. influenzae, and N. meningitidis, respectively. Cefotaxime only achieved a high likelihood of bactericidal attainment against N. meningitidis (91.6%). Against S. pneumoniae and H. influenzae, cefotaxime was only calculated to achieve 84.3% and 84.8% cumulative fractions of response, respectively. CONCLUSION: In a simulated population of 10-year-old children, meropenem had a high likelihood of attaining bactericidal exposures in the cerebrospinal fluid. Cefotaxime had a >90% cumulative fraction of response against only N. meningitidis. Therefore, at the doses simulated, meropenem may be a more appropriate empiric choice for the treatment of bacterial meningitis in pediatric patients presumed to be caused by these pathogens until culture and susceptibility data are available.

Use of Monte Carlo simulation to assess the pharmacodynamics of beta-lactams against Pseudomonas aeruginosa infections in children: a report from the OPTAMA program.

BACKGROUND: Assessing the likelihood of achieving bactericidal pharmacodynamic exposures against Pseudomonas aeruginosa with intravenous antimicrobial regimens would provide insights into the selection of empiric therapy in the pediatric population. OBJECTIVE: The objective of this study was to use pharmacodynamic modeling to determine the likelihood of various pediatric antibiotic regimens achieving bactericidal exposures against P aeruginosa in children. METHODS: Minimum inhibitory concentrations (MICs) were determined for meropenem (20 and 40 mg/kg q8h), imipenem (15 and 25 mg/kg q6h), ceftazidime (50 mg/kg q8h), cefepime (50 mg/kg q8h), and piperacillin/tazobactam (75 mg/kg q6h) against P aeruginosa isolates from 2 pediatric institutions. A 5000-patient Monte Carlo simulation was performed to predict attainment of pharmacodynamic targets against P aeruginosa for each of these regimens in a population of 10-year-olds. Optimal regimens were defined as those that had a > or =90% likelihood of attaining target exposures. RESULTS: At institution 1, high-dose imipenem, high-dose meropenem, and ceftazidime achieved bactericidal pharmacodynamic exposures (likelihood of target attainment: 94%, 92%, and 92%, respectively). No other regimen was associated with a high probability of attaining bactericidal exposure (low-dose imipenem, 87%; cefepime, 85%; low-dose meropenem, 84%; piperacillin/tazobactam, 60%). At institution 2, no regimen was associated with a high likelihood of attaining bactericidal exposure; the calculated probabilities were cefepime, 78%; ceftazidime, 65%; high-dose meropenem, 58%; high-dose imipenem, 57%; low-dose imipenem, 54%; low-dose meropenem, 47%; and piperacillin/tazobactam, 47%. A lack of agreement between attainment of bactericidal exposures and percent susceptibility was apparent for many of the regimens. CONCLUSIONS: Few regimens demonstrated a high likelihood of achieving bactericidal exposures against P aeruginosa at these institutions. Importantly, percent susceptibility overestimated attainment of the bactericidal target for some regimens, suggesting that further study is necessary in pediatric patients. The findings of this study highlight differences in target attainment and MIC distributions between institutions, emphasizing the importance of using institution-specific data when selecting empiric antimicrobial therapy.

Influenza vaccination for the pediatric patient: a focus on the new intranasal, cold-adapted, live attenuated vaccine.

FluMist is the first live attenuated, cold-adapted intranasal influenza vaccine (LAIV) approved for the prevention of influenza A and B. Clinical trials have shown that annual vaccination with LAIV is effective for the prevention of influenza. LAIV appears well tolerated in healthy patients 5-49 years of age. The most common adverse events are abdominal pain, chills, cough, diarrhea, headache, irritability, lethargy, muscle aches, otitis media, rhinitis, sinusitis, sore throat, and vomiting. FluMist has a novel intranasal route of administration that allows for influenza prevention without a painful intramuscular injection. Barriers preventing acceptance of LAIV include defining the appropriate patient population, cost, and insurance coverage.

Effects of Panax ginseng on quality of life.

OBJECTIVE: To assess the time-dependent effects of Panax ginseng on health-related quality of life (HRQOL) by use of a general health status questionnaire. METHODS: Subjects were randomized in a double-blind manner to P. ginseng 200 mg/d (n = 15) or placebo (n = 15) for 8 weeks. The Short Form-36 Health Survey version 2 (SF-36v2), a validated general health status questionnaire, was used to assess HRQOL at baseline and at 4 and 8 weeks. HRQOL between the groups was compared by use of repeated-measures analysis of covariance. A p value <0.05 was considered statistically significant. RESULTS: There were no significant differences in baseline demographics and SF-36v2 scores between the groups. After 4 weeks of therapy, higher scores in social functioning (P. ginseng 54.9+/-4.6 vs. placebo 49.2+/-6.5; p = 0.014), mental health (P. ginseng 52.2+/-7.7 vs. placebo 47.2+/-7.3; p = 0.075), and the mental component summary (P. ginseng 51.3+/-7.4 vs. placebo 44.3+/-8.3; p = 0.019) scales were observed in patients randomized to P. ginseng; these differences did not persist to the 8-week time point. The incidence of adverse effects was 33% in the P. ginseng group compared with 17% in the placebo group (p = 0.40). Subjects given P. ginseng (58%) were more likely to state that they received active therapy than subjects given placebo (17%; p < 0.05). CONCLUSIONS: P. ginseng improves aspects of mental health and social functioning after 4 weeks of therapy, although these differences attenuate with continued use.

A Spatial Model of Atmospheric Deposition for the Northeastern U.S.

Spatial patterns of atmospheric deposition across the northeastern United States were evaluated and summarized in a simple model as a function of elevation and geographic position within the region. For wet deposition, 3-11 yr of annual concentration data for the major ions in precipitation were obtained from the National Atmospheric Deposition Program/National Trend Network (NADP/NTN) for 26 sites within the region. Concentration trends were evaluated by regression of annual mean concentrations against latitude and longitude. For nitrate, sulfate, and ammonium concentrations, a more than twofold linear decrease occurs from western New York and Pennsylvania to eastern Maine. These trends were combined with regional and elevational trends of precipitation amount, obtained from 30-yr records of annual precipitation at >300 weather stations, to provide long-term patterns of wet deposition. Regional trends of dry deposition of N and S compounds were determined using 2-3 yr of particle and gas concentration data collected by the National Dry Deposition Network (NDDN) and several other sources, in combination with estimates of deposition velocities. Contrary to wet deposition trends, the dominant air concentration trends were steep decreases from south to north, creating regional decreases in total deposition (wet + dry) from the southwest to the northeast. This contrast between wet and dry deposition trends suggests that within the northeast the two deposition forms are received in different proportions from different source areas, wet deposited materials primarily from areas to the west and dry deposited materials primarily from urban areas along the southern edge of the region. The equations generated describing spatial patterns of wet and dry deposition within the region were entered into a geographic information system (GIS) containing a digital elevation model (DEM) in order to develop spatially explicit predictions of atmospheric deposition for the region.