Comparison of Omadacycline and Tigecycline Pharmacokinetics in the Plasma, Epithelial Lining Fluid, and Alveolar Cells of Healthy Adult Subjects.

The steady-state concentrations of omadacycline and tigecycline in the plasma, epithelial lining fluid (ELF), and alveolar cells (AC) of 58 healthy adult subjects were obtained. Subjects were administered either omadacycline at 100 mg intravenously (i.v.) every 12 h for two doses followed by 100 mg i.v. every 24 h for three doses or tigecycline at an initial dose of 100 mg i.v. followed by 50 mg i.v. every 12 h for six doses. A bronchoscopy and bronchoalveolar lavage were performed once in each subject following the start of the fifth dose of omadacycline at 0.5, 1, 2, 4, 8, 12, or 24 h and after the start of the seventh dose of tigecycline at 2, 4, 6, or 12 h. The value of the area under the concentration-time curve (AUC) from time zero to 24 h postdosing (AUC0-24) (based on mean concentrations) in ELF and the ratio of the ELF to total plasma omadacycline concentration based on AUC0-24 values were 17.23 mg · h/liter and 1.47, respectively. The AUC0-24 value in AC was 302.46 mg · h/liter, and the ratio of the AC to total plasma omadacycline concentration was 25.8. In comparison, the values of the AUC from time zero to 12 h postdosing (AUC0-12) based on the mean concentrations of tigecycline in ELF and AC were 3.16 and 38.50 mg · h/liter, respectively. The ratio of the ELF and AC to total plasma concentrations of tigecycline based on AUC0-12 values were 1.71 and 20.8, respectively. The pharmacokinetic advantages of higher and sustained concentrations of omadacycline compared to those of tigecycline in plasma, ELF, and AC suggest that omadacycline is a promising antibacterial agent for the treatment of lower respiratory tract bacterial infections caused by susceptible pathogens.

Pharmacokinetic drug evaluation of ceftobiprole for the treatment of MRSA.

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA), while decreasing in overall incidence, is still a prominent concern world-wide. New agents coming to market in the last 10 years allow practitioners to optimize treatment for MRSA infections. Ceftobiprole is a cephalosporin agent with MRSA activity, currently approved in selected countries for the treatment of community-acquired pneumonia and hospital-acquired pneumonia. Areas covered: Relevant literature regarding spectrum of activity, pharmacokinetics, pharmacodynamics, and clinical trials will be discussed. Expert opinion: Ceftobiprole is an addition to a growing number of antimicrobials with activity against MRSA. Concern for appropriate dosing in critically ill patients remains due to its ineffectiveness for the treatment of ventilator-associated pneumonia (VAP). While ceftobiprole has activity against gram-negative organisms, the allowance for use of an additional agent for gram-negative infections in clinical trials limits recommendations for monotherapy for empirical treatment of HAP. Ceftobiprole's place in therapy will lie in its activity against gram positive organisms, such as Streptococcus spp. and Staphylococcus spp.

Review of Intranasally Administered Medications for Use in the Emergency Department.

BACKGROUND: Intranasal (IN) medication delivery is a viable alternative to other routes of administration, including intravenous (IV) and intramuscular (IM) administration. The IN route bypasses the risk of needle-stick injuries and alleviates the emotional trauma that may arise from the insertion of an IV catheter. OBJECTIVE: This review aims to evaluate published literature on medications administered via the IN route that are applicable to practice in emergency medicine. DISCUSSION: The nasal mucosa is highly vascularized, and the olfactory tissues provide a direct conduit to the central nervous system, bypass first-pass metabolism, and lead to an onset of action similar to IV drug administration. This route of administration has also been shown to decrease delays in drug administration, which can have a profound impact in a variety of emergent scenarios, such as seizures, acutely agitated or combative patients, and trauma management. IN administration of midazolam, lorazepam, flumazenil, dexmedetomidine, ketamine, fentanyl, hydromorphone, butorphanol, naloxone, insulin, and haloperidol has been shown to be a safe, effective alternative to IM or IV administration. As the use of IN medications becomes a more common route of administration in the emergency department setting, and in prehospital and outpatient settings, it is increasingly important for providers to become more familiar with the nuances of this novel route of medication delivery. CONCLUSIONS: IN administration of the reviewed medications has been shown to be a safe and effective alternative to IM or IV administration. Use of IN is becoming more commonplace in the emergency department setting and in prehospital settings.

Preliminary findings of long-term neurodevelopmental outcomes of infants treated with intravenous fat emulsion reduction for the management of parenteral nutrition-associated cholestasis.

INTRODUCTION: Parenteral nutrition-associated cholestasis (PNAC) is linked with the administration of soybean-based intravenous fat emulsion (IVFE). IVFE reduction (IFER) may be an effective management strategy for PNAC; however, long-term associated neurodevelopmental outcomes (NDOs) for infants undergoing IFER have not been measured previously. This single-institution, prospective study examined the risk for negative NDOs and key predictors of NDOs associated with IFER. METHODS: Patients (2-5 years) treated with soybean-based IFER as neonates underwent NDO measurements, including Ages and Stages Questionnaires-3 (ASQ-3), Parents' Evaluations of Developmental Status (PEDS), and Behavior Assessment System for Children, Second Edition Preschool, Parent (BASC-2 PRS-P). The relationship between NDOs and predictive variables was evaluated. RESULTS: A total of 25 children had a complete PEDS survey, and 17 were found to be "not at risk." The BASC-2 PRS-P evaluation (n = 18 patients) showed that all 4 composite domains fell within the normative developmental range, and 67%-89% of patients were observed to be "typically developing." For the primary outcome measure, ASQ-3, 82.4%-94.4% of patients were "not at risk." Logistical regression analyses were performed to examine risk factors contributing to negative NDOs. Of children completing all NDO studies, IFER-related variables (eg, development of essential fatty acid deficiency, duration of IFER, and mean IVFE dose) were not found to be predictors of adverse NDOs. CONCLUSIONS: This study represents the first report of NDOs in pediatric patients treated with IFER. IFER-treated patients score within the normative range most of the time. IFER-related variables were not found to be associated with negative NDOs. The results set the stage for a larger, multicenter, prospective study.

Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans.

Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement. To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population. Current annual worldwide potato crop losses due to late blight are conservatively estimated at $6.7 billion. Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars. Here we report the sequence of the P. infestans genome, which at approximately 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for approximately 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.