Use of an In Vitro Pharmacodynamic Model To Derive a Moxifloxacin Regimen That Optimizes Kill of Yersinia pestis and Prevents Emergence of Resistance▿

Yersinia pestis, the causative agent of bubonic, septicemic, and pneumonic plague, is classified as a CDC category A bioterrorism pathogen. Streptomycin and doxycycline are the “gold standards” for the treatment of plague. However, streptomycin is not available in many countries, and Y. pestis isolates resistant to streptomycin and doxycycline occur naturally and have been generated in laboratories. Moxifloxacin is a fluoroquinolone antibiotic that demonstrates potent activity against Y. pestis in in vitro and animal infection models. However, the dose and frequency of administration of moxifloxacin that would be predicted to optimize treatment efficacy in humans while preventing the emergence of resistance are unknown. Therefore, dose range and dose fractionation studies for moxifloxacin were conducted for Y. pestis in an in vitro pharmacodynamic model in which the half-lives of moxifloxacin in human serum were simulated so as to identify the lowest drug exposure and the schedule of administration that are linked with killing of Y. pestis and with the suppression of resistance. In the dose range studies, simulated moxifloxacin regimens of ≥175 mg/day killed drug-susceptible bacteria without resistance amplification. Dose fractionation studies demonstrated that the AUC (area under the concentration-time curve)/MIC ratio predicted kill of drug-susceptible Y. pestis, while the Cmax (maximum concentration of the drug in serum)/MIC ratio was linked to resistance prevention. Monte Carlo simulations predicted that moxifloxacin at 400 mg/day would successfully treat human infection due to Y. pestis in 99.8% of subjects and would prevent resistance amplification. We conclude that in an in vitro pharmacodynamic model, the clinically prescribed moxifloxacin regimen of 400 mg/day is predicted to be highly effective for the treatment of Y. pestis infections in humans. Studies of moxifloxacin in animal models of plague are warranted

Personal Identity Development in Hispanic Immigrant Adolescents: Links with Positive Psychosocial Functioning, Depressive Symptoms, and Externalizing Problems

The present study was designed to examine trajectories of personal identity coherence and confusion among Hispanic recent-immigrant adolescents, as well as the effects of these trajectories on psychosocial and risk-taking outcomes. Personal identity is extremely important in anchoring young immigrants during a time of acute cultural change. A sample of 302 recently immigrated (5 years or less in the United States at baseline) Hispanic adolescents (M(age) = 14.51 years at baseline; SD = 0.88 years, range 14–17) from Miami and Los Angeles (47 % girls) completed measures of personal identity coherence and confusion at the first five waves of a six-wave longitudinal study; and reported on positive psychosocial functioning, depressive symptoms, and externalizing problems at baseline and at Time 6. Results indicated that identity coherence increased linearly across time, but that there were no significant changes in confusion over time and no individual differences in confusion trajectories. Higher baseline levels of, and improvements in, coherence predicted higher levels of self-esteem, optimism, and prosocial behavior at the final study timepoint. Higher baseline levels of confusion predicted lower self-esteem, greater depressive symptoms, more aggressive behavior, and more rule breaking at the final study timepoint. These results are discussed in terms of the importance of personal identity for Hispanic immigrant adolescents, and in terms of implications for intervention