In vitro antibiotic susceptibilities of Burkholderia mallei (causative agent of glanders) determined by broth microdilution and E-test.

In vitro susceptibilities to 28 antibiotics were determined for 11 strains of Burkholderia mallei by the broth microdilution method. The B. mallei strains demonstrated susceptibility to aminoglycosides, macrolides, quinolones, doxycycline, piperacillin, ceftazidime, and imipenem. For comparison and evaluation, 17 antibiotic susceptibilities were also determined by the E-test. E-test values were always lower than the broth dilution values. Establishing and comparing antibiotic susceptibilities of specific B. mallei strains will provide reference information for assessing new antibiotic agents.

Motor-vehicle occupant injury: strategies for increasing use of child safety seats, increasing use of safety belts, and reducing alcohol-impaired driving.

The Task Force on Community Preventive Services has conducted systematic reviews of interventions designed to increase use of child safety seats, increase use of safety belts, and reduce alcohol-impaired driving. The Task Force strongly recommends the following interventions: laws requiring use of child safety seats, distribution and education programs for child safety seats, laws requiring use of safety belts, both primary and enhanced enforcement of safety belt use laws, laws that lower the legal blood alcohol concentration (BAC) limit for adult drivers to 0.08%, laws that maintain the minimum legal drinking age at 21 years, and use of sobriety checkpoints. The Task Force recommends communitywide information and enforcement campaigns for use of child safety seats, incentive and education programs for use of child safety seats, and a lower legal BAC for young drivers (in the United States, those under the minimum legal drinking age). This report provides additional information regarding these recommendations, briefly describes how the reviews were conducted, and provides information to help apply the interventions locally.

Preparing for communities of care for child and family mental health for the twenty-first century.

In a period of unprecedented change in the American health care system, a strong reform movement for child and family mental health services has developed in the last two decades that provides blueprints and models for the development of communities of care to provide individualized, strength-based services tailored to the needs of each child and family. To bring the spirit and substance of this reform into the twenty-first century, a two-pronged strategy is proposed, focusing on the broad implementation of value-based outcome measures and the development of skilled clinician leaders to ensure the effectiveness of the new delivery system.

Comparative efficacy of a Coxiella burnetii chloroform:methanol residue (CMR) vaccine and a licensed cellular vaccine (Q-Vax) in rodents challenged by aerosol.

Q fever is an acute and self-limited febrile illness caused by the obligate intracellular bacterium Coxiella burnetii. While phase I cellular Q fever vaccines are efficacious in humans, vaccination of immune individuals may result in sterile abscesses and granulomas. The chloroform:methanol residue vaccine (CMR) was developed as a safer alternative. The efficacy of a licensed phase I cellular vaccine (Q-Vax) was compared with that of CMR vaccine in A/J mice and Hartley guinea pigs challenged with virulent phase I C. burnetii by aerosol. Both vaccines were efficacious. The CMR vaccine dose required to protect 50% of mice (PD50) against lethal aerosol challenge (11 LD50) was one-third of the Q-Vax dose. However, the PD50 for CMR was four times the Q-Vax dose in guinea pigs challenged by aerosol (60 LD50). It was concluded that CMR is an efficacious alternative to cellular Q fever vaccines for the prevention of Q fever.

Time of peak drug concentration after a single dose and a dose at steady state.

The time of peak concentration after administration of oral drug is an often quoted and used pharmacokinetic parameter. It is not well appreciated, however, that the peak times after a single dose and a dose at steady state during a multiple administration regimen can differ significantly. This article derives the mathematical relationships that determine how a peak time at steady state differs from that after a single or first dose. These relationships are then evaluated using three different approaches: 1) graphic simulations of time courses of drug concentration for three hypothetical drugs; 2) comparisons of predicted and observed peak times using examples from the literature; and 3) comparisons of predicted and simulated peak times based on different sampling schedules for three hypothetical drugs. The key finding is that peak times after a dose at steady state can occur considerably earlier after administration than after a single dose. However, the manner by which peak times are usually determined, that is, the sampling time corresponding to the highest measured drug concentration, imposes significant limitations on the usefulness of this parameter.

Women and managed care.

The nation's health care system is undergoing a period of rapid change that will profoundly affect women's health care services and, ultimately, women's health. Although managed care is quickly becoming the predominant mode of health care delivery in the United States, a new, more consumer-focused, and accountable model known as organized systems of care (OSC) is emerging. OSC development has been driven by large private and public employers seeking to purchase the highest quality health care for the best price. The changes in health care delivery encouraged by these innovative employers will provide women with optimal care and attention, which will in turn help them attract and retain a competitive and productive workforce.

Immunogenicity of a new lot of Francisella tularensis live vaccine strain in human volunteers.

A new lot of Francisella tularensis live vaccine strain (LVS) was tested for immunogenicity in 19 human volunteers. Scarification vaccination induced specific cell-mediated and humoral immune responses. We noted a significant rise in antibodies against irradiation-killed LVS, formalin-killed virulent strain SCHU4, and an ether extracted antigen preparation (EEx) beginning 14 days after vaccination. A main target of the humoral immune response was lipopolysaccharide. Eighty percent of vaccinated volunteers developed a positive IgG response to EEx by day 14 and 100% of vaccinees responded positively by day 21. Background IgA titers were lower than corresponding IgG or IgM titers. No early IgM rise was noted with any antigen. By day 14 after vaccination, in vitro lymphocyte responses to LVS, the rough variant of LVS, and EEx were significantly increased compared to controls. Seventy percent of volunteers had a positive in vitro lymphocyte response to EEx within 14 days of vaccination. We predict that EEx will be a useful antigen for diagnosing tularemia and for evaluating the immunogenicity of vaccines against tularemia. We are testing this antigen using sera from human cases of tularemia and control sera.

Cell-mediated and humoral immune responses after vaccination of human volunteers with the live vaccine strain of Francisella tularensis.

The specific humoral and cell-mediated immune responses of human volunteers vaccinated with the Francisella tularensis live vaccine strain (LVS) were evaluated. In the search for an optimal antigen to measure the immunogenicity of the vaccine in an enzyme-linked immunosorbent assay, we tested irradiation-killed LVS, an aqueous ether extract of the LVS (EEx), lipopolysaccharide (LPS) from LVS, and a virulent strain (SCHU4). Volunteers were immunized with LVS by scarification. Immunoglobulin G (IgG) responses to LVS and LPS gave the highest background titers when tested with sera from unimmunized volunteers, whereas IgA, IgG, and IgM background titers to EEx and SCHU4 were low. Vaccination caused a significant rise (P < 0.01) in IgA, IgG, and IgM titers to all antigens tested, except for the IgG response to LPS. Eighty percent of vaccinated volunteers developed a positive IgG response to EEx 14 days postvaccination, while 50% were positive to LVS. By day 14 after vaccination, 70% of immunized volunteers exhibited a positive response to EEx in an in vitro peripheral blood lymphocyte proliferation assay. EEx, a specific and sensitive antigen for evaluating immune responses of vaccinated volunteers, may be a superior antigen for the diagnosis of tularemia.

Estimation of pharmacokinetic parameters for simulations of time courses of drug concentrations after oral administration.

Simulations of time courses of drug concentrations after oral administration are frequently hampered by the lack of pharmacokinetic parameters after oral dosing. This article presents methods by which to estimate such parameters from pharmacokinetic parameters after intravenous dosing and knowledge of time of peak concentration and bioavailability after oral dosing. The application of these approaches enables the generation of meaningful graphic simulations of time courses of drug concentrations after oral administration that can have educational and illustrative uses.