The Impact of a Change in Antibacterial Prophylaxis from Ceftazidime to Levofloxacin in Allogeneic Hematopoietic Cell Transplantation

Antibiotic prophylaxis has been used during the initial phases of myeloablative hematopoietic cell transplantation (HCT) for more than two decades. However, the optimal regimen in terms of both cost and clinical effectiveness is unclear. We retrospectively compared the clinical and microbiological impact of a change in antibiotic prophylaxis practice from ceftazidime (n=216 patients with HCT in 2000–2002) to levofloxacin (n=219 patients, August 2002–2005) in patients receiving myeloablative conditioning. Levofloxacin prophylaxis was associated with fever and a change in antibiotics during neutropenia, but this strategy was not associated with any adverse outcomes. Patients receiving levofloxacin had lower rates of significant bacteremia than did those receiving ceftazidime (day 100, 19.2 vs 29.6%, P=0.02). The use of levofloxacin was associated with lower antibiotic acquisition costs. There was no deleterious impact caused by levofloxacin prophylaxis on survival, emergence of antibiotic resistance, detection of Clostridium difficile Ag in stool specimens, incidence of viridans group streptococcal bacteremia or Pseudomonas infections. There was a trend toward lower rates of bacteriuria, wound and bacterial respiratory infections in the levofloxacin than in the ceftazidime group, but these differences were not statistically significant. These data support the use of levofloxacin as prophylaxis in myeloablative allogeneic HCT when prophylaxis is used

Rapid Development of an Integrated Network Infrastructure to Conduct Phase 3 COVID-19 Vaccine Trials

Importance: The COVID-19 pandemic has caused millions of infections and deaths and resulted in unprecedented international public health social and economic crises. As SARS-CoV-2 spread across the globe and its impact became evident, the development of safe and effective vaccines became a priority. Outlining the processes used to establish and support the conduct of the phase 3 randomized clinical trials that led to the rapid emergency use authorization and approval of several COVID-19 vaccines is of major significance for current and future pandemic response efforts. Observations: To support the rapid development of vaccines for the US population and the rest of the world, the National Institute of Allergy and Infectious Diseases established the COVID-19 Prevention Network (CoVPN) to assist in the coordination and implementation of phase 3 efficacy trials for COVID-19 vaccine candidates and monoclonal antibodies. By bringing together multiple networks, CoVPN was able to draw on existing clinical and laboratory infrastructure, community partnerships, and research expertise to quickly pivot clinical trial sites to conduct COVID-19 vaccine trials as soon as the investigational products were ready for phase 3 testing. The mission of CoVPN was to operationalize phase 3 vaccine trials using harmonized protocols, laboratory assays, and a single data and safety monitoring board to oversee the various studies. These trials, while staggered in time of initiation, overlapped in time and course of conduct and ultimately led to the successful completion of multiple studies and US Food and Drug Administration-licensed or -authorized vaccines, the first of which was available to the public less than 1 year from the discovery of the virus. Conclusions and Relevance: This Special Communication describes the design, geographic distribution, and underlying principles of conduct of these efficacy trials and summarizes data from 136 382 prospectively followed-up participants, including more than 2500 with documented COVID-19. These successful efforts can be replicated for other important research initiatives and point to the importance of investments in clinical trial infrastructure integral to pandemic preparedness

Understanding Caregiver Perspective on Social Determinants of Health Interventions in Pediatric Primary Care.

Comprehensive social risk screening has become standard practice in primary care. Evidence is lacking, however, on whether and how interventions provided for positive screens are being utilized. This study aimed to create a standardized follow-up process to evaluate caregiver perspective and usage of community resources provided during well-child visits. Follow-up calls were made to families with positive screens for food insecurity (FI) and/or utility insecurity (UI) (nn=n347). Phone interviews assessed resource usage, effectiveness, influence on stress level, and current insecurity status. Caregiver responses regarding barriers to resource usage were inductively analyzed and developed into major themes. The sample included 228 (65.7%) families with positive screens for FI and 166 (47.8%) families screening positive for UI. Of those who completed interviews (nn=n108), 77 (71.3%) caregivers recalled being provided resources during their child's visit with only 33 (42.9%) reporting use of those resources. Twelve (36.4%) of those caregivers who used the resources confirmed that their insecurity was still a concern. Five major themes for barriers to resource usage emerged: (1) improved situation, (2) perception, (3) access barriers, (4) conflicting priorities, and (5) too busy/overwhelmed. The majority of caregivers (95.7% of asked) noted that their insecurity caused increased stress with 70.5% acknowledging decreased stress levels after discussion with a provider. Integrating caregiver input through a standardized follow-up protocol into provided interventions for screened social risks can improve not only the quality and effectiveness of provided resources, but also provide insight into the impact of those interventions on insecurity from the caregiver perspective