Model for Evaluating Antimicrobial Therapy To Prevent Life-Threatening Bacterial Infections following Exposure to a Medically Significant Radiation Dose.

More evidence is needed to support recommendations for medical management of acute radiation syndrome (ARS) and associated infections resulting from a radiological/nuclear event. While current guidelines recommend the administration of antibiotics to chemotherapy patients with febrile neutropenia, the clinical benefit is unclear for acute radiation injury patients. A well-characterized nonhuman primate (NHP) model of hematopoietic ARS was developed that incorporates supportive care postirradiation. This model evaluated the efficacy of myeloid growth factors within 24 to 48 h after total body irradiation (TBI). However, in this model, NHPs continued to develop life-threatening bacterial infections, even when granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor was administered in combination with antibiotic monotherapy. In this study, we evaluated the efficacy of combination antibiotic therapies administered to NHPs following 7.4-Gy TBI to understand the occurrence of bacterial infection in NHPs with hematopoietic ARS. We compared enrofloxacin-linezolid, enrofloxacin-cefepime, and enrofloxacin-ertapenem to enrofloxacin monotherapy. The primary endpoint was 60-day postirradiation mortality, with secondary endpoints of overall survival time, incidence of bacterial infection, and bacteriologic culture with antimicrobial susceptibility testing. We observed that enrofloxacin-ertapenem significantly increased survival compared to enrofloxacin monotherapy. Bacteria isolated from nonsurviving macaques with systemic bacterial infections exhibited uniform resistance to enrofloxacin and variable resistance to beta-lactam antibiotics, linezolid, gentamicin, and azithromycin. Multidrug antibiotic resistance was observed in Enterococcus spp. and Escherichia coli. We conclude that antibiotic combination therapies appear to be more effective than monotherapy alone but acknowledge that more work is needed to identify an optimal antimicrobial therapy.

Outcomes and Cost-Effectiveness of Integrating HIV and Nutrition Service Delivery: Pilots in Malawi and Mozambique.

This paper provides the first estimates of impact and cost-effectiveness for integrated HIV and nutrition service delivery in sub-Saharan Africa. HIV and undernutrition are synergistic co-epidemics impacting millions of children throughout the region. To alleviate this co-epidemic, UNICEF supported small-scale pilot programs in Malawi and Mozambique that integrated HIV and nutrition service delivery. We use trends from integration sites and comparison sites to estimate the number of lives saved, infections averted and/or undernutrition cases cured due to programmatic activities, and to estimate cost-effectiveness. Results suggest that Malawi's program had a cost-effectiveness of $11-29/DALY, while Mozambique's was $16-59/DALY. Some components were more effective than others ($1-4/DALY for Malawi's Male motivators vs. $179/DALY for Mozambique's One stop shops). These results suggest that integrating HIV and nutrition programming leads to a positive impact on health outcomes and should motivate additional work to evaluate impact and determine cost-effectiveness using an appropriate research design.