Search

Vancomycin and daptomycin are frequently used in outpatient parenteral antimicrobial therapy (OPAT). We analyze health care utilization and cost to the health care system for vancomycin vs daptomycin in the outpatient setting and find that vancomycin results in significantly higher health care utilization and similar cost per course compared with daptomycin in OPAT. [ABSTRACT FROM AUTHOR]

Data evaluating dalbavancin use for vertebral osteomyelitis remain limited. In our retrospective cohort, 29 of 34 (85.3%) patients completed their dalbavancin course. Adverse reactions occurred for 6 (17.6%) and infection recurrence in 3 (8.8%) within 90 days. Dalbavancin appears to be safe and well-tolerated for vertebral osteomyelitis. [ABSTRACT FROM AUTHOR]

The bud emergence ( BEM)46 proteins are evolutionarily conserved members of the α/β-hydrolase superfamily, which includes enzymes with diverse functions and a wide range of substrates. Here, we identified a P lasmodium BEM46-like protein ( PBLP) and characterized it throughout the life cycle of the rodent malaria parasite P lasmodium yoelii. The P lasmodium BEM46-like protein is shown to be closely associated with the parasite plasma membrane of asexual erythrocytic stage schizonts and exo-erythrocytic schizonts; however, PBLP localizes to unique intracellular structures in sporozoites. Generation and analysis of P . yoelii knockout (Δ pblp) parasite lines showed that PBLP has an important role in erythrocytic stage merozoite development with Δ pblp parasites forming fewer merozoites during schizogony, which results in decreased parasitemia when compared with wild-type ( WT) parasites. Δ pblp parasites showed no defects in gametogenesis or transmission to mosquitoes; however, because they formed fewer oocysts there was a reduction in the number of developed sporozoites in infected mosquitoes when compared with WT. Although Δ pblp sporozoites showed no apparent defect in mosquito salivary gland infection, they showed decreased infectivity in hepatocytes in vitro. Similarly, mice infected with Δ pblp sporozoites exhibited a delay in the onset of blood-stage patency, which is likely caused by reduced sporozoite infectivity and a discernible delay in exo-erythrocytic merozoite formation . These data are consistent with the model that PBLP has an important role in parasite invasive-stage morphogenesis throughout the parasite life cycle. [ABSTRACT FROM AUTHOR]

Summary: Plasmodium parasites infect the liver and replicate inside hepatocytes before they invade erythrocytes and trigger clinical malaria. Analysis of host signaling pathways affected by liver-stage infection could provide critical insights into host–pathogen interactions and reveal targets for intervention. Using protein lysate microarrays, we found that Plasmodium yoelii rodent malaria parasites perturb hepatocyte regulatory pathways involved in cell survival, proliferation, and autophagy. Notably, the prodeath protein p53 was substantially decreased in infected hepatocytes, suggesting that it could be targeted by the parasite to foster survival. Indeed, mice that express increased levels of p53 showed reduced liver-stage parasite burden, whereas p53 knockout mice suffered increased liver-stage burden. Furthermore, boosting p53 levels with the use of the small molecule Nutlin-3 dramatically reduced liver-stage burden in vitro and in vivo. We conclude that perturbation of the hepatocyte p53 pathway critically impacts parasite survival. Thus, host pathways might constitute potential targets for host-based antimalarial prophylaxis. [ABSTRACT FROM AUTHOR]

Background Outpatient parenteral antimicrobial therapy (OPAT), widely used for serious infections, has high failure rates in people with substances use disorders (SUD)1–2. At our institution, completing therapy in the hospital was previously the best option for high-risk patients; but long hospital stays are often unacceptable to patients and costly. To improve outcomes, our Infectious Diseases division, OPAT program, and Improving Addiction Care Team (IMPACT) developed and implemented a novel multidisciplinary conference (OPTIONS-DC) for inpatients with SUD requiring prolonged antibiotics. This study describes the conference development, tool, and initial experience. Methods From June 2017 to June 2018, diverse stakeholders collaboratively created and implemented a structured conference to discuss treatment options that balance medical efficacy, patient preferences, and feasibility using harm-reduction principles. After 10 months of hospital-wide implementation, we elicited provider feedback and performed a content analysis of OPTIONS-DC notes and patient records to evaluate the impact. Results The goal of conference development was prioritizing patient preferences and engaging multidisciplinary input. One RN facilitates the conference using the tool (Figure 1) to elicit input from the relevant providers. The tool systematically addresses components that may predict treatment success (i.e. working phone) while emphasizing patient preference and harm reduction. The IMPACT social work PICC safety assessment informs risks for IV access. Antibiotic recommendations are not a binary of optimal/suboptimal choices for the infection but options that best fit patient context. The average conference length was 28 minutes (IQR 21). Preliminary data shows good clinical outcomes and savings to inpatient days and cost. Initial feedback suggests the model was positively experienced by medical providers (Figure 2) and supported patient preferences. Conclusion A multidisciplinary patient-centered conference that prioritizes patient preference and uses harm-reduction principles for this high-risk population is practical, effective, and positively experienced by providers. This model may serve as a roadmap for other institutions. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]