Infection with Zika virus (ZIKV) is associated with human congenital fetal anomalies. To model fetal outcomes in nonhuman primates, we administered Asian-lineage ZIKV subcutaneously to four pregnant rhesus macaques. While non-pregnant animals in a previous study contemporary with the current report clear viremia within 10–12 days, maternal viremia was prolonged in 3 of 4 pregnancies. Fetal head growth velocity in the last month of gestation determined by ultrasound assessment of head circumference was decreased in comparison with biparietal diameter and femur length within each fetus, both within normal range. ZIKV RNA was detected in tissues from all four fetuses at term cesarean section. In all pregnancies, neutrophilic infiltration was present at the maternal-fetal interface (decidua, placenta, fetal membranes), in various fetal tissues, and in fetal retina, choroid, and optic nerve (first trimester infection only). Consistent vertical transmission in this primate model may provide a platform to assess risk factors and test therapeutic interventions for interruption of fetal infection. The results may also suggest that maternal-fetal ZIKV transmission in human pregnancy may be more frequent than currently appreciated.

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Infection with Zika virus (ZIKV) is associated with human congenital fetal anomalies. To model fetal outcomes in nonhuman primates, we administered Asian-lineage ZIKV subcutaneously to four pregnant rhesus macaques. While non-pregnant animals in a previous study contemporary with the current report clear viremia within 10-12 days, maternal viremia was prolonged in 3 of 4 pregnancies. Fetal head growth velocity in the last month of gestation determined by ultrasound assessment of head circumference was decreased in comparison with biparietal diameter and femur length within each fetus, both within normal range. ZIKV RNA was detected in tissues from all four fetuses at term cesarean section. In all pregnancies, neutrophilic infiltration was present at the maternal-fetal interface (decidua, placenta, fetal membranes), in various fetal tissues, and in fetal retina, choroid, and optic nerve (first trimester infection only). Consistent vertical transmission in this primate model may provide a platform to assess risk factors and test therapeutic interventions for interruption of fetal infection. The results may also suggest that maternal-fetal ZIKV transmission in human pregnancy may be more frequent than currently appreciated. Author summaryMaternal ZIKV infection in pregnancy is associated with severe fetal anomalies, including microcephaly. It has been shown that infection manifests differently in pregnancy than in the non-pregnant state, with prolonged maternal viremia. ZIKV is spread by mosquitos and through sexual contact and since its first detection in early 2015, has become endemic to the Americas. While much has been learned from studying infected human pregnancies, there are still many questions concerning transmission of ZIKV from mother to fetus. Investigating ZIKV infection in non-human primates could help answer these questions due to similarities in the immune system, and the tissues separating the fetus from the mother during pregnancy. Our study serves to model ZIKV transmission in early and late pregnancy, as well as study the effects of this infection on the fetus and mother at these different times in pregnancy. The data collected provides an important insight on ZIKV in pregnancy where the pregnancies have been monitored throughout the entire infection period until term, and suggests that vertical transmission may be very efficient, although severe fetal outcomes are uncommon.

Background-There is a paucity of data available regarding the dosing of antimicrobials in obesity. However, data are available demonstrating that vancomycin should be dosed based on actual body weight.

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BACKGROUND: Patients with severe bacterial infections often experience delay in receiving appropriate treatment. Consolidated evidence of the impact of delayed appropriate treatment is needed to guide treatment and improve outcomes. RESEARCH QUESTION: What is the impact of delayed appropriate antibacterial therapy on clinical outcomes in patients with severe bacterial infections? STUDY DESIGN AND METHODS: Literature searches of MEDLINE and Embase, conducted on July 24, 2018, identified studies published after 2007 reporting the impact of delayed appropriate therapy on clinical outcomes for hospitalized adult patients with bacterial infections. Where appropriate, results were pooled and analyzed with delayed therapy modeled three ways: delay vs no delay in receiving appropriate therapy; duration of delay; and inappropriate vs appropriate initial therapy. This article reports meta-analyses on the effect of delay and duration of delay. RESULTS: The eligibility criteria were met by 145 studies, of which 37 contributed data to analyses of effect of delay. Mortality was significantly lower in patients receiving appropriate therapy without delay compared with those experiencing delay (OR, 0.57; 95% CI, 0.45-0.72). Mortality was also lower in the no-delay group compared with the delay group in subgroups of studies reporting mortality at 20 to 30 days, during ICU stay, or in patients with bacteremia (OR, 0.57 [95% CI, 0.43-0.76]; OR, 0.47 [95% CI, 0.27-0.80]; and OR, 0.54 [95% CI, 0.40-0.75], respectively). No difference was found in time to appropriate therapy between those who died and those who survived (P ¼ .09), but heterogeneity between studies was high. INTERPRETATION: Avoiding delayed appropriate therapy is essential to reduce mortality in patients with severe bacterial infections.

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Lactobacilli are low-virulence, commensal organisms of the gastrointestinal and genitourinary tracts and are commonly used as "probiotic supplements." Herein, we describe an episode of respiratory syncytial virus (RSV) bronchiolitis with bacterial superinfection secondary to administration of Lactobacillus rhamnosus in an 11-month-old female with trisomy 21. CASE REPORT