Significant Publications on Infectious Diseases Pharmacotherapy in 2022.

Purpose: To provide summarization of the most significant infectious diseases (ID) pharmacotherapy articles published in peer-reviewed literature in 2022. Summary: Members of the Houston Infectious Diseases Network (HIDN) nominated notable articles providing significant contributions to ID pharmacotherapy in 2022. Article nominations included those pertaining to general ID, as well as those including coronavirus disease 2019 (COVID-19), and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) pharmacotherapy. A total of 71 articles were nominated by HIDN. Members: 68 articles pertaining to general ID pharmacotherapy and 3 articles focusing on HIV/AIDS. To aid selection of the most these most notable articles of 2022, a survey was created and distributed to members of the Society of Infectious Diseases Pharmacists (SIDP). Of the 153 SIDP members who participated in the survey, there were 128 recorded votes for the top 10 general ID pharmacotherapy articles and 30 votes recorded for the top HIV/AIDS article. The most notable publications are summarized. Conclusion: Post pandemic significant advances in antimicrobial stewardship and infectious disease states continues to occur in a world recently focused on the coronavirus disease 2019 (COVID-19) global pandemic. Continuous growth in publication of ID-related articles over the past year lends towards the aims of this review to aid clinicians in remaining current on key practice-changing ID pharmacotherapy publications from 2022.

Clinical Impact of Oral Step-Down Therapy for Gram-Negative Bacteremia: A Retrospective Study.

Background: In recent years, there has been a growing body of evidence that supports oral step-down therapy for the treatment of gram-negative bacteremia. The purpose of this study was to compare outcomes for hospitalized patients who received intravenous-only (IV-only) therapy versus oral step-down therapy with low, moderate, and highly bioavailable antimicrobials for the treatment of gram-negative bacteremia. Methods: In this retrospective, single-center, observational study, we examined data from adult patients hospitalized with gram-negative bacteremia in a 1-year period. Data analysis was performed using information collected from electronic medical records and a clinical surveillance system. Results: A total of 199 patients were included in this study. Patients in the IV-only group had higher Charlson comorbidity index scores at baseline and higher rates of intensive care unit admission while bacteremic (P = .0096 and .0026, respectively). The primary outcome of 30-day all-cause mortality was significantly lower in the oral step-down group (P < .0001). Secondary outcomes of 30-day bacteremia recurrence, line-associated complications, and hospital length of stay were similar between groups. The total duration of antibiotic therapy was one day longer for oral step-down patients (P = .0015) and the estimated cost of antibiotic therapy was significantly lower in this group (P < .00001). Conclusion: In this retrospective study, oral step-down therapy was not associated with increased 30- day all-cause mortality. Oral step-down therapy was also more cost-effective than IV-only therapy, while both groups had similar bacteremia recurrence within 30 days.

Significant Publications on Infectious Diseases Pharmacotherapy in 2020.

Purpose. To summarize the most highly esteemed, peer-reviewed, infectious diseases (ID) pharmacotherapy articles published in 2020. Summary. Members of the Houston Infectious Diseases Network (HIDN) nominated articles that were deemed to have noteworthy contributions to ID pharmacotherapy in 2020, including those on coronavirus disease 2019 (COVID-19) and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). To select the most significant articles of 2020, a survey was created and distributed to members of the Society of Infectious Diseases Pharmacists (SIDP) to vote on their top 10 articles of general ID and COVID-19 pharmacotherapy and one noteworthy HIV/AIDS publication. A total of 40 articles were nominated by HIDN: 35 articles pertaining to general ID/COVID-19 pharmacotherapy and 5 articles with HIV/AIDS involvement. Of the 247 SIDP members who responded to the survey, 205 and 42 members voted for general ID/COVID-19 pharmacotherapy articles and HIV/AIDS related articles, respectively. The top publications are summarized. Conclusion. In a taxing year of a global pandemic, the abundant and rapid distribution of ID literature has made it challenging for clinicians to stay informed of significant publications across the ID spectrum. This review summarizes significant ID-related publications in 2020 with the goal of aiding clinicians in staying up to date on the most relevant publications in ID pharmacotherapy.

Significant Publications on Infectious Diseases Pharmacotherapy in 2021.

Purpose: To summarize the most noteworthy infectious diseases (ID) pharmacotherapy articles published in peer-reviewed literature in 2021. Summary: Members of the Houston Infectious Diseases Network (HIDN) nominated articles that were deemed to have significant contributions to ID pharmacotherapy in 2021. These nominations included articles pertaining to both general ID, including coronavirus disease 2019 (COVID-19), and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) pharmacotherapy. A total of 35 articles were nominated by HIDN: 30 articles pertaining to general ID pharmacotherapy and 5 articles with HIV/AIDS focus. To select the most influential articles of 2021, a survey was created and distributed to members of the Society of Infectious Diseases Pharmacists (SIDP). Of the 239 SIDP members who responded to the survey, there were 192 recorded votes for the top 10 general ID pharmacotherapy articles and 47 recorded votes for the top HIV/AIDS article, respectively. The top publications are summarized. Conclusion: Antimicrobial stewardship and the optimal management of infectious disease states continues to be a priority in the midst of the ongoing coronavirus disease 2019 (COVID-19) global pandemic. In light of the sheer volume of ID-related articles published in the past year, this review aims to aid clinicians in remaining up-to-date on key practice-changing ID pharmacotherapy publications from 2021.

Complement in Reproductive White Adipose Tissue Characterizes the Obese Preeclamptic-Like BPH/5 Mouse Prior to and During Pregnancy.

Preeclampsia (PE) is a serious hypertensive disorder of pregnancy characterized by abnormal placental development with an unknown etiology. To better understand which women will develop PE, a number of maternal risk factors have been identified, including obesity. Visceral white adipose tissue (WAT) contains inflammatory mediators that may contribute to PE. To explore this, we utilized the blood pressure high (BPH)/5 mouse model of superimposed PE that spontaneously recapitulates the maternal PE syndrome. We hypothesized that BPH/5 visceral WAT adjacent to the female reproductive tract (reproductive WAT) is a source of complement factors that contribute to the inflammatory milieu and angiogenic imbalance at the maternal-fetal interface in this model and in preeclamptic women. To test our hypothesis, we calorie-restricted BPH/5 females for two weeks prior to pregnancy and the first seven days of pregnancy, which attenuated complement component 3 (C3) but not complement factor B, nor complement factor D, (adipsin) in the reproductive WAT or the implantation site in BPH/5. Furthermore, calorie restriction during pregnancy restored vascular endothelial and placental growth factor mRNA levels in the BPH/5 implantation site. These data show maternal reproductive WAT may be a source of increased C3 during pregnancy, which is increased at the maternal-fetal interface in preeclamptic BPH/5 mice. It also suggests that calorie restriction could regulate inflammatory mediators thought to contribute to placental dysfunction in PE. Future studies are necessary to examine the effect of calorie restriction on C3 throughout pregnancy and the role of maternal obesity in PE.

The Design of a Randomized Clinical Trial to Evaluate a Pragmatic and Scalable eHealth Intervention for the Management of Gestational Weight Gain in Low-Income Women: Protocol for the SmartMoms in WIC Trial.

BACKGROUND: Less than one-third of women gain an appropriate amount of weight during pregnancy, which can influence the long-term health of both the mother and the child. Economically disadvantaged women are the most vulnerable to maternal obesity, excessive weight gain during pregnancy, and poor birth outcomes. Effective and scalable health care strategies to promote healthy weight gain during pregnancy specifically tailored for these women are lacking. OBJECTIVE: This paper presents the design and protocol of a biphasic, community-based eHealth trial, SmartMoms in WIC, to increase the adherence to healthy gestational weight gain (GWG) recommendations in low-income mothers receiving women, infant, and children (WIC) benefits. METHODS: Phase 1 of the trial included using feedback from WIC mothers and staff and participants from 2 community peer advisory groups to adapt an existing eHealth gestational weight management intervention to meet the needs of women receiving WIC benefits. The health curriculum, the format of delivery, and incentive strategies were adapted to be culturally relevant and at an appropriate level of health literacy. Phase 2 included a pragmatic randomized controlled trial across the 9 health care regions in Louisiana with the goal of enrolling 432 women. The SmartMoms in WIC intervention is an intensive 24-week behavioral intervention, which includes nutrition education and exercise strategies, and provides the technology to assist with weight management, delivered through a professionally produced website application. RESULTS: Phase 1 of this trial was completed in July 2019, and recruitment for phase 2 began immediately thereafter. All data are anticipated to be collected by Spring 2023. CONCLUSIONS: The SmartMoms in WIC curriculum was methodically developed using feedback from community-based peer advisory groups to create a culturally relevant, mobile behavioral intervention for mothers receiving WIC benefits. The randomized clinical trial is underway to test the effectiveness of a sustainable eHealth program on the incidence rates of appropriate GWG. SmartMoms in WIC may be able to offer an innovative, cost-effective, and scalable solution for GWG management in women served by WIC. TRIAL REGISTRATION: ClinicalTrials.gov NCT04028843; https://clinicaltrials.gov/ct2/show/NCT04028843. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/18211.

Modifications to Infant Formula Instructions Improve the Accuracy of Formula Dispensing.

Readability of infant formula preparation instructions is universally poor, which may result in inaccurate infant feeding. Given that inaccurate formula dispensing can lead to altered infant growth and increased adiposity, there is an increased need for easy to follow instructions for formula preparation. We hypothesize that altering infant formula instruction labels using feedback from iterative focus groups will improve the preparation accuracy of powdered infant formula in a randomized controlled trial. Participants were recruited from the community, 18 years of age or older, willing to disclose demographic information for focus group matching, and willing to participate freely in the first (n = 21) or second (n = 150) phase of the study. In the second phase, participants were randomized to use the standard manufacturer instructions or to use the modified instructions created in the first phase. Accuracy was defined as the percent error between manufacturer-intended powder formula quantity and the amount dispensed by the participant. Participants who were assigned to the modified instructions were able to dispense the powdered formula more accurately than participants who used the standard manufacturer instructions (-0.67 ± 0.76 vs. -4.66 ± 0.74% error; p < 0.0001). Accuracy in powdered formula dispensing was influenced by bottle size (p = 0.02) but not by body mass index (p = 0.17), education level (p = 0.75), income (p = 0.7), age (p = 0.89) or caregiver status (p = 0.18). Percent error of water measurement was not different between the groups (standard: -1.4 ± 0.6 vs. modified: 0.7 ± 0.6%; p = 0.38). Thus, caloric density was more accurate in the modified instructions group compared to the standard manufacturer instructions group (-0.3 ± 0.6 vs.-2.9 ± 0.9%; p = 0.03). Infant formula label modifications using focus group feedback increased infant formula preparation accuracy.

Dyslipidemia and the role of adipose tissue in early pregnancy in the BPH/5 mouse model for preeclampsia.

The hypertensive pregnancy disorder preeclampsia (PE) is a leading cause of fetal and maternal morbidity/mortality. Obesity increases the risk to develop PE, presumably via the release of inflammatory mediators from the adipose tissue, but the exact etiology remains largely unknown. Using obese PE-like blood pressure high subline 5 (BPH/5) and lean gestational age-matched C57Bl6 mice, we aimed to obtain insight into differential reproductive white adipose tissue (rWAT) gene expression, circulating lipids and inflammation at the maternal-fetal interface during early pregnancy. In addition, we investigated the effect of 7 days 25% calorie restriction (CR) in early pregnancy on gene expression in rWAT and implantation sites. Compared with C57Bl6, female BPH/5 are dyslipidemic before pregnancy and show an amplification of rWAT mass, circulating cholesterol, free fatty acids, and triacylglycerol levels throughout pregnancy. RNA sequencing showed that pregnant BPH/5 mice have elevated gene enrichment in pathways related to inflammation and cholesterol biosynthesis at embryonic day (e) 7.5. Expression of cholesterol-related HMGCS1, MVD, Cyp51a1, and DHCR was validated by quantitative reverse-transcription-polymerase chain reaction. CR during the first 7 days of pregnancy restored the relative mRNA expression of these genes to a level comparable to C57Bl6 pregnant females and reduced the expression of circulating leptin and proinflammatory prostaglandin synthase 2 in both rWAT and implantation sites in BPH/5 mice at e7.5. Our data suggest a possible role for rWAT in the dyslipidemic state and inflammatory uterine milieu that might underlie the pathogenesis of PE. Future studies should further address the physiological functioning of the adipose tissue in relation to PE-related pregnancy outcomes.

Obesity "complements" preeclampsia.

Preeclampsia (PE) is a devastating adverse outcome of pregnancy. Characterized by maternal hypertension, PE, when left untreated, can result in death of both mother and baby. The cause of PE remains unknown, and there is no way to predict which women will develop PE during pregnancy. The only known treatment is delivery of both the fetus and placenta; therefore, an abnormal placenta is thought to play a causal role. Women with obesity before pregnancy have an increased chance of developing PE. Increased adiposity results in a heightened state of systemic inflammation that can influence placental development. Adipose tissue is a rich source of proinflammatory cytokines and complement proteins, which have been implicated in the pathogenesis of PE by promoting the expression of antiangiogenic factors in the mother. Because an aggravated inflammatory response, angiogenic imbalance, and abnormal placentation are observed in PE, we hypothesize that maternal obesity and complement proteins derived from adipose tissue play an important role in the development of PE.

Celecoxib restores angiogenic factor expression at the maternal-fetal interface in the BPH/5 mouse model of preeclampsia.

Preeclampsia (PE), a hypertensive disease of pregnancy, is a leading cause of fetal and maternal morbidity/mortality. Early angiogenic and inflammatory disturbances within the placenta are thought to underlie the development of the maternal PE syndrome and poor pregnancy outcomes. However, the exact etiology remains largely unknown. Here, we use the BPH/5 mouse model of PE to elucidate the way in which inflammation early in pregnancy contributes to abnormal expression of angiogenic factors at the maternal-fetal interface. We have previously described improvement in maternal hypertension and fetal growth restriction in this model after treatment with the anti-inflammatory cyclooxygenase-2 (Cox2) specific inhibitor celecoxib. To further characterize the mechanisms by which celecoxib improves poor pregnancy outcomes in BPH/5 mice, we determined expression of angiogenic factors and complement pathway components after celecoxib. In BPH/5 implantation sites there was increased hypoxia inducible factor-1α ( Hif1α), heme oxygenase-1 ( Ho-1), and stem cell factor ( Scf) mRNA concomitant with elevated prostaglandin synthase 2 ( Ptgs2), encoding Cox2, and elevated VEGF protein. Angiopoietin 1 ( Ang1), tunica interna endothelial cell kinase-2 receptor ( Tie2), complement factor 3 ( C3), and complement factor B ( CfB) were increased in midgestation BPH/5 placentae. Whereas BPH/5 expression levels of VEGF, Ang1, and Tie2 normalized after celecoxib, placental C3 and CfB mRNA remained unchanged. However, celecoxib did reduce the pregnancy-specific circulating soluble fms-like tyrosine kinase-1 (sFlt-1) rise in BPH/5 mice at midgestation. These data show that elevated Cox2 during implantation contributes to placental angiogenic factor imbalances in the BPH/5 mouse model of PE.