Empiric antibiotics in management of inpatient pregnant women infected with coronavirus disease 2019 (COVID-19): Focusing on inflammation and preterm labor.
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ABSTRACT:
SUBMITTER: Norooznezhad AH
PROVIDER: S-EPMC7486858 | biostudies-literature | 2020 Nov
REPOSITORIES: biostudies-literature
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Empiric antibiotics in management of inpatient pregnant women infected with coronavirus disease 2019 (COVID-19): Focusing on inflammation and preterm labor.
Norooznezhad Amir Hossein AH Hantoushzadeh Sedigheh S Shamshirsaz Alireza A AA
Medical hypotheses 20200912
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Project description:AbstractRegarding the risk of antibiotic therapy during pregnancy, any medication given to the mother should be according to the indications due to the risk of possible side effects. Antibiotics are one of the most important groups of these medications to be considered. Along with direct antibiotic-induced side effects, indirect pathways also affect the fetus through the maternal changes. According to the data, different cytokines including interleukin-1? (IL-1?), IL-6, and tumor necrosis factor-? (TNF-?) are involved in both term and preterm parturition. These cytokines could trigger expression of different substances such as prostaglandins (PGs), their receptors, and PGs synthetizing molecules with already proven roles in parturition. Moreover, IL-1, IL-6, and TNF-? knocked?-out mice have delayed parturition and lower levels of PGs compared to the wild types. The earlier?-mentioned cytokines are able to induce matrix metalloproteinases and are also involved in parturition. Certain antibiotics have been shown capable of inducing inflammation cascade directly. Both in?-vivo and in?-vitro studies in human have also demonstrated this inflammation as elevated levels of inflammatory cytokines especially IL-1, IL-6, and TNF-?. This increase has been observed both in the presence and the absence of lipopolysaccharide (LPS). Moreover, antibiotics can induce endotoxemia in healthy cases which finally leads to the pro-inflammatory cytokine release. Regarding the role of mentioned pro-inflammatory cytokines in both term and preterm parturition, it seems that non-indicated use of antibiotics during pregnancy may increase the risk of preterm labor.
| S-EPMC7261809 | biostudies-literature
Project description: Not available
| S-EPMC7194835 | biostudies-literature
Project description:Preterm labor caused by uterine contractions is a major contributor to neonatal morbidity and mortality. Treatment intended to reduce uterine contractions include tocolytic agents, such as indomethacin. Unfortunately, clinically used tocolytics are frequently inefficient and cross the placenta causing fetal side effects. Here we show for the first time in obstetrics the use of a targeted nanoparticle directed to the pregnant uterus and loaded with a tocolytic for reducing its placental passage and sustaining its efficacy. Nanoliposomes encapsulating indomethacin and decorated with clinically used oxytocin receptor antagonist were designed and evaluated in-vitro, ex-vivo and in-vivo. The proposed approach resulted in targeting uterine cells in-vitro, inhibiting uterine contractions ex-vivo, while doubling uterine drug concentration, decreasing fetal levels, and maintaining the preterm birth rate in vivo in a pregnant mouse model. This promising approach opens new horizons for drug development in obstetrics that could greatly impact preterm birth, which currently has no successful treatments.
| S-EPMC5057095 | biostudies-literature
Project description: Not available
| S-EPMC8143774 | biostudies-literature
Project description:BackgroundEarly-onset sepsis is an important cause of neonatal morbidity and mortality in the preterm population. Infants perceived to be at increased risk for early-onset sepsis are often treated empirically with broad-spectrum antibiotics while awaiting confirmatory blood cultures, despite an overall incidence of early-onset sepsis of 2-3% among extremely-low-birthweight (ELBW) infants. Recent observational studies associate perinatal antibiotic use with an increased incidence of necrotizing enterocolitis, late-onset sepsis, and mortality among ELBW infants. Given currently available data and variability in clinical practice, we designed a prospective multi-institutional randomized controlled trial to determine the safety of early antibiotic use in ELBW infants.MethodsThe NICU Antibiotics and Outcomes (NANO) trial is a multicenter, double-blinded, randomized controlled trial. A sample of 802 ELBW preterm infants will undergo web-based stratified block randomization to receive empiric antibiotics (EA; ampicillin and gentamicin) or placebo during routine evaluation for early-onset sepsis. Participating sites will use preexisting institutional protocols for antibiotic dosage and duration. Infants born at participating sites with a gestational age of 29 weeks or less are eligible for enrollment. Exclusion criteria include maternal intrauterine infection, hemodynamic or respiratory instability, delivery by caesarean section for maternal indications without labor or prolonged rupture of membranes, and prior administration of antibiotics. The primary outcome is the composite incidence of necrotizing enterocolitis, late-onset sepsis, or death during participants' index hospitalization. Maternal and infant samples will be collected longitudinally and assessed for differences in microbiome composition and diversity.DiscussionThe NANO trial is designed to compare the rate of adverse outcomes of EA use at birth versus placebo in ELBW preterm infants. If EA at birth worsens clinical outcomes, then the results of the trial may help providers decrease antibiotic utilization in the NICU and subsequently decrease the incidence of complications associated with early antibiotic use in ELBW infants. If we instead find that EA improve outcomes, then the trial will validate a longstanding clinical practice that has not previously been supported by high-quality data. Future studies will assess long-term clinical and microbial outcomes in infants who received empiric antibiotics following delivery.Trial registrationTrial registration data: June 25, 2019 NCT03997266 .
| S-EPMC9125935 | biostudies-literature
Project description:Diabetes is associated with poor clinical outcomes in hospitalized patients with coronavirus disease 2019 (COVID-19). During this pandemic, many hospitals have already become overwhelmed around the world and are rapidly entering crisis mode. While there are global efforts to boost personal protective equipment (PPE) production, many centers are improvising care strategies, including the implementation of technology to prevent healthcare workers' exposures and reduce the waste of invaluable PPE. Not optimizing glycemic control due to clinical inertia driven by fear or lack of supplies may lead to poor outcomes in patients with diabetes and COVID-19. Individualized care strategies, novel therapeutic regimens, and the use of diabetes technology may reduce these barriers. However, systematic evaluation of these changes in care is necessary to evaluate both patient- and community-centered outcomes.
| S-EPMC7673193 | biostudies-literature
Project description:ObjectiveThe coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on imaging utilization across practice settings. The purpose of this study was to quantify the change in the composition of inpatient imaging volumes for modality types and Current Procedural Terminology-coded groups during the COVID-19 pandemic.MethodsA retrospective study of inpatient imaging volumes in a large health care system was performed, analyzing weekly imaging volumes by modality types (radiography, CT, MRI, ultrasound, interventional radiology, nuclear medicine) in years 2020 and 2019. The data set was split to compare pre-COVID-19 (weeks 1-9) and post-COVID-19 (weeks 10-16) periods. Further subanalyses compared early post-COVID-19 (weeks 10-13) and late post-COVID-19 (weeks 14-16) periods. Statistical comparisons were performed using χ2 and independent-samples t tests.ResultsCompared with 2019, total inpatient imaging volume in 2020 post-COVID-19, early and late post-COVID-19 periods, declined by 13.6% (from 78,902 to 68,168), 16.6% (from 45,221 to 37,732), and 9.6% (from 33,681 to 30,436), respectively. By week 16, inpatient imaging volume rebounded and was only down 4.2% (from 11,003 to 10,546). However, a statistically significant shift (P < .0001) in the 2020 composition mix was observed largely comprised of radiography (74.3%), followed by CT (12.7%), ultrasound (8%), MRI (2.4%), interventional radiology (2.3%), and nuclear medicine (0.4%). Although the vast majority of imaging studies declined, few Current Procedural Terminology-coded groups showed increased trends in imaging volumes in the late post-COVID-19 period, including CT angiography chest, radiography chest, and ultrasound venous duplex.DiscussionDuring the COVID-19 pandemic, we observed a decrease in inpatient imaging volumes accompanied by a shift away from cross-sectional imaging toward radiography. These findings could have significant implications in planning for a potential resurgence.
| S-EPMC7301132 | biostudies-literature
Project description:ObjectiveTo describe the clinical presentation, symptomology, and disease course of coronavirus disease 2019 (COVID-19) in pregnancy.MethodsThe PRIORITY (Pregnancy CoRonavIrus Outcomes RegIsTrY) study is an ongoing nationwide prospective cohort study of people in the United States who are pregnant or up to 6 weeks postpregnancy with known or suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed the clinical presentation and disease course of COVID-19 in participants who tested positive for SARS-CoV-2 infection and reported symptoms at the time of testing.ResultsOf 991 participants enrolled from March 22, 2020, until July 10, 2020, 736 had symptoms of COVID-19 at the time of testing; 594 tested positive for SARS-CoV-2 infection and 142 tested negative in this symptomatic group. Mean age was 31.3 years (SD 5.1), and 37% will nulliparous. Ninety-five percent were outpatients. Participants who tested positive for SARS-CoV-2-infection were a geographically diverse cohort: 34% from the Northeast, 25% from the West, 21% from the South, and 18% from the Midwest. Thirty-one percent of study participants were Latina, and 9% were Black. The average gestational age at enrollment was 24.1 weeks, and 13% of participants were enrolled after pregnancy. The most prevalent first symptoms in the cohort of patients who tested positive for SARS-CoV-2 infection were cough (20%), sore throat (16%), body aches (12%), and fever (12%). Median time to symptom resolution was 37 days (95% CI 35-39). One quarter (25%) of participants who tested positive for SARS-CoV-2 infection had persistent symptoms 8 or more weeks after symptom onset.ConclusionCOVID-19 has a prolonged and nonspecific disease course during pregnancy and in the 6 weeks after pregnancy.Clinical trial registrationClinicalTrials.gov, NCT04323839.
| S-EPMC7673633 | biostudies-literature
Project description:ObjectiveUterine overdistention is thought to induce preterm labor in women with twin and multiple pregnancies, but the pathophysiology remains unclear. We investigated for the first time the pathogenesis of preterm birth associated with rapid uterine distention in a pregnant nonhuman primate model.Study designA nonhuman primate model of uterine overdistention was created using preterm chronically catheterized pregnant pigtail macaques (Macaca nemestrina) by inflation of intraamniotic balloons (N = 6), which were compared to saline controls (N = 5). Cesarean delivery was performed due to preterm labor or at experimental end. Microarray, quantitative reverse transcriptase polymerase chain reaction, Luminex (Austin, TX), and enzyme-linked immunosorbent assay were used to measure messenger RNA (mRNA) and/or protein levels from monkey (amniotic fluid, myometrium, maternal plasma) and human (amniocytes, amnion, myometrium) tissues. Statistical analysis employed analysis of covariance and Wilcoxon rank sum. Biomechanical forces were calculated using the law of Laplace.ResultsPreterm labor occurred in 3 of 6 animals after balloon inflation and correlated with greater balloon volume and uterine wall stress. Significant elevations of inflammatory cytokines and prostaglandins occurred following uterine overdistention in an "inflammatory pulse" that correlated with preterm labor (interleukin [IL]-1β, tumor necrosis factor [TNF]-α, IL-6, IL-8, CCL2, prostaglandin E2, prostaglandin F2α, all P < .05). A similar inflammatory response was observed in amniocytes in vitro following mechanical stretch (IL1β, IL6, and IL8 mRNA multiple time points, P < .05), in amnion of women with polyhydramnios (IL6 and TNF mRNA, P < .05) and in amnion (TNF-α) and myometrium of women with twins in early labor (IL6, IL8, CCL2, all P < .05). Genes differentially expressed in the nonhuman primate after balloon inflation and in women with polyhydramnios and twins are involved in tissue remodeling and muscle growth.ConclusionUterine overdistention by inflation of an intraamniotic balloon is associated with an inflammatory pulse that precedes and correlates with preterm labor. Our results indicate that inflammation is an early event after a mechanical stress on the uterus and leads to preterm labor when the stress is sufficiently great. Further, we find evidence of uterine tissue remodeling and muscle growth as a common, perhaps compensatory, response to uterine distension.
| S-EPMC4679421 | biostudies-literature
Project description:Abstract Background The ongoing circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a diagnostic challenge because symptoms of coronavirus disease 2019 (COVID-19) are difficult to distinguish from other respiratory diseases. Our goal was to use statistical analyses and machine learning to identify biomarkers that distinguish patients with COVID-19 from patients with influenza. Methods Cytokine levels were analyzed in plasma and serum samples from patients with influenza and COVID-19, which were collected as part of the Centers for Disease Control and Prevention's Hospitalized Adult Influenza Vaccine Effectiveness Network (inpatient network) and the US Flu Vaccine Effectiveness (outpatient network). Results We determined that interleukin (IL)-10 family cytokines are significantly different between COVID-19 and influenza patients. The results suggest that the IL-10 family cytokines are a potential diagnostic biomarker to distinguish COVID-19 and influenza infection, especially for inpatients. We also demonstrate that cytokine combinations, consisting of up to 3 cytokines, can distinguish SARS-CoV-2 and influenza infection with high accuracy in both inpatient (area under the receiver operating characteristics curve [AUC] = 0.84) and outpatient (AUC = 0.81) groups, revealing another potential screening tool for SARS-CoV-2 infection. Conclusions This study not only reveals prospective screening tools for COVID-19 infections that are independent of polymerase chain reaction testing or clinical condition, but it also emphasizes potential pathways involved in disease pathogenesis that act as potential targets for future mechanistic studies. Influenza and COVID-19 can be separated by concentrations of serum inflammatory cytokines. IL-10 family cytokines differentiate inpatient and outpatient COVID-19 from influenza. Machine learning can define novel combinations of serum biomarkers that separate COVID-19 from influenza.
| S-EPMC10026548 | biostudies-literature