Utility of Metagenomic Next-Generation Sequencing in Infective Endocarditis: A Systematic Review

Blood cultures have been the gold standard for identifying pathogens in infective endocarditis (IE). Blood culture-negative endocarditis (BCNE), however, occurs in 40% or more of IE cases with the bulk of them due to recent antibiotic exposure prior to obtaining blood cultures. Increasingly, molecular techniques are being used for pathogen identification in cases of BCNE and more recently has included metagenomic next-generation sequencing (mNGS). We therefore performed a literature search on August 31, 2022, that assessed the mNGS in IE and 13 publications were identified and included in a systematic review. Eight (61.5%) of them focused only on IE with mNGS performed on cardiac valve tissue in four studies, plasma in three studies and cardiac implantable electronic devices (CIED) in one study. Gram-positive cocci, including Staphylococcus aureus (n = 31, 8.9%), coagulase-negative staphylococci (n = 61, 17.6%), streptococci (n = 130, 37.5%), and Enterococcus faecalis (n = 23, 6.6%) were the predominant organisms identified by mNGS. Subsequent investigations are needed to further define the utility of mNGS in BCNE and its impact on patient outcomes. Despite some pitfalls, mNGS seems to be of value in pathogen identification in IE cases, particularly in those with BCNE. This study was registered and on the Open Science Framework platform

Reactivation of BK polyomavirus during pregnancy, vertical transmission, and clinical significance: A meta-analysis

BACKGROUND: Studies have shown conflicting results on the prevalence and the risks of BK reactivation among pregnant women. In addition, the prevalence of vertical transmission and its clinical significance during pregnancy are not well studied. OBJECTIVES: The study\u27s aims were (1) to investigate the prevalence, and (2) to assess the risk of BK Polyomavirus reactivation and its clinical significance in pregnant women and fetuses. STUDY DESIGN: A literature search was performed using MEDLINE, EMBASE and Cochrane Database from inception through May 31, 2017. We included studies that reported prevalence, relative risks, odds ratios, or hazard ratios of BK Polyomavirus reactivation during pregnancy. Pooled odds ratios (ORs) and 95% CI were calculated using a random-effect model. The protocol for this study is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42017063919). RESULTS: 17 observational studies with a total of 2553 pregnant women were enrolled. The estimated prevalence of BK seropositivity and BK in urine (viruria) among pregnant women were 79.2% (95%CI: 69.6%-86.4%) and 18.9% (95%CI: 10.4%-31.8%). When compared to non-pregnant women, the pooled ORs of BK seropositivity and BK viruria in pregnant women were 1.84 (95%CI: 1.05-3.22) and 6.02 (95%CI: 2.43-14.92), respectively. The estimated prevalence of positive BK-specific IgM antibody in cord blood was 4.9% (95%CI: 0.5%-36.2%). The data on the fetal effects of BK virus were limited. Although BK was detected in fetal organs, available data suggested no association between BK infection and adverse consequences such as miscarriage during pregnancy or childhood malignancy. CONCLUSION: Our meta-analysis demonstrates a significantly increased risk of BK Polyomavirus reactivation during pregnancy. Although vertical transmission can occur with an overall estimated prevalence of 4.9%, there are currently no data suggesting harm to pregnant women and fetuses from BK Polyomavirus

The effects of first-line anti-tuberculosis drugs on the actions of vitamin D in human macrophages

Tuberculosis (TB) is a major global health problem. Patients with TB have a high rate of vitamin D deficiency, both at diagnosis and during the course of treatment with anti-tuberculosis drugs. Although data on the efficacy of vitamin D supplementation on Mycobacterium tuberculosis (Mtb) clearance are uncertain from randomized controlled trials (RCTs), vitamin D enhances the expression of the anti-microbial peptide human cathelicidin (hCAP18) in cultured macrophages in vitro. One possible explanation for the mixed (primarily negative) results of RCTs examining vitamin D treatment in TB infection is that anti-TB drugs given to enrolled subjects may impact actions of vitamin D to enhance cathelicidin in macrophages. To address this hypothesis, human macrophage-like monocytic (THP-1) cells were treated with varying doses of first-line anti-tuberculosis drugs in the presence of the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). The expression of hCAP18 was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). 1,25(OH)2D3 strongly induced expression of hCAP18 mRNA in THP-1 cells (fold-change from control). The combination of the standard 4-drug TB therapy (isoniazid, rifampicin, pyrazinamide and ethambutol) in the cultured THP-1 cells demonstrated a significant decrease in hCAP18 mRNA at the dosage of 10 µg/mL. In 31 subjects with newly diagnosed drug-sensitive TB randomized to either high-dose vitamin D3 (1.2 million IU over 8 weeks, n = 13) versus placebo (n = 18), there was no change from baseline to week 8 in hCAP18 mRNA levels in peripheral blood mononuclear cells or in plasma concentrations of LL-37, the protein product of hCAP18. These data suggest that first-line anti-TB drugs may alter the vitamin D-dependent increase in hCAP18 and LL-37 human macrophages

Prior Statins Use and Risk of Mortality and Severe Disease from COVID-19: A Systematic Review and Meta-Analysis

Background Statins up-regulate angiotensin converting enzyme-2, the receptor of SARS-CoV-2, while also exhibiting pleiotropic antiviral, antithrombotic and anti-inflammatory properties. Uncertainties exist about their effect on the course of SARS-CoV-2 infection. Objectives We sought to systematically review the literature and perform a meta-analysis to examine the association between prior statins use and outcomes of patients with COVID-19. Methods We searched Ovid MEDLINE, Web of Science, Scopus, and the preprint server MedRxiv from inception to December 2020. We assessed the quality of eligible studies with the Newcastle-Ottawa quality scale. We pooled adjusted risk ratios (aRR) of the association between prior statins use and outcomes of patients with COVID-19 using the DerSimonian-Laird random effects model and assessed heterogeneity using the I 2-index. Results Overall, 19 (16 cohorts and 3 case-control) studies were eligible, with a total of 395,513 patients. Sixteen of 19 studies had low- or moderate-risk of bias. Among 109,080 patients enrolled in 13 separate studies, prior statins use was associated with a lower risk of mortality, (pooled aRR 0.65 (95% CI 0.56-0.77, I 2 = 84.1%) and a reduced risk of severe COVID-19 was also observed in 48,110 patients enrolled in 9 studies, (pooled aRR of 0.73 (95% CI 0.57-0.94, I 2 = 82.8%), with no evidence of publication bias. Conclusions Cumulative evidence suggests that prior statins use is associated with lower risks of mortality or severe disease in patients with COVID-19. These data support the continued use of statins medications in patients with an indication for lipid-lowering therapy during the COVID-19 pandemic

Bloodstream Infection Due to Coagulase-Negative Staphylococci: Impact of Species on Prevalence of Infective Endocarditis

(1) Background: Coagulase-negative staphylococci (CoNS) are an important group of organisms that can cause bloodstream infection (BSI) and infective endocarditis (IE). The prevalence of IE in patients with BSI due to different CoNS species, however, has received limited attention; (2) Methods: A retrospective study of adults with monomicrobial CoNS BSI who had undergone echocardiography and a risk factor analysis was done to determine the most common CoNS species that cause definite IE; (3) Results: 247 patients with CoNS BSI were included in the investigation; 49 (19.8%) had definite IE, 124 (50.2%) possible IE, and 74 (30.0%) BSI only. The latter two entities were grouped in one category for further analysis. The most common species in CoNS BSI was Staphylococcus epidermidis (79.4%) and most patients (83.2%) had possible IE/BSI only. 59.1% of patients with BSI due to S. lugdunensis had definite IE. The majority of CoNS were healthcare-associated/nosocomial bacteremia. Multivariable analysis demonstrated that valve disease (p = 0.002) and a foreign cardiovascular material (p S. lugdunensis BSI had an 8-fold higher risk of definite IE than did those with S. epidermidis BSI and nearly a 13-fold higher risk than did patients with BSI due to other species of CoNS (p = 0.002); (4) Conclusions: The prevalence of definite IE in patients with BSI due to different CoNS species was significant. CoNS bacteremia, particularly with S. lugdunensis, confers a significant risk of IE, particularly in patients with a valve disease or intravascular foreign body material and should not be immediately dismissed as a contaminant

Comparable outcomes of outpatient remdesivir and sotrovimab among high-risk patients with mild to moderate COVID-19 during the omicron BA.1 surge

Abstract Studies conducted prior to SARS-CoV-2 Omicron demonstrated that sotrovimab and remdesivir reduced hospitalization among high-risk outpatients with mild to moderate COVID-19. However, their effectiveness has not been directly compared. This study examined all high-risk outpatients with mild to moderate COVID-19 who received either remdesivir or sotrovimab at Mayo Clinic during the Omicron BA.1 surge from January to March 2022. COVID-19-related hospitalization or death within 28 days were compared between the two treatment groups. Among 3257 patients, 2158 received sotrovimab and 1099 received remdesivir. Patients treated with sotrovimab were younger and had lower comorbidity but were more likely to be immunocompromised than remdesivir-treated patients. The majority (89%) had received at least one dose of COVID-19 vaccine. COVID-19-related hospitalization (1.5% and 1.0% in remdesivir and sotrovimab, respectively, p = .15) and mortality within 28 days (0.4% in both groups, p = .82) were similarly low. A propensity score weighted analysis demonstrated no significant difference in the outcomes between the two groups. We demonstrated favorable outcomes that were not significantly different between patients treated with remdesivir or sotrovimab