infection Costs of Venous Thromboembolism, Catheter-Associated Urinary Tract Infection, and Pressure Ulcer By pediatrics.aappublications.org Published On :: 2015-08-10T00:07:45-07:00 In adults, there is significant increased length of stay, cost, and/or resource use associated with hospital-acquired conditions. Less is known about the epidemiology and impact of many hospital-acquired conditions in pediatric populations.We find increased pediatric length of stay and costs due to venous thromboembolism and catheter-associated urinary tract infections. This is essential information for hospital administrators and safety departments who are planning interventions to reduce harm associated with these hospital-acquired conditions. (Read the full article) Full Article
infection Infection-Related Hospitalization in Childhood and Adult Metabolic Outcomes By pediatrics.aappublications.org Published On :: 2015-08-17T00:06:43-07:00 Childhood inflammatory mediators are associated with adult obesity, but the stimuli that initiate and perpetuate chronic inflammation start in early life are largely unknown.Childhood infection-related hospitalization was independently associated with adverse adult metabolic variables, which suggests that infections and/or their treatment in childhood may contribute to causal pathways leading to adult cardiometabolic diseases. (Read the full article) Full Article
infection Disorders in Children With Congenital Cytomegalovirus Infection By pediatrics.aappublications.org Published On :: 2015-09-07T00:07:56-07:00 Congenital cytomegalovirus infection is the leading infectious cause of neurologic disabilities and sensorineural hearing loss in children. Little is known concerning the frequency and impact of vestibular disorders induced by cytomegalovirus infection.This study reports on the largest cohort of vestibular assessment of children congenitally infected with cytomegalovirus, demonstrating vestibular damages, and analyzes the correlations between vestibular dysfunction and hearing impairment or severity of infection. Cytomegalovirus infection affects postural development in children. (Read the full article) Full Article
infection Sources of Infant Pertussis Infection in the United States By pediatrics.aappublications.org Published On :: 2015-09-07T00:07:56-07:00 The source of infant pertussis infection is typically identified ~50% of the time. Historically, mothers have been identified as the most common source of pertussis transmission to infants.This analysis of 8 years of enhanced pertussis surveillance data has uncovered a shift in the most common source of infant pertussis infection in the United States from mothers to siblings. (Read the full article) Full Article
infection Comparison of Cefepime/Cefpirome and Carbapenem Therapy for Acinetobacter Bloodstream Infection: A Multicentre Study [Clinical Therapeutics] By aac.asm.org Published On :: 2020-03-16T08:17:37-07:00 Carbapenems are currently the preferred agents for the treatment of serious Acinetobacter infections. However, whether cefepime/cefpirome can be used to treat Acinetobacter bloodstream infection (BSI) if it is active against the causative pathogens is not clear. This study aimed to compare the efficacy of cefepime/cefpirome and carbapenem monotherapy in patients with Acinetobacter BSI. The population included 360 patients with monomicrobial Acinetobacter BSI receiving appropriate antimicrobial therapy admitted to four medical centres in Taiwan in 2012–2017. The predictors of 30-day mortality were determined by Cox regression analysis. The overall 30-day mortality rate in the appropriate antibiotic treatment group was 25.0% (90/360 patients), respectively. The crude 30-day mortality rates for cefepime/cefpirome and carbapenem therapy were 11.5% (7/61 patients) and 26.3% (21/80 patients), respectively. The patients receiving cefepime/cefpirome/carbapenem therapy were infected by Acinetobacter nosocomialis (51.8%), A. baumannii (18.4%) and A. pittii (12.1%). After adjusting for age, Sequential Organ Failure Assessment (SOFA) score, invasive procedures, and underlying diseases, cefepime/cefpirome therapy was not independently associated with a higher or lower 30-day mortality compared to the carbapenem therapy. SOFA score (hazard ratio [HR], 1.324; 95% confidence interval [CI], 1.137–1.543; P < 0.001) and neutropenia (HR, 7.060; 95% CI, 1.607–31.019; P = 0.010) were independent risk factors for 30-day mortality of patients receiving cefepime/cefpirome or carbapenem monotherapy. The incidence density of 30-day mortality for cefepime/cefpirome versus carbapenem therapy was 0.40% versus 1.04%. The therapeutic response of cefepime/cefpirome therapy was comparable to that of carbapenems among patients with Acinetobacter BSI receiving appropriate antimicrobial therapy. Full Article
infection Ceftobiprole Activity against Bacteria from Skin and Skin Structure Infections in the United States from 2016 through 2018 [Susceptibility] By aac.asm.org Published On :: 2020-03-16T08:17:36-07:00 Ceftobiprole medocaril is an advanced-generation cephalosporin prodrug that has qualified infectious disease product status granted by the US-FDA and is currently being evaluated in phase 3 clinical trials in patients with acute bacterial skin and skin structure infections (ABSSSIs) and in patients with Staphylococcus aureus bacteremia. In this study, the activity of ceftobiprole and comparators was evaluated against more than 7,300 clinical isolates collected in the United States from 2016 through 2018 from patients with skin and skin structure infections. The major species/pathogen groups were S. aureus (53%), Enterobacterales (23%), Pseudomonas aeruginosa (7%), β-hemolytic streptococci (6%), Enterococcus spp. (4%), and coagulase-negative staphylococci (2%). Ceftobiprole was highly active against S. aureus (MIC50/90, 0.5/1 mg/L; 99.7% susceptible by EUCAST criteria; 42% methicillin-resistant S. aureus [lsqb]MRSA[rsqb]). Ceftobiprole also exhibited potent activity against other Gram-positive cocci. The overall susceptibility of Enterobacterales to ceftobiprole was 84.8% (>99.0% susceptible for isolate subsets that exhibited a non-extended-spectrum β-lactamase [lsqb]ESBL[rsqb]-phenotype). A total of 74.4% of P. aeruginosa, 100% of β-hemolytic streptococci and coagulase-negative staphylococci, and 99.6% of Enterococcus faecalis isolates were inhibited by ceftobiprole at ≤4 mg/L. As expected, ceftobiprole was largely inactive against Enterobacterales that contained ESBL genes and Enterococcus faecium. Overall, ceftobiprole was highly active against most clinical isolates from the major Gram-positive and Gram-negative skin and skin structure pathogen groups collected at U.S. medical centers participating in the SENTRY Antimicrobial Surveillance Program during 2016–2018. The broad-spectrum activity of ceftobiprole, including potent activity against MRSA, supports its further evaluation for the potential ABSSSI indication. Full Article
infection Rapid-Release Griffithsin Fibers for the Dual Prevention of HSV-2 and HIV-1 Infections [Antiviral Agents] By aac.asm.org Published On :: 2020-03-30T10:04:32-07:00 The biologic Griffithsin (GRFT) has recently emerged as a candidate to safely prevent sexually transmitted infections (STIs) including human immunodeficiency virus (HIV-1) and herpes simplex virus 2 (HSV-2). However, to date, there are few delivery platforms that are available to effectively deliver biologics to the female reproductive tract (FRT). The goal of this work was to evaluate rapid-release polyethylene oxide (PEO), polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP) fibers, that incorporate GRFT, in in vitro (HIV-1 and HSV-2) and in vivo (HSV-2) infection models. GRFT loading was determined via ELISA, and the bioactivity of GRFT fibers was assessed using in vitro HIV-1 pseudovirus and HSV-2 plaque assays. Afterwards, the efficacy of GRFT fibers was assessed in a murine model of lethal HSV-2 infection. Finally, murine reproductive tracts and vaginal lavages were evaluated for histology and cytokine expression, 24 and 72 hr after fiber administration, to determine safety. All rapid-release formulations achieved high levels of GRFT incorporation and were completely efficacious against in vitro HIV-1 and HSV-2 infections. Importantly, all rapid-release GRFT fibers provided potent protection in a murine model of HSV-2 infection. Moreover, histology and cytokine levels, evaluated from collected murine reproductive tissues and vaginal lavages treated with blank fibers, showed no increased cytokine production or histological aberrations, demonstrating the preliminary safety of rapid-release GRFT fibers in vaginal tissue. Full Article
infection Pharmacokinetics-pharmacodynamics of enmetazobactam combined with cefepime in a neutropenic murine thigh infection model [Pharmacology] By aac.asm.org Published On :: 2020-04-06T08:49:25-07:00 Third-generation cephalosporin (3GC)-resistant Enterobacteriaceae are classified as critical priority pathogens, with extended-spectrum β-lactamases (ESBLs) as principal resistance determinants. Enmetazobactam (formerly AAI101) is a novel ESBL inhibitor developed in combination with cefepime for empiric treatment of serious Gram-negative infections in settings where ESBLs are prevalent. Cefepime-enmetazobactam has been investigated in a phase 3 trial in patients with complicated urinary tract infections or acute pyelonephritis. This study examined pharmacokinetic-pharmacodynamic (PK-PD) relationships of enmetazobactam, in combination with cefepime, for ESBL-producing isolates of Klebsiella pneumoniae in 26-hour murine neutropenic thigh infection models. Enmetazobactam dose fractionation identified time above a free threshold concentration (fT > CT) as the PK-PD index predictive of efficacy. Nine ESBL-producing isolates of K. pneumoniae, resistant to cefepime and piperacillin-tazobactam, were included in enmetazobactam dose-ranging studies. The isolates encoded CTX-M-type, SHV-12, DHA-1 and OXA-48 β-lactamases and covered a cefepime-enmetazobactam MIC range from 0.06 to 2 μg/ml. Enmetazobactam restored the efficacy of cefepime against all isolates tested. Sigmoid curve fitting across the combined set of isolates identified enmetazobactam PK-PD targets for stasis and for a 1-log10 bioburden reduction of 8% and 44% fT > 2 μg/ml, respectively, with a concomitant cefepime PK-PD target of 40 – 60% fT > cefepime-enmetazobactam MIC. These findings support clinical dose selection and breakpoint setting for cefepime-enmetazobactam. Full Article
infection Fenbendazole controls in vitro growth, virulence potential and animal infection in the Cryptococcus model [Experimental Therapeutics] By aac.asm.org Published On :: 2020-04-06T08:49:25-07:00 The human diseases caused by the fungal pathogens Cryptococcus neoformans and C. gattii are associated with high indices of mortality, and toxic and/or cost-prohibitive therapeutic protocols. The need for affordable antifungals to combat cryptococcal disease is unquestionable. Previous studies suggested benzimidazoles as promising anti-cryptococcal agents combining low cost and high antifungal efficacy, but their therapeutic potential has not been demonstrated so far. In this study, we investigated the antifungal potential of fenbendazole, the most effective anti-cryptococcal benzimidazole. Fenbendazole was inhibitory against 17 different isolates of C. neoformans and C. gattii at a low concentration. The mechanism of anti-cryptococcal activity of fenbendazole involved microtubule disorganization, as previously described for human parasites. In combination with fenbendazole, the concentrations of the standard antifungal amphotericin B required to control cryptococcal growth were lower than those required when this antifungal was used alone. Fenbendazole was not toxic to mammalian cells. During macrophage infection, the anti-cryptococcal effects of fenbendazole included inhibition of intracellular proliferation rates and reduced phagocytic escape through vomocytosis. Fenbendazole deeply affected the cryptococcal capsule. In a mice model of cryptococcosis, the efficacy of fenbendazole to control animal mortality was similar to that observed for amphotericin B. These results indicate that fenbendazole is a promising candidate for the future development of an efficient and affordable therapeutic tool to combat cryptococcosis. Full Article
infection Oral Fosfomycin Treatment for Enterococcal Urinary Tract Infections in a Dynamic In Vitro Model [Pharmacology] By aac.asm.org Published On :: 2020-04-06T08:49:25-07:00 There are limited treatment options for enterococcal urinary tract infections, especially vancomycin-resistant Enterococcus (VRE). Oral fosfomycin is a potential option, although limited data are available guiding dosing and susceptibility. We undertook pharmacodynamic profiling of fosfomycin against E. faecalis and E. faecium isolates using a dynamic in vitro bladder infection model. Eighty-four isolates underwent fosfomycin agar dilution susceptibility testing (E. faecalis MIC50/90 32/64 μg/mL; E. faecium MIC50/90 64/128 μg/mL). Sixteen isolates (including E. faecalis ATCC 29212 and E. faecium ATCC 35667) were chosen to reflect the MIC range and tested in the bladder infection model with synthetic human urine (SHU). Under drug-free conditions, E. faecium demonstrated greater growth restriction in SHU compared to E. faecalis (E. faecium maximal growth 5.8 ± 0.6 log10 CFU/mL; E. faecalis 8.0 ± 1.0 log10 CFU/mL). Isolates were exposed to high and low fosfomycin urinary concentrations after a single dose, and two-doses given daily with low urinary exposure. Simulated concentrations closely matched the target (bias 2.3%). E. faecalis isolates required greater fosfomycin exposure for 3 log10 kill from the starting inoculum compared with E. faecium. The fAUC0-72/MIC and f%T > MIC0-72 for E. faecalis was 672 and 70%, compared to 216 and 51% for E. faecium, respectively. There was no rise in fosfomycin MIC post-exposure. Two doses of fosfomycin with low urinary concentrations resulted in equivalent growth inhibition to a single dose with high urinary concentrations. With this urinary exposure, fosfomycin was effective in promoting suppression of regrowth (>3 log10 kill) in the majority of isolates. Full Article
infection Repurposing the antiamoebic drug diiodohydroxyquinoline for treatment of Clostridioides difficile infections [Experimental Therapeutics] By aac.asm.org Published On :: 2020-04-06T08:49:25-07:00 Clostridioides difficile, the leading cause of nosocomial infections, is an urgent health threat worldwide. The increased incidence and severity of disease, the high recurrence rates, and the dearth of effective anticlostridial drugs have created an urgent need for new therapeutic agents. In an effort to discover new drugs for treatment of Clostridioides difficile infections (CDIs), we investigated a panel of FDA-approved antiparasitic drugs against C. difficile and identified diiodohydroxyquinoline (DIHQ), an FDA-approved oral antiamoebic drug. DIHQ exhibited potent activity against 39 C. difficile isolates, inhibiting growth of 50% and 90% of these isolates at the concentrations of 0.5 μg/mL and 2 μg/mL, respectively. In a time-kill assay, DIHQ was superior to vancomycin and metronidazole, reducing a high bacterial inoculum by 3-log10 within six hours. Furthermore, DIHQ reacted synergistically with vancomycin and metronidazole against C. difficile in vitro. Moreover, at subinhibitory concentrations, DIHQ was superior to vancomycin and metronidazole in inhibiting two key virulence factors of C. difficile, toxin production and spore formation. Additionally, DIHQ did not inhibit growth of key species that compose the host intestinal microbiota, such as Bacteroides, Bifidobacterium and Lactobacillus spp. Collectively, our results indicate that DIHQ is a promising anticlostridial drug that warrants further investigation as a new therapeutic for CDIs. Full Article
infection Phase 2a Pharmacokinetic, Safety, and Exploratory Efficacy Evaluation of Oral Gepotidacin (GSK2140944) in Female Participants With Uncomplicated Urinary Tract Infection (Acute Uncomplicated Cystitis) [Clinical Therapeutics] By aac.asm.org Published On :: 2020-04-13T08:15:31-07:00 Gepotidacin, a triazaacenaphthylene bacterial type II topoisomerase inhibitor, is in development for treatment of uncomplicated urinary tract infection (uUTI). This Phase 2a study in female participants with uUTI evaluated the pharmacokinetics (primary objective), safety, and exploratory efficacy of gepotidacin. Eligible participants (N = 22) were confined to the clinic at baseline, received oral gepotidacin 1,500 mg twice daily for 5 days (on-therapy; Days 1 to 5), and returned to the clinic for test-of-cure (Days 10 to 13) and follow-up (Day 28±3). Pharmacokinetic, safety, clinical, and microbiological assessments were performed. Maximum plasma concentrations were observed approximately 1.5 to 2 hours postdose. Steady state was attained by Day 3. Urinary exposure over the dosing interval increased from 3,742 μg.h/ml (Day 1) to 5,973 μg.h/ml (Day 4), with trough concentrations of 322 to 352 μg/ml from Day 3 onward. Gepotidacin had an acceptable safety-risk profile with no treatment-limiting adverse events and no clinically relevant safety trends. Clinical success was achieved in 19 (86%) and 18 (82%) of 22 participants at test-of-cure and follow-up, respectively. Eight participants had a qualifying baseline uropathogen (growth; ≥105 CFU/ml). A therapeutic (combined clinical and microbiological [no growth; <103 CFU/ml]) successful response was achieved in 6 (75%) and 5 (63%) of 8 participants at test-of-cure and follow-up, respectively. Plasma area under the free-drug concentration-time curve over 24 hours at steady state divided by the MIC (fAUC0-24/MIC) and urine AUC0-24/MIC ranged from 6.99 to 90.5 and 1,292 to 121,698, respectively. Further evaluation of gepotidacin in uUTI is warranted. (NCT03568942) Full Article
infection Pharmacokinetic-Pharmacodynamic Characterization of Omadacycline Against Haemophilus influenzae Using a One-Compartment In Vitro Infection Model [Pharmacology] By aac.asm.org Published On :: 2020-04-13T08:15:30-07:00 Omadacycline is a novel aminomethylcycline with activity against Gram-positive and -negative organisms, including Haemophilus influenzae, which is one of the leading causes of community-acquired bacterial pneumonia (CABP). The evaluation of antimicrobial agents against H. influenzae using standard murine infection models is challenging due to the low pathogenicity of this species in mice. Therefore, 24-hour dose-ranging studies using a one-compartment in vitro infection model were undertaken with the goal of characterizing the magnitude of the ratio of the area under the concentration-time curve (AUC) to the MIC (AUC/MIC ratio) associated with efficacy for a panel of five clinical H. influenzae isolates. These five isolates, which had MIC values of 1 or 2 mg/L, were exposed to omadacycline total-drug epithelial lining fluid (ELF) concentration-time profiles based on those observed in healthy volunteers following intravenous omadacycline administration. Relationships between change in log10 colony forming units (CFU) from baseline at 24 hours and total-drug ELF AUC/MIC ratio for each isolate and the isolates pooled together were evaluated using Hill-type models and non-linear least squares regression. As evidenced by the high coefficient of determination (r2) of 0.88 to 0.98, total-drug ELF AUC/MIC ratio described the data well for each isolate and the isolates pooled together. The median total-drug ELF AUC/MIC ratio associated with net bacterial stasis and 1- and 2-log10 CFU/mL reductions from baseline at 24 hours was 6.91, 8.91, and 11.1, respectively. These data were useful to support the omadacycline dosing regimens selected for the treatment of patients with CABP, as well as susceptibility breakpoints for H. influenzae. Full Article
infection The Emerging Role of {beta}-lactams in the Treatment of Methicillin-Resistant Staphylococcus aureus Bloodstream Infections [Minireviews] By aac.asm.org Published On :: 2020-04-20T08:36:46-07:00 Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) are associated with substantial morbidity and mortality. Monotherapy with first-line antimicrobials such as vancomycin (VAN; glycopeptide) and daptomycin (DAP; lipopeptide) are inadequate in some cases due to reduced antibiotic susceptibilities or therapeutic failure. In recent years, β-lactam antibiotics have emerged as a potential option for combination therapy with VAN/DAP that may meet an unmet therapeutic need for MRSA BSI. Ceftaroline (CPT), the only commercially available β-lactam in the United States with intrinsic in vitro activity against MRSA, has been increasingly studied in the setting of VAN and DAP failures. Novel combinations of first-line agents (VAN and DAP) with β-lactams have been the subject of many recent investigations due to in vitro findings such as the "see-saw effect", where β-lactam susceptibility may be improved in the presence of decreased glycopeptide and lipopeptide susceptibility. The combination of CPT and DAP, in particular, has become the focus of many scientific evaluations, due to intrinsic anti-MRSA activities and potent in vitro synergistic activity against various MRSA strains. This article reviews the available literature describing these innovative therapeutic approaches for MRSA BSI, focusing on preclinical and clinical studies, and evaluates the potential benefits and limitations of each strategy. Full Article
infection Prediction of antibiotic susceptibility for urinary tract infection in a hospital setting [Epidemiology and Surveillance] By aac.asm.org Published On :: 2020-04-20T08:36:46-07:00 Objectives: Empiric antibiotic prescribing can be supported by guidelines and/or local antibiograms, but these have limitations. We sought to use data from a comprehensive electronic health record to use statistical learning to develop predictive models for individual antibiotics that incorporate patient-, and hospital-specific factors. This paper reports on the development and validation of these models on a large retrospective cohort.Methods: This is a retrospective cohort study including hospitalized patients with positive urine cultures in the first 48 hours of hospitalization at a 1500 bed, tertiary care hospital over a 4.5 year period. All first urine cultures with susceptibilities were included. Statistical learning techniques, including penalized logistic regression, were used to create predictive models for cefazolin, ceftriaxone, ciprofloxacin, cefepime, and piperacillin-tazobactam. These were validated on a held-out cohort.Results: The final dataset used for analysis included 6,366 patients. Final model covariates included demographics, comorbidity score, recent antibiotic use, recent antimicrobial resistance, and antibiotic allergies. Models had acceptable to good discrimination in the training dataset and acceptable performance in the validation dataset, with a point estimate for area under the receiver operating characteristic curve (AUC) that ranged from 0.65 for ceftriaxone to 0.69 for cefazolin. All models had excellent calibration.Conclusion: In this study we used electronic health record data to create predictive models to estimate antibiotic susceptibilities for UTIs in hospitalized patients. Our models had acceptable performance in a held-out validation cohort. Full Article
infection Impact of vanA-positive Enterococcus faecium exhibiting diverse susceptibility phenotypes to glycopeptides on 30-day mortality of patients with a bloodstream infection [Epidemiology and Surveillance] By aac.asm.org Published On :: 2020-04-27T08:14:57-07:00 Introduction: This study was performed to evaluate the impacts of vanA-positivity of Enterococcus faecium (EFM) exhibiting diverse susceptibility phenotypes to glycopeptides on clinical outcomes in patients with a bloodstream infection (BSI) through a prospective, multicenter, observational study.Methods: A total of 509 patients with an EFM BSI from eight sentinel hospitals in South Korea during a two-year period were enrolled in this study. Risk factors of the hosts and causative EFM isolates were assessed to determine associations with the 30-day mortality of EFM BSI patients via multivariable logistic regression analyses.Results: The vanA gene was detected in 35.2% (179/509) of EFM isolates; 131 EFM isolates exhibited typical VanA phenotypes (group vanA-VanA), while the remaining 48 EFM isolates exhibited atypical phenotypes (group vanA-Atypical), including VanD (n = 43) and vancomycin-variable phenotypes (n = 5). A multivariable logistic regression indicated that vanA-positivity of causative pathogens was independently associated with the increased 30-day mortality rate in the patients with an EFM BSI; however, there was no significant difference in the survival rates between the patients of the vanA-VanA and vanA-Atypical groups (log-rank test, P = 0.904).Conclusions: A high 30-day mortality rate was observed in patients with vanA-positive EFM BSIs, and vanA-positivity of causative EFM was an independent risk factor for early mortality irrespective of the susceptibility phenotypes to glycopeptides; thus, intensified antimicrobial stewardship is needed to improve clinical outcome of patients with vanA-positive EFM BSI. Full Article
infection Quercetin blocks Ebola Virus infection by counteracting the VP24 Interferon inhibitory function [Antiviral Agents] By aac.asm.org Published On :: 2020-05-04T08:49:24-07:00 Ebola Virus (EBOV) is among the most devastating pathogens causing fatal hemorrhagic fever in humans. The 2013–2016 epidemics resulted in over 11000 deaths, while another outbreak is currently ongoing. Since there is no FDA-approved drug so far to fight EBOV infection, there is an urgent need to focus on drug discovery. Considering the tight correlation between the high EBOV virulence and its ability to suppress the type-I Interferon (IFN-I) system, identifying molecules targeting viral protein VP24, one of the main virulence determinants blocking IFN response, is a promising novel anti-EBOV therapy approach. Hence, in the effort of finding novel EBOV inhibitors, a screening of a small set of flavonoids was performed, showing that Quercetin and Wogonin can suppress the VP24 effect on IFN-I signaling inhibition. The mechanism of action of the most active compound, Quercetin, showing an IC50 value of 7.4 μM, was characterized to significantly restore the IFN-I signaling cascade, blocked by VP24, by directly interfering with the VP24 binding to karyopherin-α and thus restoring P-STAT1 nuclear transport and IFN genes transcription. Quercetin significantly blocked viral infection, specifically targeting EBOV VP24 anti-IFN-I function. Overall, Quercetin is the first identified inhibitor of the EBOV VP24 anti-IFN function, representing a molecule interacting with a viral binding site that is very promising for further drug development aiming to block EBOV infection at the early steps. Full Article
infection Inhibition of SARS-CoV-2 infection by the cyclophilin inhibitor Alisporivir (Debio 025) [Antiviral Agents] By aac.asm.org Published On :: 2020-05-06T08:16:52-07:00 Cyclophilins play a key role in the lifecycle of coronaviruses. Alisporivir (Debio 025) is a non-immunosuppressive analogue of cyclosporin A with potent cyclophilin inhibition properties. Alisporivir reduced SARS-CoV-2 RNA production in a dose-dependent manner in VeroE6 cell line, with an EC50 of 0.46±0.04 μM. Alisporivir inhibited a post-entry step of the SARS-CoV-2 lifecycle. These results justify that a proof-of-concept Phase 2 trial be rapidly conducted with alisporivir in patients with SARS-CoV-2 infection. Full Article
infection Performance of the Modified Boston and Philadelphia Criteria for Invasive Bacterial Infections By pediatrics.aappublications.org Published On :: 2020-04-01T01:00:57-07:00 BACKGROUND: The ability of the decades-old Boston and Philadelphia criteria to accurately identify infants at low risk for serious bacterial infections has not been recently reevaluated. METHODS: We assembled a multicenter cohort of infants 29 to 60 days of age who had cerebrospinal fluid (CSF) and blood cultures obtained. We report the performance of the modified Boston criteria (peripheral white blood cell count [WBC] ≥20 000 cells per mm3, CSF WBC ≥10 cells per mm3, and urinalysis with >10 WBC per high-power field or positive urine dip result) and modified Philadelphia criteria (peripheral WBC ≥15 000 cells per mm3, CSF WBC ≥8 cells per mm3, positive CSF Gram-stain result, and urinalysis with >10 WBC per high-power field or positive urine dip result) for the identification of invasive bacterial infections (IBIs). We defined IBI as bacterial meningitis (growth of pathogenic bacteria from CSF culture) or bacteremia (growth from blood culture). RESULTS: We applied the modified Boston criteria to 8344 infants and the modified Philadelphia criteria to 8131 infants. The modified Boston criteria identified 133 of the 212 infants with IBI (sensitivity 62.7% [95% confidence interval (CI) 55.9% to 69.3%] and specificity 59.2% [95% CI 58.1% to 60.2%]), and the modified Philadelphia criteria identified 157 of the 219 infants with IBI (sensitivity 71.7% [95% CI 65.2% to 77.6%] and specificity 46.1% [95% CI 45.0% to 47.2%]). The modified Boston and Philadelphia criteria misclassified 17 of 53 (32.1%) and 13 of 56 (23.3%) infants with bacterial meningitis, respectively. CONCLUSIONS: The modified Boston and Philadelphia criteria misclassified a substantial number of infants 29 to 60 days old with IBI, including those with bacterial meningitis. Full Article
infection HIV Testing Among Adolescents With Acute Sexually Transmitted Infections By pediatrics.aappublications.org Published On :: 2020-04-01T01:00:57-07:00 BACKGROUND AND OBJECTIVES: Rates of sexually transmitted infections (STIs) have increased over the decade. Guidelines recommend HIV testing with incident STIs. Prevalence and factors associated with HIV testing in acute STIs are unknown in adolescents. Our objective was to determine the prevalence of completed HIV testing among adolescents with incident STIs and identify patient and health care factors associated with HIV testing. METHODS: Retrospective study of STI episodes (gonorrhea, Chlamydia, trichomoniasis, or syphilis) of adolescents between 13 and 24 years old from July 2014 to December 2017 in 2 urban primary care clinics. We performed mixed effects logistic regression modeling to identify patient and health care factors associated with HIV testing within 90 days of STI diagnosis. RESULTS: The 1313 participants contributed 1816 acute STI episodes. Mean age at STI diagnosis was 17.2 years (SD = 1.7), 75% of episodes occurred in females, and 97% occurred in African Americans. Only half (55%) of acute STI episodes had a completed HIV test. In the adjusted model, female sex, previous STIs, uninsured status, and confidential sexual health encounters were associated with decreased odds of HIV testing. Patients enrolled in primary care at the clinics, compared with those receiving sexual health care alone, and those with multipathogen STI diagnoses were more likely to have HIV testing. CONCLUSIONS: HIV testing rates among adolescents with acute STIs are suboptimal. Patient and health care factors were found to be associated with receipt of testing and should be considered in clinical practice. Full Article
infection Oral Versus Initial Intravenous Therapy for Urinary Tract Infections in Young Febrile Children By pediatrics.aappublications.org Published On :: 1999-07-01 Alejandro HobermanJul 1, 1999; 104:79-86ARTICLES Full Article
infection Febrile Infants at Low Risk for Serious Bacterial Infection--An Appraisal of the Rochester Criteria and Implications for Management By pediatrics.aappublications.org Published On :: 1994-09-01 Julie A. JaskiewiczSep 1, 1994; 94:390-396COMMENTARY Full Article
infection Palivizumab, a Humanized Respiratory Syncytial Virus Monoclonal Antibody, Reduces Hospitalization From Respiratory Syncytial Virus Infection in High-risk Infants By pediatrics.aappublications.org Published On :: 1998-09-01 The IMpact-RSV Study GroupSep 1, 1998; 102:531-537ARTICLES Full Article
infection Fin24.com | Northam mine reports first Coronavirus infection By www.fin24.com Published On :: Wed, 06 May 2020 22:01:21 +0200 The employee had travelled from Polokwane with four other colleagues who are currently in isolation at the mine's health facility. Full Article
infection Early Neonatal SARS-CoV-2 Infection Manifesting With Hypoxemia Requiring Respiratory Support By pediatrics.aappublications.org Published On :: 2020-05-04T00:05:41-07:00 Full Article
infection Co-infection and Other Clinical Characteristics of COVID-19 in Children By pediatrics.aappublications.org Published On :: 2020-05-06T00:05:31-07:00 Full Article
infection Defence Research Body Installs UV Disinfection Chamber At Cochin Airport By www.ndtv.com Published On :: Fri, 08 May 2020 03:31:43 +0530 The Defence Research and Development Organisation (DRDO) has installed its Ultra Violet disinfection chamber at the Cochin International Airport in Kerala. Full Article All India
infection Automated Coronavirus disinfection for car cabin with this sprinkle system-style spray By www.financialexpress.com Published On :: 2020-04-28T11:10:42+05:30 This apparatus can be used to sanitize the seats of cars, taxis, ambulances, goods vans, buses, flights, trains, and could even sanitize elevators, etc. Full Article
infection Coronavirus in Bangladesh: COVID-19 cases cross 11,000 with 790 new infections reported in one day By www.financialexpress.com Published On :: 2020-05-06T18:07:00+05:30 Directorate General of Health Services (DGHS) Additional Director General (administration) Nasima Sultana said that two of the deceased were over 60 years while one was aged between 41 and 50 years. Full Article Health Lifestyle
infection Coronavirus pandemic: WHO says 80,000 COVID-19 cases reported daily in April; India, Bangladesh see spike in infections By www.financialexpress.com Published On :: 2020-05-07T16:35:59+05:30 WHO Director-General Tedros Adhanom Ghebreyesus said on Wednesday that countries must also be able to manage any risk of the disease being imported into their territories, and communities should be fully educated to adjust to what will be a "new norm". Full Article Health Lifestyle
infection Most COVID-19 patients may lose sense of smell by third day of infection: Study By www.financialexpress.com Published On :: 2020-05-08T11:55:00+05:30 The telephonic study, whose results were published in the journal Otolaryngology-Head and Neck Surgery, examined characteristics and symptoms of 103 patients who were diagnosed with COVID-19 over a six-week period. Full Article Health Lifestyle
infection Coronairus: Bharat Biotech-led group to develop human antibodies as therapy for COVID-19 infections By www.financialexpress.com Published On :: 2020-05-08T17:26:00+05:30 Therefore, an alternate therapeutic regimen for early deployment is critical, the vaccine-maker said in the statement. Full Article Health Lifestyle
infection Vistara airlines issues inflight modifications to tackle Coronavirus infection; Read full list By www.financialexpress.com Published On :: 2020-04-30T15:44:00+05:30 The airline may make further changes in compliance with regulatory guidelines once they are finalized and notified, Vistara said in a statement. Full Article Lifestyle Travel & Tourism
infection WP-VCD Malware Is No. 1 In WordPress Infections Since August By packetstormsecurity.com Published On :: Mon, 11 Nov 2019 15:12:03 GMT Full Article headline malware fraud wordpress
infection French Hospital Contracts 6,000 PC-Locking Ransomware Infections By packetstormsecurity.com Published On :: Sun, 24 Nov 2019 20:33:15 GMT Full Article headline malware cybercrime fraud france terror cryptography
infection [Ticker] German infections could be 10 times higher: report By euobserver.com Published On :: Tue, 05 May 2020 07:22:16 +0200 A new study out of Germany has suggested that the coronavirus infection rate there could be much higher than initially thought and that some 1.8m people could be infected nationwide, a quarter of them without symptoms, Deutsche Welle reports. The number of coronavirus infections in Germany could be 10 times higher than currently thought, says a much-discussed Heinsberg Report, which took a closer look at one small community in Germany. Full Article
infection Coronavirus - Compliance risks for companies under the Infection Protection Law - Germany By www.eversheds.com Published On :: 2020-03-31 I. Introduction The Covid-19 pandemic poses new challenges to society as a whole and to each individual. The rapid spread of the virus is currently prompting political decision-makers to react just as quickly by developing and adopting new measures... Full Article
infection 17 deaths and 663 new infections for SA as Covid-19 cases surge to 8895 By Published On :: Fri, 08 May 2020 20:08:00 GMT Health Minister Zweli Mkhize has announced 663 new Covid-19 infections and 17 new deaths - the highest for new cases and deaths - taking SA's Covid-19 cases over 8800 and deaths to 171. Full Article
infection Alg�rie: COVID-19 - Op�ration de d�sinfection des espaces publics de la commune de Gharda�a By article.wn.com Published On :: Sat, 09 May 2020 15:33 GMT Ghardaia -Une large op�ration de... Full Article
infection BREAKING NEWS: 8 new deaths and 525 new infections for SA as Covid-19 cases surge ... By article.wn.com Published On :: Sat, 09 May 2020 15:43 GMT Johannesburg - South Africa now has over 9420 confirmed cases of the Covid-19 coronavirus and 8 more deaths, Health Minister Zweli Mkhize announced on Saturday. Mkhize said there were 525 new infections, taking the total cases to 9420, while there were also 8 more deaths, taking the death toll to 186. The total number of... Full Article
infection Kuwait- Covid-19 infections in Austria up by 60 to 15,735 By article.wn.com Published On :: Sat, 09 May 2020 16:47 GMT (MENAFN - Kuwait News Agency (KUNA)) KUWAIT, May 9 (KUNA) -- Sixty more people have tested positive for the novel coronavirus (Covid-19) in Austria, b... ...... Full Article
infection Brunei's coronavirus infections remain unchanged at 141 By article.wn.com Published On :: Sat, 09 May 2020 16:47 GMT (MENAFN) The overall tally of patients who have tested positive for the novel coronavirus in Brunei has remained unaffected at 141, as zero more cases... ...... Full Article
infection Keidanren to suggest four-day workweek to reduce virus infection risk By www.japantimes.co.jp Published On :: Sat, 09 May 2020 22:09:35 +0900 Japan's largest business lobby plans to suggest that member companies introduce a four-day workweek as part of efforts to reduce risks of novel coronavirus infection.A ... Full Article News Keidanren covid-19 covid-19 in Japan
infection Bowing to pressure, Tokyo releases COVID-19 testing and infection data dating back to January By www.japantimes.co.jp Published On :: Sun, 10 May 2020 04:45:10 +0900 The release, which marks a significant shift in disclosure policy, details the capital's testing totals, daily infection counts and infection rates. Full Article News Tokyo medicine health Yuriko Koike covid-19 covid-19 in Japan
infection Coronavirus: South Korea reports new infection cluster linked to nightclubs By www.scmp.com Published On :: Fri, 08 May 2020 14:16:23 +0800 South Korea confirmed 12 new coronavirus cases on Friday, its first increase above 10 in five days, as authorities warned numbers would increase as it had identified a new cluster of infections linked to a 29-year-old man.The IT company employee had spread the virus to at least 14 others as he wandered around the capital Seoul and four neighbouring cities over a long weekend period at the start of the month, said the Korea Centres for Disease Control and Prevention.While the 12 cases were those… Full Article
infection Coronavirus: four new infections in Hong Kong, all involving residents returning from Pakistan By www.scmp.com Published On :: Thu, 07 May 2020 15:17:09 +0800 Hong Kong recorded four new coronavirus infections on Thursday, all involving returnees from Pakistan the previous night, as the city prepared to bring back more residents stranded in South Asia.The diagnoses ended a two-day streak without any new cases, and takes the city’s total number of confirmed infections to 1,044.Dr Chuang Shuk-kwan, head of the communicable diseases branch of the Centre for Health Protection (CHP), said the patients in question, aged between 11 and 47, all returned to… Full Article
infection Amid slowing infections, Germany takes first steps to restart public life By www.smh.com.au Published On :: Thu, 16 Apr 2020 02:20:39 GMT New infections in Germany have slowed in recent weeks, but Merkel cautioned that the country has achieved only "a fragile intermediate success". Full Article
infection Coronavirus infection surge threatens to collapse Japan's hospitals By www.smh.com.au Published On :: Sat, 18 Apr 2020 07:04:03 GMT Two Japanese medical associations warn that the country's healthcare system is on the brink of collapse. Full Article
infection Abnormal increase in asymptomatic cases, local infection By feedproxy.google.com Published On :: Sat, 09 May 2020 06:00:00 +0500 ISLAMABAD: Eight out of 10 coronavirus patients didn’t have symptoms but found positive only after they were tested, countrywide data obtained by The News has determined.Similarly, local transmission of pandemic has considerably increased as around nine in 10 patients have contracted virus... Full Article
infection Abnormal increase in asymptomatic cases, local infection By feedproxy.google.com Published On :: Sat, 09 May 2020 06:00:00 +0500 ISLAMABAD: Eight out of 10 coronavirus patients didn’t have symptoms but found positive only after they were tested, countrywide data obtained by The News has determined. Similarly, local transmission of pandemic has considerably increased as around nine in 10 patients have contracted virus... Full Article