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Racial Differences in Antibiotic Prescribing by Primary Care Pediatricians

Racial disparities in health care have been reported in multiple settings, but not thoroughly examined at the clinician level. The frequent occurrence of respiratory tract infections allows the evaluation of differences in the management of children seen by the same clinician.

Racial differences in the management of common pediatric infections occur among children treated by the same clinician. Given persistent concerns about nonjudicious antibiotic use, examining racial differences may inform our understanding of prescribing practices and identify opportunities for intervention. (Read the full article)




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Factors Affecting Caregivers' Use of Antibiotics Available Without a Prescription in Peru

Self-medication with antibiotics available without prescription is among the main causes of antibiotic misuse in the developing world and is associated with antibiotic resistance. Inappropriate antibiotic prescription is common in children. Patient expectations seem to influence physicians’ advice.

This study demonstrates that even in places where antibiotics are unregulated, improving physician prescribing habits could reduce irrational use overall and also future caregiver-driven misuse. Physician training in adequate antibiotic prescription could be a cost-effective intervention in these settings. (Read the full article)




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Probiotic Administration in Early Life, Atopy, and Asthma: A Meta-analysis of Clinical Trials

The intestinal microbiome may play a role in immune system maturation, and it has been postulated that early-life probiotic administration may reduce the risk of allergies and asthma in childhood. To date, however, results from clinical trials have been inconsistent.

In this meta-analysis, administration of probiotics in early life may reduce total immunoglobulin E level and protect against atopic sensitization but do not seem to protect against asthma/wheezing. Future trials should carefully select probiotic strains and include longer follow-up. (Read the full article)




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Treatment Outcomes of Infants With Cyanotic Congenital Heart Disease Treated With Synbiotics

Several studies have suggested that probiotics may prevent necrotizing enterocolitis and death in preterm infants. However, there are no data on the preventive effect of probiotics in infants with cyanotic congenital heart disease.

Although duration of hospitalization was not significantly decreased, Bifidobacterium lactis plus inulin appears to decrease the rate of nosocomial infection, necrotizing enterocolitis, and death in infants with cyanotic congenital heart disease. (Read the full article)




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Probiotic Effects on Late-onset Sepsis in Very Preterm Infants: A Randomized Controlled Trial

Late-onset sepsis is a frequent complication of prematurity, contributing to morbidity and mortality. Although evidence is accumulating that administration of probiotics to very preterm infants reduces necrotizing enterocolitis (NEC) and all-cause mortality, the effect on late-onset sepsis is less clear.

The probiotic combination Bifidobacterium infantis, Streptococcus thermophilus, and Bifidobacterium lactis reduced NEC in very preterm infants, but not mortality or late-onset sepsis. Probiotics may be of greatest global value in neonatal settings with high rates of NEC. (Read the full article)




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Comparative Effectiveness of Empiric Antibiotics for Community-Acquired Pneumonia

Broad-spectrum antibiotics are frequently used to empirically treat children hospitalized with community-acquired pneumonia despite recent national recommendations to use narrow-spectrum antibiotics.

Narrow-spectrum antibiotics are similar to broad-spectrum antibiotics for the treatment of children hospitalized with community-acquired pneumonia in terms of clinical outcomes and resource utilization. This study provides scientific evidence to support national consensus guidelines. (Read the full article)




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Recent Trends in Outpatient Antibiotic Use in Children

Antibiotic use for children has decreased dramatically over the last 20 years. Programs encouraging judicious antibiotic use have focused both on decreasing overall antibiotic use and appropriate prescribing of broad-spectrum agents.

Large declines in antibiotic rates were prominent in the early 2000s. This trend has attenuated, and use has leveled off in some age groups and locales; continued improvement in the use of broad-spectrum agents is possible. (Read the full article)




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Stool Microbiota and Vaccine Responses of Infants

Oral vaccine responses are low in children from less-developed countries perhaps as a result of intestinal dysbiosis. New high-throughput DNA-based methods allow characterization of intestinal microbiota as a predictor of vaccine responses.

High abundance of stool Actinobacteria, including Bifidobacterium, was associated with higher responses to oral and parenteral vaccines and a larger thymus in Bangladeshi infants. Conversely, high abundance of Clostridiales, Enterobacteriales, and Pseudomonadales was associated with neutrophilia and lower vaccine responses. (Read the full article)




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Race, Otitis Media, and Antibiotic Selection

A previous study suggested that physicians in 1 practice network were less likely to diagnose otitis media (OM) and to prescribe broad-spectrum antibiotics for OM for black versus nonblack children.

Nationally, black children with OM are more likely to receive guideline-recommended, narrow-spectrum antibiotics than nonblack children. These findings may reflect inappropriate treatment of OM with the use of broad-spectrum antibiotics in a majority of US children. (Read the full article)




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Etiology of Childhood Bacteremia and Timely Antibiotics Administration in the Emergency Department

Childhood bacteremia caused by vaccine-preventable organisms has substantially declined over the last decade. Recognition of bacteremia in children is difficult, and delayed administration of antibiotics is associated with poor outcomes. Adults with health care–associated Gram-negative bacteremia experience delays in receiving appropriate antibiotics.

Bacteremia in children presenting to the emergency department is increasingly health care associated and resistant to empirical antibiotics. These infections are associated with increased length of stay. Rates of Gram-negative bacteremia have increased, and children with Gram-negative bacteremia experience delayed antibiotic administration. (Read the full article)




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Cardiac Biomarkers and Acute Kidney Injury After Cardiac Surgery

Acute kidney injury (AKI) occurs in up to 50% of children after cardiopulmonary bypass and is associated with adverse outcomes. Renal biomarkers have been shown to predict postoperative AKI, but few studies have examined cardiac biomarkers for risk classification.

Preoperative levels of creatine kinase-MB and heart-type fatty acid binding protein are strongly associated with the development of postoperative AKI after pediatric cardiac surgery and can be used to improve preoperative clinical risk prediction. (Read the full article)




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Antibiotic Exposure in Infancy and Risk of Being Overweight in the First 24 Months of Life

Subtherapeutic doses of antibiotics have been used as growth promoters in animal farming since the 1950s. Antibiotic exposure during infancy is associated with increased body mass in humans.

The weight-promoting effect of antibiotics is most pronounced when the exposure occurs at <6 months of age or repeatedly during infancy. Increased body mass is distinctly associated with exposure to cephalosporins and macrolides, especially in boys. (Read the full article)




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Neonatal Intensive Care Unit Antibiotic Use

Although treatment of infection is a mainstay of neonatal intensive care, little attention has focused on the proportion of patient antibiotic exposures validated by clinical indications that are unambiguous.

Septic workups in 127 California NICUs reveal similar burdens of proven infection, yet patient antibiotic exposures in those NICUs vary 40-fold. Because antibiotic stewardship principles dictate that antibiotic use should correlate with burden of infection, some NICUs overuse antibiotics. (Read the full article)




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Biomarkers of Alzheimer Disease, Insulin Resistance, and Obesity in Childhood

Insulin resistance plays a role in obesity. Recently it has been associated with increased risk of AD. Aβ42 and PSEN1 are molecules associated with increased risk of later AD. Patients affected by AD show elevated levels of plasma Aβ42.

Levels of Aβ42 and PSEN1 are significantly elevated in obese adolescents and correlated with the degree of both adiposity and systemic insulin resistance. (Read the full article)




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Antibiotic Choice for Children Hospitalized With Pneumonia and Adherence to National Guidelines

The 2011 national guidelines for the management of pediatric community-acquired pneumonia recommended narrow-spectrum antibiotic therapy (eg, ampicillin) for most children hospitalized with pneumonia. Before the release of the guidelines, the use of broader-spectrum antibiotics (eg, third-generation cephalosporins) was much more common.

After release of the guidelines, third-generation cephalosporin use declined and penicillin/ampicillin use increased among children hospitalized with pneumonia. Changes were most apparent among institutions that proactively disseminated the guidelines, underscoring the importance of local efforts for timely guideline implementation. (Read the full article)




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Cost-Effectiveness Analysis of a National Newborn Screening Program for Biotinidase Deficiency

Biotinidase deficiency (BD) might cause severe and permanent consequences. Cases detected through newborn screening and under treatment are shown to remain asymptomatic. However, some countries, including Spain, do not provide universal BD screening within their national newborn screening programs.

It provides a first estimate of the lifetime costs and health outcomes of a Spanish birth cohort with and without neonatal screening for BD. It shows that newborn screening for BD is likely to be a cost-effective use of resources. (Read the full article)




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Antibiotic Exposure and Juvenile Idiopathic Arthritis: A Case-Control Study

The etiology of juvenile idiopathic arthritis (JIA) is poorly understood. A recent study suggested a link between antibiotics and JIA but did not examine the potential for confounding from infections or the role of antibiotic timing.

Antibiotics were associated with newly diagnosed JIA in a dose- and time-dependent manner after adjusting for infection and other confounders. Antibiotics may play a role in the pathogenesis of JIA. (Read the full article)




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Prevalence of Parental Misconceptions About Antibiotic Use

Attitudes and knowledge about appropriate management of common childhood illnesses may lead parents to mistakenly believe antibiotics are needed. Differences existed in antibiotic knowledge and attitudes between parents of Medicaid- and commercially insured children and according to other sociodemographic variables.

Despite efforts to decrease unnecessary antibiotic use, misconceptions about antibiotic use persist and continue to be more prevalent among parents of Medicaid-insured children. Tailored efforts for socioeconomically disadvantaged populations remain warranted to decrease parental drivers of unnecessary antibiotic prescribing. (Read the full article)




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Biochemical Characterization of QPX7728, a New Ultra-Broad-Spectrum Beta-lactamase Inhibitor of Serine and Metallo-Beta-Lactamases [Mechanisms of Resistance]

QPX7728 is a new ultra-broad-spectrum inhibitor of serine and metallo beta-lactamases from a class of cyclic boronates that gave rise to vaborbactam. The spectrum and mechanism of beta-lactamase inhibition by QPX7728 were assessed using purified enzymes from all molecular classes. QPX7728 inhibits class A ESBLs (IC50 range 1-3 nM) and carbapenemases such as KPC (IC50 2.9±0.4 nM) as well as class C P99 (IC50 of 22±8 nM) with a potency that is comparable or higher than recently FDA approved BLIs avibactam, relebactam and vaborbactam. Unlike those other BLIs, QPX7728 is also a potent inhibitor of class D carbapenemases such as OXA-48 from Enterobacteriaceae and OXA enzymes from A. baumannii (OXA-23/24/58, IC50 range 1-2 nM) as well as MBLs such as NDM-1 (IC50 55±25 nM), VIM-1 (IC50 14±4 nM) and IMP-1 (IC50 610±70 nM). Inhibition of serine enzymes by QPX7728 is associated with progressive inactivation with a high efficiency k2/K ranging from of 6.3 x 104 (for P99) to 9.9 x 105 M-1 s-1 (for OXA-23). This inhibition is reversible with variable stability of the QPX7728-beta-lactamase complexes with target residence time ranging from minutes to several hours: 5-20 minutes for OXA carbapenemases from A. baumanii, ~50 minutes for OXA-48 and 2-3 hours for KPC and CTX-M-15. QPX7728 inhibited all tested serine enzymes at 1:1 molar ratio. Metallo-beta-lactamases NDM, VIM, and IMP were inhibited by a competitive mechanism with fast-on-fast-off kinetics, with Kis of 7.5±2.1 nM, 32±14 nM and 240±30 nM for VIM-1, NDM-1 and IMP-1, respectively. QPX7728 ultra-broad-spectrum of BLI inhibition combined with its high potency enables combinations with multiple different beta-lactam antibiotics.




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An engineered double lipid II binding motifs-containing lantibiotic displays potent and selective antimicrobial activity against E. faecium [Chemistry; Biosynthesis]

Lipid II is an essential precursor of the bacterial cell wall biosynthesis and thereby an important target for various antibiotics. Several lanthionine-containing peptide antibiotics target lipid II with lanthionine-stabilized lipid II-binding motifs. Here, we used the biosynthesis system of the lantibiotic nisin to synthesize a two lipid II binding motifs-containing lantibiotic, termed TL19, which contains the N-terminal lipid II binding motif of nisin and the distinct C-terminal lipid II binding motif of one peptide of the two-component haloduracin (i.e. HalA1). Further characterization demonstrated that (i) TL19 exerts 64-fold stronger antimicrobial activity against E. faecium than nisin (1-22), which has only one lipid II binding site, and (ii) both the N- and C-terminal domains are essential for the potent antimicrobial activity of TL19, as evidenced by mutagenesis of each single and double domains. These results show the feasibility of a new approach to synthesize potent lantibiotics with two different lipid II binding motifs to treat specific antibiotic-resistant pathogens.




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Evaluation of the efficacy of antibiotic combinations against multidrug-resistant Pseudomonas aeruginosa in automated time-lapse microscopy and static time-kill experiments [Clinical Therapeutics]

Objectives: Antibiotic combination therapy is used for severe infections caused by multidrug-resistant (MDR) Gram-negative bacteria. Yet, data of which combinations are most effective is lacking. This study aimed to evaluate the in vitro efficacy of polymyxin B in combination with 13 other antibiotics against four clinical strains of MDR Pseudomonas aeruginosa.

Methods: We evaluated the interactions of polymyxin B in combination with amikacin, aztreonam, cefepime, chloramphenicol, ciprofloxacin, fosfomycin, meropenem, minocycline, rifampicin, temocillin, thiamphenicol or trimethoprim by automated time-lapse microscopy using predefined cut-off values indicating inhibition of growth (≤106 CFU/mL) at 24 h. Promising combinations were subsequently evaluated in static time-kill experiments.

Results: All strains were intermediate or resistant to polymyxin B, anti-pseudomonal β-lactams, ciprofloxacin and amikacin. Genes encoding β-lactamases (e.g., blaPAO and blaOXA-50) and mutations associated with permeability and efflux were detected in all strains. In the time-lapse microscopy experiments, positive interactions were found with 39 of 52 antibiotic combination/bacterial strain setups. Enhanced activity was found against all four strains with polymyxin B used in combination with aztreonam, cefepime, fosfomycin, minocycline, thiamphenicol and trimethoprim. Time kill experiments showed additive or synergistic activity with 27 of the 39 tested polymyxin B combinations, most frequently with aztreonam, cefepime, and meropenem.

Conclusion: Positive interactions were frequently found with the tested combinations, also against strains that harboured several resistance mechanisms to the single drugs and with antibiotics that are normally not active against P. aeruginosa. Further study is needed to explore the clinical utility of these combinations.




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Mutations in ArgS arginine-tRNA synthetase confer additional antibiotic-tolerance protection to ESBL-producing Burkholderia thailandensis [Mechanisms of Resistance]

Highly conserved PenI-type class A β-lactamase in pathogenic members of Burkholderia can evolve to extended-spectrum β-lactamase (ESBL), which exhibits hydrolytic activity towards third-generation cephalosporins, while losing its activity towards the original penicillin substrates. We describe three single-amino-acid-substitution mutations in the ArgS arginine-tRNA synthetase that confer extra antibiotic tolerance protection to ESBL-producing Burkholderia thailandensis. This pathway can be exploited to evade antibiotic tolerance induction in developing therapeutic measures against Burkholderia species, targeting their essential aminoacyl-tRNA synthetases.




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Spectrum of Beta-Lactamase Inhibition by the Cyclic Boronate QPX7728, an Ultra-Broad-Spectrum Beta-lactamase Inhibitor of Serine and Metallo Beta-Lactamases: Enhancement of Activity of Multiple Antibiotics Against Isogenic Strains Expressing Single {beta}

QPX7728 is an ultra-broad-spectrum boronic acid beta-lactamase inhibitor with potent inhibition of key serine and metallo beta-lactamases observed in biochemical assays. Microbiological studies using characterized strains were used to provide a comprehensive characterization of the spectrum of beta-lactamase inhibition by QPX7728. The MIC of multiple IV only (ceftazidime, piperacillin, cefepime, ceftolozane and meropenem) and orally bioavailable (ceftibuten, cefpodoxime, tebipenem) antibiotics alone and in combination with QPX7728 (4 μg/ml), as well as comparator agents, were determined against the panels of laboratory strains of P. aeruginosa and K. pneumoniae expressing over 55 diverse serine and metallo beta-lactamases. QPX7728 significantly enhanced the potency of antibiotics against the strains expressing Class A extended spectrum beta-lactamases (CTX-M, SHV, TEM, VEB, PER) and carbapenemases (KPC, SME, NMC-A, BKC-1), consistent with beta-lactamase inhibition demonstrated in biochemical assays. It also inhibits both plasmidic (CMY, FOX, MIR, DHA) and chromosomally encoded (P99, PDC, ADC) Class C beta-lactamases and Class D enzymes including carbapenemases such as OXA-48 from Enterobacteriaceae and OXA enzymes from Acinetobacter baumannii (OXA-23/24/72/58). QPX7728 is also a potent inhibitor of many class B metallo beta-lactamases (NDM, VIM, CcrA1, IMP, GIM but not SPM or L1). Addition of QPX7728 (4 μg/ml) reduced the MICs in a majority of strains to the level observed for the vector alone control, indicative of complete beta-lactamase inhibition. The ultra-broad-spectrum beta-lactamase inhibition profile makes QPX7728 a viable candidate for further development.




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Complex response of the CpxAR two-component system to {beta}-lactams on antibiotic resistance and envelop homeostasis in Enterobacteriaceae [Mechanisms of Resistance]

The Cpx stress response is widespread among Enterobacteriaceae. We have previously reported a mutation in cpxA in a multidrug resistant strain of Klebsiella aerogenes isolated from a patient treated with imipenem. This mutation yields to a single amino acid substitution (Y144N) located in the periplasmic sensor domain of CpxA. In this work, we sought to characterize this mutation in Escherichia coli by using genetic and biochemical approaches. Here, we show that cpxAY144N is an activated allele that confers resistance to β-lactams and aminoglycosides in a CpxR-dependent manner, by regulating the expression of the OmpF porin and the AcrD efflux pump, respectively. We also demonstrate the intimate interconnection between Cpx system and peptidoglycan integrity on the expression of an exogenous AmpC β-lactamase by using imipenem as a cell wall active antibiotic or inactivation of penicillin-binding proteins. Moreover, our data indicate that the Y144N substitution abrogates the interaction between CpxA and CpxP and increase phosphotransfer activity on CpxR. Because the addition of a strong AmpC inducer such as imipenem is known to causes abnormal accumulation of muropeptides (disaccharide-pentapeptide, N-acetylglucosamyl-1,6-anhydro-N-acetylmuramyl-l-alanyl-d-glutamy-meso-diaminopimelic-acid-d-alanyl-d-alanine) in the periplasmic space, we propose these molecules activate the Cpx system by displacing CpxP from the sensor domain of CpxA. Altogether, these data could explain why large perturbations to peptidoglycan caused by imipenem lead to mutational activation of the Cpx system and bacterial adaptation through multidrug resistance. These results also validate the Cpx system, in particular the interaction between CpxA and CpxP, as a promising therapeutic target.




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Nonclinical Pharmacokinetics, Protein Binding, and Elimination of KBP-7072, An Aminomethylcycline Antibiotic in Animal Models [Pharmacology]

KBP-7072 is a semi-synthetic aminomethylcycline with broad-spectrum activity against Gram-positive and Gram-negative pathogens including multidrug resistant bacterial strains. The pharmacokinetics (PK) of KBP-7072 after oral and intravenous (IV) administration of single and multiple doses were investigated in animal models including during fed and fasted states and also evaluated the protein binding and excretion characteristics. In Sprague-Dawley (SD) rats, Beagle dogs, and CD-1 mice, KBP-7072 demonstrated a linear PK profile after administration of single oral and IV and multiple oral doses. Oral bioavailability ranged from 12% to 32%. Mean Tmax ranged from 0.5 to 4 hours, and mean half-life ranged from approximately 6 to 11 hours. Administration of oral doses in the fed state resulted in a marked reduction in Cmax and AUC compared with dosing in fasted animals. The mean bound fractions of KBP-7072 were 77.5%, 69.8%, 64.5%, 69.3%, and 69.2% in mouse, rat, dog, monkey, and human plasma, respectively. Following a single 22.5 mg/kg oral dose of KBP-7072 in SD rats, cumulative excretion in feces was 64% and in urine was 2.5% of the administered dose. The PK results in animal models are consistent with single and multiple ascending dose studies in healthy volunteers and confirm the suitability of KBP-7072 for once daily oral and IV administration in clinical studies.




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Development of probiotic formulations for oral candidiasis prevention: Gellan gum as a carrier to deliver Lactobacillus paracasei 28.4 [Experimental Therapeutics]

Probiotics might provide an alternative approach for the control of oral candidiasis. However, studies on the antifungal activity of probiotics in the oral cavity are based on the consumption of yogurt or other dietary products, and there is a necessary to use appropriate biomaterials and specific strains to obtain probiotic formulations targeting local oral administration. In this study, we impregnated gellan gum, a natural biopolymer used as a food-additive, with a probiotic and investigated its antifungal activity against Candida albicans. Lactobacillus paracasei 28.4, a strain recently isolated from the oral cavity of a caries-free individual, was incorporated in several concentrations of gellan gum (0.6% to 1%). All tested concentrations could incorporate L. paracasei cells while maintaining bacterial viability. Probiotic/gellan formulations were stable for 7 days when stored at room temperature or 4°C. Long-term storage of bacteria-impregnated gellan gum was achieved when L. paracasei 28.4 was lyophilized. The probiotic/gellan formulations provided a release of L. paracasei cells over 24 hours that was sufficient to inhibit the growth of C. albicans with effects dependent on the cell concentrations incorporated into gellan gum. The probiotic/gellan formulations also had inhibitory activity against Candida spp. biofilms by reducing the number of Candida spp. cells (p < 0.0001), decreasing the total biomass (p = 0.0003), and impairing hyphae formation (p = 0.0002), compared to the control group which received no treatment. Interestingly, probiotic formulation of 1% w/v gellan gum provided an oral colonization of L. paracasei in mice with approximately 6 log of CFU/mL after 10 days. This formulation inhibited the C. albicans growth (p < 0.0001), prevented the development of candidiasis lesions (p = 0.0013), and suppressed inflammation (p = 0.0006) when compared to the mice not treated in the microscopic analysis of the tongue dorsum. These results indicate that gellan gum is a promising biomaterial and can be used as a carrier system to promote oral colonization for probiotics that prevent oral candidiasis.




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Prediction of antibiotic susceptibility for urinary tract infection in a hospital setting [Epidemiology and Surveillance]

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.




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In vitro and in vivo antibiotic capacity of two host defence peptides [Mechanisms of Action]

Two non-amidated host defence peptides named Pin2[G] and FA1 were evaluated against three types of pathogenic bacteria; two isolated from diabetic foot ulcer patients, Staphylococcus aureus UPD13 and Pseudomonas aeruginosa UPD3, and another from a commercial collection, Salmonella enterica serovar Typhimurium (ATCC 14028). In vitro experiments showed that the antimicrobial performance of the synthetic peptides, Pin2[G] and FA1, was modest, although FA1 was more effective than Pin2[G]. In contrast Pin2[G] had superior in vivo anti-infective activity to FA1 in rabbit wound infections by the diabetic foot ulcer pathogens S. aureus UPD13 and P. aeruginosa UPD3. Indeed, Pin2[G] reduced bacterial colony counts of both S. aureus UPD13 and P. aeruginosa UPD3 by >100,000-fold after 48-72 h on skin wounds of infected rabbits, while in similar infected wounds, FA1 had no major effects at 72-96 h of treatment. Ceftriaxone was equally effective vs. Pseudomonas but less effective vs. S. aureus infections. Additionally, the two peptides were evaluated in mice against intragastrically inoculated S. enterica ser. Typhimurium (ATCC 14028). Only Pin2[G], at 0.56 mg/kg, was effective in reducing systemic (liver) infection by >67-fold, equivalent to the effect of treatment with levofloxacin. Pin2[G] showed superior immunomodulatory activity in increasing chemokine production by a human bronchial cell line and suppressing poly(IC)-induced pro-inflammatory IL6 production. These data showed that the in vitro antimicrobial activity of these peptides was not correlated with their in vivo anti-infective activity, and suggest that other factors such as immunomodulatory activity were more important.




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Clinically relevant epithelial lining fluid concentrations of meropenem with ciprofloxacin provide synergistic killing and resistance suppression of hypermutable Pseudomonas aeruginosa in a dynamic biofilm model [Pharmacology]

Treatment of exacerbations of chronic Pseudomonas aeruginosa infections in patients with cystic fibrosis (CF) is highly challenging due to hypermutability, biofilm formation and an increased risk of resistance emergence. We evaluated the impact of ciprofloxacin and meropenem as monotherapy and in combination in the dynamic in vitro CDC biofilm reactor (CBR). Two hypermutable P. aeruginosa strains, PAOmutS (MICciprofloxacin 0.25 mg/L, MICmeropenem 2 mg/L) and CW44 (MICciprofloxacin 0.5 mg/L, MICmeropenem 4 mg/L), were investigated for 120h. Concentration-time profiles achievable in epithelial lining fluid (ELF) following FDA-approved doses were simulated in the CBR. Treatments were ciprofloxacin 0.4g every 8h as 1h-infusions (80% ELF penetration), meropenem 6 g/day as continuous infusion (CI; 30% and 60% ELF penetration) and their combinations. Counts of total and less-susceptible planktonic and biofilm bacteria and MICs were determined. Antibiotic concentrations were quantified by UHPLC-PDA. For both strains, all monotherapies failed with substantial regrowth and resistance of planktonic (≥8log10 CFU/mL) and biofilm (>8log10 CFU/cm2) bacteria at 120h (MICciprofloxacin up to 8 mg/L, MICmeropenem up to 64 mg/L). Both combination treatments demonstrated synergistic bacterial killing of planktonic and biofilm bacteria of both strains from ~48h onwards and suppressed regrowth to ≤4log10 CFU/mL and ≤6log10 CFU/cm2 at 120h. Overall, both combination treatments suppressed amplification of resistance of planktonic bacteria for both strains, and biofilm bacteria for CW44. The combination with meropenem at 60% ELF penetration also suppressed amplification of resistance of biofilm bacteria for PAOmutS. Thus, combination treatment demonstrated synergistic bacterial killing and resistance suppression against difficult-to-treat hypermutable P. aeruginosa strains.




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Inhibition of SARS-CoV-2 infection by the cyclophilin inhibitor Alisporivir (Debio 025) [Antiviral Agents]

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.




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Antibiotic Use and Outcomes in Children in the Emergency Department With Suspected Pneumonia

BACKGROUND AND OBJECTIVES:

Antibiotic therapy is often prescribed for suspected community-acquired pneumonia (CAP) in children despite a lack of knowledge of causative pathogen. Our objective in this study was to investigate the association between antibiotic prescription and treatment failure in children with suspected CAP who are discharged from the hospital emergency department (ED).

METHODS:

We performed a prospective cohort study of children (ages 3 months–18 years) who were discharged from the ED with suspected CAP. The primary exposure was antibiotic receipt or prescription. The primary outcome was treatment failure (ie, hospitalization after being discharged from the ED, return visit with antibiotic initiation or change, or antibiotic change within 7–15 days from the ED visit). The secondary outcomes included parent-reported quality-of-life measures. Propensity score matching was used to limit potential bias attributable to treatment selection between children who did and did not receive an antibiotic prescription.

RESULTS:

Of 337 eligible children, 294 were matched on the basis of propensity score. There was no statistical difference in treatment failure between children who received antibiotics and those who did not (odds ratio 1.0; 95% confidence interval 0.45–2.2). There was no difference in the proportion of children with return visits with hospitalization (3.4% with antibiotics versus 3.4% without), initiation and/or change of antibiotics (4.8% vs 6.1%), or parent-reported quality-of-life measures.

CONCLUSIONS:

Among children with suspected CAP, the outcomes were not statistically different between those who did and did not receive an antibiotic prescription.




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Antibiotic Use and Outcomes in Children in the Emergency Department With Suspected Pneumonia

Matthew J. Lipshaw
Apr 1, 2020; 145:e20193138-e20193138
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Prolonged Duration of Initial Empirical Antibiotic Treatment Is Associated With Increased Rates of Necrotizing Enterocolitis and Death for Extremely Low Birth Weight Infants

C. Michael Cotten
Jan 1, 2009; 123:58-66
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Factors Influencing the Composition of the Intestinal Microbiota in Early Infancy

John Penders
Aug 1, 2006; 118:511-521
ARTICLES




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Schuylkill Speaks: Senior biology major Steve Shalamanda eyes optometry degree

Senior Steven Shalamanda began his education at Penn State Schuylkill knowing he was interested in becoming an optometrist. But it was this high-achieving biology student’s internship with a local practice that affirmed his vision for the future. In fall 2020, Shalamanda will begin his doctor of optometry program at the Pennsylvania College of Optometry.




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Parliament Committee to hear from leading microbiologist on the impact of COVID-19

A Scottish Parliament Committee will take evidence from a leading microbiologist, Professor Hugh Pennington, as it begins its scrutiny of the Government’s response to COVID-19.




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Coronairus: Bharat Biotech-led group to develop human antibodies as therapy for COVID-19 infections

Therefore, an alternate therapeutic regimen for early deployment is critical, the vaccine-maker said in the statement.




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As trade war looms, EU sets limits on Palm Oil in Biofuels

The biggest palm oil producers stepped up lobbying in Brussels to defend its future in the European market.




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Hyderabad biotech firm working on intranasal vaccine against Covid-19 with US company, varsity

The institute has a high-level bio-safety facility designated Biosafety Level 3 Agriculture with the ability to safely handle and study pathogens like highly pathogenic influenza viruses and the novel coronavirus.




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ICMR approves Molbio Dignostics’ Covid-19 test kit

The highly contagious novel coronavirus has resulted in over 70,000 deaths globally so far. The Moblio test kit will enable same day testing and reporting, enabling patient isolation when necessary.




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Bharat Biotech to lead monoclonal antibodies project for Covid-19 therapy

This project brings together National Centre for Cell Science (NCCS), Pune; Indian Institute of Technology, Indore, and Gurgaon-based PredOmix Technologies in a collaborative mode for a public health emergency.




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ICMR teams up with Bharat Biotech to develop COVID-19 vaccine

The death toll due to COVID-19 rose to 1,981 and the number of cases climbed to 59,662 in the country on Saturday, the Health Ministry said.




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Canada Requires Biometrics of Foreigners to Apply for Permanent Residence

Canada has opened Service centers across the country for taking biometrics related to foreign nationals who apply to stay in it.A New Approach for EfficiencyBefore December 3rd, such immigration candidates, who were applying away from Canada, needed…





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Zoetis to Expand BioDevice Solutions for Poultry Industry with Acquisition of Hatchery Automation Technology Leader KL Products, Inc.







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T20-2020 BIOVIA Direct 2020: Support of BIOVIA Direct on Oracle Exadata Database Machine

BIOVIA Direct 2020




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T23-2020 Notification regarding BIOVIA Pipeline Pilot Chemistry 2019 Hot Fix 3

BIOVIA Pipeline Pilot Chemistry SDK 2019