drug Correction: Sequerra, Goyal et al., "NMDA Receptor Signaling Is Important for Neural Tube Formation and for Preventing Antiepileptic Drug-Induced Neural Tube Defects" By www.jneurosci.org Published On :: 2018-11-28T09:30:21-08:00 Full Article
drug Garcia sentenced to 33 months: Charged with importing drugs into Ketchikan By www.ketchikandailynews.com Published On :: Full Article
drug Former champ Lance Mackey wiped from 2020 Iditarod standings over failed drug test By www.cbc.ca Published On :: Fri, 8 May 2020 15:46:42 EDT Veteran musher Lance Mackey has had his 21st place finish in this year's Iditarod Trail Sled Dog Race vacated because of a failed drug test, race officials announced Thursday. Full Article News/Canada/North
drug Man convicted of double murder in Fort Frances charged in $2.2M Winnipeg drug bust By www.cbc.ca Published On :: Wed, 6 May 2020 11:42:58 EDT Two men are charged in connection with an illegal drug distribution operation after Winnipeg police seized more than $2.2 million worth of methamphetamine, cocaine and ecstasy. Full Article News/Canada/Manitoba
drug NIH clinical trial evaluates antiviral plus anti-inflammatory drug for COVID-19 By www.news-medical.net Published On :: Fri, 08 May 2020 23:53:00 -0400 A randomized, controlled clinical trial evaluating the safety and efficacy of a treatment regimen of the investigational antiviral remdesivir plus the anti-inflammatory drug baricitinib for coronavirus disease 2019 (COVID-19) has begun. Full Article
drug Fentanyl found in P.E.I. drugs linked to 3 overdoses in 1 day By www.cbc.ca Published On :: Fri, 8 May 2020 13:12:05 EDT P.E.I.'s Chief Public Health Officer Dr. Heather Morrison says the powerful and potentially deadly drug fentanyl has been found in street drugs in the province. Full Article News/Canada/PEI
drug Woman at centre of deadly drugstore stabbing could be allowed to live in community: review board By www.cbc.ca Published On :: Thu, 7 May 2020 16:37:03 EDT A woman found not criminally responsible for fatally stabbing a stranger in the heart at the makeup counter of a Toronto drugstore five years ago could ultimately be allowed to live in the community if the mental health facility where she is staying decides she can, the Ontario Review Board says. Full Article News/Canada/Toronto
drug Hamilton couple face drug trafficking charges after search warrant executed on their home By www.cbc.ca Published On :: Fri, 8 May 2020 15:07:13 EDT A search warrant executed by Hamilton police vice and drugs officers at an address in the city’s east end has resulted in the arrest of a couple and multiple charges, police said in a Friday release. Full Article News/Canada/Hamilton
drug What the Orphan Drug Act Has Done Lately for Children With Rare Diseases: A 10-Year Analysis By pediatrics.aappublications.org Published On :: 2012-02-27T00:08:27-08:00 Rare diseases in childhood can be debilitating and require lifelong care. Since 1983, the Orphan Drug Act incentives have stimulated the development and significantly improved the availability of treatment products for patients with rare diseases.We report an increasing pediatric orphan product designations and approvals from 2000 to 2009. The trend indicates that the Orphan Drug Act has continued to address this important unmet need. (Read the full article) Full Article
drug Trends of Outpatient Prescription Drug Utilization in US Children, 2002-2010 By pediatrics.aappublications.org Published On :: 2012-06-18T00:07:31-07:00 A wide variety of prescription drugs are prescribed to US children. Although one of the steps in assessing the risk/benefit of therapies in the pediatric population is to understand how they are used, pediatric drug utilization is not well characterized.By using large prescription databases, this study examines the frequency and patterns of national outpatient drug utilization (acute and chronic medications) in US infants, children, and adolescents for 2002 through 2010. (Read the full article) Full Article
drug Pediatric Versus Adult Drug Trials for Conditions With High Pediatric Disease Burden By pediatrics.aappublications.org Published On :: 2012-07-23T00:07:50-07:00 Many drugs are not approved for use in pediatric patients and there is limited evidence on their safety and efficacy in children. Furthermore, there is concern that the quality of pediatric trials is inferior compared with adult trials.For conditions with a high disease burden in children, only a small proportion of clinical drug trials study pediatric patients. Most pediatric trials are not funded by industry, and the deficiency of evidence is largest in developing countries. (Read the full article) Full Article
drug One-Year Outcomes of Prenatal Exposure to MDMA and Other Recreational Drugs By pediatrics.aappublications.org Published On :: 2012-08-20T00:07:44-07:00 3,4-Methylenedioxymetham-phetamine (MDMA, ecstasy) is a widely used recreational drug affecting the serotonergic system. Preclinical studies indicate learning/memory problems with fetal exposure. Human infant prenatal exposure was related to alterations in gender ratio and poorer motor development at 4 months.This is the first study documenting that heavier prenatal 3,4-methylenedioxymethamphetamine exposure predicts poorer infant mental and motor development at 12 months with significant, persistent neurotoxic effects. Language and emotional regulation were unaffected. (Read the full article) Full Article
drug Protective Factors Can Mitigate Behavior Problems After Prenatal Cocaine and Other Drug Exposures By pediatrics.aappublications.org Published On :: 2012-11-26T05:32:39-08:00 Prenatal cocaine exposure is associated with the trajectories of childhood behavior problems. Exposure effects may also be related to maternal use of other substances during pregnancy, and risk factors other than prenatal exposure may augment the detrimental cocaine effects.The balance between cumulative risk and protective indexes predicts behavior outcomes, independent of prenatal drug exposure. A high protective index even with a high level of risks can mitigate the detrimental effects of drug exposure on behavior problem trajectory. (Read the full article) Full Article
drug Nonsteroidal Antiinflammatory Drugs in Late Pregnancy and Persistent Pulmonary Hypertension of the Newborn By pediatrics.aappublications.org Published On :: 2012-12-03T00:07:41-08:00 Knowledge is limited regarding the epidemiology of persistent pulmonary hypertension of the newborn (PPHN). Previous work has implicated a host of perinatal risk factors and a few antenatal antecedents of PPHN, including maternal consumption during pregnancy of nonsteroidal antiinflammatory medications.In contrast to results of previous studies, we found no association between PPHN and maternal consumption during late pregnancy of nonsteroidal antiinflammatory drugs in general or ibuprofen in particular. (Read the full article) Full Article
drug Analysis of Pediatric Clinical Drug Trials for Neuropsychiatric Conditions By pediatrics.aappublications.org Published On :: 2013-05-06T00:07:33-07:00 Neuropsychiatric conditions comprise a substantial and growing disease burden among children. Pharmacotherapy represents an important treatment option for these conditions, although most drugs are not approved for use in children.Very few drug trials studying neuropsychiatric conditions focus on children. Furthermore, these trials examine and provide pediatric evidence for only a fraction of all available drugs in the treatment of common neuropsychiatric conditions. (Read the full article) Full Article
drug Adult Prescription Drug Use and Pediatric Medication Exposures and Poisonings By pediatrics.aappublications.org Published On :: 2013-06-03T00:07:02-07:00 Medication ingestions are increasing among children despite a number of public health interventions. The majority of these poisonings are related to prescription as opposed to over-the-counter medications.Rising rates of poisonings in children are strongly correlated with rising use of hypoglycemics, antihyperlipidemics, β-blockers, and opioids among adults. These events are associated with considerable health care utilization, both in terms of emergency department visits and hospital admissions. (Read the full article) Full Article
drug Risk Factors and Outcomes for Multidrug-Resistant Gram-Negative Bacteremia in the NICU By pediatrics.aappublications.org Published On :: 2014-01-13T00:07:01-08:00 There is a perception that Gram-negative bacilli (GNB) bloodstream infection is increasing in the NICU, and those infections caused by a multidrug-resistant (MDR) strain are a growing threat to hospitalized patients.Exposure to broad-spectrum antibiotics is the most important risk factor for MDR GNB bacteremia, which is associated with higher mortality. Neonates with risk factors for bacteremia caused by a MDR GNB strain may benefit from empirical antimicrobial therapy with carbapenem. (Read the full article) Full Article
drug Validity of Brief Screening Instrument for Adolescent Tobacco, Alcohol, and Drug Use By pediatrics.aappublications.org Published On :: 2014-04-21T00:06:54-07:00 The widely disseminated National Institute on Alcohol Abuse and Alcoholism screening tool for adolescent alcohol use was developed based on epidemiologic data. It has not been validated in a clinical sample and does not screen for tobacco or drug use.This study found that a measure that expanded the National Institute on Alcohol Abuse and Alcoholism adolescent alcohol use tool to include tobacco and drugs was sensitive and specific for identifying substance use disorders in a pediatric clinic patient population. (Read the full article) Full Article
drug Adverse Drug Event-Related Emergency Department Visits Associated With Complex Chronic Conditions By pediatrics.aappublications.org Published On :: 2014-05-19T00:06:58-07:00 Children who experience outpatient adverse drug events represent 0.5% of pediatric emergency department visits. The subset of children with complex chronic conditions often take multiple medications, but the incidence and severity of adverse drug events in these children is unknown.Children with complex chronic conditions have a higher risk of emergency department visits related to adverse drug events, compared with other children. The implicated drugs with the highest rates include psychotropic agents, antimicrobial agents, anticonvulsants, hormones/steroids, and analgesics. (Read the full article) Full Article
drug Impact of Pediatric Exclusivity on Drug Labeling and Demonstrations of Efficacy By pediatrics.aappublications.org Published On :: 2014-07-14T00:07:16-07:00 Most therapeutic products used in children have not been studied in that population. There is a need for special incentives and market protection (pediatric exclusivity) to compensate drug sponsors for studying these products in children.Of 189 products studied under pediatric exclusivity, 173 (92%) received new labeling information. Pediatric efficacy was not established for 78 (42%), including 81% of oncology drugs. Probability of demonstrating efficacy was related to therapeutic area and year exclusivity was granted. (Read the full article) Full Article
drug Small Geographic Area Variations in Prescription Drug Use By pediatrics.aappublications.org Published On :: 2014-08-11T00:06:54-07:00 Prescribing patterns in the US pediatric population are changing but not uniformly. A detailed examination of prescription variation is needed to better understand pharmacotherapy of children and to inform future exploration of the causes and consequences of diverse practices.We examine pediatric pharmacotherapy and quantify payer type differences and small geographic area variation. Substantial payer-type differences and regional variations were found, likely reflecting local practice cultures. Variation was greatest for medications used in situations of diagnostic and therapeutic uncertainty. (Read the full article) Full Article
drug Potential Drug-Drug Interactions in Infant, Child, and Adolescent Patients in Children's Hospitals By pediatrics.aappublications.org Published On :: 2014-12-15T00:06:45-08:00 Hospitalized pediatric patients are often exposed to many medications during an inpatient admission. Drug–drug interactions may increase the risk of developing medication-related adverse drug events, leading to serious clinical morbidity and mortality.Exposure to "major" potential drug–drug interactions occurs in 41% of pediatric hospitalizations in children’s hospitals. One-half of all these exposures were due to less common specific drug pairs (≤3% of patients exposed per hospital day) and thus may be less clinically familiar. (Read the full article) Full Article
drug Assessment of drug resistance during phase 2b clinical trials of presatovir in adults naturally infected with respiratory syncytial virus [Antiviral Agents] By aac.asm.org Published On :: 2020-02-18T08:15:40-08:00 Background: This study summarizes drug resistance analyses in 4 recent phase 2b trials of the respiratory syncytial virus (RSV) fusion inhibitor presatovir in naturally infected adults.Methods: Adult hematopoietic cell transplant (HCT) recipients, lung transplant recipients, or hospitalized patients with naturally acquired, laboratory-confirmed RSV infection were enrolled in 4 randomized, double-blind, placebo-controlled studies with study-specific presatovir dosing. Full-length RSV F sequences amplified from nasal swabs obtained at baseline and postbaseline were analyzed by population sequencing. Substitutions at RSV fusion inhibitor resistance-associated positions are reported.Results: Genotypic analyses were performed on 233 presatovir-treated and 149 placebo-treated subjects. RSV F variant V127A was present in 8 subjects at baseline. Population sequencing detected treatment-emergent substitutions in 10/89 (11.2%) HCT recipients with upper and 6/29 (20.7%) with lower respiratory tract infection, 1/35 (2.9%) lung transplant recipients, and 1/80 (1.3%) hospitalized patients treated with presatovir; placebo-treated subjects had no emergent resistance-associated substitutions. Subjects with substitutions at resistance-associated positions had smaller decreases in viral load during treatment relative to those without, but similar clinical outcomes.Conclusions: Subject population type and dosing regimen may have influenced RSV resistance development during presatovir treatment. Subjects with vs without genotypic resistance development had decreased virologic responses but comparable clinical outcomes. Full Article
drug A histone methyltransferase inhibitor can reverse epigenetically acquired drug resistance in the malaria parasite Plasmodium falciparum [Mechanisms of Resistance] By aac.asm.org Published On :: 2020-03-16T08:17:37-07:00 Malaria parasites invade and replicate within red blood cells (RBCs), extensively modifying their structure and gaining access to the extracellular environment by placing the plasmodial surface anion channel (PSAC) into the RBC membrane. Expression of members of the cytoadherence linked antigen gene 3 (clag3) family is required for PSAC activity, a process that is regulated epigenetically. PSAC is a well-established route of uptake for large, hydrophilic antimalarial compounds and parasites can acquire resistance by silencing clag3 gene expression, thereby reducing drug uptake. We found that exposure to sub-IC50 concentrations of the histone methyltransferase inhibitor chaetocin caused substantial changes in both clag3 gene expression and RBC permeability, reversing acquired resistance to the antimalarial compound blasticidin S that is transported through PSAC. Chaetocin treatment also altered progression of parasites through their replicative cycle, presumably by changing their ability to modify chromatin appropriately to enable DNA replication. These results indicate that targeting histone modifiers could represent a novel tool for reversing epigenetically acquired drug resistance in P. falciparum. Full Article
drug Effect of drug pressure on promoting the emergence of antimalarial resistant parasites among pregnant women in Ghana [Mechanisms of Resistance] By aac.asm.org Published On :: 2020-03-16T08:17:37-07:00 Continuous spread of antimalarial drug resistance is a threat to current chemotherapy efficacy. Therefore, characterizing the genetic diversity of drug resistance markers is needed to follow treatment effectiveness and further update control strategies. Here, we genotyped Plasmodium falciparum resistance gene markers associated with sulfadoxine-pyrimethamine (SP) and artemisinin-based combination therapy (ACT) in isolates from pregnant women in Ghana. The prevalence of the septuple IRNI-A/FGKGS/T pfdhfr/pfdhps haplotypes including the pfdhps A581G and A613S/T mutations was high at delivery among post-SP treatment isolates (18.2%) compared to those of first-antenatal care (before initiation of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP); 6.1%; p = 0.03). Regarding the pfk13 marker gene, two non-synonymous mutations (N458D and A481C) were detected at positions previously related to artemisinin resistance in isolates from Southeast-Asia. These mutations were predicted in silico to alter the stability of the pfk13 propeller-encoding domain. Overall, these findings highlight the need for intensified monitoring and surveillance on additional mutations associated with increased SP resistance as well as emergence of resistance against artemesinin derivatives. Full Article
drug Significant efficacy of single low dose primaquine compared to stand alone artemisinin combination therapy in reducing gametocyte carriage in Cambodian patients with uncomplicated multidrug resistant Plasmodium falciparum malaria [Epidemiology and Surveil By aac.asm.org Published On :: 2020-03-16T08:17:37-07:00 Since 2012, single low dose of primaquine (SLDPQ, 0.25mg/kg) has been recommended with artemisinin-based combination therapies, as first-line treatment of acute uncomplicated Plasmodium falciparum malaria, to interrupt its transmission, especially in low transmission settings of multidrug, including artemisinin, resistance. Policy makers in Cambodia have been reluctant to implement this recommendation due to primaquine safety concerns and lack of data on its efficacy.In this randomized controlled trial, 109 Cambodians with acute uncomplicated P. falciparum malaria received dihydroartemisinin-piperaquine (DP) alone or combined with SLDPQ on the first treatment day. Transmission-blocking efficacy of SLDPQ was evaluated on Days 0, 1, 2, 3, 7, 14, 21, 28 and recrudescence by reverse transcriptase polymerase chain reaction (RT-PCR) (gametocyte prevalence) and membrane-feeding assays with Anopheles minimus mosquitoes (gametocyte infectivity). Without the influence of recrudescent infections, DP+SLDPQ reduced gametocyte carriage 3 fold compared to DP. Of 48 patients tested on Day 0, only three patients were infectious to mosquitoes (~6%). Post-treatment, three patients were infectious: on D14 (3.5%, 1/29), and on the first and seventh day of recrudescence (8.3%, 1/12 for each); this overall low infectivity precluded our ability to assess its transmission blocking efficacy.Our study confirms effective gametocyte clearance of SLDPQ when combined with DP in multidrug resistant P. falciparum and the negative impact of recrudescent infections due to poor DP efficacy. Artesunate-mefloquine (ASMQ) has replaced DP and ASMQ-SLDPQ has been deployed to treat all P. falciparum symptomatic patients to further support the elimination of multidrug resistant P. falciparum in Cambodia. Full Article
drug Evaluation of the efficacy of antibiotic combinations against multidrug-resistant Pseudomonas aeruginosa in automated time-lapse microscopy and static time-kill experiments [Clinical Therapeutics] By aac.asm.org Published On :: 2020-03-16T08:17:37-07:00 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. Full Article
drug Imipenem population pharmacokinetics: therapeutic drug monitoring data collected in critically ill patients with or without extracorporeal membrane oxygenation [Pharmacology] By aac.asm.org Published On :: 2020-04-06T08:49:26-07:00 Carbapenem pharmacokinetic profiles are significantly changed in critically ill patients because of the drastic variability of the patients' physiological parameters. Published population PK studies have mainly focused on specific diseases and the majority of these studies had small sample sizes. The aim of this study was to develop a population PK model of imipenem in critically ill patients that estimated the influence of various clinical and biological covariates and the use of Extracorporeal Membrane Oxygenation (ECMO) and Continuous Renal Replacement Therapy (CRRT). A two-compartment population PK model with Creatinine clearance (CrCL), body weight (WT), and ECMO as fixed effects was developed using the non-linear mixed effect model (NONMEM). A Monte Carlo simulation was performed to evaluate various dosing schemes and different levels of covariates based on the pharmacokinetic/pharmacodynamic index (f%T>MIC) for the range of clinically relevant minimum inhibitory concentrations(MICs). The results showed that there may be insufficient drug use in the clinical routine drug dose regimen, and 750mg Q6h could achieve a higher treatment success rate. The blood concentrations of imipenem in ECMO patients were lower than that of non-ECMO patients, therefore dosage may need to be increased. The dosage may need adjustment for patients with CrCL ≤ 70ml/min, but dose should be lowered carefully to avoid the insufficient drug exposure. Dose adjustment is not necessary for patients within the WT ranging from 50-80 kg. Due to the large variation in PK profile of imipenem in critically ill patients, TDM should be carried out to optimize drug regimens. Full Article
drug 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
drug Safety, Pharmacokinetics, and Drug:Drug Interaction Potential of Intravenous Durlobactam, a {beta}-lactamase Inhibitor, in Healthy Subjects [Pharmacology] By aac.asm.org Published On :: 2020-04-13T08:15:30-07:00 Durlobactam (DUR, also known as ETX2514) is a novel β-lactamase inhibitor with broad activity against Ambler class A, C, and D β-lactamases. Addition of DUR to sulbactam (SUL) in vitro restores SUL activity against clinical isolates of Acinetobacter baumannii. The safety and pharmacokinetics (PK) of DUR alone and with SUL and/or imipenem/cilastatin (IMI/CIL) were evaluated in healthy subjects. This was a randomized, placebo-controlled study. In Part A, subjects including an elderly cohort (DUR 1 g) received single ascending doses of DUR 0.25-8 g. In Part B, multiple ascending dose of DUR 0.25-2 g were administered every 6 hours (q6h) for 29 doses. In Parts C and D, the drug-drug interaction (DDI) potential, including safety, of DUR (1 g) with SUL (1 g) and/or IMI/CIL (0.5/0.5 g) was investigated after single and multiple doses. Plasma and urine concentrations of DUR, SUL, and IMI/CIL were determined. Among 124 subjects, DUR was generally safe and well tolerated either alone or in combination with SUL and/or IMI/CIL. After single and multiple doses, DUR demonstrated linear dose proportional exposure across the studied dose ranges. Renal excretion was a predominant clearance mechanism. No drug:drug interaction potential was identified between DUR and SUL and/or IMI/CIL. SUL-DUR, 1 g (of each component) administered q6h with a 3 hour IV infusion, is under development for the treatment of serious infections due to A. baumannii. Full Article
drug Epidemiological study on prevalence, serovar diversity, multi-drug resistance and CTX-M-type extended-spectrum {beta}-lactamases of Salmonella spp. from patients with diarrhea, food of animal origin, and pets in several provinces of China [Epidemiology an By aac.asm.org Published On :: 2020-04-20T08:36:46-07:00 A total of 2,283 Salmonella spp. isolates were recovered from 18,334 samples including patients with diarrhea, food of animal origin and pets across 5 provinces of China. The highest prevalence of Salmonella spp. was detected in chicken meats (39.3%, 486/1,237). Fifteen serogroups and 66 serovars were identified, with Typhimurium and Enteritidis being the most dominant. Most (85.5%, 1,952/2,283) isolates exhibited resistant to ≥ 1 antimicrobial and 56.4% were multi-drug resistant (MDR). A total of 222 isolates harbored extended-spectrum β-lactamases (ESBLs), 200 of which were CTX-M-type that were mostly detected from chicken meat and turtle fecal. Overall, eight blaCTX-M genes were identified, with blaCTX-M-65, blaCTX-M-123, blaCTX-M-14, blaCTX-M-79, and blaCTX-M-130 being the most prevalent. Totally, 166 of the 222 ESBL-producing isolates had amino acid substitutions in GyrA (S83Y, S83F, D87G, D87N, and D87Y) and ParC (and S80I), whilst the PMQR-encoding genes oqxA/B, qepA, and qnrB/S were detected in almost all isolates. Of the fifteen sequence types (STs) identified in the 222 ESBLs, ST17, ST11, ST34, and ST26 ranked among the top 5 in the number of isolates. Our study revealed considerable serovars diversity, high prevalence of co-occurrence of MDR determinants, including CTX-M-type ESBLs, QRDRs mutations and PMQR genes. This is the first report of CTX-M-130 Salmonella spp. from patients with diarrhea and QRDRs mutations from turtle fecal samples. Our study emphasizes the importance of actions, both in the health care settings and in the veterinary medicine sector, to control the dissemination of MDR, especially the CTX-M Salmonella spp. isolates. Full Article
drug Advanced quantification methods to improve the 18b dormancy model for assessing the activity of tuberculosis drugs in vitro. [Clinical Therapeutics] By aac.asm.org Published On :: 2020-04-27T08:14:57-07:00 One of the reasons for the lengthy tuberculosis (TB) treatment is the difficult to treat non-multiplying mycobacterial subpopulation. In order to assess the ability of (new) TB drugs to target this subpopulation, we need to incorporate dormancy models in our pre-clinical drug development pipeline. In most available dormancy models it takes a long time to create a dormant state and it is difficult to identify and quantify this non-multiplying condition.The Mycobacterium tuberculosis 18b strain might overcome some of these problems, because it is dependent on streptomycin for growth and becomes non-multiplying after 10 days of streptomycin starvation, but still can be cultured on streptomycin-supplemented culture plates. We developed our 18b dormancy time-kill kinetic model to assess the difference in the activity of isoniazid, rifampicin, moxifloxacin and bedaquiline against log-phase growth compared to the non-multiplying M. tuberculosis subpopulation by CFU counting including a novel AUC-based approach as well as time-to-positivity (TTP) measurements.We observed that isoniazid and moxifloxacin were relatively more potent against replicating bacteria, while rifampicin and high dose bedaquiline were equally effective against both subpopulations. Moreover, the TTP data suggest that including a liquid culture-based method could be of additional value as it identifies a specific mycobacterial subpopulation that is non-culturable on solid media.In conclusion, the results of our study underline that the time-kill kinetics 18b dormancy model in its current form is a useful tool to assess TB drug potency and thus has its place in the TB drug development pipeline. Full Article
drug Distribution of linezolid in tuberculosis lesions in patients with spinal multidrug-resistant tuberculosis [Pharmacology] By aac.asm.org Published On :: 2020-05-04T08:49:24-07:00 Linezolid has strong antimicrobial activity against the multidrug-resistant (MDR) strains of Mycobacterium tuberculosis. Little is known about the distribution of linezolid in tuberculosis (TB) lesions in patients with MDR-TB. The aim of this study is to evaluate the distribution of linezolid in TB lesions in patients with spinal MDR-TB. Nine patients with spinal MDR-TB were enrolled prospectively from August 2019 to February 2020. The patients received a linezolid-containing anti-TB treatment regimen and needed surgery for the removal of TB lesions. During the operation, nine blood samples, eight diseased bone tissue samples, seven pus samples and four granulation tissue samples were collected simultaneously and 2 h after the oral administration of 600 mg of linezolid. Linezolid concentrations in plasma, diseased bone tissue, pus, and granulation tissue samples were subjected to high-performance liquid chromatography–tandem mass spectrometry. At sample collection, the mean concentrations of linezolid in plasma, diseased bone tissue, pus, and granulation tissue samples of the nine patients were 11.14 ± 5.82, 5.94 ± 4.27, 11.09 ± 4.58, 14.08 ± 10.61 mg/L, respectively. The mean ratios of linezolid concentration in diseased bone/plasma, pus/plasma, and granulation/plasma were 53.84%, 91.69%, and 103.57%, respectively. The mean ratios of linezolid concentration in pus/plasma and granulation/plasma were higher than those in diseased bone/plasma, and the difference was statistically significant (t =-2.810, p = 0.015; t =-4.901, p = 0.001). In conclusion, linezolid had different concentration distributions in different types of TB infected tissues in patients with spinal MDR-TB. Full Article
drug Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs [Antiviral Agents] By aac.asm.org Published On :: 2020-05-04T08:49:24-07:00 Drug repositioning is the only feasible option to address the COVID-19 global challenge immediately. We screened a panel of 48 FDA-approved drugs against SARS-CoV-2 which were pre-selected by an assay of SARS-CoV and identified 24 potential antiviral drug candidates against SARS-CoV-2 infection. Some drug candidates showed very low micromolar IC50s and in particular, two FDA-approved drugs - niclosamide and ciclesonide – were notable in some respects. Full Article
drug Fin24.com | Stocks struggle as antiviral drug hopes fade By www.fin24.com Published On :: Fri, 24 Apr 2020 16:55:37 +0200 Stock markets struggled on Friday as hopes of quickly finding a treatment for coronavirus were dashed, analysts said, and more crushing economic data delivered a body blow to confidence. Full Article
drug Fin24.com | Positive virus drug trial news spurs stocks By www.fin24.com Published On :: Wed, 29 Apr 2020 17:54:49 +0200 The surge in stocks was on the back of positive news from trials being conducted on a potential treatment for the coronavirus. With most economies looking to partially reopen their economies, this brought a jump across most asset classes including commodities. Full Article
drug Pediatric Orphan Drug Indications: 2010-2018 By pediatrics.aappublications.org Published On :: 2020-04-01T01:00:57-07:00 BACKGROUND: Orphan drug development is crucial for children, who are disproportionately affected by rare diseases. Data are lacking on the number, nature, and benefit of recently approved pediatric orphan indications. METHODS: We classified the 402 orphan indications the US Food and Drug Administration approved between 2010 and 2018 as "pediatric" if they were approved for children only or targeted pediatric diseases. We determined the number of unique diseases targeted by pediatric orphan indications and calculated the proportion that were for (1) novel drugs, (2) non-novel drugs approved to treat ≥1 common disease, and (3) non-novel drugs approved only to treat rare diseases. Among pediatric orphan indications eligible for US Food and Drug Administration breakthrough designation (granted to drugs potentially representing major therapeutic advances), we calculated the proportion receiving this designation. RESULTS: Of the 402 orphan indications, 136 (33.8%) were pediatric. These 136 indications targeted 87 unique diseases; 21 diseases were targeted by ≥1 indication. Of the 136 pediatric orphan indications, 60 (44.1%) were for novel drugs, 45 (33.1%) were for non-novel drugs approved to treat ≥1 common disease, and 31 (22.8%) were for non-novel drugs approved only to treat rare diseases. Among 97 indications eligible for breakthrough designation, 20 (20.6%) received this designation. CONCLUSIONS: Recent orphan drug development has increased the availability of treatments for pediatric rare diseases. Most pediatric orphan indications expanded use of existing drugs, and many targeted the same disease. Some indications may represent breakthroughs, but substantial unmet need for treatments remains for most pediatric rare diseases. Full Article
drug Hershey Medical Center joins clinical trial evaluating antiviral drug remdesivir By news.psu.edu Published On :: Thu, 16 Apr 2020 08:00 -0400 Penn State Health Milton S. Hershey Medical Center has begun enrolling participants in an international clinical trial evaluating an investigational antiviral drug, remdesivir, for treatment of coronavirus disease 2019 (COVID-19). Full Article
drug Leaders of Drug Operation Sentenced to Prison By news.delaware.gov Published On :: Fri, 18 Oct 2019 19:34:31 +0000 Other defendants convicted on murder, manslaughter, weapons, and drug charges Three men at the helm of a massive drug dealing enterprise were sentenced to prison in Superior Court. Dwayne White, 36, of Wilmington, Eric Lloyd, 40, of New Castle, and Damon Anderson, 40, were convicted of numerous charges in June for their roles in the […] Full Article Criminal Division Department of Justice Department of Justice Press Releases Attorney General Kathy Jennings Delaware Department of Justice superior court
drug Drug Investigation Leads to Man Wanted For Shooting By news.delaware.gov Published On :: Fri, 03 Jan 2020 18:59:49 +0000 Deputy Attorney General Rebecca Anderson secured a guilty plea and prison sentence for a man wanted for a shooting in Seaford, arrested while police were investigating illegal drug activity in Bridgeville. Teron West, 33, of Seaford, was arrested in July 2019, when members of the Delaware State Police Sussex County Governor’s Task Force executed a […] Full Article Criminal Division Department of Justice Department of Justice Press Releases Attorney General Kathy Jennings Delaware Department of Justice superior court
drug Wilmington jury convicts drug trafficker in murder-for-hire plot By news.delaware.gov Published On :: Fri, 24 Jan 2020 19:23:28 +0000 A Superior Court jury has convicted a Wilmington man for his central role in a June 2016 murder. Witness testimony, cell phone evidence, and collaboration with an FBI task force demonstrated that Brian Wilson, also known as Fudayl Wakim, arranged the murder of Allen Cannon through a $10,000 bounty and a conspiracy with co-defendant Eric […] Full Article Department of Justice Department of Justice Press Releases News
drug Anti-Viral Drug Trio Found To Shorten COVID-19 Illness: Study By www.ndtv.com Published On :: Sat, 09 May 2020 04:23:05 +0530 Researchers in Hong Kong have found that patients suffering milder illness caused by the new coronavirus recover more quickly if they are treated with a three-drug antiviral cocktail soon after... Full Article World
drug Drug proves effective against coronavirus in US study By www.dailystar.com.lb Published On :: 2020-04-29T20:39:00.0000000 An experimental drug has proved effective against the new coronavirus in a major study, shortening the time it takes for patients to recover by four days on average, U. Full Article Health
drug Drug Court Diversion Services By bids.delaware.gov Published On :: 4/30/2020 Agency: HSS Closing Date: 6/11/2020 Full Article
drug 24 Locations in Delaware to Participate in Drug Take-Back Day, April 28, 2018 By news.delaware.gov Published On :: Tue, 24 Apr 2018 20:10:08 +0000 Delaware will hold its 16th Drug Take-Back Day on Saturday, April 28, 2018, to help reduce the risk of prescription medications being diverted for misuse. Delawareans can discard their expired or unused medications at 24 locations statewide between 10 a.m. and 2 p.m. Full Article Division of Public Health Governor John Carney News Office of the Governor Addiction DEA DPH Drug Take Back Day drugs Help Is Here opioids treatment
drug Drug Take-Back Day Event Collects 5,385 Pounds of Unwanted Or Expired Medications By news.delaware.gov Published On :: Wed, 15 May 2019 19:07:33 +0000 DOVER (May 15, 2019) – During the 18th Prescription Drug Take-Back Day event on April 27, 2019, Delaware collected 5,385 pounds of unwanted or expired medicine, according to the U.S. Drug Enforcement Administration (DEA) and the Division of Public Health (DPH). That amount is approximately 1,600 pounds more than the 3,739 pounds collected in October. […] Full Article Delaware Health and Social Services Division of Public Health News DE Division of Public Health Delaware Division of Public Health Drug Take Back Drug Take Back Day Help Is Here opioid epidemic
drug Partnership for Drug-Free Kids, DHSS Bring New Statewide Resources for Families in Crisis By news.delaware.gov Published On :: Wed, 05 Jun 2019 12:54:12 +0000 The Delaware Department of Health and Social Services (DHSS) and Partnership for Drug-Free Kids are collaborating to bring dedicated, science-based resources and support to Delaware families. The two entities will work together to provide innovative, digital resources and one-on-one support to parents and caregivers as they help a loved one struggling with opioids or other […] Full Article Delaware Health and Social Services Department of Services for Children Youth and their Families Governor John Carney Lt. Governor Bethany Hall-Long News Office of the Governor Office of the Lieutenant Governor addiction epidemic atTAcK Addiction Division of Substance Abuse and Mental Health family specialists family support HelpIsHereDE.com hope NAMI Delaware Partnership for Drug-Free Kids
drug DPH Releases First Drug Overdose Mortality Surveillance Report By news.delaware.gov Published On :: Wed, 14 Aug 2019 15:59:04 +0000 WILMINGTON – For the first time, the Delaware Division of Public Health (DPH) through the integration of 12 multi-agency datasets, has developed a demographic picture of the Delawareans who died from drug overdoses in 2017. DPH released the Drug Overdose Mortality Surveillance Report, Delaware, 2017, in Wilmington on Wednesday, Aug. 14, 2019. In addition to […] Full Article Delaware Health and Social Services Division of Public Health News drug overdose opioid epidemic overdose mortality surveillance report public health
drug DPH Encourages Residents to Participate in National Prescription Drug Take-Back Day By news.delaware.gov Published On :: Tue, 22 Oct 2019 17:10:29 +0000 Sat., Oct. 26, 2019: Delaware residents can safely dispose of their unused or expired prescription medications at designated sites throughout the state as part of the 18th National Prescription Drug Take-Back Day. Full Article Division of Public Health DE Division of Public Health Drug Take Back Day Opioid