cte Prevention of Invasive Cronobacter Infections in Young Infants Fed Powdered Infant Formulas By pediatrics.aappublications.org Published On :: 2012-10-08T00:07:34-07:00 Invasive Cronobacter infection is a rare but devastating disease known to affect hospitalized premature or immunocompromised infants fed powdered infant formulas (PIFs). PIF labels imply that powdered formulas are safe for healthy, term infants if the label instructions are followed.Cronobacter can also infect healthy, term infants in the first months of life, even if PIF label instructions are followed. Invasive Cronobacter infection is extremely rare in exclusively breastfed infants or those fed commercially sterile, ready-to-feed formulas. (Read the full article) Full Article
cte Variation in Occult Injury Screening for Children With Suspected Abuse in Selected US Children's Hospitals By pediatrics.aappublications.org Published On :: 2012-10-15T00:08:07-07:00 Clinical guidelines for the evaluation of suspected physical abuse in young children emphasize performing radiologic imaging to screen for occult fractures. Little is known about the degree of adherence to guidelines for screening for occult fractures among pediatric hospitals.Adherence to guidelines related to screening for occult fractures in young children diagnosed with physical abuse varies significantly among pediatric hospitals. Use of screening in infants who have injuries associated with a high likelihood of abuse also varies among pediatric hospitals. (Read the full article) Full Article
cte Pediatric Chronic Nonbacterial Osteomyelitis By pediatrics.aappublications.org Published On :: 2012-10-15T00:08:10-07:00 Chronic nonbacterial osteomyelitis (CNO) is a sterile inflammatory bone disorder of presumed autoimmune or autoinflammatory etiology predominantly affecting children. There are limited data on the characteristics and optimal treatment of CNO in the United States.A US-based cohort of pediatric CNO patients revealed high rates of personal and familial autoimmunity. Coexisting autoimmunity was a risk factor for widespread involvement. Response to nonsteroidal antiinflammatory drugs was inferior to that with immunosuppressive and biologic agents. (Read the full article) Full Article
cte Secondary Sexual Characteristics in Boys: Data From the Pediatric Research in Office Settings Network By pediatrics.aappublications.org Published On :: 2012-10-20T00:05:41-07:00 Recent investigations of pubertal onset in US girls suggest earlier maturation. The situation for US boys is unknown, and existing investigations are outdated and lack information on a key physical marker of male puberty: testicular enlargement.US boys appear to be developing secondary sexual characteristics and achieving testicular enlargement 6 months to 2 years earlier than commonly used norms, with African American boys entering Tanner stages 2 to 4 earlier than white or Hispanic boys. (Read the full article) Full Article
cte Carnitine Palmitoyltransferase I and Sudden Unexpected Infant Death in British Columbia First Nations By pediatrics.aappublications.org Published On :: 2012-10-22T00:07:42-07:00 The CPT1A p.P479L variant is common to northern aboriginal populations, leads to reduced enzyme activity, and may be associated with increased infant mortality rates.The p.P479L variant is common in British Columbia First Nations with a coastal distribution correlated with regions of high infant mortality. Homozygotes display an altered acylcarnitine profile and are overrepresented in cases of sudden unexpected infant death in these areas. (Read the full article) Full Article
cte Expected Body Weight in Adolescents: Comparison Between Weight-for-Stature and BMI Methods By pediatrics.aappublications.org Published On :: 2012-11-12T00:08:24-08:00 In adolescents with eating disorders, percent expected body weight (EBW) is used for diagnosis and to make clinical decisions. The assumption is that the weight-for-stature (WFS) and BMI methods of determining EBW are equivalent, but that may not be true.This study demonstrates that EBWWFS is ~3.5% higher than EBWBMI. Differences are most pronounced at extremes of height. Compared with the EBWWFS method, sensitivity of EBWBMI to detect those <75% EBW is low. (Read the full article) Full Article
cte Prevalence and Characteristics of Rib Fractures in Ex-preterm Infants By pediatrics.aappublications.org Published On :: 2012-11-19T00:07:58-08:00 Osteopathy of prematurity continues to occur in preterm infants. Osteopathy of prematurity can cause rib fractures in ex-preterm infants.Rib fractures in ex-preterm infants are often posterior and multiple. Posterior rib fractures may not be diagnostic of nonaccidental injury in ex-preterm infants. (Read the full article) Full Article
cte Readability, Suitability, and Characteristics of Asthma Action Plans: Examination of Factors That May Impair Understanding By pediatrics.aappublications.org Published On :: 2012-12-03T00:07:40-08:00 National asthma treatment guidelines include the recommendation that all asthma patients receive a written asthma action plan. No previous study has sought to examine the readability, suitability, and content of asthma action plans within a nationally representative sample.Although variability was found across written asthma action plans, and improvements in readability, suitability, and content are needed, there were also many common elements that would support a move to a single universal standard action plan. (Read the full article) Full Article
cte Characteristics of the Strengths and Difficulties Questionnaire in Preschool Children By pediatrics.aappublications.org Published On :: 2013-01-06T23:57:27-08:00 Validated questionnaires can improve the identification of psychosocial problems among children. The Strengths and Difficulties Questionnaire (SDQ) 3-4 is a promising option. However, no studies are available that examine the psychometric properties of the SDQ parent form 3-4.The results of this study show that the SDQ 3-4 is a valid tool for the identification of psychosocial problems in preschool-aged children. (Read the full article) Full Article
cte Biochemical Characteristics and Risk Factors for Insulin Resistance at Different Levels of Obesity By pediatrics.aappublications.org Published On :: 2013-03-11T00:06:33-07:00 Although the metabolic syndrome is associated with obesity, not all obese children have insulin resistance and metabolic syndrome, and nonobese children may develop these abnormalities. Associated factors have not been well described.There was a 6.6% prevalence of nonobese children who were insulin-resistant, associated with a family history of hypertension. There was a 21.3% prevalence of obese who were not insulin-resistant, associated with a low waist circumference. (Read the full article) Full Article
cte Teen Birth Rates in Sexually Abused and Neglected Females By pediatrics.aappublications.org Published On :: 2013-03-25T01:07:29-07:00 Despite downward trends, the US teen birth rate remains among the highest of developed nations. Childhood maltreatment may place teens at higher risk, but inferences are weak given a lack of prospective study and control for alternative explanations.Results from the first controlled, prospective study of nulliparous teenagers confirm that victims of maltreatment are more than twice as likely as their nonmaltreated peers to experience a teen childbirth after controlling for demographic confounds and other known risk factors. (Read the full article) Full Article
cte Characteristics of Screen Media Use Associated With Higher BMI in Young Adolescents By pediatrics.aappublications.org Published On :: 2013-04-08T00:06:54-07:00 Rates of screen media use have risen in parallel with rates of obesity among young people. Identifying the specific characteristics of media use that are associated with obesity can help elucidate the explanatory processes and inform effective interventions.This study examines the associations between BMI and characteristics of media use including the type of device, duration of use, and attention to the medium. The more that participants paid primary attention to television, the higher their BMI. (Read the full article) Full Article
cte Bacteremia Risk and Outpatient Management of Febrile Patients With Sickle Cell Disease By pediatrics.aappublications.org Published On :: 2013-05-13T00:07:01-07:00 Before the introduction of conjugate pneumococcal vaccines and routine penicillin prophylaxis, febrile patients with sickle cell disease were known to have a 3% to 5% risk of bacteremia. Consequently, hospitalization rates for febrile episodes are >70%.We observed no mortality or morbidity among those managed completely as outpatients, and bacteremia occurred in <1%. Physicians should strongly consider outpatient management of febrile children with sickle cell disease if there are no other indications for admission. (Read the full article) Full Article
cte Differences in Characteristics of Dying Children Who Receive and Do Not Receive Palliative Care By pediatrics.aappublications.org Published On :: 2013-06-10T00:08:51-07:00 Pediatric palliative care (PC) can be beneficial to children with life-threatening conditions and their families by providing symptom management and control, sibling support, bereavement services, spiritual guidance, support in decision-making about limiting burdensome medical interventions, and advance directives.Little is known about actual receipt of PC by dying children. This study compares characteristics of dying children by receipt of PC and highlights underserved patient groups who could be targeted to improve access. (Read the full article) Full Article
cte Inpatient Characteristics of the Child Admitted With Chronic Pain By pediatrics.aappublications.org Published On :: 2013-07-01T00:07:01-07:00 Children with chronic pain complaints seem to represent an increasing portion of general pediatric inpatient services. Few data exist, however, on the characteristics of this population, their length of stay, or the best approach to their evaluation and management.This study defines the demographic, diagnostic, procedural, and episode of care characteristics for children admitted to the acute care setting with chronic pain syndromes. Admission rates are rising, lengths of stay are substantial, and comorbid diagnoses are common. (Read the full article) Full Article
cte Characteristics of Pain in Children and Youth With Cerebral Palsy By pediatrics.aappublications.org Published On :: 2013-07-15T00:07:09-07:00 Pain in children with cerebral palsy is underrecognized and undertreated and negatively affects quality of life. Communication challenges and multiple pain etiologies complicate management. There is a wide range of pain prevalence reported in the literature (14% to 73%).The impact of pain on activities in children with cerebral palsy across a wide age range and motor abilities is investigated. Physician-identified causes of pain are systematically assessed and reported. Concordance of physician and caregiver identification of pain is evaluated. (Read the full article) Full Article
cte Unexpected Relationship Between Tympanometry and Mortality in Children With Nontraumatic Coma By pediatrics.aappublications.org Published On :: 2013-08-12T00:07:18-07:00 Tympanometry provides a measure of middle ear function. There has been no description of the relationship between measurements of middle ear function in the absence of gross anatomic defects and clinical outcome among children with acute nontraumatic coma.This study reveals an unexpected association between abnormal middle ear function and death in childhood acute coma. These findings call for more investigations on the relationship between middle and inner ear anatomy and function and intracranial dynamics and clinical outcomes. (Read the full article) Full Article
cte Clinical Characteristics of Pediatric Myasthenia: A Surveillance Study By pediatrics.aappublications.org Published On :: 2013-09-09T00:07:22-07:00 Pediatric myasthenia encompasses a group of rare and underdiagnosed conditions affecting the neuromuscular junction. Symptoms include fluctuating skeletal muscle weakness, which can progress to respiratory failure if left untreated. The autoimmune form of this condition, in particular, is treatable.This study describes the incidence, clinical features, diagnostic testing, and treatment trends of pediatric myasthenia in Canada, which have not been previously reported in the literature. (Read the full article) Full Article
cte Potential Asphyxia and Brainstem Abnormalities in Sudden and Unexpected Death in Infants By pediatrics.aappublications.org Published On :: 2013-11-11T00:07:42-08:00 Certain characteristics of the sleep environment increase the risk for sleep-related, sudden, and unexplained infant death. These characteristics have the potential to generate asphyxia. The relationship between the deaths occurring in these environments and neurochemical abnormalities in the brainstem that may impair protective responses to asphyxia is unknown.We report neurochemical brainstem abnormalities underlying cases of sudden infant death that are associated with and without potential asphyxial situations in the sleep environment at death. The means to detect and treat these abnormalities in infants at risk are needed. (Read the full article) Full Article
cte Epidemiology of Bacteremia in Febrile Infants in the United States By pediatrics.aappublications.org Published On :: 2013-11-11T00:07:40-08:00 Bacteremia occurs in 2.2% of febrile infants who have a blood culture drawn. Regional data suggest that Escherichia coli, group B Streptococcus, and Staphylococcus aureus are leading causes; however, the geographic boundaries of these data limit universal applicability.This is the first national study examining epidemiology of bacteremia in febrile infants admitted to a general inpatient unit. The most common pathogens were Escherichia coli (42%), group B Streptococcus (23%), and Streptococcus pneumoniae (6%). No Listeria monocytogenes was identified. (Read the full article) Full Article
cte Violent Film Characters' Portrayal of Alcohol, Sex, and Tobacco-Related Behaviors By pediatrics.aappublications.org Published On :: 2013-12-09T00:06:37-08:00 Youth are frequent consumers of movies that contain high levels of violence, and violent content in films, especially those rated PG-13, has been increasing over time.Content analyses seldom examine how violence is portrayed with other health risk behaviors, such smoking, drinking, and sex. This study presents an innovative way to characterize on-screen violent content and demonstrates the extent to which risk behaviors co-occur within films. (Read the full article) Full Article
cte Characteristics of Youth Seeking Emergency Care for Assault Injuries By pediatrics.aappublications.org Published On :: 2013-12-09T00:06:36-08:00 The emergency department (ED) is a critical contact location for youth violence interventions. Information on the characteristics of youth, motivations for fights leading to the injury, as well as previous health service utilization of assault-injured youth seeking care is lacking.Assault-injured youth are characterized in a systematic sample demonstrating frequent ED use and the need to address substance use and lethal means of force in interventions; context and motivations for the fight are novel and will inform intervention efforts. (Read the full article) Full Article
cte Prospective Evaluation of a Clinical Pathway for Suspected Appendicitis By pediatrics.aappublications.org Published On :: 2013-12-30T00:06:59-08:00 Although appendicitis is the most common surgical cause of abdominal pain in pediatrics, its diagnosis remains elusive. When evaluated independently, clinical scoring systems and ultrasonography have been shown to have low to moderate sensitivity in the diagnosis of appendicitis.Our study evaluated the accuracy of a clinical practice guideline combining the Samuel’s pediatric appendicitis score and selective ultrasonography as the primary imaging modality for children with suspected appendicitis. Our clinical pathway demonstrated high sensitivity and specificity. (Read the full article) Full Article
cte 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
cte Empiric Combination Therapy for Gram-Negative Bacteremia By pediatrics.aappublications.org Published On :: 2014-04-07T00:06:46-07:00 Existing data do not demonstrate a need for combination therapy after antimicrobial susceptibility data indicate adequate in vitro activity with β-lactam monotherapy. However, the role of empirical combination therapy for the treatment of Gram-negative bacteremia in children remains unsettled.We conducted a retrospective, propensity-score matched study demonstrating no improvement in 10-day mortality of children who have Gram-negative bacteremia receiving empirical β-lactam and aminoglycoside combination therapy compared with β-lactam monotherapy, unless the bacteremic episode was attributable to a multidrug-resistant organism. (Read the full article) Full Article
cte United States Birth Weight Reference Corrected For Implausible Gestational Age Estimates By pediatrics.aappublications.org Published On :: 2014-04-28T00:07:23-07:00 Population-based references of birth weight for gestational age are useful indices of birth size in clinical and research settings.This article uses 2009–2010 US natality data and corrects for likely errors in gestational age dating to yield an up-to-date birth weight for gestational age reference. (Read the full article) Full Article
cte Characteristics of a Pediatric Hospice Palliative Care Program Over 15 Years By pediatrics.aappublications.org Published On :: 2014-08-25T00:07:22-07:00 Palliative care is an increasingly important element of pediatric care for children with noncurable, terminal conditions. Freestanding hospices represent one model of care provision; however, little research on this approach has been conducted.This report documents the experience of North America’s first freestanding hospice over 15 years to better understand the characteristics of children and families enrolled and to establish baseline information for future studies and program planning. (Read the full article) Full Article
cte Characteristics of Recurrent Utilization in Pediatric Emergency Departments By pediatrics.aappublications.org Published On :: 2014-09-15T00:06:28-07:00 Although frequent utilizers of emergency departments (EDs) are targeted for quality improvement initiatives across the United States, little is known about the health services these patients receive in the ED.Eight percent of children account for 24% of ED visits and 31% of all costs. Frequent utilizers of pediatric EDs, especially infants without a chronic condition, are least likely to need medications, testing, and hospital admission during their ED visits. (Read the full article) Full Article
cte Bacterial Prevalence and Antimicrobial Prescribing Trends for Acute Respiratory Tract Infections By pediatrics.aappublications.org Published On :: 2014-09-15T00:06:28-07:00 Many pediatric acute respiratory tract infections (ARTI) are viral and do not require antimicrobial treatment. Recent estimates of antimicrobial overprescribing for these infections, defined based on the published bacterial disease prevalence among all ARTI, are not available.Based on the published bacterial prevalence rates for pediatric ARTI, antimicrobial agents are prescribed almost twice as often as expected to outpatients nationally, amounting to an estimated 11.4 million potentially preventable antimicrobial prescriptions annually. (Read the full article) Full Article
cte Prevalence and Characteristics of Fetal Alcohol Spectrum Disorders By pediatrics.aappublications.org Published On :: 2014-10-27T00:06:33-07:00 Most studies of fetal alcohol syndrome and fetal alcohol spectrum disorders (FASD) prevalence in the general population of the United States have been carried out using passive methods (surveillance or clinic-based studies), which underestimate rates of FASD.Using active case ascertainment methods among children in a representative middle class community, rates of fetal alcohol syndrome and total FASD are found to be substantially higher than most often cited estimates for the general US population. (Read the full article) Full Article
cte Etiology of Childhood Bacteremia and Timely Antibiotics Administration in the Emergency Department By pediatrics.aappublications.org Published On :: 2015-03-09T00:05:25-07:00 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) Full Article
cte Outcomes of Infants Born to Women Infected With Hepatitis B By pediatrics.aappublications.org Published On :: 2015-04-20T00:05:24-07:00 Timely immunoprophylaxis and completion of the 3-dose hepatitis B vaccine series represents the cornerstone of perinatal hepatitis B prevention. Immunoprophylaxis for infants born to hepatitis B surface antigen–positive mothers reduces up to 95% of perinatal hepatitis B virus infections.Despite recommended immunoprophylaxis, perinatal hepatitis B virus infection occurs among ~1% of infants. Infants born to mothers who are younger, hepatitis B e-antigen positive, or who have a high viral load or infants who receive <3 hepatitis B vaccine doses are at greatest risk of infection. (Read the full article) Full Article
cte Outcomes of Infants With Indeterminate Diagnosis Detected by Cystic Fibrosis Newborn Screening By pediatrics.aappublications.org Published On :: 2015-05-11T00:05:25-07:00 Little is known about the prevalence or outcomes of infants with indeterminate diagnostic results after a positive cystic fibrosis (CF) newborn screen (CF transmembrane conductance regulator–related metabolic syndrome [CRMS]).CRMS accounted for 15.7% of newborn screened diagnoses in the CF Patient Registry from 2010 to 2012 (CRMS:CF ratio = 5.0:1.0). Although most infants were healthy, some infants demonstrated clinical features concerning for CF. (Read the full article) Full Article
cte Estimated Number of Infants Detected and Missed by Critical Congenital Heart Defect Screening By pediatrics.aappublications.org Published On :: 2015-05-11T00:05:25-07:00 Newborn screening for critical congenital heart defects (CCHDs) has been implemented in many hospitals, yet there is uncertainty about the number of infants with CCHDs that might be detected through universal implementation of newborn CCHD screening in the United States.We estimated that ~875 infants with CCHDs might be detected, and ~880 missed, annually through universal CCHD screening in the United States. Increases in prenatal diagnosis are unlikely to substantially impact the number of infants detected through CCHD screening. (Read the full article) Full Article
cte Pneumococcal Conjugate Vaccine and Clinically Suspected Invasive Pneumococcal Disease By pediatrics.aappublications.org Published On :: 2015-06-15T00:06:46-07:00 Conventional invasive pneumococcal disease (IPD) definition using laboratory confirmation lacks sensitivity. Using a vaccine-probe design, the FinIP trial showed that IPD disease burden and vaccine-preventable disease incidence were fourfold higher when a more sensitive outcome, clinically suspected IPD, was used.Vaccine-preventable disease incidence (ie, absolute reduction due to PCV10 vaccination) during routine vaccination program was threefold with the more sensitive outcome of clinically suspected IPD compared with the conventional IPD definition. This has major implications for cost-effectiveness of PCVs. (Read the full article) Full Article
cte Emergency Department Visits for Self-Inflicted Injuries in Adolescents By pediatrics.aappublications.org Published On :: 2015-06-15T00:06:46-07:00 Self-harm behavior is a major public health problem and a leading cause of death in adolescents. The majority of patients who self-injure do not die, but they are at increased risk for a successful future suicide attempt.Emergency department visits for self-inflicted injuries in adolescents increased from 2009 to 2012, whereas visits for self-inflicted firearm injuries decreased. The presence of any comorbid condition increased risk for self-harm, indicating that increased attempts at prevention may be warranted in these young people. (Read the full article) Full Article
cte Critical Elements in the Medical Evaluation of Suspected Child Physical Abuse By pediatrics.aappublications.org Published On :: 2015-06-22T00:06:55-07:00 Previous research has described important variability in the medical evaluation of suspected child physical abuse. This variability may contribute to bias and reduce reliability in the medical diagnosis of abuse.A panel of child abuse pediatricians participated in a Delphi Process, defining critical elements for the medical evaluation of suspected physical abuse in children. Results can be used to reduce practice variability that may contribute to potential bias in evaluation. (Read the full article) Full Article
cte Identifying Priorities for Mental Health Interventions in War-Affected Youth: A Longitudinal Study By pediatrics.aappublications.org Published On :: 2015-07-06T00:06:48-07:00 War-affected youth often suffer from multiple co-occurring mental health problems. The relationship of these conditions to later mental health has yet to be thoroughly investigated. There is a need to explore potential targets for mental health interventions.After controlling for preexisting conditions and contemporary confounders, internalizing (depression and anxiety) remained the major predictor of future mental health symptoms (internalizing symptoms, prosocial attitudes/behaviors, and posttraumatic stress symptoms). Interventions targeting internalizing in war-affected youth hold promise. (Read the full article) Full Article
cte Incidence and Characteristics of Autoimmune Hepatitis By pediatrics.aappublications.org Published On :: 2015-10-19T00:07:47-07:00 Pediatric autoimmune hepatitis is an uncommon condition; children and youth can present with a diverse and insidious clinical course and biochemical features. Response to treatment is generally good, and transplantation is rarely needed.This population-based study adds knowledge regarding the incidence of pediatric autoimmune hepatitis in Canada, as well as a description of diagnostic and therapeutic approaches among centers. Long-term outcomes are also described. (Read the full article) Full Article
cte Characteristics of Physicians Who Dismiss Families for Refusing Vaccines By pediatrics.aappublications.org Published On :: 2015-11-02T00:06:44-08:00 The American Academy of Pediatrics discourages providers from dismissing families who refuse vaccines for their children, yet some providers continue to do so.We show that ~1 in 5 pediatricians dismiss families who refuse vaccines, and there is significant regional variation in the practice. Dismissing families for refusing vaccines was also associated with stricter state nonmedical exemption policies. (Read the full article) Full Article
cte Understanding the impacts of unexpected shift to digital learning By news.psu.edu Published On :: Mon, 04 May 2020 12:16 -0400 The unexpected transition to online classes due to the COVID-19 pandemic has prompted many changes for undergraduate students and their instructors. To understand the magnitude of these impacts and potentially improve digital learning, researchers in the Penn State School of Engineering Design and Professional Programs have received a $196,136 grant from the National Science Foundation. Full Article
cte The Best Academic Schools in Tennessee Feature the Best Character Program in the Country By feedproxy.google.com Published On :: Tue, 11 Dec 2018 00:00:00 +0000 Valor Collegiate Academies has been in the top 5 percent of Tennessee schools on growth and achievement every year since it started in 2014. But Tom visited Valor because of the well-regarded Valor Compass, a holistic human-development program. Full Article Professionaldevelopment
cte College of Agricultural Sciences stays connected with alumni during pandemic By news.psu.edu Published On :: Fri, 01 May 2020 15:32 -0400 Penn State’s College of Agricultural Sciences is staying connected to alumni during the COVID-19 pandemic by moving its monthly Alumni Society board meetings and other alumni activities online. Full Article
cte Efficacy of early oral switch with beta-lactams for low-risk Staphylococcus aureus bacteremia. [Clinical Therapeutics] By aac.asm.org Published On :: 2020-02-03T08:23:03-08:00 Objectives. The aim of this study was to assess the safety of early oral switch (EOS) prior to 14 days for low-risk Staphylococcus aureus bacteremia (LR-SAB), which is the primary treatment strategy employed at our institution. Usually recommended therapy is 14 days of intravenous (IV) antibiotics.Methods. All patients with SAB at our hospital were identified between 1 January 2014 and 31 December 2018. Those meeting low-risk criteria (healthcare-associated, no evidence of deep infection or demonstrated involvement of prosthetic material, and no further positive blood cultures after 72-hours) were included in the study. The primary outcome was occurrence of a SAB-related complication within 90 days.Results. There were 469 SAB episodes during the study period, 100 (21%) of whom met inclusion criteria. EOS was performed in 84 patients. In this group, line infection was the source in 79%, methicillin-susceptible S. aureus caused 95% of SABs and 74% of patients received IV flucloxacillin. The median duration of IV and oral antibiotics in the EOS group was 5 (IQR 4-6) and 10 days (IQR 9-14), respectively. Seventy-one percent of patients received flucloxacillin as their EOS agent. Overall, 86% of oral step-down therapy was with beta-lactams. One patient (1%) undergoing EOS had SAB relapse within 90 days. No deaths attributable to SAB occurred within 90 days.Conclusions. In this low MRSA prevalence LR-SAB cohort, EOS was associated with a low incidence of SAB-related complications. This was achieved with oral beta-lactam therapy in most patients. Larger prospective studies are needed to confirm these findings. Full Article
cte 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
cte Biochemical Characterization of QPX7728, a New Ultra-Broad-Spectrum Beta-lactamase Inhibitor of Serine and Metallo-Beta-Lactamases [Mechanisms of Resistance] By aac.asm.org Published On :: 2020-03-09T08:34:13-07:00 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. Full Article
cte In Vitro and In Vivo Characterization of Potent Antileishmanial Methionine Aminopeptidase-1 Inhibitors [Experimental Therapeutics] By aac.asm.org Published On :: 2020-03-16T08:17:37-07:00 Leishmania major is the causative agent of cutaneous leishmaniasis (CL). No human vaccine is available for CL and current drug regimens present several drawbacks such as emerging resistance, severe toxicity, medium effectiveness, and/or high cost. Thus, the need for better treatment options against CL is a priority. In the present study, we validate the enzyme methionine aminopeptidase-1 (MetAP1), a metalloprotease that catalyzes the removal of N-terminal methionine from peptides and proteins, as a chemotherapeutic target against CL infection. The in vitro antileishmanial activity of eight novel MetAP1 inhibitors (OJT001-OJT008) were investigated. Three compounds OJT006, OJT007, and OJT008 demonstrated potent anti-proliferative effect in macrophages infected with L. major amastigotes and promastigotes at submicromolar concentrations, with no cytotoxicity against host cells. Importantly, the leishmanicidal effect was diminished by almost 10-fold in transgenic L. major promastigotes overexpressing MetAP1LM in comparison to wild-type promastigotes. Furthermore, the in vivo activity of OJT006, OJT007, and OJT008 were investigated in L. major-infected BALB/c mice. In comparison to the control group, OJT008 significantly decreased footpad parasite load by 86%, and exhibited no toxicity against in treated mice. We propose MetAP1 inhibitor OJT008 as a potential chemotherapeutic candidate against CL infection caused by L. major infection. Full Article
cte 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
cte 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
cte Emergence of the phenicol exporter gene fexA in Campylobacter coli and Campylobacter jejuni of animal origin [Letters] By aac.asm.org Published On :: 2020-03-30T10:04:32-07:00 Bacteria of the genus Campylobacter are major foodborne pathogens which have become increasingly resistant to clinically important antimicrobial agents (1).... Full Article