RESUMO
BACKGROUND: Surgical site infections (SSIs) are a common complication in liver transplant (LT) recipients. Lack of pediatric prophylaxis guidelines results in variation in preventative antibiotic regimens. METHODS: We performed a retrospective observational study of LT recipients <18 years old using a merged data set that included data from the Pediatric Health Information System and the United Network for Organ Sharing between 2006 and 2017. The exposure was defined as the antibiotic(s) received within 24â hours of LT, with 6 categories, ranging from narrow (category 1: cefazolin), to broad). The primary outcome was presence or absence of SSI in the index admission. Mixed-effects logistic regression compared the effectiveness of each category in preventing SSI, relative to category 1. RESULTS: Of the 2586 LT, 284 (11%) met SSI criteria. The SSI rate was higher in the younger subcohort (16.2%) than in the older (8.6%), necessitating a stratified analysis. Antibiotics from category 5 were most commonly used. In the younger subcohort, the adjusted risk was increased in all categories compared with the reference, most notably in category 3 (odds ratio [OR], 2.58 [95% confidence interval: .69-9.59]) and category 6 (2.76 [.66-11.56]). In the older subcohort, estimated ORs were also increased for each category, most notably in category 4 (2.49 [95% confidence interval: .99-6.27]). None of the ORs suggested benefit from broader-spectrum prophylaxis. Our E-value assessment suggests that it's unlikely there is unmeasured confounding by indication to the degree necessary to revert ORs to protective. CONCLUSIONS: There was wide variation in antibiotic prophylaxis. Adjusted analyses did not reveal a protective benefit of broader-spectrum prophylaxis in either subcohort, suggesting that narrower regimens may be adequate.
Assuntos
Antibacterianos , Antibioticoprofilaxia , Transplante de Fígado , Infecção da Ferida Cirúrgica , Humanos , Infecção da Ferida Cirúrgica/prevenção & controle , Estudos Retrospectivos , Transplante de Fígado/efeitos adversos , Masculino , Feminino , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Criança , Antibioticoprofilaxia/métodos , Pré-Escolar , Adolescente , Lactente , Transplantados , Assistência Perioperatória/métodosRESUMO
Data on the potential benefits and risks of induction therapy in pediatric liver transplantation (LT) are limited. This was a retrospective cohort study of 2748 pediatric LT recipients at 26 children's hospitals between January 1, 2006 to May 31, 2017 using data from the pediatric health information system linked to the United Network for Organ Sharing database. The induction regimen was obtained from the pediatric health information system day-by-day pharmacy resource utilization. Cox proportional hazards evaluated the association of induction regimen (none/corticosteroid-only, nondepleting, and depleting) on patient and graft survival. Additional outcomes, including opportunistic infections and posttransplant lymphoproliferative disorder, were studied using multivariable logistic regression. Overall, 64.9% received none/corticosteroid-only induction, whereas 28.1% received nondepleting, 8.3% received depleting, and 2.5% other antibody regimens. Differences in patient characteristics were small, but center practices were heterogeneous. Compared with none/corticosteroid-only induction, nondepleting induction was associated with reduced acute rejection (odd ratio [OR], 0.53; P <.001) but with the increased posttransplant lymphoproliferative disorder (OR, 1.75; P =.021). Depleting induction was associated with improved graft survival (hazard ratio [HR], 0.64; P =.028) but with increased noncytomegalovirus opportunistic infections (OR, 1.46; P =.046). Depleting induction is underused yet may offer long-term benefits in this large multicenter cohort. Greater consensus guidance in this aspect of pediatric LT care is warranted.
Assuntos
Transplante de Fígado , Transtornos Linfoproliferativos , Humanos , Criança , Estados Unidos/epidemiologia , Imunossupressores/uso terapêutico , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Terapia de Imunossupressão/métodos , Anticorpos Monoclonais , Corticosteroides , Transtornos Linfoproliferativos/epidemiologia , Transtornos Linfoproliferativos/etiologia , Rejeição de Enxerto , Sobrevivência de EnxertoRESUMO
Transplant center performance and practice variation for pediatric post-liver transplantation (LT) outcomes other than survival are understudied. This was a retrospective cohort study of pediatric LT recipients who received transplants between January 1, 2006, and May 31, 2017, using United Network for Organ Sharing (UNOS) data that were merged with the Pediatric Health Information System database. Center effects for the acute rejection rate at 1 year after LT (AR1) using UNOS coding and the biliary complication rate at 1 year after LT (BC1) using inpatient billing claims data were estimated by center-specific rescaled odds ratios that accounted for potential differences in recipient and donor characteristics. There were 2216 pediatric LT recipients at 24 freestanding children's hospitals in the United States during the study period. The median unadjusted center rate of AR1 was 36.92% (interquartile range [IQR], 22.36%-44.52%), whereas that of BC1 was 32.29% (IQR, 26.14%-40.44%). Accounting for recipient case mix and donor factors, 5/24 centers performed better than expected with regard to AR1, whereas 3/24 centers performed worse than expected. There was less heterogeneity across the center effects for BC1 than for AR1. There was no relationship observed between the center effects for AR1 or BC1 and center volume. Beyond recipient and allograft factors, differences in transplant center management are an important driver of center AR1 performance, and less so of BC1 performance. Further research is needed to identify the sources of variability so as to implement the most effective solutions to broadly enhance outcomes for pediatric LT recipients.
Assuntos
Transplante de Fígado , Criança , Bases de Dados Factuais , Sobrevivência de Enxerto , Humanos , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Doadores de Tecidos , Transplantados , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Influenza vaccination of healthcare workers (HCWs) has been recommended for more than 30 years. In 2009, HCWs were designated as a priority group by the Centers for Disease Control and Prevention. Current HCW vaccination rates are 78% across all settings and reach approximately 92% among those employed in hospital settings. Over the last decade, it has become clear that mandatory vaccine policies result in maximal rates of HCW immunization. METHODS: In this observational 10-year study, we describe the implementation of a mandatory influenza vaccination policy in a dedicated quaternary pediatric hospital setting by a multidisciplinary team. We analyzed 10 years of available data from deidentified occupational health records from 2009-2010 through the 2018-2019 influenza seasons. Descriptive statistics were performed using Stata v15 and Excel. RESULTS: Sustained increases in HCW immunization rates above 99% were observed in the 10 years postimplementation, in addition to a reduction in exemption requests and healthcare-associated influenza. In the year of implementation, 145 (1.6%) HCWs were placed on temporary suspension for failure to receive the vaccine without documentation of an exemption, with 9 (0.06%) subsequently being terminated. Since then, between 0 and 3 HCWs are terminated yearly for failure to receive the vaccine. CONCLUSIONS: Implementation of our mandatory influenza vaccination program succeeded in successfully increasing the proportion of immunized HCWs at a quaternary care children's hospital, reducing annual exemption requests with a small number of terminations secondary to vaccine refusal. Temporal trends suggest a positive impact on the safety of our patients.
Assuntos
Vacinas contra Influenza , Influenza Humana , Atitude do Pessoal de Saúde , Criança , Pessoal de Saúde , Humanos , Influenza Humana/prevenção & controle , Programas Obrigatórios , Políticas , VacinaçãoRESUMO
Intravenous immunoglobulin (IVIg) therapy is increasingly used in the pediatric population, in particular among children with immune-compromising conditions. Pooled immunoglobulin products are routinely tested for hepatitis B surface antigen (HBsAg) and nucleic acid; however, screening for hepatitis B core antibody (anti-HBc) is not commonly performed. Thus, the administration of IVIg containing anti-HBc to children with immune-compromising conditions may complicate the interpretation of hepatitis B serologic testing in that a positive anti-HBc test may represent passive transfer of antibody from IVIg or may indicate resolved or chronic hepatitis B infection. Due to the risk of hepatitis B reactivation in immunocompromised patients, a positive anti-HBc test must be carefully considered. As part of a quality improvement initiative, we identified and reviewed the records of all pediatric patients at our institution who tested positive for anti-HBc over an 18-month period. Of 44 total patients with positive anti-HBc tests, we found that 22 (50%) had previously received IVIg in the preceding 4 months. All but one of these, 21/22 (95%), went on to receive immunosuppressive therapy (IS). Among the patients who received IS, 19 (86%) had not undergone hepatitis B serologic testing prior to IVIg administration and 16 (73%) did not have subsequent testing to distinguish between passive acquisition of anti-HBc from IVIg and chronic hepatitis B infection. Our single-center experience reveals that a high proportion of positive anti-HBc tests in children are presumed to be because of the passive antibody transfer from IVIg. However, a low proportion of patients undergo confirmatory testing, despite the risk of hepatitis B reactivation during IS. We thus propose a risk-based algorithm for interpretation and monitoring of hepatitis B testing in immunocompromised children.
Assuntos
Anticorpos Anti-Hepatite B/sangue , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Hepatite B/sangue , Hospedeiro Imunocomprometido , Ativação Viral , Adolescente , Algoritmos , Criança , Estudos de Coortes , DNA Viral , Feminino , Hepatite B/diagnóstico , Hepatite B Crônica/sangue , Hepatite B Crônica/diagnóstico , Humanos , Imunização Passiva , Imunoglobulinas Intravenosas/administração & dosagem , Masculino , Programas de Rastreamento , Fatores de RiscoRESUMO
BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is the most common neurobehavioral disorder of childhood, affecting 5-8% of children. It has been observed that these children have poor sedation experiences; however, to date there is minimal research on procedural sedation in this population. AIM: To examine whether children with ADHD required larger doses of propofol for magnetic resonance imaging (MRI) sedation. METHODS: The hospital's administrative billing database was used to identify all billing codes for MRI brain scans (with and without contrast) in children aged between 5 and 12 years over the preceding 5.5 years. The hospital's electronic medical record database provided baseline demographics. The sedation record was reviewed for propofol dose, psychostimulant use, and prescribed dose. All children received a standard weight-based dose of midazolam prior to receiving the necessary amount of propofol. Primary outcome was the dose of propofol administered (mg·kg(-1) ) to achieve adequate sedation. RESULTS: A total of 258 procedures met the inclusion criteria. The sample was 52% male, 74% White, 7.8% Black, 7.8% Hispanic, 4.3% Asian, and 6.2% other. ADHD was documented for 49 procedures with a prevalence of 18.5%. Patients with ADHD were older, more likely to be male, Hispanic, or to report race as 'Refused/Unknown'. Indications for MRI for patients with ADHD varied significantly, with 'Behavioral' and 'Neurocutaneous' being significantly overrepresented in the ADHD group. The average sedative dose for all patients was 2.8 mg·kg(-1) (95% CI 2.62-2.94). Sedative dose was similar among children with and without ADHD diagnosis. CONCLUSIONS: Our study illustrates that children with ADHD do not have higher sedative requirements to achieve a successful brain MRI.
Assuntos
Anestésicos Intravenosos/farmacologia , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Imageamento por Ressonância Magnética , Propofol/farmacologia , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Humanos , MasculinoRESUMO
This white paper provides clinicians and hospital leaders with practical guidance on the prevention and control of viral respiratory infections in the neonatal intensive care unit (NICU). This document serves as a companion to Centers for Disease Control and Prevention Healthcare Infection Control Practices Advisory Committee (HICPAC)'s "Prophylaxis and Screening for Prevention of Viral Respiratory Infections in Neonatal Intensive Care Unit Patients: A Systematic Review." It provides practical, expert opinion and/or evidence-based answers to frequently asked questions about viral respiratory detection and prevention in the NICU. It was developed by a writing panel of pediatric and pathogen-specific experts who collaborated with members of the HICPAC systematic review writing panel and the SHEA Pediatric Leadership Council to identify questions that should be addressed. The document has been endorsed by SHEA, the American Hospital Association (AHA), The Joint Commission, the Pediatric Infectious Diseases Society (PIDS), the Association for Professionals in Infection Control and Epidemiology (APIC), the Infectious Diseases Society of America (IDSA), and the National Association of Neonatal Nurses (NANN).
Assuntos
Doenças Transmissíveis , Infecções Respiratórias , Viroses , Recém-Nascido , Estados Unidos , Criança , Humanos , Unidades de Terapia Intensiva Neonatal , Controle de Infecções , Hospitais , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/prevenção & controleRESUMO
Objectives: Data on triage practices of children admitted to Princess Marina Hospital in Gaborone, Botswana is limited. The inpatient triage, assessment, and treatment score was developed for low resource settings to predict mortality in children. We assess its performance among children admitted to Princess Marina Hospital and their demographic, clinical, and risk factors for death. Methods: This was a secondary data analysis of a prospective cohort study comprising 299 children ages 1 month to 13 years admitted June to September 2018. Descriptive statistics, bivariate analysis, and multivariate logistic regression were used. Sensitivity and specificity data were generated for the inpatient triage, assessment, and treatment score. Results: Thirteen children died (13/284, 4.6%). Comorbidity (adjusted odds ratio 4.0, p = 0.020) and high inpatient triage, assessment, and treatment score (adjusted odds ratio 5.0, p = 0.017) increased odds of death. The area under the receiver operating characteristic curve was 0.81. Using inpatient triage, assessment, and treatment cutoff of 4, the sensitivity, specificity, and likelihood ratio were 31%, 94%, and 5.0, respectively. Conclusion: Implementing the inpatient triage, assessment, and treatment score in low resource settings may improve identification, treatment, and evaluation of the sickest children.
RESUMO
Rotavirus (RV) was a common healthcare-associated infection prior to the introduction of the RV vaccine. Following widespread RV vaccination, healthcare-associated rotavirus cases are rare. We describe an investigation of a cluster of rotavirus infections in a pediatric hospital in which an uncommon genotype not typically circulating in the United States was detected.
Assuntos
Gastroenterite , Infecções por Rotavirus , Vacinas contra Rotavirus , Rotavirus , Criança , Humanos , Lactente , Rotavirus/genética , Hospitais Pediátricos , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/prevenção & controle , Genótipo , VacinaçãoRESUMO
OBJECTIVES: A disproportionate number of neonatal deaths occur in low/middle-income countries, with sepsis a leading contributor of mortality. In this study, we investigate risk factors for mortality in a cohort of high-risk hospitalised neonates in Botswana. Independent predictors for mortality for infants experiencing either a sepsis or a non-sepsis-related death are described. METHODS: This is a prospective observational cohort study with infants enrolled from July to October 2018 at the neonatal unit (NNU) of Princess Marina Hospital (PMH) in Gaborone, Botswana. Data on demographic, clinical and unit-specific variables were obtained. Neonates were followed to death or discharge, including transfer to another hospital. Death was determined to be infectious versus non-infectious based on primary diagnosis listed on day of death by lead clinician on duty. RESULTS: Our full cohort consisted of 229 patients. The overall death rate was 227 per 1000 live births, with cumulative proportion of deaths of 22.7% (n=47). Univariate analysis revealed that sepsis, extremely low birth weight (ELBW) status, hypoxic ischaemic encephalopathy, critical illness and infants born at home were associated with an increased risk of all-cause mortality. Our multivariate model revealed that critical illness (HR 3.07, 95% CI 1.56 to 6.03) and being born at home (HR 4.82, 95% CI 1.76 to 13.19) were independently associated with all-cause mortality. Low birth weight status was independently associated with a decreased risk of mortality (HR 0.24, 95% CI 0.11 to 0.53). There was a high burden of infection in the cohort with more than half of infants (140, 61.14%) diagnosed with sepsis at least once during their NNU admission. Approximately 20% (n=25) of infants with sepsis died before discharge. Our univariate subanalysis of the sepsis cohort revealed that ELBW and critical illness were associated with an increased risk of death. These findings persisted in the multivariate model with HR 3.60 (95% CI 1.11 to 11.71) and HR 2.39 (95% CI 1 to 5.77), respectively. CONCLUSIONS: High rates of neonatal mortality were noted. Urgent interventions are needed to improve survival rates at PMH NNU and to prioritise care for critically ill infants at time of NNU admission, particularly those born at home and/or of ELBW.
Assuntos
Estado Terminal , Sepse , Recém-Nascido , Lactente , Humanos , Botsuana , Estudos de Coortes , Mortalidade Infantil , Fatores de RiscoRESUMO
Objectives: Over the past decade, concerning trends in antimicrobial resistance have emerged in Southern Africa. Given a paucity of pediatric data, our objectives were to (1) describe antibiotic utilization trends at a national referral center in Southern Africa and (2) assess the proportion of patients receiving antibiotics appropriately. In addition, risk factors for inappropriate use were explored. Methods: We performed a prospective cohort study on medical and surgical pediatric patients aged below 13 years admitted to the country's tertiary care referral hospital in Gaborone, Botswana. We collected demographics, clinical, laboratory, and microbiology details, in addition to information on antibiotic use. We separately categorized antibiotic prescriptions using the World Health Organization AWaRe Classification of Access, Watch, and Restrict. Results: Our final cohort of 299 patients was 44% female and 27% HIV-exposed; most (68%) were admitted to the General Pediatrics ward. Infections were a common cause of hospitalization in 29% of the cohort. Almost half of our cohort were prescribed at least one antibiotic during their stay, including 40% on admission; almost half (47%) of these prescriptions were deemed appropriate. At the time of discharge, 52 (21%) patients were prescribed an antibiotic, of which 37% were appropriate. Of all antibiotics prescribed, 42% were from the World Health Organization Access antibiotic list, 58% were from the Watch antibiotic list, and 0% were prescribed antibiotics from the Restrict antibiotic list. Univariate analyses revealed that surgical patients were significantly more likely to have inappropriate antibiotics prescribed on admission. Patients who were treated for diseases for which there was a clinical pathway, or who had blood cultures sent at the time of admission were less likely to have inappropriate antibiotics prescribed. On multivariate analysis, apart from admission to the surgical unit, there were no independent predictors for inappropriate antibiotic use, although there was a trend for critically ill patients to receive inappropriate antibiotics. Conclusion: Our study reveals high rates of antibiotic consumption, much of which was inappropriate. Promising areas for antimicrobial stewardship interventions include (1) standardization of management approaches in the pediatric surgical population and (2) the implementation of feasible and generalizable clinical pathways in this tertiary care facility.
RESUMO
INTRODUCTION: Healthcare-associated viral infections (HAVI) are a common cause of patient harm in the pediatric population. We implemented a HAVI prevention bundle in 2015, which included 6 core elements: caregiver screening, symptom-based isolation, personal protective equipment (PPE), hand hygiene, staff illness procedures, and monitoring of environmental cleanliness. Enhanced bundle elements were introduced at the start of the COVID-19 pandemic, which provided an opportunity to observe the effectiveness of the bundle with optimal adherence to prevention practices, and to measure the impact on respiratory HAVI epidemiology. METHODS: Respiratory HAVIs were confirmed through review of medical records and application of the National Health Safety Network (NHSN) surveillance criteria for upper respiratory infections (URIs) with predetermined incubation periods for unit attribution. Descriptive statistics of the study population were examined, and comparative analyses were performed on demographic and process metrics. Data analysis was conducted using R statistical software. RESULTS: We observed an overall decrease in respiratory HAVI of 68%, with prepandemic rates of 0.19 infections per 1,000 patient significantly decreased to a rate of 0.06 per 1,000 patient days in the pandemic period (P < .01). Rhinovirus made up proportionally more of our respiratory HAVI in the pandemic period (64% vs 53%), with respiratory HAVI secondary only to rhinovirus identified during 8 of 16 months in the pandemic period. Compliance with our HAVI prevention bundle significantly improved during pandemic period. CONCLUSIONS: Enhancement of our HAVI bundle during the COVID-19 pandemic contributed toward significant reduction in nosocomial transmission of respiratory HAVI. Even with prevention practices optimized, respiratory HAVIs secondary to rhinovirus continued to be reported, likely due to the capacity of rhinovirus to evade bundle elements in hospital, and infection prevention efforts at large in the community, leaving vulnerable patients at continued risk.
Assuntos
COVID-19 , Infecção Hospitalar , COVID-19/epidemiologia , COVID-19/prevenção & controle , Criança , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Atenção à Saúde , Humanos , Pandemias/prevenção & controle , RhinovirusRESUMO
Early in the coronavirus disease 2019 (COVID-19) pandemic, the CDC recommended collection of a lower respiratory tract (LRT) specimen for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) testing in addition to the routinely recommended upper respiratory tract (URT) testing in mechanically ventilated patients. Significant operational challenges were noted at our institution using this approach. In this report, we describe our experience with routine collection of paired URT and LRT sample testing. Our results revealed a high concordance between the 2 sources, and that all children tested for SARS-CoV-2 were appropriately diagnosed with URT testing alone. There was no added benefit to LRT testing. Based on these findings, our institutional approach was therefore adjusted to sample the URT alone for most patients, with LRT sampling reserved for patients with ongoing clinical suspicion for SARS-CoV-2 after a negative URT test.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Criança , COVID-19/diagnóstico , Pandemias , Teste para COVID-19 , Sistema RespiratórioAssuntos
Babesia/isolamento & purificação , Babesiose/diagnóstico , Babesiose/patologia , Transmissão de Doença Infecciosa , Reação Transfusional/diagnóstico , Reação Transfusional/patologia , Transplantados , Sangue/parasitologia , Pré-Escolar , Humanos , Hospedeiro Imunocomprometido , Masculino , Microscopia , ParasitemiaRESUMO
OBJECTIVES: Empirical broad-spectrum antibiotics are routinely administered for short durations to children with suspected bacteremia while awaiting blood culture results. Our aim for this study was to estimate the proportion of broad-spectrum antibiotic use accounted for by these "rule-outs." METHODS: The Pediatric Health Information System was used to identify children aged 3 months to 20 years hospitalized between July 2016 and June 2017 who received broad-spectrum antibiotics for suspected bacteremia. Using an electronic definition for a rule-out, we estimated the proportion of all broad-spectrum antibiotic days of therapy accounted for by this indication. Clinical and demographic characteristics, as well as antibiotic choice, are reported descriptively. RESULTS: A total of 67 032 episodes of suspected bacteremia across 42 hospitals were identified. From these, 34 909 (52%) patients were classified as having received an antibiotic treatment course, and 32 123 patients (48%) underwent an antibiotic rule-out without a subsequent treatment course. Antibiotics prescribed for rule-outs accounted for 12% of all broad-spectrum antibiotic days of therapy. Third-generation cephalosporins and vancomycin were the most commonly prescribed antibiotics, and substantial hospital-level variation in vancomycin use was identified (range: 16%-58% of suspected bacteremia episodes). CONCLUSIONS: Broad-spectrum intravenous antibiotic use for rule-out infections appears common across children's hospitals, with substantial hospital-level variation in the use of vancomycin in particular. Antibiotic stewardship programs focused on intervening on antibiotics prescribed for longer durations may consider this novel opportunity to further standardize antibiotic regimens and reduce antibiotic exposure.
RESUMO
The severe acute respiratory coronavirus-2 (SARS-CoV-2) is the cause of the global outbreak of COVID-19. Evidence suggests that the virus is evolving to allow efficient spread through the human population, including vaccinated individuals. Here, we report a study of viral variants from surveillance of the Delaware Valley, including the city of Philadelphia, and variants infecting vaccinated subjects. We sequenced and analyzed complete viral genomes from 2621 surveillance samples from March 2020 to September 2021 and compared them to genome sequences from 159 vaccine breakthroughs. In the early spring of 2020, all detected variants were of the B.1 and closely related lineages. A mixture of lineages followed, notably including B.1.243 followed by B.1.1.7 (alpha), with other lineages present at lower levels. Later isolations were dominated by B.1.617.2 (delta) and other delta lineages; delta was the exclusive variant present by the last time sampled. To investigate whether any variants appeared preferentially in vaccine breakthroughs, we devised a model based on Bayesian autoregressive moving average logistic multinomial regression to allow rigorous comparison. This revealed that B.1.617.2 (delta) showed 3-fold enrichment in vaccine breakthrough cases (odds ratio of 3; 95% credible interval 0.89-11). Viral point substitutions could also be associated with vaccine breakthroughs, notably the N501Y substitution found in the alpha, beta and gamma variants (odds ratio 2.04; 95% credible interval of1.25-3.18). This study thus overviews viral evolution and vaccine breakthroughs in the Delaware Valley and introduces a rigorous statistical approach to interrogating enrichment of breakthrough variants against a changing background. IMPORTANCE SARS-CoV-2 vaccination is highly effective at reducing viral infection, hospitalization and death. However, vaccine breakthrough infections have been widely observed, raising the question of whether particular viral variants or viral mutations are associated with breakthrough. Here, we report analysis of 2621 surveillance isolates from people diagnosed with COVID-19 in the Delaware Valley in southeastern Pennsylvania, allowing rigorous comparison to 159 vaccine breakthrough case specimens. Our best estimate is a 3-fold enrichment for some lineages of delta among breakthroughs, and enrichment of a notable spike substitution, N501Y. We introduce statistical methods that should be widely useful for evaluating vaccine breakthroughs and other viral phenotypes.
Assuntos
COVID-19 , Vacinas , Humanos , SARS-CoV-2 , Teorema de Bayes , Vacinas contra COVID-19 , DelawareRESUMO
The severe acute respiratory coronavirus-2 (SARS-CoV-2) is the cause of the global outbreak of COVID-19. Evidence suggests that the virus is evolving to allow efficient spread through the human population, including vaccinated individuals. Here we report a study of viral variants from surveillance of the Delaware Valley, including the city of Philadelphia, and variants infecting vaccinated subjects. We sequenced and analyzed complete viral genomes from 2621 surveillance samples from March 2020 to September 2021 and compared them to genome sequences from 159 vaccine breakthroughs. In the early spring of 2020, all detected variants were of the B.1 and closely related lineages. A mixture of lineages followed, notably including B.1.243 followed by B.1.1.7 (alpha), with other lineages present at lower levels. Later isolations were dominated by B.1.617.2 (delta) and other delta lineages; delta was the exclusive variant present by the last time sampled. To investigate whether any variants appeared preferentially in vaccine breakthroughs, we devised a model based on Bayesian autoregressive moving average logistic multinomial regression to allow rigorous comparison. This revealed that B.1.617.2 (delta) showed three-fold enrichment in vaccine breakthrough cases (odds ratio of 3; 95% credible interval 0.89-11). Viral point substitutions could also be associated with vaccine breakthroughs, notably the N501Y substitution found in the alpha, beta and gamma variants (odds ratio 2.04; 95% credible interval of 1.25-3.18). This study thus provides a detailed picture of viral evolution in the Delaware Valley and a geographically matched analysis of vaccine breakthroughs; it also introduces a rigorous statistical approach to interrogating enrichment of viral variants.
RESUMO
Influenza is a significant cause of childhood morbidity and death; it contributes to up to 16% of hospitalizations for respiratory illnesses worldwide. Novel rapid viral diagnostic tests, including molecular diagnostic tests, have the potential to significantly affect both time to diagnosis and selection of optimal anti-infective therapy. However, little is known about current treatment algorithms used in US hospitals. In this study, for hospitalized children in the United States, we aimed to define the current approaches to influenza diagnosis and treatment and to explore reasons for their potential variation. In this study, we aimed to define the current approaches to pediatric influenza diagnosis and treatment in US hospitals, and to explore reasons for their potential variation. Our results suggest a rise in the availability and use of rapid molecular diagnostic testing in addition to continued variability in anti-infective management, particularly with regard to antiviral use.
Assuntos
Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Influenza Humana/diagnóstico , Técnicas de Diagnóstico Molecular , Padrões de Prática Médica , Algoritmos , Gestão de Antimicrobianos , Criança , Criança Hospitalizada , Pesquisas sobre Atenção à Saúde , Hospitalização , Humanos , Influenza Humana/tratamento farmacológico , Influenza Humana/virologia , Oseltamivir/uso terapêutico , Pediatria , Estados UnidosRESUMO
BACKGROUND: Implementing antimicrobial stewardship programs (ASPs) can be challenging due to prescriber resistance. Although barriers to implementing new ASPs have been identified, little is known about how prescribers perceive established programs. This information is critical to promoting the sustainability of ASPs. OBJECTIVE: To identify how prescribers perceive an established pediatric inpatient ASP that primarily utilizes prior authorization. METHODS: We conducted a cross-sectional survey administered from February through June 2017 in a large children's hospital. The survey contained closed- and open-ended questions. Descriptive statistics and thematic content analysis approaches were used to analyze responses. RESULTS: Of 394 prescribers invited, 160 (41%) responded. Prescribers had an overall favorable impression of the ASP, believing that it improves the quality of care (92.4% agree) and takes their judgment seriously (73.8%). The most common criticism of the ASP was that it threatened efficiency (26.0% agreed). In addition, 68.7% of respondents reported occasionally engaging in workarounds. Analysis of 133 free-text responses revealed that prescribers perceived that interacting with the ASP involved too many phone calls, caused communication breakdowns with the dispensing pharmacy, and led to gaps between approval and dispensing of antibiotics. Reasons given for workarounds included not wanting to change therapy that appears to be working, consultant disagreement with ASP recommendations, and the desire to do everything possible for patients. CONCLUSIONS: Prescribers had a generally favorable opinion of an established ASP but found aspects to be inefficient. They reported engaging in workarounds occasionally for social and emotional reasons. Established ASPs should elicit feedback from frontline prescribers to optimize program impact.