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1.
Emerg Infect Dis ; 30(6): 1182-1192, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38781929

RESUMO

In adults, viral load and disease severity can differ by SARS-CoV-2 variant, patterns less understood in children. We evaluated symptomatology, cycle threshold (Ct) values, and SARS-CoV-2 variants among 2,299 pediatric SARS-CoV-2 patients (0-21 years of age) in Colorado, USA, to determine whether children infected with Delta or Omicron had different symptom severity or Ct values than during earlier variants. Children infected during the Delta and Omicron periods had lower Ct values than those infected during pre-Delta, and children <1 year of age had lower Ct values than older children. Hospitalized symptomatic children had lower Ct values than asymptomatic patients. Compared with pre-Delta, more children infected during Delta and Omicron were symptomatic (75.4% pre-Delta, 95.3% Delta, 99.5% Omicron), admitted to intensive care (18.8% pre-Delta, 39.5% Delta, 22.9% Omicron), or received oxygen support (42.0% pre-Delta, 66.3% Delta, 62.3% Omicron). Our data reinforce the need to include children, especially younger children, in pathogen surveillance efforts.


Assuntos
COVID-19 , SARS-CoV-2 , Índice de Gravidade de Doença , Carga Viral , Humanos , COVID-19/epidemiologia , COVID-19/virologia , Criança , Colorado/epidemiologia , Pré-Escolar , Lactente , Adolescente , Masculino , Feminino , Recém-Nascido , Adulto Jovem , Hospitalização
2.
Emerg Infect Dis ; 30(3): 423-431, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38407198

RESUMO

Surveillance for emerging pathogens is critical for developing early warning systems to guide preparedness efforts for future outbreaks of associated disease. To better define the epidemiology and burden of associated respiratory disease and acute flaccid myelitis (AFM), as well as to provide actionable data for public health interventions, we developed a multimodal surveillance program in Colorado, USA, for enterovirus D68 (EV-D68). Timely local, state, and national public health outreach was possible because prospective syndromic surveillance for AFM and asthma-like respiratory illness, prospective clinical laboratory surveillance for EV-D68 among children hospitalized with respiratory illness, and retrospective wastewater surveillance led to early detection of the 2022 outbreak of EV-D68 among Colorado children. The lessons learned from developing the individual layers of this multimodal surveillance program and how they complemented and informed the other layers of surveillance for EV-D68 and AFM could be applied to other emerging pathogens and their associated diseases.


Assuntos
Viroses do Sistema Nervoso Central , Enterovirus Humano D , Mielite , Doenças Neuromusculares , Doenças Respiratórias , Criança , Humanos , Colorado/epidemiologia , Estudos Prospectivos , Estudos Retrospectivos , Águas Residuárias , Vigilância Epidemiológica Baseada em Águas Residuárias
3.
Pediatr Blood Cancer ; 71(2): e30794, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38059641

RESUMO

While the survival of children with cancer has improved over time, infection remains a major morbidity and mortality risk. We conducted a systematic literature review to determine the unmet needs in diagnosing infection in immunocompromised children with cancer. The comprehensive search strategy followed the guidelines established by the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement, and spanned multiple bibliographic databases and other public sources from January 1, 2012 to June 23, 2022. From 5188 records, 34 unique pediatric-focused studies met inclusion criteria. This review highlights the lack of published data on infectious disease testing in pediatric oncology patients, and the need for well-designed clinical impact and cost-effectiveness studies of both existing and novel diagnostic platforms. Such studies are necessary to optimize diagnostic and antimicrobial stewardship, leading to improvement in patient outcomes.


Assuntos
Oncologia , Neoplasias , Humanos , Criança , Neoplasias/complicações
4.
Emerg Infect Dis ; 29(11): 2315-2324, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37877582

RESUMO

Enterovirus D68 (EV-D68) causes cyclical outbreaks of respiratory disease and acute flaccid myelitis. EV-D68 is primarily transmitted through the respiratory route, but the duration of shedding in the respiratory tract is unknown. We prospectively enrolled 9 hospitalized children with EV-D68 respiratory infection and 16 household contacts to determine EV-D68 RNA shedding dynamics in the upper respiratory tract through serial midturbinate specimen collections and daily symptom diaries. Five (31.3%) household contacts, including 3 adults, were EV-D68-positive. The median duration of EV-D68 RNA shedding in the upper respiratory tract was 12 (range 7-15) days from symptom onset. The most common symptoms were nasal congestion (100%), cough (92.9%), difficulty breathing (78.6%), and wheezing (57.1%). The median illness duration was 20 (range 11-24) days. Understanding the duration of RNA shedding can inform the expected rate and timing of EV-D68 detection in associated acute flaccid myelitis cases and help guide public health measures.


Assuntos
Enterovirus Humano D , Infecções por Enterovirus , Infecções Respiratórias , Criança , Adulto , Humanos , Enterovirus Humano D/genética , Colorado/epidemiologia , Sistema Respiratório , Infecções por Enterovirus/epidemiologia , Surtos de Doenças , RNA , Infecções Respiratórias/epidemiologia
5.
Emerg Infect Dis ; 29(5): 929-936, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36972709

RESUMO

To compare SARS-CoV-2 antibody seroprevalence among children with seropositive confirmed COVID-19 case counts (case ascertainment by molecular amplification) in Colorado, USA, we conducted a cross-sectional serosurvey during May-July 2021. For a convenience sample of 829 Colorado children, SARS-CoV-2 seroprevalence was 36.7%, compared with prevalence of 6.5% according to individually matched COVID-19 test results reported to public health. Compared with non-Hispanic White children, seroprevalence was higher among Hispanic, non-Hispanic Black, and non-Hispanic other race children, and case ascertainment was significantly lower among Hispanic and non-Hispanic Black children. This serosurvey accurately estimated SARS-CoV-2 prevalence among children compared with confirmed COVID-19 case counts and revealed substantial racial/ethnic disparities in infections and case ascertainment. Continued efforts to address racial and ethnic differences in disease burden and to overcome potential barriers to case ascertainment, including access to testing, may help mitigate these ongoing disparities.


Assuntos
COVID-19 , Humanos , Criança , COVID-19/epidemiologia , SARS-CoV-2 , Colorado/epidemiologia , Estudos Soroepidemiológicos , Estudos Transversais
6.
J Pediatr ; 260: 113491, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37201680

RESUMO

OBJECTIVE: To compare demographic characteristics, clinical features, and outcomes of children hospitalized with respiratory syncytial virus (RSV), influenza, or severe acute respiratory syndrome coronavirus 2 during their cocirculation 2021-2022 respiratory virus season. METHODS: We conducted a retrospective cohort study using Colorado's hospital respiratory surveillance data comparing coronavirus disease 2019 (COVID-19)-, influenza-, and RSV-hospitalized cases < 18 years of age admitted and undergoing standardized molecular testing between October 1, 2021, and April 30, 2022. Multivariable log-binomial regression modeling evaluated associations between pathogen type and diagnosis, intensive care unit admission, hospital length of stay, and highest level of respiratory support received. RESULTS: Among 847 hospitalized cases, 490 (57.9%) were RSV associated, 306 (36.1%) were COVID-19 associated, and 51 (6%) were influenza associated. Most RSV cases were <4 years of age (92.9%), whereas influenza hospitalizations were observed in older children. RSV cases were more likely to require oxygen support higher than nasal cannula compared with COVID-19 and influenza cases (P < .0001), although COVID-19 cases were more likely to require invasive mechanical ventilation than influenza and RSV cases (P < .0001). Using multivariable log-binomial regression analyses, compared with children with COVID-19, the risk of intensive care unit admission was highest among children with influenza (relative risk, 1.97; 95% CI, 1.22-3.19), whereas the risk of pneumonia, bronchiolitis, longer hospital length of stay, and need for oxygen were more likely among children with RSV. CONCLUSIONS: In a season with respiratory pathogen cocirculation, children were hospitalized most commonly for RSV, were younger, and required higher oxygen support and non-invasive ventilation compared with children with influenza and COVID-19.


Assuntos
COVID-19 , Influenza Humana , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Humanos , Criança , Lactente , Influenza Humana/diagnóstico , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/terapia , Infecções por Vírus Respiratório Sincicial/diagnóstico , Estudos Retrospectivos , Estações do Ano , Colorado/epidemiologia , COVID-19/epidemiologia , Hospitalização , Oxigênio
7.
N Engl J Med ; 380(24): 2327-2340, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31189036

RESUMO

BACKGROUND: Metagenomic next-generation sequencing (NGS) of cerebrospinal fluid (CSF) has the potential to identify a broad range of pathogens in a single test. METHODS: In a 1-year, multicenter, prospective study, we investigated the usefulness of metagenomic NGS of CSF for the diagnosis of infectious meningitis and encephalitis in hospitalized patients. All positive tests for pathogens on metagenomic NGS were confirmed by orthogonal laboratory testing. Physician feedback was elicited by teleconferences with a clinical microbial sequencing board and by surveys. Clinical effect was evaluated by retrospective chart review. RESULTS: We enrolled 204 pediatric and adult patients at eight hospitals. Patients were severely ill: 48.5% had been admitted to the intensive care unit, and the 30-day mortality among all study patients was 11.3%. A total of 58 infections of the nervous system were diagnosed in 57 patients (27.9%). Among these 58 infections, metagenomic NGS identified 13 (22%) that were not identified by clinical testing at the source hospital. Among the remaining 45 infections (78%), metagenomic NGS made concurrent diagnoses in 19. Of the 26 infections not identified by metagenomic NGS, 11 were diagnosed by serologic testing only, 7 were diagnosed from tissue samples other than CSF, and 8 were negative on metagenomic NGS owing to low titers of pathogens in CSF. A total of 8 of 13 diagnoses made solely by metagenomic NGS had a likely clinical effect, with 7 of 13 guiding treatment. CONCLUSIONS: Routine microbiologic testing is often insufficient to detect all neuroinvasive pathogens. In this study, metagenomic NGS of CSF obtained from patients with meningitis or encephalitis improved diagnosis of neurologic infections and provided actionable information in some cases. (Funded by the National Institutes of Health and others; PDAID ClinicalTrials.gov number, NCT02910037.).


Assuntos
Líquido Cefalorraquidiano/microbiologia , Encefalite/microbiologia , Genoma Microbiano , Meningite/microbiologia , Metagenômica , Adolescente , Adulto , Líquido Cefalorraquidiano/virologia , Criança , Pré-Escolar , Encefalite/diagnóstico , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Infecções/diagnóstico , Tempo de Internação , Masculino , Meningite/diagnóstico , Meningoencefalite/diagnóstico , Meningoencefalite/microbiologia , Pessoa de Meia-Idade , Mielite/diagnóstico , Mielite/microbiologia , Estudos Prospectivos , Análise de Sequência de DNA , Análise de Sequência de RNA , Adulto Jovem
8.
J Pediatr ; 244: 161-168.e1, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35150729

RESUMO

OBJECTIVE: To investigate the optimal implementation and clinical and financial impacts of the FilmArray Meningitis Encephalitis Panel (MEP) multiplex polymerase chain reaction testing of cerebrospinal fluid (CSF) in children with suspected central nervous system infection. STUDY DESIGN: A pre-post quasiexperimental cohort study to investigate the impact of implementing MEP using a rapid CSF diagnostic stewardship program was conducted at Children's Hospital Colorado (CHCO). MEP was implemented with electronic medical record indication selection to guide testing to children meeting approved use criteria: infants <2 months, immunocompromised, encephalitis, and ≥5 white blood cells/µL of CSF. Positive results were communicated with antimicrobial stewardship real-time decision support. All cases with CSF obtained by lumbar puncture sent to the CHCO microbiology laboratory meeting any of the 4 aforementioned criteria were included with preimplementation controls (2015-2016) compared with postimplementation cases (2017-2018). Primary outcome was time-to-optimal antimicrobials compared using log-rank test with Kaplan-Meier analysis. RESULTS: Time-to-optimal antimicrobials decreased from 28 hours among 1124 preimplementation controls to 18 hours (P < .0001) among 1127 postimplementation cases (72% with MEP testing conducted). Postimplementation, time-to-positive CSF results was faster (4.8 vs 9.6 hours, P < .0001), intravenous antimicrobial duration was shorter (24 vs 36 hours, P = .004), with infectious neurologic diagnoses more frequently identified (15% vs 10%, P = .03). There were no differences in time-to-effective antimicrobials, hospital admissions, antimicrobial starts, or length of stay. Costs of microbiologic testing increased, but total hospital costs were unchanged. CONCLUSIONS: Implementation of MEP with a rapid central nervous system diagnostic stewardship program improved antimicrobial use with faster results shortening empiric therapy. Routine MEP testing for high-yield indications enables antimicrobial optimization with unchanged overall costs.


Assuntos
Anti-Infecciosos , Infecções do Sistema Nervoso Central , Encefalite , Meningite , Malformações do Sistema Nervoso , Antibacterianos , Anti-Infecciosos/uso terapêutico , Infecções do Sistema Nervoso Central/líquido cefalorraquidiano , Infecções do Sistema Nervoso Central/diagnóstico , Infecções do Sistema Nervoso Central/tratamento farmacológico , Criança , Estudos de Coortes , Encefalite/diagnóstico , Humanos , Lactente , Meningite/diagnóstico , Estudos Retrospectivos
9.
J Med Virol ; 94(12): 6103-6110, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35882541

RESUMO

Upper respiratory illnesses due to viruses are the most common reason for pediatric emergency department (ED) visits in the United States. We explored the clinical characteristics, hospitalization risk, and symptom duration of children in an ED setting by respiratory pathogen including coinfections. A retrospective analysis was conducted from a randomized controlled trial evaluating a rapid molecular pathogen panel among 931 children 1 month to 18 years of age with acute respiratory illness. We assessed hospitalization risk by pathogen using multivariable Poisson regression with robust variance. Symptom duration was assessed using multivariable Cox proportional hazards models. Among 931 children, 702 (75%) were aged 0-5 years and 797 (85%) tested positive for a respiratory pathogen. Children with respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and human rhinovirus/enterovirus (HRV/EV) had higher hospitalization risk compared with influenza (adjusted risk ratio [aRR]: 2.95, 95% confidence interval [CI]: 1.17-7.45; 3.56, 95% CI: 1.05-12.02; aRR: 2.58, 95% CI: 1.05-6.35, respectively). Children with RSV, parainfluenza and atypical bacterial pathogens had longer illness duration compared with influenza (adjusted hazards ratio [aHR]: 2.16 95% CI: 1.41-3.29; aHR: 1.67, 95% CI:1.06-2.64; aHR: 2.60 95% CI: 1.30-5.19, respectively). Children with RSV, hMPV, and atypical bacterial pathogens had higher illness severity and duration compared with other respiratory pathogens. Coinfection was not associated with increased illness severity.


Assuntos
Coinfecção , Influenza Humana , Metapneumovirus , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Vírus , Criança , Coinfecção/complicações , Coinfecção/epidemiologia , Serviço Hospitalar de Emergência , Humanos , Lactente , Infecções Respiratórias/diagnóstico , Estudos Retrospectivos
10.
Pediatr Blood Cancer ; 68(12): e29277, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34453477

RESUMO

OBJECTIVES: We evaluated the length of time immunocompromised children (ICC) remain positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), identified factors associated with viral persistence, and determined cycle threshold (CT ) values of children with viral persistence as a surrogate of viral load. METHODS: We conducted a retrospective cohort study of ICC at a pediatric hospital from March 2020 to March 2021. Immunocompromised status was defined as primary, secondary, or acquired due to medical comorbidities/immunosuppressive treatment. The primary outcome was time to first of two consecutive negative SARS-CoV-2 polymerase chain reaction (PCR) tests at least 24 hours apart. Testing of sequential clinical specimens from the same subject was conducted using the Centers for Disease Control (CDC) 2019-nCoV real-time reverse transcriptase (RT)-PCR Diagnostic Panel assay. Descriptive statistics, Kaplan-Meier curve median event times and log-rank tests were used to compare outcomes between groups. RESULTS: Ninety-one children met inclusion criteria. Median age was 15.5 years (interquartile range [IQR] 8-18), 64% were male, 58% were White, and 43% were Hispanic/Latinx. Most (67%) were tested in outpatient settings and 58% were asymptomatic. The median time to two negative tests was 42 days (IQR 25.0-55.0), with no differences in median time by illness presentation or level of immunosuppression. Seven children had more than one sample available for repeat testing, and five of seven (71%) children had initial CT values of <30 (moderate to high viral load); four children had CT values of <30, 3-4 weeks later, suggesting persistent moderate to high viral loads. CONCLUSIONS: Most ICC with SARS-CoV-2 infection had mild disease, with prolonged viral persistence >6 weeks and moderate to high viral load.


Assuntos
COVID-19/imunologia , Hospedeiro Imunocomprometido , Adolescente , COVID-19/diagnóstico , Teste de Ácido Nucleico para COVID-19 , Criança , Pré-Escolar , Humanos , Masculino , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação , Carga Viral
11.
J Infect Dis ; 221(3): 356-366, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31314899

RESUMO

BACKGROUND: The effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear. METHODS: We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Patients with a LoS of <1 day and those who died while hospitalized were excluded. RESULTS: We analyzed data on 18 309 patients from 70 clinical centers. After adjustment, NAI treatment initiated at hospitalization was associated with a 19% reduction in the LoS among patients with clinically suspected or laboratory-confirmed influenza A(H1N1)pdm09 infection (IRR, 0.81; 95% CI, .78-.85), compared with later or no initiation of NAI treatment. Similar statistically significant associations were seen in all clinical subgroups. NAI treatment (at any time), compared with no NAI treatment, and NAI treatment initiated <2 days after symptom onset, compared with later or no initiation of NAI treatment, showed mixed patterns of association with the LoS. CONCLUSIONS: When patients hospitalized with influenza are treated with NAIs, treatment initiated on admission, regardless of time since symptom onset, is associated with a reduced LoS, compared with later or no initiation of treatment.


Assuntos
Antivirais/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/tratamento farmacológico , Influenza Humana/epidemiologia , Tempo de Internação , Neuraminidase/antagonistas & inibidores , Pandemias , Adolescente , Corticosteroides/uso terapêutico , Adulto , Idoso , Antibacterianos/uso terapêutico , Criança , Inibidores Enzimáticos/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
12.
J Mol Cell Cardiol ; 146: 12-18, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32634388

RESUMO

BACKGROUND: Kawasaki Disease (KD) is an acute vasculitis of unknown etiology in children that can lead to coronary artery lesions (CAL) in 25% of untreated patients. There is currently no diagnostic test for KD, and the clinical presentation is often difficult to differentiate from other febrile childhood illnesses. Circulating microRNAs (miRNAs) are small noncoding RNA molecules that control gene expression by inducing transcript degradation or by blocking translation. We hypothesize that the expression of circulating miRNAs will differentiate KD from non-KD febrile illnesses in children. METHODS: Circulating miRNA profiles from 84 KD patients and 29 non-KD febrile controls (7 viral and 22 bacterial infections) were evaluated. 3 ul of serum from each subject was submitted to 3 freeze/heat cycles to ensure miRNA release from microvesicles or interaction with serum proteins. miRNAs were reverse transcribed using a pool of primers specific for each miRNA. Real-time PCR reactions were performed in a 384 well plate containing sequence-specific primers and TaqMan probes in the ABI7900. '. RESULTS: KD patients (3.6 ± 2.2 yrs., 58% male) were found to have a unique circulating miRNA profile, including upregulation of miRNA-210-3p, -184, and -19a-3p (p < .0001), compared to non-KD febrile controls (8.5 ± 6.1 yrs., 72% male). CONCLUSIONS: Circulating miRNAs can differentiate KD from infectious febrile childhood diseases, supporting their potential as a diagnostic biomarker for KD.


Assuntos
MicroRNA Circulante/sangue , Febre/sangue , Febre/genética , Infecções/sangue , Infecções/genética , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/genética , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , MicroRNA Circulante/genética , Feminino , Febre/complicações , Redes Reguladoras de Genes , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Infecções/complicações , Masculino , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico
13.
Am J Transplant ; 20(8): 2133-2142, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32064754

RESUMO

Hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients are at increased risk for Clostridioides difficile infection (CDI). We conducted a multicenter retrospective study to describe the incidence of CDI in children transplanted between January 2010 and June 2013. Nested case-control substudies, matched 1:1 by transplant type, institution, patient age, and time of year (quartile) of transplant, identified CDI risk factors. Cohorts included 1496 HCT and 1090 SOT recipients. Among HCT recipients, 355 CDI episodes were diagnosed in 265 recipients (18.2%). Nested case-control study identified prior history of CDI (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.5-4.7), proton pump inhibitors (PPIs; OR 2.1, 95% CI 1.3-3.4), and exposure to third- (OR 2.4, 95% CI 1.4-4.2) or fourth-generation (OR 2.1, 95% CI 1.2-3.7) cephalosporins as risk factors. Notably, fluoroquinolone exposure appeared protective (OR 0.6, 95% CI 0.3-0.9). Ninety-two episodes of CDI were diagnosed among 79 SOT recipients (7.3%), and exposure to PPIs (OR 2.4, 95% CI 1.1-5.4) and third-generation cephalosporin therapy (OR 3.9, 95% CI 1.4-10.5) were identified as risk factors. Strategies to decrease PPI use and changes in the class of prophylactic antibiotics may impact CDI incidence and warrant further study.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Transplante de Células-Tronco Hematopoéticas , Transplante de Órgãos , Antibacterianos/uso terapêutico , Estudos de Casos e Controles , Criança , Clostridioides , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Transplante de Órgãos/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Transplantados
14.
J Pediatr ; 218: 157-165.e3, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32089179

RESUMO

OBJECTIVES: To evaluate whether the implementation of a multiplex gastrointestinal pathogen panel (GIP) was associated with changes in Clostridioides difficile (C difficile) testing and detection rates. STUDY DESIGN: We conducted an observational study using interrupted time series analysis and included pediatric patients with testing capable of detecting C difficile. From 2013 to 2015 ("conventional diagnostic era"), stool testing included C difficile-selective polymerase chain reaction and other pathogen-specific tests. From 2015 to 2017 ("GIP era"), C difficile polymerase chain reaction was available along with the GIP, which detected 22 pathogens including C difficile, and replaced the need for additional tests. Outcomes included C difficile testing and detection rates in ambulatory, emergency department, and inpatient settings. RESULTS: There were 6841 tests performed and 1214 C difficile positive results. Across the 3 settings, GIP era had significantly higher C difficile testing (1.7-2.3 times higher) and C difficile detection rates (1.9-3.4 times higher) compared with conventional diagnostic era. After adjusting for the number of tests performed, detection rates were no longer significantly different. Of C difficile positive GIPs, 31% were coinfected with another organism. With GIP testing, patients 1 year of age had a significantly higher C difficile percent positivity than 2-year-old (P = .02) and 3- to 18-year-old children (P < .01). Younger children with C difficile were more likely to be coinfected (P < .01). CONCLUSIONS: Introducing a multiplex panel led to increased C difficile testing, which resulted in increased C difficile detection rates and potential identification and treatment of colonized patients. This highlights an important target for diagnostic stewardship and the challenges associated with multiplex testing.


Assuntos
Clostridioides difficile/isolamento & purificação , Diarreia/microbiologia , Fezes/microbiologia , Gastroenteropatias/diagnóstico , Gastroenteropatias/microbiologia , Adolescente , Criança , Pré-Escolar , Clostridioides difficile/classificação , Diarreia/diagnóstico , Feminino , Humanos , Incidência , Masculino , Reação em Cadeia da Polimerase Multiplex , Reação em Cadeia da Polimerase , Prevalência
15.
J Pediatr ; 212: 228-231, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31208781

RESUMO

An immunocompetent toddler came to medication attention with gastroenteritis, complicated by encephalopathy and hepatitis. Multiplexed testing using a polymerase chain reaction meningitis panel was positive for human herpesvirus 6 (HHV-6). Clinical correlation, quantitative HHV-6 polymerase chain reaction, and metagenomic next-generation sequencing supported a likely diagnosis of primary HHV-6B infection.


Assuntos
Encefalopatias/virologia , Exantema Súbito/virologia , Gastroenterite/virologia , Hepatite/virologia , Herpesvirus Humano 6/isolamento & purificação , Reação em Cadeia da Polimerase Multiplex , Herpesvirus Humano 6/genética , Humanos , Imunocompetência , Lactente , Masculino , Medição de Risco
16.
J Pediatr ; 215: 107-117.e12, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31561960

RESUMO

OBJECTIVES: To determine the safety, tolerability, pharmacokinetics, and immunomodulatory effects of a 6-week course of atorvastatin in patients with acute Kawasaki disease with coronary artery (CA) aneurysm (CAA). STUDY DESIGN: This was a Phase I/IIa 2-center dose-escalation study of atorvastatin (0.125-0.75 mg/kg/day) in 34 patients with Kawasaki disease (aged 2-17 years) with echocardiographic evidence of CAA. We measured levels of the brain metabolite 24(S)-hydroxycholesterol (24-OHC), serum lipids, acute-phase reactants, liver enzymes, and creatine phosphokinase; peripheral blood mononuclear cell populations; and CA internal diameter normalized for body surface area before atorvastatin treatment and at 2 and 6 weeks after initiation of atorvastatin treatment. RESULTS: A 6-week course of up to 0.75 mg/kg/day of atorvastatin was well tolerated by the 34 subjects (median age, 5.3 years; IQR, 2.6-6.4 years), with no serious adverse events attributable to the study drug. The areas under the curve for atorvastatin and its metabolite were larger in the study subjects compared with those reported in adults, suggesting a slower rate of metabolism in children. The 24-OHC levels were similar between the atorvastatin-treated subjects and matched controls. CONCLUSIONS: Atorvastatin was safe and well tolerated in our cohort of children with acute Kawasaki disease and CAA. A Phase III efficacy trial is warranted in this patient population, which may benefit from the known anti-inflammatory and immunomodulatory effects of this drug.


Assuntos
Atorvastatina/administração & dosagem , Aneurisma Coronário/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Administração Oral , Adolescente , Atorvastatina/efeitos adversos , Atorvastatina/farmacocinética , Criança , Pré-Escolar , Aneurisma Coronário/etiologia , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacocinética , Masculino , Síndrome de Linfonodos Mucocutâneos/complicações
17.
J Clin Microbiol ; 56(10)2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29875197

RESUMO

The American Academy of Pediatrics currently recommends herpes simplex virus (HSV) culture or PCR for testing of swabs of the conjunctivae, mouth, nasopharynx, and rectum (surface swabs) from neonates. The objectives of this study were to compare the performance and time to results of HSV PCR with those of HSV culture with surface swabs from neonates. Banked multisource surface swab samples that were collected from infants less than or equal to 30 days old from January 2017 to December 2017 and that had previously been cultured for HSV were identified and tested retrospectively by HSV PCR. Surface swab samples from 97 patients were included in the study. Of these 97 patients, 7 (7%) had clinical HSV disease. Of the 7 neonates with HSV disease, 3 (42.9%) had surface swabs positive by culture and 6 (85.7%) had swabs positive by PCR. Limiting the analysis to specimens that were positive only by culture or only by PCR, the specificity for both methods was 100%, but the sensitivity of PCR was 100%, whereas it was 50% for culture. During the study period, 341 HSV cultures and 426 HSV PCRs were performed. The median time from swab collection to reporting of results was 7.6 days (interquartile range [IQR], 7.1 to 7.9 days) for culture and 0.8 days (IQR, 0.6 to 1.0 days) for PCR. HSV PCR of surface swabs from neonates was considerably more rapid and sensitive than HSV culture without yielding false-positive results. Although larger studies are needed to support our findings, strong consideration should be given to utilize PCR instead of culture for the detection of HSV in surface swabs from neonates.


Assuntos
Herpes Simples/diagnóstico , Técnicas de Diagnóstico Molecular/normas , Complicações Infecciosas na Gravidez/diagnóstico , Simplexvirus/isolamento & purificação , Cultura de Vírus/normas , Feminino , Herpes Simples/virologia , Humanos , Recém-Nascido , Masculino , Reação em Cadeia da Polimerase , Complicações Infecciosas na Gravidez/virologia , Estudos Retrospectivos , Sensibilidade e Especificidade , Manejo de Espécimes/normas , Fatores de Tempo
18.
J Pediatr ; 194: 123-127.e1, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29198534

RESUMO

OBJECTIVE: To assess the safety, efficacy, and relative expense of a nurse-led fecal microbiota transplantation (FMT) program for the treatment of recurrent Clostridium difficile infection (CDI). STUDY DESIGN: Retrospective cohort study design in children aged 1-18 years with recurrent CDI. The intervention was an intragastric FMT with stool derived from a donor stool bank. Primary outcome was resolution of diarrhea at 3 months post-transplantation. A secondary analysis compared charge data associated with FMT by intragastric delivery vs administration by colonoscopy or nasoduodenal tube. RESULTS: A total of 47 intragastric FMT procedures were performed in 42 children (median age 9 years) with recurrent CDI. Response to treatment varied by disease status, with 94% success in previously healthy children, 75% in medically complex children, and 54% in children with inflammatory bowel disease (P = .04). FMT via intragastric delivery showed lower facility and professional charges by 85% and 78% compared with delivery via colonoscopy and radiology-placed nasoduodenal tube, respectively. The use of stool derived from a donor stool bank decreased charges by 49% compared with charges associated with the use of a donor who was a relative. CONCLUSION: A nurse-led intragastric FMT procedure using stool derived from a donor stool bank is a relatively inexpensive and efficacious treatment for recurrent CDI in children. Intragastric FMT success in children was attenuated by the presence of underlying disease, particularly inflammatory bowel disease.


Assuntos
Infecções por Clostridium/terapia , Diarreia/terapia , Transplante de Microbiota Fecal/métodos , Adolescente , Criança , Pré-Escolar , Clostridioides difficile , Estudos de Coortes , Colonoscopia/métodos , Diarreia/etiologia , Transplante de Microbiota Fecal/efeitos adversos , Fezes/microbiologia , Feminino , Gastrostomia/métodos , Humanos , Lactente , Intubação Gastrointestinal/métodos , Masculino , Recidiva , Estudos Retrospectivos , Estômago , Resultado do Tratamento
20.
J Clin Microbiol ; 55(3): 715-723, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28031432

RESUMO

New rapid molecular diagnostic technologies for infectious diseases enable expedited accurate microbiological diagnoses. However, diagnostic stewardship and antimicrobial stewardship are necessary to ensure that these technologies conserve, rather than consume, additional health care resources and optimally affect patient care. Diagnostic stewardship is needed to implement appropriate tests for the clinical setting and to direct testing toward appropriate patients. Antimicrobial stewardship is needed to ensure prompt appropriate clinical action to translate faster diagnostic test results in the laboratory into improved outcomes at the bedside. This minireview outlines the roles of diagnostic stewardship and antimicrobial stewardship in the implementation of rapid molecular infectious disease diagnostics.


Assuntos
Anti-Infecciosos/uso terapêutico , Doenças Transmissíveis/diagnóstico , Doenças Transmissíveis/tratamento farmacológico , Uso de Medicamentos/normas , Testes de Sensibilidade Microbiana/métodos , Técnicas de Diagnóstico Molecular/métodos , Diagnóstico Precoce , Humanos , Fatores de Tempo
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