Clostridium difficile infection (CDI) is an increasingly important cause of morbidity in hospitalized children. We describe the recent epidemiology of pediatric CDI at a children's hospital, compare ...community-associated (CA) and hospital-associated (HA) infections and identify risk factors for severe disease.
Children with CDI at Texas Children's Hospital were identified from February 1, 2011, to October 31, 2011. Severe CDI was defined as the presence of a CDI-related complication or ≥2 clinical features: fever, bloody stools, leukocytosis, hypoalbuminemia or elevated creatinine. Standard epidemiologic definitions were used.
One-hundred and nine unique patients 1-21 years of age with CDI were identified throughout the study period. The proportions of CA-CDI (41%) and HA-CDI (46%) were similar, whereas community-onset indeterminate CDI (13%) was less common. Children with malignancy or solid organ transplantation were more likely to have HA-CDI. Conversely, all children with inflammatory bowel disease had CA-CDI. Twenty-three patients (21%) met criteria for severe disease and 8 experienced a CDI-related complication, including 1 death attributable to CDI. On multivariate analysis, the presence of a gastrostomy tube (adjusted odds ratio: 3.09; 95% confidence interval: 1.07-8.94) and having community-onset indeterminate disease (adjusted odds ratio: 4.62; 95% confidence interval: 1.28-16.67) were found to be associated with severe CDI.
A substantial proportion of pediatric CDI is CA and there are clinical differences between children with CA-CDI and HA-CDI. Children with CDI frequently experience severe disease, whereas complications are uncommon. Early identification and treatment of CDI should be pursued in children with gastrostomy tube and recent hospitalization.
Confirming the diagnosis of childhood tuberculosis is a major challenge. However, research on childhood tuberculosis as it relates to better diagnostics is often neglected because of technical ...difficulties, such as the slow growth in culture, the difficulty of obtaining specimens, and the diverse and relatively nonspecific clinical presentation of tuberculosis in this age group. Researchers often use individually designed criteria for enrollment, diagnostic classifications, and reference standards, thereby hindering the interpretation and comparability of their findings. The development of standardized research approaches and definitions is therefore needed to strengthen the evaluation of new diagnostics for detection and confirmation of tuberculosis in children. In this article we present consensus statements on methodological issues for conducting research of Tuberculosis diagnostics among children, with a focus on intrathoracic tuberculosis. The statements are complementary to a clinical research case definition presented in an accompanying publication and suggest a phased approach to diagnostics evaluation; entry criteria for enrollment; methods for classification of disease certainty, including the rational use of culture within the case definition; age categories and comorbidities for reporting results; and the need to use standard operating procedures. Special consideration is given to the performance of microbiological culture in children and we also recommend for alternative methodological approaches to report findings in a standardized manner to overcome these limitations are made. This consensus statement is an important step toward ensuring greater rigor and comparability of pediatric tuberculosis diagnostic research, with the aim of realizing the full potential of better tests for children.
Relatively little is known about the human genetics of susceptibility to common diseases caused by bacterial pathogens. Tuberculosis, caused by Mycobacterium tuberculosis, is a major cause of ...morbidity and mortality worldwide. So far, genetic studies of tuberculosis susceptibility have largely been focused on adult patients despite the fact that tuberculosis is highly prevalent among children. To study the host genetic component of pediatric tuberculosis susceptibility, we enrolled 184 ethnically diverse families from the Greater Houston area with at least one child affected by pediatric tuberculosis disease. Using a family-based control design, we found allelic variants of the natural resistance-associated macrophage protein gene 1 (NRAMP1) (alias SLC11A1) significantly associated with tuberculosis disease in this pediatric patient population P = 0.01; odds ratio = 1.75 (95% confidence interval, 1.10-2.77). The association of NRAMP1 with pediatric tuberculosis disease was significantly heterogeneous (P = 0.01) between simplex P <0.0008; odds ratio = 3.13 (1.54-6.25) and multiplex families (P = 1), suggesting an interplay between mechanisms of genetic control and exposure intensities. In striking contrast to previous studies in the adult population, we observed that the common alleles of NRAMP1 polymorphisms were risk factors for pediatric tuberculosis disease. To explain the different direction of allelic association between adult and pediatric disease, we hypothesize that NRAMP1 influences the speed of progression from infection to tuberculosis disease.
Interferon-γ-release assays (IGRAs) have been developed for the diagnosis of tuberculosis infection, but few data are available for children. There currently is no reference standard for the ...diagnosis of tuberculosis infection.
To compare the performance of 1 IGRA, the T-SPOT.TB assay with the tuberculin skin test (TST) in children with different epidemiologic risk factors for tuberculosis.
We conducted a prospective study of 210 patients referred to 3 pediatric tuberculosis clinics, including those with no risk factors for tuberculosis (low risk, n = 27), risk factors but no identifiable source case (intermediate risk, n = 78), contact with a known source case (high risk, n = 74), and active disease (n = 31). Children were tested with TST and T-SPOT.TB. Concordance analyses were performed, and assay outcomes were modeled by multivariate logistic regression.
For 13 children with culture-confirmed tuberculosis disease, sensitivity of TST and T-SPOT.TB was 77% and 92%, respectively, and concordance was 69%. For high-risk children, concordance was 94% for BCG-unimmunized children and 88% for BCG-immunized children. For intermediate-risk children, concordance was 74% for BCG-unimmunized children and 33% for BCG-immunized children. For low-risk children, concordance was 74% for BCG-unimmunized children and 20% for BCG-immunized children. Multivariate analysis revealed that contact with a source case was associated with T-SPOT.TB result, but age and BCG immunization were not.
T-SPOT.TB is comparable to the TST in the diagnosis of tuberculosis disease and identification of high-risk children with tuberculosis infection and is more specific than the TST in children who have received the BCG vaccine.
The Pediatric and Neonatal Working group developed new ventilator associated events (VAE) definitions for children and neonates. VAE includes ventilator-associated condition (VAC), infection-related ...ventilator-associated complication (IVAC), and ventilator-associated pneumonia (VAP). Acute kidney injury (AKI) and fluid overload (FO) have been associated with worse clinical outcomes of ventilated children. Fluid Overload and Kidney Injury Score (FOKIS) is an automatically calculated score that combines AKI and FO in one numeric quantifiable metric. This study analyzed the association between FOKIS and VAE.
Retrospective matched case control study.
A freestanding children's hospital.
A total of 168 who were ventilated > 2 days.
None.
We identified 42 VAC cases (18 IVAC and 24 non-infection-related VAC cases). Controls were matched to cases for age, immunocompromised status and ventilator days prior to VAC. VAC cases had longer ICU days, median (IQR), 28.5 (15, 47) vs. controls 11 (6, 16),
< 0.001; longer ventilation days, 19.5 (13, 32) vs. 9 (4,13),
< 0.001; and higher hospital mortality, 45.2 vs. 18%,
< 0.001. VACs had a higher incidence of AKI, 85.7 vs. 47.3%,
< 0.001; higher peak daily FO% within 3 days preceding VAC, mean (SD), 8.1(7.8) vs. 4.1 (3.4),
< 0.005; and higher peak FOKIS, 6.4(3.8) vs. 3.7(2.8), (
< 0.001). Multivariate regression model adjusted for severity of illness identified peak FOKIS (odds ratio OR 1.29, 95%CI: 1.14-1.48,
< 0.001) and peak inspiratory pressure (OR 1.08, 95%CI: 1.02-1.15,
= 0.007) as risk factors for VAC.
The FOKIS and its clinical variables were associated risk factors for ventilator-associated events. Further studies will determine the utility of FOKIS as a predictor for VAEs.
Background. Globally, >30 000 children fall sick with multidrug-resistant (MDR) tuberculosis every year. Without robust pediatric data, clinical management follows international guidelines that are ...based on studies in adults and expert opinion. We aimed to identify baseline predictors of death, treatment failure, and loss to follow-up among children with MDR tuberculosis disease treated with regimens tailored to their drug susceptibility test (DST) result or to the DST result of a source case. Methods. This retrospective cohort study included all children ≤15 years old with confirmed and probable MDR tuberculosis disease who began tailored regimens in Lima, Peru, between 2005 and 2009. Using logistic regression, we examined associations between baseline patient and treatment characteristics and (1) death or treatment failure and (2) loss to follow-up. Results. Two hundred eleven of 232 (90.9%) children had known treatment outcomes, of whom 163 (77.2%) achieved cure or probable cure, 29 (13.7%) were lost to follow-up, 10 (4.7%) experienced treatment failure, and 9 (4.3%) died. Independent baseline predictors of death or treatment failure were the presence of severe disease (adjusted odds ratio aOR, 4.96; 95% confidence interval CI, 1.61–15.26) and z score ≤−1 (aOR, 3.39; 95% CI, 1.20–9.54). We did not identify any independent predictors of loss to follow-up. Conclusions. High cure rates can be achieved in children with MDR tuberculosis using tailored regimens containing second-line drugs. However, children faced significantly higher risk of death or treatment failure if they had severe disease or were underweight. These findings highlight the need for early interventions that can improve treatment outcomes for children with MDR tuberculosis.
Policy Statement: Antibiotic Stewardship in Pediatrics Gerber, Jeffrey S; Jackson, Mary Anne; Tamma, Pranita D ...
Journal of the Pediatric Infectious Diseases Society,
05/2021, Letnik:
10, Številka:
5
Journal Article
Odprti dostop
Abstract
Antibiotic overuse contributes to antibiotic resistance, which is a threat to public health. Antibiotic stewardship is a practice dedicated to prescribing antibiotics only when necessary ...and, when antibiotics are considered necessary, promoting the use of the appropriate agent(s), dose, duration, and route of therapy to optimize clinical outcomes while minimizing the unintended consequences of antibiotic use. Because there are differences in common infectious conditions, drug-specific considerations, and the evidence surrounding treatment recommendations (eg, first-line therapy and duration of therapy) between children and adults, this statement provides specific guidance for the pediatric population. This policy statement discusses the rationale for inpatient and outpatient antibiotic stewardship programs (ASPs); essential personnel, infrastructure, and activities required; approaches to evaluating their effectiveness; and gaps in knowledge that require further investigation. Key guidance for both inpatient and outpatient ASPs are provided.
Background Guidelines differ on screening recommendations for latent tuberculosis infection (LTBI) prior to immunosuppressive therapy. We aimed to determine the most cost-effective LTBI screening ...strategy before long-term steroid therapy in a child with new-onset idiopathic nephrotic syndrome. Study Design Markov state-transition model. Setting & Population 5-year-old boy with new-onset idiopathic nephrotic syndrome. Model, Perspective, & Timeframe The Markov model took a societal perspective over a lifetime horizon. Intervention 3 strategies were compared: universal tuberculin skin testing (TST), targeted screening using a risk-factor questionnaire, and no screening. A secondary model included the newer interferon γ release assays (IGRAs), requiring only one visit and having greater specificity than TST. Outcomes Marginal cost-effectiveness ratios (2010 US dollars) with effectiveness measured as quality-adjusted life-years (QALYs). Results At an LTBI prevalence of 1.1% (the average US childhood prevalence in our base case), a no-screening strategy dominated ($2,201; 29.3356 QALYs) targeted screening ($2,218; 29.3356 QALYs) and universal TST ($2,481; 29.3347 QALYs). At a prevalence >10.3%, targeted screening with a risk-factor questionnaire was the most cost-effective option. Higher than a prevalence of 58.5%, universal TST was preferred. In the secondary model, targeted screening with a questionnaire followed by IGRA testing was cost-effective compared with no screening in the base case when the LTBI prevalence was >4.9%. Limitations There is no established gold standard for the diagnosis of LTBI. Results of any modeling task are limited by the accuracy of available data. Conclusions Prior to starting steroid therapy, only patients in areas with a high prevalence of LTBI will benefit from universal TST. As more evidence becomes available about the use of IGRA testing in children, the assay may become a component of cost-effective screening protocols in populations with a higher burden of LTBI.
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