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Background: Pediatric stewardship programs have been successful at reducing unnecessary antibiotic use. Data from nonfreestanding children's hospitals are currently limited. This study is an analysis of antibiotic use after implementation of an antimicrobial stewardship program at a community nonfreestanding children's hospital., Methods: In April 2013, an antimicrobial stewardship program that consisted of physician-group engagement and pharmacist prospective auditing and feedback was initiated. We compared antibiotic use in the preintervention period (April 2012 to March 2013) with that in the postintervention period (April 2013 to March 2015) in all units except the neonatal intensive care unit and the emergency department. In addition, drug-acquisition costs, antibiotic-specific use, death, length of stay, and case-mix index were examined., Results: Antibiotic use decreased by 16.8% (95% confidence interval, 18.0% to -9.2%; P < .001) in the postintervention period. Vancomycin use decreased by 38% (P = .001), whereas antipseudomonal β-lactam use was unaltered. Drug-acquisition cost savings were estimated to be $67 000/year over the 2-year postintervention period. Lengths of stay and mortality rates were unchanged in the postintervention period after adjusting for case-mix index., Conclusions: Implementation of a simple stewardship initiative with limited resources at a community nonfreestanding children's hospital effectively reduced antibiotic use without an overt negative impact on overall clinical outcomes. The results of this study suggest that nonfreestanding children's hospitals can achieve substantial reductions in antibiotic use despite limited resources., (© The Author 2016. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Individuals infected with Mycobacterium tuberculosis (Mtb) may develop symptoms and signs of disease (tuberculosis disease) or may have no clinical evidence of disease (latent tuberculosis infection [LTBI]). Tuberculosis disease is a leading cause of infectious disease morbidity and mortality worldwide, yet many questions related to its diagnosis remain., Methods: A task force supported by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America searched, selected, and synthesized relevant evidence. The evidence was then used as the basis for recommendations about the diagnosis of tuberculosis disease and LTBI in adults and children. The recommendations were formulated, written, and graded using the Grading, Recommendations, Assessment, Development and Evaluation (GRADE) approach., Results: Twenty-three evidence-based recommendations about diagnostic testing for latent tuberculosis infection, pulmonary tuberculosis, and extrapulmonary tuberculosis are provided. Six of the recommendations are strong, whereas the remaining 17 are conditional., Conclusions: These guidelines are not intended to impose a standard of care. They provide the basis for rational decisions in the diagnosis of tuberculosis in the context of the existing evidence. No guidelines can take into account all of the often compelling unique individual clinical circumstances., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: Individuals infected with Mycobacterium tuberculosis (Mtb) may develop symptoms and signs of disease (tuberculosis disease) or may have no clinical evidence of disease (latent tuberculosis infection [LTBI]). Tuberculosis disease is a leading cause of infectious disease morbidity and mortality worldwide, yet many questions related to its diagnosis remain., Methods: A task force supported by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America searched, selected, and synthesized relevant evidence. The evidence was then used as the basis for recommendations about the diagnosis of tuberculosis disease and LTBI in adults and children. The recommendations were formulated, written, and graded using the Grading, Recommendations, Assessment, Development and Evaluation (GRADE) approach., Results: Twenty-three evidence-based recommendations about diagnostic testing for latent tuberculosis infection, pulmonary tuberculosis, and extrapulmonary tuberculosis are provided. Six of the recommendations are strong, whereas the remaining 17 are conditional., Conclusions: These guidelines are not intended to impose a standard of care. They provide the basis for rational decisions in the diagnosis of tuberculosis in the context of the existing evidence. No guidelines can take into account all of the often compelling unique individual clinical circumstances., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Objectives: The optimal duration of antimicrobial prophylaxis following pediatric cardiac surgery is still debated. Adult studies suggest that shorter durations are adequate, but there is a paucity of data on pediatric patients., Methods: This quasi-experimental study reviewed the charts of patients 18 years and younger who underwent cardiac surgery from April 2011 to November 2014 at a single institution. Starting in April 2013, a protocol was implemented to limit antimicrobial prophylaxis to 48 hours following sternal closure. Two analyses were performed: (1) identification of risk factors for surgical site infections from the entire cohort, and (2) comparison of surgical site infection incidence in the pre- and postprotocol groups., Results: In the entire cohort, delayed sternal closure (adjusted odds ratio [OR], 5.7; 95% confidence interval [CI], 1.8-17.9) and younger age (adjusted OR, 2.1; 95% CI, 1.1-3.8) were associated with incidence of surgical site infection. Following the protocol change, duration of antimicrobial prophylaxis decreased from 4.2 ± 2.7 to 1.9 ± 1.3 days (P < .0001). After adjusting for age and delayed sternal closure, the postprotocol group had an adjusted OR of 0.98 (95% CI, 0.32-3.00) for occurrence of surgical site infection. Other outcomes were not altered following the protocol change., Conclusions: Restricting antimicrobial prophylaxis to 48 hours following pediatric cardiac surgery did not increase the incidence of surgical site infection at our institution. Further study is needed to validate this finding and to identify practices that reduce surgical site infections in those with delayed sternal closure., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: In the Federated States of Micronesia and then the Republic of the Marshall Islands (RMI), levofloxacin pharmacokinetics were studied in children receiving directly observed once-daily regimens (10 mg/kg, age >5 years; 15-20 mg/kg, age ≤5 years) for either multidrug-resistant tuberculosis disease or latent infection after multidrug-resistant tuberculosis exposure, to inform future dosing strategies., Methods: Blood samples were collected at 0 (RMI only), 1, 2 and 6 hours (50 children, aged 6 months to 15 years) after oral levofloxacin at >6 weeks of treatment. Clinical characteristics and maximal drug concentration (Cmax) of levofloxacin, elimination half-life and area under the curve from 0 to 24 hours (AUC0-24 hours × μg/mL) were correlated to determine the optimal dosage and to examine associations. Population pharmacokinetics and target attainment were modeled. With results from the Federated States of Micronesia, dosages were increased in RMI toward the target Cmax for Mycobacterium tuberculosis, 8-12 µg/mL., Results: Cmax correlated linearly with per-weight dosage. Neither Cmax nor half-life was associated with gender, age, body mass index, concurrent medications or predose meals. At levofloxacin dosage of 15-20 mg/kg, Cmax ≥8 µg/mL was observed, and modeling corroborated a high target attainment across the ratio of the area under the free concentration versus time curve to minimum inhibitory concentration (fAUCss,0-24/MIC) values., Conclusions: Levofloxacin dosage should be 15-20 mg/kg for Cmax ≥8 µg/mL and a high target attainment across fAUCss,0-24/MIC values in children ≥2 years of age., Competing Interests: The authors have no conflicts of interest or funding to disclose

Central nervous system tuberculosis (TB) was identified in 20 cases of unexplained encephalitis referred to the California Encephalitis Project. Atypical features (encephalitic symptoms, rapid onset, age) and diagnostic challenges (insensitive cerebrospinal fluid [CSF] TB PCR result, elevated CSF glucose levels in patients with diabetes, negative result for tuberculin skin test) complicated diagnosis.

Pediatric tuberculosis (TB) is different than that in adults in several ways. (1) The diagnosis of TB is more difficult in children due to non-specific or complete absence of symptoms and difficulty in confirming the diagnosis microbiologically. (2) Young children suffer more extrapulmonary and disseminated TB than adults. (3) Treatment of TB in children is challenging due to the lack of pediatric drug formulations and challenges in monitoring for toxicity. Fortunately, children generally do very well with treatment and tolerate the medications well. Treatment regimens are very similar to those used in adults. Four drug treatment should be initiated for treatment of presumed active TB if there are any risks of drug resistance in the child or adult source case (including residence or travel to an area where there is > 4% resistance to INH). (4) Children should be TB skin tested only if they have risks for TB infection, are likely to progress to active TB, or are suspected of having active TB. Unlike adults, all children should be treated for latent TB infection if identified because the therapy is very safe in young people, they were likely to have been infected relatively recently, and they have a long time to reactivate their latent infection. (5) Young children are not contagious with active TB and acquired their disease from shared airspace with adolescents or adults with pulmonary TB or ingestion of unpasturized milk products (M. bovis).

To better understand the molecular epidemiology of tuberculosis (TB) transmission for culture-confirmed patients <5 years of age, data were analyzed from a population-based study conducted in seven U.S. sites from 1996 to 2000. Mycobacterium tuberculosis isolates were genotyped with IS6110-based restriction fragment length polymorphism analysis and spoligotyping. Case-patient data were obtained from the Centers for Disease Control and Prevention s national tuberculosis registry and health department records. Routine public health investigations conducted by local health departments identified suspected source patients for 57 (51%) of 111 culture-confirmed patients <5 years of age. For 8 (15%) of 52 culture-confirmed patients <5 years of age and their suspected source patients with complete genotyping results, genotypes suggested infection with different TB strains. Potential differences between sources for patients <5 years of age and source patients that transmitted TB to adolescent and adult patients were identified.

Background: Antibiotic-resistant Gram-positive pathogens are an increasingly common cause of serious pediatric infections. Although quinupristin/dalfopristin demonstrates favorable activity against resistant Gram-positive pathogens (including many vancomycin-resistant and methicillin-resistant staphylococci), published experience in the pediatric patient population is limited., Methods: We retrospectively analyzed data from the global quinupristin/dalfopristin Emergency-Use Program, which enrolled patients with serious Gram-positive infections who had no further therapy options because of resistance to, failure on or intolerance to standard antibiotic treatments. Our subset included safety and efficacy data from pediatric patients (age <18 years). There were no restrictions on underlying diseases, severity of illness or prior/concomitant antimicrobial use., Results: Between May 1995 and October 1999, 127 pediatric patients with 131 infections were enrolled. Microbiologic confirmation of etiology was available in 124 patients. All patients had 1 or more concomitant conditions, including malignancy and solid organ or bone marrow transplantation. The most frequent causative pathogens were vancomycin-resistant (80%), spp. (7%), methicillin-resistant (6%) and (4%). All but 21 patients received intravenous quinupristin/dalfopristin 7.5 mg/kg every 8 h. The favorable clinical response rate of quinupristin/dalfopristin was 86 of 124 (69%); the favorable microbiologic response rate was 97 of 124 (78%). Eleven patients (8%) had nonvenous adverse events classified as possibly or probably related to quinupristin/dalfopristin., Conclusions: Quinupristin/dalfopristin demonstrated favorable response rates and was reasonably well-tolerated in pediatric patients with serious Gram-positive infections unable to receive alternative therapy. In our opinion quinupristin/dalfopristin is a therapeutic option for the management of such infections.

Background: Children with a perforated or gangrenous appendix become clinically stable after medical and/or surgical therapy but often remain in the hospital solely to complete parenteral antibiotic therapy. This prospective study investigates the outcomes when children who meet specified criteria are discharged to complete parenteral antibiotic therapy at home., Methods: Children age 1 to 17 years with appendicitis complicated by generalized peritonitis or intraabdominal abscess were eligible to participate. Subjects whose fever was decreasing, who were able to tolerate oral liquids and for whom further parenteral antibiotic therapy was deemed necessary were discharged from the hospital to receive outpatient parenteral antiinfective therapy (OPAT) with meropenem. Therapy was administered by a family member and supervised by home care nurses. Study personnel visited the home daily to collect data on adverse events, compliance and resource utilization. Pa tients served as their own controls in models of reduced hospitalization and net cost savings., Results: Discharged on average on the fourth postoperative day, 87 children received 4.5 +/- 2.1 days of OPAT. Six (7%) children were subsequently readmitted for complications including bowel obstruction (4 children), intraabdominal abscess (1 child) and pleural effusion (1 child). Another child developed a viral syndrome during OPAT. All other patients recovered uneventfully. Six (7%) children discontinued meropenem prematurely because of rash (4 patients) or diarrhea (2 patients). According to models in which each day of OPAT replaced a day of inpatient care, discharge to OPAT reduced hospitalization by 42 +/- 15% and saved a median of $2908 (10th to 90th percentile range, $1,077 to $4,707) per patient., Conclusion: Convalescent phase OPAT is a cost-effective alternative to continued hospitalization for children with complicated appendicitis who are clinically stable yet require further parenteral antibiotic therapy.

Rifampin has limited use in monotherapy because of the rapid development of resistance. In combination therapy with a variety of antimicrobials, it has many applications for treatment of serious infections.

Objective: To compare the yields of gastric aspirates collected for culture of Mycobacterium tuberculosis from children evaluated as outpatients versus inpatients and to determine factors associated with a positive culture., Methods: Retrospective study of 100 children <12 years of age with tuberculosis diagnosed at a pediatric referral hospital or in one of two tuberculosis control programs in California., Results: Of the 100 children who had tuberculosis, 80 had at least one gastric aspirate collected. M tuberculosis was isolated from 33 (41%) of the 80 children who had a gastric aspirate; 4 children had a positive culture from an aspirate subsequent to the first. Inpatients had a higher proportion of positive gastric aspirates than that of children who had aspirates collected as outpatients (48% vs 37%); however, this difference was not statistically significant. Resistance to isoniazid was found in three isolates (9%) of children all of whose presumptive source case had a susceptible strain of M tuberculosis. Characteristics that were associated with an approximately 50% yield from gastric aspirates were identification of a source case, age <2 years, birth in the United States, symptomatic tuberculosis, and pulmonary disease., Conclusions: The culture of M tuberculosis from gastric aspirates of children in the outpatient setting has a yield comparable to aspirates collected from hospitalized children. Collection of gastric aspirates in the outpatient setting will reduce both the cost and the inconvenience of the procedure. Although the yield from gastric aspirates is relatively low, important information including drug susceptibility patterns may be obtained. tuberculosis, gastric aspirate, children.

The incidence of acute rheumatic fever has varied over the past several decades. The usual source of case ascertainment has been medical record discharge diagnosis coding. By reviewing both the Children's Hospital of Pittsburgh medical records discharge data and the Division of Cardiology computer database for the years 1982 to 1993, 173 cases of acute rheumatic fever were identified including 63 patients who were managed exclusively as outpatients. Seventy-three percent of patients diagnosed before 1990 were managed as inpatients, compared with 48% of patients diagnosed 1990 and later. The incidence of acute rheumatic fever may be underestimated if patients managed without hospitalization are not identified.