Publications by authors named "Matthew P Kronman"

67 Publications

Clinical Practice Guideline by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America: 2021 Guideline on Diagnosis and Management of Acute Hematogenous Osteomyelitis in Pediatrics.

J Pediatric Infect Dis Soc 2021 Aug 5. Epub 2021 Aug 5.

Department of Medical Microbiology and Infection Control, Vancouver General Hospital, Vancouver, British Columbia, Canada.

This clinical practice guideline for the diagnosis and treatment of acute hematogenous osteomyelitis (AHO) in children was developed by a multidisciplinary panel representing Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA). This guideline is intended for use by healthcare professionals who care for children with AHO, including specialists in pediatric infectious diseases, orthopedics, emergency care physicians, hospitalists, and any clinicians and healthcare providers caring for these patients. The panel's recommendations for the diagnosis and treatment of AHO are based upon evidence derived from topic-specific systematic literature reviews. Summarized below are the recommendations for the diagnosis and treatment of AHO in children. The panel followed a systematic process used in the development of other IDSA and PIDS clinical practice guidelines, which included a standardized methodology for rating the certainty of the evidence and strength of recommendation using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. A detailed description of background, methods, evidence summary and rationale that support each recommendation, and knowledge gaps can be found online in the full text.
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http://dx.doi.org/10.1093/jpids/piab027DOI Listing
August 2021

Association Between Number of Intravenous Antipseudomonal Antibiotics and Clinical Outcomes of Pediatric Cystic Fibrosis Pulmonary Exacerbations.

Clin Infect Dis 2021 Jun 8. Epub 2021 Jun 8.

Division of Pulmonary & Sleep Medicine, Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA.

Background: Pulmonary exacerbations (PEx) in people with cystic fibrosis (PwCF) are associated with significant morbidity. While standard PEx treatment for PwCF with Pseudomonas aeruginosa infection includes two IV antipseudomonal antibiotics, little evidence exists to recommend this approach. This study aimed to compare clinical outcomes of single versus double antipseudomonal antibiotic use for PEx treatment.

Methods: Retrospective cohort study using the linked CF Foundation Patient Registry-Pediatric Health Information System dataset. PwCF were included if hospitalized between 2007-2018 and 6-21 years of age. Regression modeling accounting for repeated measures was used to compare lung function outcomes between single versus double IV antipseudomonal antibiotic regimens using propensity-score weighting to adjust for relevant confounding factors.

Results: Among 10,660 PwCF in the dataset, we analyzed 2,578 PEx from 1,080 PwCF, of which 455 and 2,123 PEx were treated with 1 versus 2 IV antipseudomonal antibiotics, respectively. We identified no significant differences between PEx treated with 1 versus 2 IV antipseudomonal antibiotics either in change between pre- and post-PEx percent predicted forced expiratory volume in one second (ppFEV1) (-0.84%, [95% CI -2.25, 0.56]; p=0.24), odds of returning to ≥90% of baseline ppFEV1 within 3 months following PEx (Odds Ratio 0.83, [95% CI 0.61, 1.13]; p=0.24) or time to next PEx requiring IV antibiotics (Hazard Ratio 1.04, [95% CI 0.87, 1.24]; p=0.69).

Conclusion: Use of 2 IV antipseudomonal antibiotics for PEx treatment in young PwCF was not associated with greater improvements in measured respiratory and clinical outcomes compared to treatment with 1 IV antipseudomonal antibiotic.
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http://dx.doi.org/10.1093/cid/ciab525DOI Listing
June 2021

Pediatric radiologic manifestations of COVID-19.

Clin Imaging 2021 Jul 30;75:165-170. Epub 2021 Mar 30.

Department of Radiology, University of Washington and Seattle Children's Hospital, 4800 Sand Point Way NE, Seattle, WA 98105, United States of America.

Purpose: While full description of pediatric COVID-19 manifestations is evolving, children appear to present less frequently, and often display a less severe disease phenotype. There is correspondingly less data regarding pediatric radiologic findings. To describe the imaging findings of pediatric COVID-19, we evaluated the radiologic imaging of the initial patient cohort identified at our institution.

Methods: In this IRB approved study, all patients at our institution aged 0-21 with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on PCR or immunoglobulin testing were identified. Imaging was reviewed by the co-authors and presence of abnormalities determined by consensus. Pre-existing comorbidities and alternative diagnoses were recorded. Rates of each finding were calculated. Findings were compared to published data following review of the available literature.

Results: Out of 130 Covid-19 positive patients, 24 patients underwent imaging, including 21 chest radiographs and 4 chest CT scans. Chest x-rays were normal in 33%. Patchy or streaky opacities were the most common radiographic abnormality, each seen in 38% of patients. CT findings included ill-defined or geographic ground glass opacities, dense opacities, septal thickening and crazy paving, and small pleural effusions. Results are similar to those reported in adults. Multiple COVID-19 positive children presented for symptoms due to an additional acute illness, including appendicitis and urinary infection.

Conclusions: Radiologic findings of COVID-19 in pediatric patients range from normal to severe ARDS type appearance. During this ongoing pandemic, these radiographic signs can be useful for the evaluation of disease status and guiding care, particularly in those with comorbidities.

Precis: Radiologic findings of COVID-19 in pediatric patients are similar to those seen in adults, and may range from normal to severe ARDS type appearance.
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http://dx.doi.org/10.1016/j.clinimag.2021.03.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008832PMC
July 2021

Antibiotic-Associated Adverse Events in Hospitalized Children.

J Pediatric Infect Dis Soc 2021 May;10(5):622-628

Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Background: Antibiotic-associated adverse events (AEs) in hospitalized children have not been comprehensively characterized.

Methods: We conducted a retrospective observational study of children hospitalized at The Johns Hopkins Hospital receiving ≥24 hours of systemic antibiotics. Consensus regarding antibiotic-associated AE definitions was established by 5 infectious diseases specialists prior to data collection. Two physicians reviewed potential AEs and determined whether they were more likely than not related to antibiotics after comprehensive manual chart review. Inpatient and post-discharge AEs were identified using the Epic Care Everywhere network. AEs evaluated from the initiation of antibiotics until 30 days after antibiotic completion included gastrointestinal, hematologic, hepatobiliary, renal, neurologic, dermatologic, cardiac, myositis, vascular access device-related events, and systemic reactions. Ninety-day AEs included Clostridioides difficile infections, multidrug-resistant organism infections, and clinically significant candidal infections. The impact of AEs was categorized as necessitating additional diagnostic testing, changes in medications, unplanned medical encounters, prolonged or new hospitalizations, or death.

Results: Among 400 antibiotic courses, 21% were complicated by at least one AE and 30% occurred post-discharge. Each additional day of antibiotics was associated with a 7% increased odds of an AE. Of courses complicated by an AE, 66% required further intervention. Hematologic, gastrointestinal, and renal AEs were the most common, accounting for 31%, 15%, and 11% of AEs, respectively. AEs complicated 35%, 35%, 19%, and 18% of courses of piperacillin-tazobactam, tobramycin, ceftazidime, and vancomycin, respectively.

Conclusions: More than 1 in 5 courses of antibiotics administered to hospitalized children are complicated by AEs. Clinicians should weigh the risk of harm against expected benefit when prescribing antibiotics.
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http://dx.doi.org/10.1093/jpids/piaa173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162628PMC
May 2021

Effect of Concomitant Azithromycin and Tobramycin Use on Cystic Fibrosis Pulmonary Exacerbation Treatment.

Ann Am Thorac Soc 2021 02;18(2):266-272

Division of Pulmonary and Sleep Medicine, Department of Pediatrics, Seattle Children's Hospital.

Pulmonary exacerbations (PExs) are associated with significant morbidity in people with cystic fibrosis (CF). Severe PExs are treated with intravenous antibiotics, including tobramycin. CF care guidelines recommend continuing chronic maintenance medications during PEx treatment. Azithromycin (AZM) is one of the most widely prescribed chronic medications for CF in the United States. Recent evidence has identified a potential antagonistic relationship between AZM and tobramycin. To determine whether, among PEx treated with intravenous tobramycin, concomitant AZM use is associated with worse clinical outcomes. Retrospective cohort study using the CF Foundation Patient Registry-Pediatric Health Information System (CFFPR-PHIS)-linked dataset. People with CF age 6-21 years were included if they were hospitalized between 2006 and 2016 for a PEx. Inverse probability of treatment weighing was used to minimize the effects of confounders, including indication bias. Associations of concomitant treatment with AZM and lung function outcomes were determined using linear mixed-effect models and generalized estimating equations. Cox proportional hazard regression models were used to evaluate associations with time to next PEx. Among the 10,660 people with CF included in the CFFPR-PHIS-linked dataset, 2,294 children and adolescents with 5,022 PExs that had intravenous tobramycin use were identified. A little less than half ( = 2,247; 45%) of all PExs were treated concomitantly with AZM and intravenous tobramycin. AZM use both at the most recent outpatient clinic encounter and during PEx treatment in combination with intravenous tobramycin was associated with a significantly lower absolute improvement in percentage-predicted forced expiratory volume in 1 second (ppFEV) (-0.93%; 95% confidence interval [CI], -1.78 to -0.07;  = 0.033), a lesser odds of returning to 90% or more of baseline ppFEV (odds ratio, 0.79; 95% CI, 0.68-0.93;  = 0.003), and a shorter time to next PEx requiring intravenous antibiotics (hazard ratio, 1.22; 95% CI, 1.14-1.31;  < 0.001) compared with intravenous tobramycin use without concomitant AZM. Concomitant AZM and intravenous tobramycin use for in-hospital PEx treatment was associated with poorer clinical outcomes than treatment with intravenous tobramycin without AZM. These results support the hypothesis that an antagonistic relationship between these two medications might exist.
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http://dx.doi.org/10.1513/AnnalsATS.202002-176OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869777PMC
February 2021

Reducing Antibiotic Prescribing in Primary Care for Respiratory Illness.

Pediatrics 2020 09 3;146(3). Epub 2020 Aug 3.

Kaiser Permanente Washington Health Research Institute, Seattle, Washington.

Background: One-third of outpatient antibiotic prescriptions for pediatric acute respiratory tract infections (ARTIs) are inappropriate. We evaluated a distance learning program's effectiveness for reducing outpatient antibiotic prescribing for ARTI visits.

Methods: In this stepped-wedge clinical trial run from November 2015 to June 2018, we randomly assigned 19 pediatric practices belonging to the Pediatric Research in Office Settings Network or the NorthShore University HealthSystem to 4 wedges. Visits for acute otitis media, bronchitis, pharyngitis, sinusitis, and upper respiratory infection for children 6 months to <11 years old without recent antibiotic use were included. Clinicians received the intervention as 3 program modules containing online tutorials and webinars on evidence-based communication strategies and antibioti c prescribing, booster video vignettes, and individualized antibiotic prescribing feedback reports over 11 months. The primary outcome was overall antibiotic prescribing rates for all ARTI visits. Mixed-effects logistic regression compared prescribing rates during each program module and a postintervention period to a baseline control period. Odds ratios were converted to adjusted rate ratios (aRRs) for interpretability.

Results: Among 72 723 ARTI visits by 29 762 patients, intention-to-treat analyses revealed a 7% decrease in the probability of antibiotic prescribing for ARTI overall between the baseline and postintervention periods (aRR 0.93; 95% confidence interval [CI], 0.90-0.96). Second-line antibiotic prescribing decreased for streptococcal pharyngitis (aRR 0.66; 95% CI, 0.50-0.87) and sinusitis (aRR 0.59; 95% CI, 0.44-0.77) but not for acute otitis media (aRR 0.93; 95% CI, 0.83-1.03). Any antibiotic prescribing decreased for viral ARTIs (aRR 0.60; 95% CI, 0.51-0.70).

Conclusions: This program reduced antibiotic prescribing during outpatient ARTI visits; broader dissemination may be beneficial.
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http://dx.doi.org/10.1542/peds.2020-0038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461202PMC
September 2020

Association of Inhaled Antibiotics in Addition to Standard Intravenous Therapy and Outcomes of Pediatric Inpatient Pulmonary Exacerbations.

Ann Am Thorac Soc 2020 12;17(12):1590-1598

Division of Pulmonary and Sleep Medicine, Department of Pediatrics.

Considerable morbidity and disease progression in people with cystic fibrosis (CF) result from pulmonary exacerbations (PExs). PEx guidelines note insufficient evidence to recommend for or against the concomitant use of inhaled and intravenous antibiotics. We hypothesize that the addition of inhaled antibiotics for PEx therapy is associated with improvements in lung function and a longer time to next PEx compared with standard intravenous antibiotics alone. We performed a retrospective cohort study using the CF Foundation Patient Registry-Pediatric Health Information System linked dataset. People with CF were included if they were hospitalized for PEx between 2006 and 2016 and 6 to 21 years of age. Lung function outcomes were assessed by linear mixed effect modeling and generalized estimating equations. The time to next PEx was assessed by Cox proportional hazards regression. To estimate independent causal effects while accounting for indication bias and other confounders, inverse probabilities of treatment weights were calculated based on covariates believed to influence the likelihood of inhaled antibiotic use during PEx treatment. A total of 3,253 children and adolescents contributed 9,040 PEx events for analysis. Inhaled antibiotics were used in 23% of PEx events but were not associated with better pre- to post-PEx percent predicted forced expiratory volume in 1 second responses (mean difference, -1.11%; 95% confidence interval [CI], -1.83 to -0.38;  = 0.003), higher odds of returning to lung function baseline (odds ratio, 0.94; 95% CI, 0.82 to 1.07;  = 0.34), or longer time to next PEx (hazard ratio, 1.05; 95% CI, 0.99 to 1.12;  = 0.098). The addition of inhaled antibiotics to standard intravenous antibiotic PEx treatment was not associated with improved lung function outcomes or a longer time to next PEx.
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http://dx.doi.org/10.1513/AnnalsATS.202002-179OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924435PMC
December 2020

The current state of antifungal stewardship among pediatric antimicrobial stewardship programs.

Infect Control Hosp Epidemiol 2020 11 14;41(11):1279-1284. Epub 2020 Jul 14.

Division of Pediatric Infectious Diseases, Department of Pediatrics, Stanford University, Stanford, California.

Objective: To characterize the current state of antifungal stewardship practices and perceptions of antifungal use among pediatric antimicrobial stewardship programs (ASPs).

Design: We developed and distributed an electronic survey, which included 17 closed-ended questions about institutional antifungal stewardship practices and perceptions, among pediatric ASPs.

Participants: ASP physicians and pharmacists of 74 hospitals participating in the multicenter Sharing Antimicrobial Reports for Pediatric Stewardship (SHARPS) Collaborative.

Results: We sent surveys to 74 hospitals and received 68 unique responses, for a response rate of 92%. Overall, 63 of 68 the respondent ASPs (93%) reported that they conduct 1 or more antifungal stewardship activities. Of these 68 hospital ASPs, 43 (63%) perform prospective audit and feedback (PAF) of antifungals. The most common reasons reported for not performing PAF of antifungals were not enough time or resources (19 of 25, 76%) and minimal institutional antifungal use (6 of 25, 24%). Also, 52 hospitals (76%) require preauthorization for 1 or more antifungal agents. The most commonly restricted antifungals were isavuconazole (42 of 52 hospitals, 80%) and posaconazole (39 of 52 hospitals, 75%). Furthermore, 33 ASPs (48%) agreed or strongly agreed that antifungals are inappropriately used at their institution, and only 25 of 68 (37%) of ASPs felt very confident making recommendations about antifungals.

Conclusions: Most pediatric ASPs steward antifungals, but the strategies employed are highly variable across surveyed institutions. Although nearly half of respondents identified inappropriate antifungal use as a problem at their institution, most ASPs do not feel confident making recommendations about antifungals. Future studies are needed to determine the rate of inappropriate antifungal use and the best antifungal stewardship strategies.
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http://dx.doi.org/10.1017/ice.2020.306DOI Listing
November 2020

Inappropriate antibiotic surgical prophylaxis in pediatric patients: A national point-prevalence study.

Infect Control Hosp Epidemiol 2020 04 4;41(4):477-479. Epub 2020 Mar 4.

Division of Pediatric Infectious Diseases, Department of Pediatrics, Washington University in St Louis, St Louis, Missouri.

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http://dx.doi.org/10.1017/ice.2020.28DOI Listing
April 2020

Appropriateness of Antibiotic Prescribing in United States Children's Hospitals: A National Point Prevalence Survey.

Clin Infect Dis 2020 11;71(8):e226-e234

Department of Pediatrics, Division of Pediatric Infectious Diseases, Washington University in St Louis, St Louis, Missouri, USA.

Background: Studies estimate that 30%-50% of antibiotics prescribed for hospitalized patients are inappropriate, but pediatric data are limited. Characterization of inappropriate prescribing practices for children is needed to guide pediatric antimicrobial stewardship.

Methods: Cross-sectional analysis of antibiotic prescribing at 32 children's hospitals in the United States. Subjects included hospitalized children with ≥ 1 antibiotic order at 8:00 am on 1 day per calendar quarter, over 6 quarters (quarter 3 2016-quarter 4 2017). Antimicrobial stewardship program (ASP) physicians and/or pharmacists used a standardized survey to collect data on antibiotic orders and evaluate appropriateness. The primary outcome was the percentage of antibiotics prescribed for infectious use that were classified as suboptimal, defined as inappropriate or needing modification.

Results: Of 34 927 children hospitalized on survey days, 12 213 (35.0%) had ≥ 1 active antibiotic order. Among 11 784 patients receiving antibiotics for infectious use, 25.9% were prescribed ≥ 1 suboptimal antibiotic. Of the 17 110 antibiotic orders prescribed for infectious use, 21.0% were considered suboptimal. Most common reasons for inappropriate use were bug-drug mismatch (27.7%), surgical prophylaxis > 24 hours (17.7%), overly broad empiric therapy (11.2%), and unnecessary treatment (11.0%). The majority of recommended modifications were to stop (44.7%) or narrow (19.7%) the drug. ASPs would not have routinely reviewed 46.1% of suboptimal orders.

Conclusions: Across 32 children's hospitals, approximately 1 in 3 hospitalized children are receiving 1 or more antibiotics at any given time. One-quarter of these children are receiving suboptimal therapy, and nearly half of suboptimal use is not captured by current ASP practices.
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http://dx.doi.org/10.1093/cid/ciaa036DOI Listing
November 2020

Ambulatory Antibiotic Prescribing for Children with Pneumonia After Publication of National Guidelines: A Cross-Sectional Retrospective Study.

Infect Dis Ther 2020 Mar 27;9(1):69-76. Epub 2019 Nov 27.

Pediatric Infectious Diseases, University of Utah, Salt Lake City, UT, USA.

Introduction: National guidelines published in 2011 recommend amoxicillin as first-line treatment for non-hospitalized children with community-acquired pneumonia (CAP). We aimed to understand visit rates, antibiotic selection, and factors associated with amoxicillin prescribing for children with CAP since guideline publication.

Methods: We performed a cross-sectional retrospective study of patients aged 90 days-18 years with an outpatient clinic or emergency department (ED) visit from 2008 to 2015 using the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey ED data files, respectively. We estimated the incidence rates of ambulatory CAP visits, examined time trends in antibiotics prescribed at CAP visits, and determined factors independently associated with first-line guideline-recommended antibiotic prescribing using multivariable logistic regression, including patient age, setting, and US census region.

Results: From 2008 to 2015, there were an estimated 1.5 million [95% confidence interval (CI) 1.3-1.7 million] pediatric CAP visits annually. Amoxicillin was prescribed in 23% (95% CI 18-30%), azithromycin was prescribed in 47% (95% CI 41-54%), and cephalosporins were prescribed in 26% (95% CI 21-31%) of antibiotic visits for CAP. There were no significant differences in annual CAP visits or prescribing by antibiotic class since guideline publication. Amoxicillin prescribing was significantly less likely in visits by older children, aged 5-18 years, [adjusted odds ratio (aOR) 0.22, 95% CI 0.10-0.49] compared to visits by younger children aged 90 days-4 years with CAP. Compared with the Northeast, amoxicillin prescribing was significantly lower in the Midwest (aOR 0.35, 95% CI 0.13-0.98) and South (aOR 0.23, 95% CI 0.08-0.63). Azithromycin prescribing was significantly more likely in visits to EDs (aOR 1.46, 95% CI 1.07-1.98) compared to physician offices.

Conclusion: Despite national guideline recommendations, amoxicillin prescribing for CAP in outpatient settings is low and azithromycin remains the predominant antibiotic prescribed, highlighting the need for dedicated antibiotic stewardship efforts in ambulatory settings.
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http://dx.doi.org/10.1007/s40121-019-00276-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054471PMC
March 2020

Reinfection rates following adherence to Infectious Diseases Society of America guideline recommendations in first cerebrospinal fluid shunt infection treatment.

J Neurosurg Pediatr 2019 Feb 15:1-9. Epub 2019 Feb 15.

Departments of1Pediatrics and.

OBJECTIVECSF shunt infection treatment requires both surgical and antibiotic decisions. Using the Hydrocephalus Clinical Research Network (HCRN) Registry and 2004 Infectious Diseases Society of America (IDSA) guidelines that were not proactively distributed to HCRN providers, the authors previously found high adherence to surgical recommendations but poor adherence to intravenous (IV) antibiotic duration recommendations. In general, IV antibiotic duration was longer than recommended. In March 2017, new IDSA guidelines expanded upon the 2004 guidelines by including recommendations for selection of specific antibiotics. The objective of this study was to describe adherence to both 2004 and 2017 IDSA guideline recommendations for CSF shunt infection treatment, and to report reinfection rates associated with adherence to guideline recommendations.METHODSThe authors investigated a prospective cohort of children younger than 18 years of age who underwent treatment for first CSF shunt infection at one of 7 hospitals from April 2008 to December 2012. CSF shunt infection was diagnosed by recovery of bacteria from CSF culture (CSF-positive infection). Adherence to 2004 and 2017 guideline recommendations was determined. Adherence to antibiotics was further classified as longer or shorter duration than guideline recommendations. Reinfection rates with 95% confidence intervals (CIs) were generated.RESULTSThere were 133 children with CSF-positive infections addressed by 2004 IDSA guideline recommendations, with 124 at risk for reinfection. Zero reinfections were observed among those whose treatment was fully adherent (0/14, 0% [95% CI 0%-20%]), and 15 reinfections were observed among those whose infection treatment was nonadherent (15/110, 14% [95% CI 8%-21%]). Among the 110 first infections whose infection treatment was nonadherent, 74 first infections were treated for a longer duration than guidelines recommended and 9 developed reinfection (9/74, 12% [95% CI 6%-22%]). There were 145 children with CSF-positive infections addressed by 2017 IDSA guideline recommendations, with 135 at risk for reinfection. No reinfections were observed among children whose treatment was fully adherent (0/3, 0% [95% CI 0%-64%]), and 18 reinfections were observed among those whose infection treatment was nonadherent (18/132, 14% [95% CI 8%-21%]).CONCLUSIONSThere is no clear evidence that either adherence to IDSA guidelines or duration of treatment longer than recommended is associated with reduction in reinfection rates. Because IDSA guidelines recommend shorter IV antibiotic durations than are typically used, improvement efforts to reduce IV antibiotic use in CSF shunt infection treatment can and should utilize IDSA guidelines.
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http://dx.doi.org/10.3171/2018.11.PEDS18373DOI Listing
February 2019

Antibiotic Prescribing for Children in United States Emergency Departments: 2009-2014.

Pediatrics 2019 02 8;143(2). Epub 2019 Jan 8.

Division of Infectious Diseases, Department of Pediatrics, University of Washington, Seattle, Washington.

: media-1vid110.1542/5972296744001PEDS-VA_2018-1056 OBJECTIVES: To characterize and compare ambulatory antibiotic prescribing for children in US pediatric and nonpediatric emergency departments (EDs).

Methods: A cross-sectional retrospective study of patients aged 0 to 17 years discharged from EDs in the United States was conducted by using the 2009-2014 National Hospital Ambulatory Medical Care Survey ED data. We estimated the proportion of ED visits resulting in antibiotic prescriptions, stratified by antibiotic spectrum, class, diagnosis, and ED type ("pediatric" defined as >75% of visits by patients aged 0-17 years, versus "nonpediatric"). Multivariable logistic regression was used to determine factors independently associated with first-line, guideline-concordant prescribing for acute otitis media, pharyngitis, and sinusitis.

Results: In 2009-2014, of the 29 million mean annual ED visits by children, 14% (95% confidence interval [CI]: 10%-20%) occurred at pediatric EDs. Antibiotics overall were prescribed more frequently in nonpediatric than pediatric ED visits (24% vs 20%, < .01). Antibiotic prescribing frequencies were stable over time. Of all antibiotics prescribed, 44% (95% CI: 42%-45%) were broad spectrum, and 32% (95% CI: 30%-34%, 2.1 million per year) were generally not indicated. Compared with pediatric EDs, nonpediatric EDs had a higher frequency of prescribing macrolides (18% vs 8%, < .0001) and a lower frequency of first-line, guideline-concordant prescribing for the respiratory conditions studied (77% vs 87%, < .001).

Conclusions: Children are prescribed almost 7 million antibiotic prescriptions in EDs annually, primarily in nonpediatric EDs. Pediatric antibiotic stewardship efforts should expand to nonpediatric EDs nationwide, particularly regarding avoidance of antibiotic prescribing for conditions for which antibiotics are not indicated, reducing macrolide prescriptions, and increasing first-line, guideline-concordant prescribing.
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http://dx.doi.org/10.1542/peds.2018-1056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581044PMC
February 2019

Route of administration for antibiotics with high oral bioavailability.

Infect Control Hosp Epidemiol 2019 Feb 27;40(2):248-249. Epub 2018 Dec 27.

Department of Pediatrics, Division of Pediatric Infectious Diseases, University of Utah, Salt Lake City, Utah.

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http://dx.doi.org/10.1017/ice.2018.329DOI Listing
February 2019

Getting Over Our Inpatient Oral Antibiotic Aversion.

Pediatrics 2018 12;142(6)

Division of Infectious Diseases, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

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http://dx.doi.org/10.1542/peds.2018-1634DOI Listing
December 2018

Effect of Congenital Heart Disease Status on Trends in Pediatric Infective Endocarditis Hospitalizations in the United States Between 2000 and 2012.

Pediatr Cardiol 2019 Feb 10;40(2):319-329. Epub 2018 Nov 10.

Seattle Children's Hospital, RC.2.820, PO Box 5371, Seattle, WA, 98145-5005, USA.

The purpose of this study was to create national estimates for the incidence of pediatric infective endocarditis (IE) in the United States and to determine if these changed after the implementation of the 2007 American Heart Association IE guidelines. It also sought to determine the effect of congenital heart disease (CHD) status on outcomes in IE. Hospital discharges with the diagnosis of IE in patients < 18 years old from the Kids' Inpatient Database were identified from the years 2000, 2003, 2006, 2009, and 2012. Discharges were grouped into Pre- and Post-2007 groups to facilitate analysis surrounding the implementation of the guidelines in 2007. Patients were categorized by age, underlying CHD, and etiologic organism. Descriptive comparisons and changes in categorical variables were made between groups. Average annual IE hospitalization rates before and after the 2007 guidelines were 10.8 and 9.3 per 1,000,000 children, respectively. The proportion of IE patients with CHD was stable between time periods, (45% vs. 47%, p = 0.50). Mortality was higher in the Post-2007 time period for CHD patients than non-CHD patients (11.1% vs. 2.4%, respectively; p < 0.001), while there was no difference noted during the Pre-2007 time period (6.5% vs. 6.6%, respectively; p = 0.95). Streptococcus was more common among CHD patients than non-CHD patients (27% vs. 17%), while Staphylococcus was more common among non-CHD patients than CHD patients (34% vs. 24%, p < 0.001). Even though the incidence of IE was stable over time, mortality was higher in CHD patients after the implementation of the 2007 AHA IE prophylaxis guidelines.
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http://dx.doi.org/10.1007/s00246-018-2020-7DOI Listing
February 2019

Epidemiology of Staphylococcus aureus infections in patients admitted to freestanding pediatric hospitals, 2009-2016.

Infect Control Hosp Epidemiol 2018 12 29;39(12):1487-1490. Epub 2018 Oct 29.

14Division of Pediatric Infectious Diseases,Department of Pediatrics,School of Medicine,University of Utah,Salt Lake City,Utah.

We observed pediatric S. aureus hospitalizations decreased 36% from 26.3 to 16.8 infections per 1,000 admissions from 2009 to 2016, with methicillin-resistant S. aureus (MRSA) decreasing by 52% and methicillin-susceptible S. aureus decreasing by 17%, among 39 pediatric hospitals. Similar decreases were observed for days of therapy of anti-MRSA antibiotics.
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http://dx.doi.org/10.1017/ice.2018.259DOI Listing
December 2018

The Burden and Impact of Antibiotic Prescribing in Ambulatory Pediatrics.

Curr Probl Pediatr Adolesc Health Care 2018 11 16;48(11):272-288. Epub 2018 Oct 16.

Division of Infectious Diseases, Children's National Medical Center, Washington, D.C., United States; Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, D.C., United States. Electronic address:

Antibiotics are one of the most commonly prescribed classes of medication for children and adolescents. While they are arguably the most powerful tool we possess against bacterial infections, they are frequently given to children whose illnesses are due to viruses or other non-infectious etiologies. When antibiotics are not used judiciously, the consequences can be serious and accumulate over time. This review article quantifies the burden of antimicrobial use in the pediatric outpatient setting in the United States, reviews recommended first line antibiotic regimens for common outpatient pediatric and adolescent conditions, investigates the reasons for inappropriate prescribing of antibiotics in outpatient healthcare settings, and explores the range of consequences of overuse and inappropriate use of antibiotics, from adverse drug reactions to impact on the microbiome to rising rates of antimicrobial resistance in common ambulatory conditions.
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http://dx.doi.org/10.1016/j.cppeds.2018.09.002DOI Listing
November 2018

Patient and Treatment Characteristics by Infecting Organism in Cerebrospinal Fluid Shunt Infection.

J Pediatric Infect Dis Soc 2019 Jul;8(3):235-243

Department of Pediatrics, University of Washington/Seattle Children's Hospital, Washington.

Background: Previous studies of cerebrospinal fluid (CSF) shunt infection treatment have been limited in size and unable to compare patient and treatment characteristics by infecting organism. Our objective was to describe variation in patient and treatment characteristics for children with first CSF shunt infection, stratified by infecting organism subgroups outlined in the 2017 Infectious Disease Society of America's (IDSA) guidelines.

Methods: We studied a prospective cohort of children <18 years of age undergoing treatment for first CSF shunt infection at one of 7 Hydrocephalus Clinical Research Network hospitals from April 2008 to December 2012. Differences between infecting organism subgroups were described using univariate analyses and Fisher's exact tests.

Results: There were 145 children whose infections were diagnosed by CSF culture and addressed by IDSA guidelines, including 47 with Staphylococcus aureus, 52 with coagulase-negative Staphylococcus, 37 with Gram-negative bacilli, and 9 with Propionibacterium acnes. No differences in many patient and treatment characteristics were seen between infecting organism subgroups, including age at initial shunt, gender, race, insurance, indication for shunt, gastrostomy, tracheostomy, ultrasound, and/or endoscope use at all surgeries before infection, or numbers of revisions before infection. A larger proportion of infections were caused by Gram-negative bacilli when antibiotic-impregnated catheters were used at initial shunt placement (12 of 23, 52%) and/or subsequent revisions (11 of 23, 48%) compared with all other infections (9 of 68 [13%] and 13 of 68 [19%], respectively). No differences in reinfection were observed between infecting organism subgroups.

Conclusions: The organism profile encountered at infection differs when antibiotic-impregnated catheters are used, with a higher proportion of Gram-negative bacilli. This warrants further investigation given increasing adoption of antibiotic-impregnated catheters.
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http://dx.doi.org/10.1093/jpids/piy035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601384PMC
July 2019

Variability in Antibiotic Use Across PICUs.

Pediatr Crit Care Med 2018 06;19(6):519-527

Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO.

Objectives: To characterize and compare antibiotic prescribing across PICUs to evaluate the degree of variability.

Design: Retrospective analysis from 2010 through 2014 of the Pediatric Health Information System.

Setting: Forty-one freestanding children's hospital.

Subjects: Children aged 30 days to 18 years admitted to a PICU in children's hospitals contributing data to Pediatric Health Information System.

Interventions: To normalize for potential differences in disease severity and case mix across centers, a subanalysis was performed of children admitted with one of the 20 All Patient Refined-Diagnosis Related Groups and the seven All Patient Refined-Diagnosis Related Groups shared by all PICUs with the highest antibiotic use.

Results: The study included 3,101,201 hospital discharges from 41 institutions with 386,914 PICU patients. All antibiotic use declined during the study period. The median-adjusted antibiotic use among PICU patients was 1,043 days of therapy/1,000 patient-days (interquartile range, 977-1,147 days of therapy/1,000 patient-days) compared with 893 among non-ICU children (interquartile range, 805-968 days of therapy/1,000 patient-days). For PICU patients, the median adjusted use of broad-spectrum antibiotics was 176 days of therapy/1,000 patient-days (interquartile range, 152-217 days of therapy/1,000 patient-days) and was 302 days of therapy/1,000 patient-days (interquartile range, 220-351 days of therapy/1,000 patient-days) for antimethicillin-resistant Staphylococcus aureus agents, compared with 153 days of therapy/1,000 patient-days (interquartile range, 130-182 days of therapy/1,000 patient-days) and 244 days of therapy/1,000 patient-days (interquartile range, 203-270 days of therapy/1,000 patient-days) for non-ICU children. After adjusting for potential confounders, significant institutional variability existed in antibiotic use in PICU patients, in the 20 All Patient Refined-Diagnosis Related Groups with the highest antibiotic usage and in the seven All Patient Refined-Diagnosis Related Groups shared by all 41 PICUs.

Conclusions: The wide variation in antibiotic use observed across children's hospital PICUs suggests inappropriate antibiotic use.
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http://dx.doi.org/10.1097/PCC.0000000000001535DOI Listing
June 2018

Reinfection after treatment of first cerebrospinal fluid shunt infection: a prospective observational cohort study.

J Neurosurg Pediatr 2018 04 2;21(4):346-358. Epub 2018 Feb 2.

6Division of Pediatric Neurosurgery, Primary Children's Hospital, Department of Neurosurgery, University of Utah, Salt Lake City, Utah.

OBJECTIVE CSF shunt infection requires both surgical and antibiotic treatment. Surgical treatment includes either total shunt removal with external ventricular drain (EVD) placement followed by new shunt insertion, or distal shunt externalization followed by new shunt insertion once the CSF is sterile. Antibiotic treatment includes the administration of intravenous antibiotics. The Hydrocephalus Clinical Research Network (HCRN) registry provides a unique opportunity to understand reinfection following treatment for CSF shunt infection. This study examines the association of surgical and antibiotic decisions in the treatment of first CSF shunt infection with reinfection. METHODS A prospective cohort study of children undergoing treatment for first CSF infection at 7 HCRN hospitals from April 2008 to December 2012 was performed. The HCRN consensus definition was used to define CSF shunt infection and reinfection. The key surgical predictor variable was surgical approach to treatment for CSF shunt infection, and the key antibiotic treatment predictor variable was intravenous antibiotic selection and duration. Cox proportional hazards models were constructed to address the time-varying nature of the characteristics associated with shunt surgeries. RESULTS Of 233 children in the HCRN registry with an initial CSF shunt infection during the study period, 38 patients (16%) developed reinfection over a median time of 44 days (interquartile range [IQR] 19-437). The majority of initial CSF shunt infections were treated with total shunt removal and EVD placement (175 patients; 75%). The median time between infection surgeries was 15 days (IQR 10-22). For the subset of 172 infections diagnosed by CSF culture, the mean ± SD duration of antibiotic treatment was 18.7 ± 12.8 days. In all Cox proportional hazards models, neither surgical approach to infection treatment nor overall intravenous antibiotic duration was independently associated with reinfection. The only treatment decision independently associated with decreased infection risk was the use of rifampin. While this finding did not achieve statistical significance, in all 5 Cox proportional hazards models both surgical approach (other than total shunt removal at initial CSF shunt infection) and nonventriculoperitoneal shunt location were consistently associated with a higher hazard of reinfection, while the use of ultrasound was consistently associated with a lower hazard of reinfection. CONCLUSIONS Neither surgical approach to treatment nor antibiotic duration was associated with reinfection risk. While these findings did not achieve statistical significance, surgical approach other than total removal at initial CSF shunt infection was consistently associated with a higher hazard of reinfection in this study and suggests the feasibility of controlling and standardizing the surgical approach (shunt removal with EVD placement). Considerably more variation and equipoise exists in the duration and selection of intravenous antibiotic treatment. Further consideration should be given to the use of rifampin in the treatment of CSF shunt infection. High-quality studies of the optimal duration of antibiotic treatment are critical to the creation of evidence-based guidelines for CSF shunt infection treatment.
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http://dx.doi.org/10.3171/2017.9.PEDS17112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5880734PMC
April 2018

Characteristics of Pediatric Antimicrobial Stewardship Programs: Current Status of the Sharing Antimicrobial Reports for Pediatric Stewardship (SHARPS) Collaborative.

Antibiotics (Basel) 2018 Jan 25;7(1). Epub 2018 Jan 25.

Division of Pediatric Infectious Diseases, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, USA.

In response to the growing epidemic of antibiotic-resistant bacterial infections, antimicrobial stewardship programs (ASP) have been rapidly implemented in the United States (US). This study examines the prevalence of the Centers for Disease Control and Prevention's (CDC) seven core elements of a successful ASP within a large subset of US Children's Hospitals. In 2016, a survey was conducted of 52 pediatric hospitals assessing the presence of the seven core elements: leadership commitment, accountability, drug expertise, action, tracking, reporting, and education. Forty-nine hospitals (94%) had established ASPs and 41 hospitals (79%) included all seven core elements. Physician accountability (87%) and a dedicated ASP pharmacist or drug expert (88%) were present in the vast majority of hospitals. However, substantial variability existed in the financial support allotted to these positions. This variability did not predict program actions, tracking, reporting, and education. When compared with previous surveys, these results document a dramatic increase in the prevalence and resources of pediatric stewardship programs, although continued expansion is warranted. Further research is required to understand the feasibility of various core stewardship activities and the impact on patient outcomes in the setting of finite resources.
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http://dx.doi.org/10.3390/antibiotics7010004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5872115PMC
January 2018

Improving Antibiotic Prescribing for Children With Urinary Tract Infection in Emergency and Urgent Care Settings.

Pediatr Emerg Care 2020 Jun;36(6):e332-e339

From the Departments of Infectious Diseases.

Objectives: Children with urinary tract infection (UTI) are often diagnosed in emergency and urgent care settings and increasingly are unnecessarily treated with broad-spectrum antibiotics. This study evaluated the effect of a quality improvement intervention on empiric antibiotic prescribing for the treatment of uncomplicated UTI in children.

Methods: A local clinical pathway for uncomplicated UTI, introduced in June 2010, recommended empiric treatment with cephalexin, a narrow-spectrum (first-generation) cephalosporin antibiotic. A retrospective quasi-experimental study of pediatric patients older than 1 month presenting to emergency and urgent care settings from January 1, 2009, to December 31, 2014, with uncomplicated UTI was conducted. Hospitalized patients and those with chronic conditions or urogenital abnormalities were excluded. Control charts and interrupted time-series analysis were used to analyze the primary outcome of narrow-spectrum antibiotic prescribing rates and the balancing measures of 72-hour revisits, resistant bacterial isolates, and subsequent inpatient admissions for UTI.

Results: A total of 2134 patients were included. There was an immediate and sustained significant increase in cephalexin prescribing before (19.2%) versus after (79.6%) pathway implementation and a concurrent significant decline in oral third-generation cephalosporin (cefixime) prescribing from 50.3% to 4.0%. There was no significant increase in 72-hour revisits, resistant bacterial isolates, or inpatient admissions for UTI.

Conclusions: A clinical pathway produced a significant and sustained increase in narrow-spectrum empiric antibiotic prescribing for pediatric UTI. Increased empiric cephalexin prescribing did not result in increased treatment failures or adverse patient outcomes. Future studies on implementing clinical pathways for children outside a pediatric hospital network are needed.
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http://dx.doi.org/10.1097/PEC.0000000000001342DOI Listing
June 2020

Expanding Existing Antimicrobial Stewardship Programs in Pediatrics: What Comes Next.

J Pediatric Infect Dis Soc 2018 Aug;7(3):241-248

Division of Infectious Diseases, Department of Pediatrics, Washington University, St. Louis, Missouri.

The prevalence of pediatric antimicrobial stewardship programs (ASPs) is increasing in acute care facilities across the United States. Over the past several years, the evidence base used to inform effective stewardship practices has expanded, and regulatory interest in stewardship programs has increased. Here, we review approaches for established, hospital-based pediatric ASPs to adapt and report standardized metrics, broaden their reach to specialized populations, expand to undertake novel stewardship initiatives, and implement rapid diagnostics to continue their evolution in improving antimicrobial use and patient outcomes.
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http://dx.doi.org/10.1093/jpids/pix104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7107461PMC
August 2018

Trends in Intravenous Antibiotic Duration for Urinary Tract Infections in Young Infants.

Pediatrics 2017 Dec 2;140(6). Epub 2017 Nov 2.

Division of Pediatric Infectious Disease and.

Objectives: To assess trends in the duration of intravenous (IV) antibiotics for urinary tract infections (UTIs) in infants ≤60 days old between 2005 and 2015 and determine if the duration of IV antibiotic treatment is associated with readmission.

Methods: Retrospective analysis of infants ≤60 days old diagnosed with a UTI who were admitted to a children's hospital and received IV antibiotics. Infants were excluded if they had a previous surgery or comorbidities, bacteremia, or admission to the ICU. Data were analyzed from the Pediatric Health Information System database from 2005 through 2015. The primary outcome was readmission within 30 days for a UTI.

Results: The proportion of infants ≤60 days old receiving 4 or more days of IV antibiotics (long IV treatment) decreased from 50% in 2005 to 19% in 2015. The proportion of infants ≤60 days old receiving long IV treatment at 46 children's hospitals varied between 3% and 59% and did not correlate with readmission (correlation coefficient 0.13; = .37). In multivariable analysis, readmission for a UTI was associated with younger age and female sex but not duration of IV antibiotic therapy (adjusted odds ratio for long IV treatment: 0.93 [95% confidence interval 0.52-1.67]).

Conclusions: The proportion of infants ≤60 days old receiving long IV treatment decreased substantially from 2005 to 2015 without an increase in hospital readmissions. These findings support the safety of short-course IV antibiotic therapy for appropriately selected neonates.
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http://dx.doi.org/10.1542/peds.2017-1021DOI Listing
December 2017

Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infections in Pediatric Hematopoietic Stem Cell Transplant Recipients.

J Pediatric Infect Dis Soc 2018 Feb;7(1):e6-e8

Center for Clinical and Translational Research, Seattle Children's Hospital Research Institute, Washington.

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http://dx.doi.org/10.1093/jpids/pix076DOI Listing
February 2018

Accuracy of Administrative Data for Antimicrobial Administration in Hospitalized Children.

J Pediatric Infect Dis Soc 2018 Aug;7(3):261-263

Division of Infectious Diseases, Children's Hospital of Philadelphia, Pennsylvania.

Administrative data are often used as a proxy for medication-administration record (MAR) data. Multicenter MAR data were compared retrospectively with administrative data from January 2010 through June 2013 from the Pediatric Health Information Systems database. We found that administrative data were more concordant with bill-upon-administration than bill-upon-dispense data.
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http://dx.doi.org/10.1093/jpids/pix064DOI Listing
August 2018

Extended Versus Narrow-spectrum Antibiotics in the Management of Uncomplicated Appendicitis in Children: A Propensity-matched Comparative Effectiveness Study.

Ann Surg 2018 07;268(1):186-192

Department of Surgery, Boston Children's Hospital - Harvard Medical School, Boston, MA.

Objective: The aim of this study was to compare the effectiveness of extended versus narrow spectrum antibiotics in preventing surgical site infections (SSIs) and hospital revisits in children with uncomplicated appendicitis.

Summary Of Background Data: There is a paucity of high-quality evidence in the pediatric literature comparing the effectiveness of extended versus narrow-spectrum antibiotics in the prevention of SSIs associated with uncomplicated appendicitis.

Methods: Clinical data from the ACS NSQIP-Pediatric Appendectomy Pilot Project were merged with antibiotic utilization data from the Pediatric Health Information System database for patients undergoing appendectomy for uncomplicated appendicitis at 17 hospitals from January 1, 2013 to June 30, 2015. Patients who received piperacillin/tazobactam (extended spectrum) were compared with those who received either cefoxitin or ceftriaxone with metronidazole (narrow spectrum) after propensity matching on demographic and severity characteristics. Study outcomes were 30-day SSI and hospital revisit rates.

Results: Of the 1389 patients included, 39.1% received piperacillin/tazobactam (range by hospital: 0% to 100%), and the remainder received narrow-spectrum agents. No differences in demographics or severity characteristics were found between groups following matching. In the matched analysis, the rates of SSI were similar between groups [extended spectrum: 2.4% vs narrow spectrum 1.8% (odds ratio, OR: 1.05, 95% confidence interval, 95% CI 0.34-3.26)], as was the rate of revisits [extended spectrum: 7.9% vs narrow spectrum 5.1% (OR: 1.46, 95% CI 0.75-2.87)].

Conclusions: Use of extended-spectrum antibiotics was not associated with lower rates of SSI or hospital revisits when compared with narrow-spectrum antibiotics in children with uncomplicated appendicitis. Our results challenge the routine use of extended-spectrum antibiotics observed at many hospitals, particularly given the increasing incidence of antibiotic-resistant organisms.
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http://dx.doi.org/10.1097/SLA.0000000000002349DOI Listing
July 2018

Development and Application of an Antibiotic Spectrum Index for Benchmarking Antibiotic Selection Patterns Across Hospitals.

Infect Control Hosp Epidemiol 2017 08 31;38(8):993-997. Epub 2017 May 31.

6Antimicrobial Stewardship Program,Office of Safety and Medical Operations,Children's Hospital of Philadelphia,Philadelphia,Pennsylvania.

Standard metrics for antimicrobial use consider volume but not spectrum of antimicrobial prescribing. We developed an antibiotic spectrum index (ASI) to classify commonly used antibiotics based on activity against important pathogens. The application of this index to hospital antibiotic use reveals how this tool enhances current antimicrobial stewardship metrics. Infect Control Hosp Epidemiol 2017;38:993-997.
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http://dx.doi.org/10.1017/ice.2017.94DOI Listing
August 2017
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