Publications by authors named "Monica I Ardura"

34 Publications

SARS-CoV-2 and pediatric solid organ transplantation: Current knowns and unknowns.

Pediatr Transplant 2021 Mar 10:e13986. Epub 2021 Mar 10.

Department of Pediatrics, Infectious Diseases and Host Defense, Nationwide Children's Hospital, The Ohio State University, Columbus, OH, USA.

The COVID-19 pandemic has proven to be a challenge in regard to the clinical presentation, prevention, diagnosis, and management of SARS-CoV-2 infection among children who are candidates for and recipients of SOT. By providing scenarios and frequently asked questions encountered in routine clinical practice, this document provides expert opinion and summarizes the available data regarding the prevention, diagnosis, and management of SARS-CoV-2 infection among pediatric SOT candidates and recipients and highlights ongoing knowledge gaps requiring further study. Currently available data are still lacking in the pediatric SOT population, but data have emerged in both the adult SOT and general pediatric population regarding the approach to COVID-19. The document provides expert opinion regarding prevention, diagnosis, and management of SARS-CoV-2 infection among pediatric SOT candidates and recipients.
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http://dx.doi.org/10.1111/petr.13986DOI Listing
March 2021

Promoting safe sexual practices and sexual health maintenance in pediatric and young adult solid organ transplant recipients.

Pediatr Transplant 2021 Feb 25;25(1):e13949. Epub 2021 Jan 25.

Pediatric Nephrology, Children's National Health System, Washington, DC, USA.

The majority of Americans make their sexual debut during their adolescent years. Preventing pregnancy and STI during this period is vital to ensuring health and safety. As survival has improved after pediatric SOT, chronically immunosuppressed adolescents seek guidance in their medical home on matters of sexual health. Transplant practitioners often do not feel equipped to fully address these needs. This review serves as an introductory sexual preventive care resource for adolescent and young adult (AYA) SOT recipients. First, we review data on safety, efficacy, and use of contraceptive options currently available for transplant recipients with child-bearing potential. Then, we suggest a personalized sexual health discussion focusing on the diagnosis and prevention of STIs in adolescent and young adult transplant recipients. Finally, we present recommendations for STI screening of asymptomatic patients, use of index of suspicion and diagnostic testing in symptomatic patients, and opportunities to optimize STI prevention strategies. Data compiled from studies of adult SOT recipients, general population studies, and published guidelines are often extrapolated for use, as limited data exist in AYA SOT recipients. This informational dearth underscores the need for future research to better characterize the unique needs of AYA SOT recipients.
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http://dx.doi.org/10.1111/petr.13949DOI Listing
February 2021

Diarrhea in the pediatric solid organ transplantation recipient: A multidisciplinary approach to diagnosis and management.

Pediatr Transplant 2021 Mar 3;25(2):e13886. Epub 2020 Nov 3.

Department of Pediatrics, Division of Infectious Diseases & Host Defense Program, Nationwide Children's Hospital & The Ohio State University, Columbus, OH, USA.

Diarrhea in the pediatric solid organ transplantation (SOT) recipient is a frequent complaint that is associated with significant morbidity and impaired quality of life. There are limited published data regarding the specific epidemiology, diagnostic evaluation, and treatment of diarrhea after SOT in children. Pediatric SOT recipients have an increased risk of developing diarrhea because of a generalized immunosuppressed state, epidemiologic exposures, and polypharmacy. There is a need to standardize the diagnostic evaluation of diarrhea in children after SOT to facilitate an accurate diagnosis and timely treatment. Herein, we review the available published data and propose a systematic, stepwise approach to the evaluation of diarrhea in this high-risk population, focusing on timely diagnosis of both infectious and non-infectious causes, in order to provide focused management. Prospective studies are needed to better assess the true prevalence, risk factors for, etiologies, and complications of diarrhea in pediatric SOT patients that will guide optimal management. Development of effective vaccines and antiviral therapies for enteric viruses may also contribute to improved outcomes.
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http://dx.doi.org/10.1111/petr.13886DOI Listing
March 2021

Osteomyelitis Due to Mycobacterium goodii in an Adolescent, United States.

Emerg Infect Dis 2020 11;26(11):2781-2783

Osteomyelitis is a rare clinical manifestation of infection with nontuberculous mycobacteria (NTM). We report an adolescent with femoral osteomyelitis associated with prosthetic material due to an emerging pathogen, Mycobacterium goodii. Application of secA1 and 16S ribosomal RNA gene sequencing reliably determined the NTM species, enabling targeted antimicrobial therapy.
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http://dx.doi.org/10.3201/eid2611.200206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588509PMC
November 2020

Severe SARS-CoV-2 disease in the context of a NF-κB2 loss-of-function pathogenic variant.

J Allergy Clin Immunol 2021 Feb 30;147(2):532-544.e1. Epub 2020 Sep 30.

Department of Pediatrics, Nationwide Children's Hospital and The Ohio State University College of Medicine, Columbus, Ohio; Center for Vaccines and Immunity, The Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, Ohio; Division of Infectious Diseases, Nationwide Children's Hospital, Columbus, Ohio.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that emerged recently and has created a global pandemic. Symptomatic SARS-CoV-2 infection, termed coronavirus disease 2019 (COVID-19), has been associated with a host of symptoms affecting numerous organ systems, including the lungs, cardiovascular system, kidney, central nervous system, gastrointestinal tract, and skin, among others.

Objective: Although several risk factors have been identified as related to complications from and severity of COVID-19, much about the virus remains unknown. The host immune response appears to affect the outcome of disease. It is not surprising that patients with intrinsic or secondary immune compromise might be particularly susceptible to complications from SARS-CoV-2 infection. Pathogenic loss-of-function or gain-of-function heterozygous variants in nuclear factor-κB2 have been reported to be associated with either a combined immunodeficiency or common variable immunodeficiency phenotype.

Methods: We evaluated the functional consequence and immunologic phenotype of a novel NFKB2 loss of function variant in a 17-year-old male patient and describe the clinical management of SARS-CoV-2 infection in this context.

Results: This patient required a 2-week hospitalization for SARS-CoV-2 infection, including 7 days of mechanical ventilation. We used biologic therapies to avert potentially fatal acute respiratory distress syndrome and treat hyperinflammatory responses. The patient had an immunologic phenotype of B-cell dysregulation with decreased switched memory B cells. Despite the underlying immune dysfunction, he recovered from the infection with intense management.

Conclusions: This clinical case exemplifies some of the practical challenges in management of patients with SARS-CoV-2 infection, especially in the context of underlying immune dysregulation.
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http://dx.doi.org/10.1016/j.jaci.2020.09.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525247PMC
February 2021

Management and prevention of varicella and measles infections in pediatric solid organ transplant candidates and recipients: An IPTA survey of current practice.

Pediatr Transplant 2020 12 23;24(8):e13830. Epub 2020 Sep 23.

Department of Women, Children and Adolescents, Division of General Pediatrics, Children's Hospital, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.

Background: Varicella and measles infections can be life-threatening after solid organ transplantation (SOT) but may be preventable with live-attenuated vaccines (LAV).

Methods: This survey conducted in January 2019 among subscribers of the International Pediatric Transplantation Association listserv aimed to explore the current strategies to prevent and manage both infections in the pediatric SOT population, including recommending LAV after SOT.

Results: The answers given by 95 pediatric SOT healthcare workers show that these strategies are not yet optimal and call for further education. In particular, 59% of respondents are unnecessarily waiting for a SOT candidate to be >1 year of age to start administrating LAV before SOT. Interestingly, most respondents are willing to administer LAV after SOT (57%), and a fifth (21%) are already doing so, off-label. The survey queried the precautions taken to improve safety evaluations after LAV, and identified knowledge gaps and practitioners' concerns.

Conclusion: The results of this survey could be used as a starting point for education and promotion of the safe administration of LAV in carefully selected SOT recipients; in turn, this would increase available data that would contribute to the development of evidence-based guidelines by the transplant societies and ultimately prevent these infections after SOT.
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http://dx.doi.org/10.1111/petr.13830DOI Listing
December 2020

Impact of a Best Practice Prevention Bundle on Central Line-associated Bloodstream Infection (CLABSI) Rates and Outcomes in Pediatric Hematology, Oncology, and Hematopoietic Cell Transplantation Patients in Inpatient and Ambulatory Settings.

J Pediatr Hematol Oncol 2021 01;43(1):e64-e72

Department of Pediatrics, Division of Infectious Diseases.

Background: Pediatric hematology, oncology, and hematopoietic cell transplantation (HCT) patients are at increased risk for bloodstream infections. The authors sought to evaluate the influence of a standardized best practice central venous catheter (CVC) maintenance bundle on the burden of and risk factors for mucosal barrier injury (MBI) and non-MBI central line-associated bloodstream infections (CLABSIs) across a common inpatient and ambulatory continuum in this high-risk population.

Methods: A retrospective cohort study of patients with underlying malignancy, hematologic disorders, and HCT recipients with a CVC in place at the time of CLABSI diagnosis in both inpatient and ambulatory settings from January 1, 2012 to December 31, 2016. Descriptive, nonparametric statistics were used to describe patient characteristics and outcomes. Logistic regression analyses were applied to identify potential risk factors for inpatient versus ambulatory and MBI versus non-MBI CLABSI.

Results: During the 5-year period, 118 of 808 (14.6%) patients had 159 laboratory-confirmed CLABSIs for ambulatory and inpatient CLABSI rates of 0.27 CLABSI/1000 and 2.2 CLABSI/1000 CVC days, respectively. CLABSI occurred more frequently in hospitalized patients after HCT and with underlying leukemia, most frequently caused by Gram-negative bacteria. MBI CLABSI accounted for 42% of all CLABSI with a 3-fold higher risk in hospitalized patients. Having multiple CVC or a CVC that was not a port independently associated with higher CLABSI risk.

Conclusions: In our cohort, non-MBI CLABSI continued to account for the majority of CLABSI. CVC type is independently associated with higher overall CLABSI risk. Further studies are needed to reliably define additional prevention strategies when CLABSI maintenance bundles elements are optimized in this high-risk population.
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http://dx.doi.org/10.1097/MPH.0000000000001950DOI Listing
January 2021

Return to School for Pediatric Solid Organ Transplant Recipients in the United States During the Coronavirus Disease 2019 Pandemic: Expert Opinion on Key Considerations and Best Practices.

J Pediatric Infect Dis Soc 2020 Nov;9(5):551-563

Division of Infectious Diseases and Host Defense, Nationwide Children's Hospital, Columbus, Ohio, USA.

The coronavirus disease 2019 (COVID-19) pandemic has created many challenges for pediatric solid organ transplant (SOT) recipients and their families. As the pandemic persists, patients and their families struggle to identify the best and safest practices for resuming activities as areas reopen. Notably, decisions about returning to school remain difficult. We assembled a team of pediatric infectious diseases (ID), transplant ID, public health, transplant psychology, and infection prevention and control specialists to address the primary concerns about school reentry for pediatric SOT recipients in the United States. Based on available literature and guidance from national organizations, we generated consensus statements pertaining to school reentry specific to pediatric SOT recipients. Although data are limited and the COVID-19 pandemic is highly dynamic, our goal was to create a framework from which providers and caregivers can identify the most important considerations for each pediatric SOT recipient to promote a safe return to school.
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http://dx.doi.org/10.1093/jpids/piaa095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454776PMC
November 2020

Pneumocystis jirovecii and toxoplasmosis prophylaxis strategies among pediatric organ transplantation recipients: A US National Survey.

Transpl Infect Dis 2020 Aug 28;22(4):e13290. Epub 2020 Apr 28.

Division of Infectious Diseases and Host Defense Program, Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University, Columbus, OH, USA.

There is a paucity of pediatric-specific data to guide consensus recommendations for the prevention of Pneumocystis jirovecii pneumonia (PCP) and toxoplasmosis after solid organ transplantation. We surveyed pediatric transplantation providers and found considerable variability in prophylaxis strategies, despite current guideline recommendations that are based primarily on adult data.
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http://dx.doi.org/10.1111/tid.13290DOI Listing
August 2020

A multicenter study to define the epidemiology and outcomes of Clostridioides difficile infection in pediatric hematopoietic cell and solid organ transplant recipients.

Am J Transplant 2020 08 10;20(8):2133-2142. Epub 2020 Mar 10.

Department of Pediatrics, Albert Einstein College of Medicine and Children's Hospital at Montefiore, Bronx, New York, USA.

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.
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http://dx.doi.org/10.1111/ajt.15826DOI Listing
August 2020

Incidence, Risk Factors, and Outcomes of Patients Who Develop Mucosal Barrier Injury-Laboratory Confirmed Bloodstream Infections in the First 100 Days After Allogeneic Hematopoietic Stem Cell Transplant.

JAMA Netw Open 2020 01 3;3(1):e1918668. Epub 2020 Jan 3.

Division of Hematology/Oncology, The University of North Carolina at Chapel Hill.

Importance: Patients undergoing hematopoietic stem cell transplant (HSCT) are at risk for bloodstream infection (BSI) secondary to translocation of bacteria through the injured mucosa, termed mucosal barrier injury-laboratory confirmed bloodstream infection (MBI-LCBI), in addition to BSI secondary to indwelling catheters and infection at other sites (BSI-other).

Objective: To determine the incidence, timing, risk factors, and outcomes of patients who develop MBI-LCBI in the first 100 days after HSCT.

Design, Setting, And Participants: A case-cohort retrospective analysis was performed using data from the Center for International Blood and Marrow Transplant Research database on 16 875 consecutive pediatric and adult patients receiving a first allogeneic HSCT from January 1, 2009, to December 31, 2016. Patients were classified into 4 categories: MBI-LCBI (1481 [8.8%]), MBI-LCBI and BSI-other (698 [4.1%]), BSI-other only (2928 [17.4%]), and controls with no BSI (11 768 [69.7%]). Statistical analysis was performed from April 5 to July 17, 2018.

Main Outcomes And Measures: Demographic characteristics and outcomes, including overall survival, chronic graft-vs-host disease, and transplant-related mortality (only for patients with malignant disease), were compared among groups.

Results: Of the 16 875 patients in the study (9737 [57.7%] male; median [range] age, 47 [0.04-82] years) 13 686 (81.1%) underwent HSCT for a malignant neoplasm, and 3189 (18.9%) underwent HSCT for a nonmalignant condition. The cumulative incidence of MBI-LCBI was 13% (99% CI, 12%-13%) by day 100, and the cumulative incidence of BSI-other was 21% (99% CI, 21%-22%) by day 100. Median (range) time from transplant to first MBI-LCBI was 8 (<1 to 98) days vs 29 (<1 to 100) days for BSI-other. Multivariable analysis revealed an increased risk of MBI-LCBI with poor Karnofsky/Lansky performance status (hazard ratio [HR], 1.21 [99% CI, 1.04-1.41]), cord blood grafts (HR, 2.89 [99% CI, 1.97-4.24]), myeloablative conditioning (HR, 1.46 [99% CI, 1.19-1.78]), and posttransplant cyclophosphamide graft-vs-host disease prophylaxis (HR, 1.85 [99% CI, 1.38-2.48]). One-year mortality was significantly higher for patients with MBI-LCBI (HR, 1.81 [99% CI, 1.56-2.12]), BSI-other (HR, 1.81 [99% CI, 1.60-2.06]), and MBI-LCBI plus BSI-other (HR, 2.65 [99% CI, 2.17-3.24]) compared with controls. Infection was more commonly reported as a cause of death for patients with MBI-LCBI (139 of 740 [18.8%]), BSI (251 of 1537 [16.3%]), and MBI-LCBI plus BSI (94 of 435 [21.6%]) than for controls (566 of 4740 [11.9%]).

Conclusions And Relevance: In this cohort study, MBI-LCBI, in addition to any BSIs, were associated with significant morbidity and mortality after HSCT. Further investigation into risk reduction should be a clinical and scientific priority in this patient population.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.18668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6991246PMC
January 2020

Previsit Planning Improves Pneumococcal Vaccination Rates in Childhood-Onset SLE.

Pediatrics 2020 01;145(1)

Infectious Diseases and Host Defense, Department of Pediatrics, The Ohio State University and Nationwide Children's Hospital, Columbus, Ohio.

Background: Childhood-onset systemic lupus erythematosus (c-SLE) is a complex autoimmune disease that requires systemic immunosuppressive therapy. Infections are the second leading cause of death in these patients, with invasive pneumococcal infections being a major preventable cause of morbidity and mortality. Pneumococcal vaccination is recommended in this population; however, vaccination rates remain low.

Methods: The plan-do-study-act method of quality improvement was applied. We calculated baseline vaccination rates for pneumococcal conjugate and pneumococcal polysaccharide vaccines in patients with c-SLE in the rheumatology clinic from January 2015 to August 2016. We developed an age-based algorithm to simplify the vaccination guidelines. The clinical pharmacist and nurses performed weekly previsit planning to update vaccine records, make targeted recommendations, and ensure vaccine availability. The primary outcome measure was the percentage patients with of c-SLE seen per month who had received age-appropriate pneumococcal vaccination.

Results: The percentage of children receiving at least 1 pneumococcal vaccine increased from 24.9% to 92.7% by 12 months. By 18 months, the compliance rate with both pneumococcal vaccines increased from 2.5% to 87.3%, with sustained results. No serious adverse events or disease flares were reported.

Conclusions: By identifying the major barriers to pneumococcal vaccination in our population with c-SLE, we significantly improved vaccination rates while decreasing time burden on providers. We attribute our success to a team-based quality improvement approach and plan to implement alerts in the electronic health record to streamline the process.
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http://dx.doi.org/10.1542/peds.2018-3141DOI Listing
January 2020

Central Venous Catheter Management in High-risk Children With Bloodstream Infections.

Pediatr Infect Dis J 2020 01;39(1):17-22

From the Department of Pediatrics, Division of Infectious Diseases.

Background: National guidelines recommend removal of central venous catheters (CVCs) for central line-associated bloodstream infections (CLABSIs) caused by Staphylococcus aureus, Pseudomonas aeruginosa, and fungi. Data regarding guideline compliance and rates of associated treatment failures in pediatric patients with attempted CVC salvage are limited.

Methods: We performed a retrospective analysis of high-risk children (age ≤ 21 years) hospitalized from 1/2009 to 12/2015 with a long-term CVC and CLABSI due to S. aureus, Pseudomonas spp., and Candida spp. Enterococcus spp. was included given differing management recommendations between short and long-term CVCs. Compliance with national guideline recommendations, as well as treatment failures including infection relapse, recurrence, and death were evaluated in relation to CVC retention or removal. Multivariate logistic regression modeling was performed to account for confounders impacting treatment failure.

Results: Fifty-three children had 108 CLABSI episodes requiring 84 hospitalizations. CVCs were removed in 36 (33%) CLABSI episodes per guideline recommendations. Optimal antimicrobial management, including targeted agent and adequate duration was provided in 54 (50%) of 106 treated episodes; no significant difference in treatment failure rates were noted compared with episodes with suboptimal management. The treatment failure rate was significantly higher in patients with CVC retention compared those with CVC removal within 7 days of the first positive blood culture (31% vs. 6%, P = 0.003).

Conclusions: Despite pathogen-specific guideline recommendations for CVC removal, compliance with national guidelines was poor. CVC salvage was attempted in the majority of CLABSI episodes in our cohort and resulted in a significantly higher treatment failure rate.
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http://dx.doi.org/10.1097/INF.0000000000002495DOI Listing
January 2020

Human parvovirus B19 in solid organ transplantation: Guidelines from the American society of transplantation infectious diseases community of practice.

Clin Transplant 2019 09 11;33(9):e13535. Epub 2019 Apr 11.

Department of Pediatrics, Infectious Diseases and Host Defense, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio.

Clinical manifestations of human parvovirus B19 infection can vary widely and may be atypical in solid organ transplant (SOT) recipients. However, disease is apparent when there is destruction of erythrocyte progenitor cells leading to severe acute or chronic anemia with lack of an appropriate reticulocyte response in the setting of active parvovirus B19 infection. Serology may not reliably establish the diagnosis. High-level viremia is more likely to be associated with symptomatic disease. Conversely, ongoing DNAemia after infection may not be clinically significant, if detected at low levels. Despite lack of robust data, intravenous immunoglobulin (IVIG) is frequently used for the treatment of SOT recipients with symptomatic parvovirus B19 infection. Although the optimal dosage and duration of IVIG is not known, most patients receive a total of 2 g/kg over a period of 2-5 days. A daily dose of 1 g/kg or more seems to be associated with higher incidence of toxicity. Application of standard and droplet isolation precautions remains the cornerstone for preventing human parvovirus B19 transmission. Additional research is needed to assess the efficacy of current and novel therapies and to develop a safe and effective parvovirus B19 vaccine.
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http://dx.doi.org/10.1111/ctr.13535DOI Listing
September 2019

Broad-range PCR Application in a Large Academic Pediatric Center: Clinical Value and Challenges in Diagnosis of Infectious Diseases.

Pediatr Infect Dis J 2019 08;38(8):786-790

Infectious Diseases, Host Defense Program, Nationwide Children's Hospital and The Ohio State University, Columbus, Ohio.

Background: Broad-range polymerase chain reaction (BR-PCR) detects infectious pathogens from clinical specimens using targets for bacteria (16S rRNA), fungi (28S rDNA), and mycobacteria (fluorescence resonance energy transfer and heat shock protein 65 gene) with reported diagnostic sensitivity and specificity ranging from 43% to 100% and 100%, respectively. We describe our experience when applying BR-PCR to clinical samples submitted for conventional infectious disease testing [conventional testing (CT)] from pediatric patients with concern for infection.

Methods: Retrospective analysis of clinical samples obtained from Nationwide Children's Hospital microbiology laboratory from January 2011 to December 2014 and sent for BR-PCR. Medical record review collected data on patient characteristics, clinical manifestations, laboratory results and antimicrobials prescribed, and a determination of clinical value of BR-PCR was assigned.

Results: There were 247 clinical samples from 163 patients identified; 71 (44%) patients were immunocompromised and 192 (78%) samples reflected pretreatment with antimicrobials. A clinically significant putative organism was identified for 59 samples (24%) between all diagnostic modalities. Conventional testing identified organisms in 41 (17%) samples, 17 of which were corroborated by BR-PCR. Broad-range polymerase chain reaction identified an organism in an additional 18 samples with negative CT results and was considered to provide additional important clinical information. Broad-range polymerase chain reaction detected a bacterial or fungal organism more frequently from tissue samples than from bronchoalveolar lavage or other fluid samples (P = 0.0096, χ).

Conclusions: In our cohort, BR-PCR was an important adjunctive diagnostic in identifying bacteria and fungi in complex clinical situations. Additional data are needed to define the optimal clinical circumstances and specimen type in which BR-PCR can provide the highest diagnostic yield.
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http://dx.doi.org/10.1097/INF.0000000000002308DOI Listing
August 2019

Infections among pediatric transplant candidates: An approach to decision-making.

Pediatr Transplant 2019 05 5;23(3):e13375. Epub 2019 Mar 5.

The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.

Introduction: The presence of infections in the immediate pretransplant period poses challenges in decision-making. Delaying transplantation because of these infections may be required, but is associated with a risk to the potential recipient. The aim of this project was to develop a structured framework based on expert opinion to guide decision-making regarding the safety of transplantation for candidates with infection immediately before transplant, and to show how this framework can be applied to clinical scenarios.

Methods: Categories were created as follows: Category A: no delay; Category B: brief delay (≤1 week); Category C: intermediate delay (>1 week); and Category D: more prolonged or indefinite delay. A survey containing 59 clinical scenarios was sent to members of the IPTA ID CARE committee. Answers were reviewed, and the level of agreement was characterized as follows: Level 1: ≥75% agreement; Level 2:51%-74% agreement; and Level 3: ≤50% agreement. 95% CIs were calculated for the mean overall agreement across 59 scenarios.

Results: Among the panel, the agreement level ranged from 33% to 92% with the mean overall agreement across the 59 scenarios being 61%. For 7/59 scenarios, the lower bound of 95% CI was greater than 50%, indicating a difference at the 5% level of significance between the observed proportion and the chance level of 0.5.

Summary: The document provides expert opinion regarding the need to delay transplantation in the setting of different infections. The most important points in the decision to proceed to SOT included the urgency of transplantation and the severity of infection.
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http://dx.doi.org/10.1111/petr.13375DOI Listing
May 2019

Pediatric Histoplasmosis in an Area of Endemicity: A Contemporary Analysis.

J Pediatric Infect Dis Soc 2019 Nov;8(5):400-407

Division of Infectious Diseases and Host Defense Program.

Background: Data on pediatric histoplasmosis have been limited to those from outbreak and case reports. We sought to evaluate the contemporary clinical manifestations, laboratory findings, and outcomes in children with histoplasmosis living in an area of endemicity.

Methods: This study was a single-center retrospective review of proven and probable cases of histoplasmosis in children aged 0 to 18 years between April 2008 and April 2014. Case ascertainment was ensured by us using International Classification of Diseases, Ninth Revision codes cross-referenced with laboratory, microbiology, and histopathology tests that detected Histoplasma capsulatum. Demographics, diagnostics, clinical management, and outcomes were evaluated.

Results: Seventy-three children with histoplasmosis (41 males; median age, 13 years [range, 3-18 years]) were diagnosed with proven (n = 17 [23%]) or probable (n = 56 [77%]) histoplasmosis, which manifested as pulmonary (n = 52 [71%]) or disseminated (n = 21 [29%]) disease. Symptoms at presentation were nonspecific; the examination of 21 (29%) patients revealed abnormal physical findings. Detection of H capsulatum by serologic methods occurred in 93% (63 of 68) of the patients tested. Histoplasma antigen in blood or urine was detected in 42% (20 of 48) and 28% (15 of 53) of the patients tested, respectively. The 16 (22%) patients who were immunocompromised had significantly higher rates of disseminated disease (56% vs 21%, respectively; P = .01), antigenuria (62% vs 18%, respectively; P = .004), and antigenemia (69% vs 31%, respectively; P = .02) and longer durations of antigenuria (403 vs 120 days, respectively; P = .003) and antigenemia (451 vs 149 days, respectively; P < .0001) than did the immunocompetent children.

Conclusions: Pediatric histoplasmosis manifests most frequently as pulmonary disease. The highest diagnostic yield was achieved when multiple diagnostic modalities were used. Presentation with disseminated disease and evidence of antigenemia, antigenuria, and delayed antigen clearance were more likely to be seen in immunocompromised children.
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http://dx.doi.org/10.1093/jpids/piy073DOI Listing
November 2019

Ascites in a Young Woman With Inflammatory Bowel Disease.

J Pediatric Infect Dis Soc 2018 Aug;7(3):264-266

Division of Pediatric Infectious Diseases, Department of Pediatrics, Nationwide Children's Hospital-The Ohio State University College of Medicine, Columbus.

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http://dx.doi.org/10.1093/jpids/pix080DOI Listing
August 2018

Overview of Infections Complicating Pediatric Hematopoietic Cell Transplantation.

Authors:
Monica I Ardura

Infect Dis Clin North Am 2018 03;32(1):237-252

Pediatric Infectious Diseases, Host Defense Program, The Ohio State University, Nationwide Children's Hospital, 700 Children's Drive, C5C-J5428, Columbus, OH 43205, USA. Electronic address:

Hematopoietic cell transplantations (HCT) are increasingly being performed in children for the treatment of malignant and nonmalignant diseases. Infections remain an important cause of morbidity and mortality after HCT, where the type and timing of infection is influenced by host, transplant, and pathogen-related factors. Herein, an overview of the epidemiology of infections is presented and organized by timing before and after HCT, understanding that infection may occur at any time point until there is successful immune reconstitution.
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http://dx.doi.org/10.1016/j.idc.2017.11.003DOI Listing
March 2018

Acanthamoeba granulomatous amoebic encephalitis after pediatric hematopoietic stem cell transplant.

Pediatr Transplant 2017 Dec 17;21(8). Epub 2017 Sep 17.

Department of Pediatrics, Division of Hematology/Oncology/BMT, Nationwide Children's Hospital and The Ohio State University, Columbus, OH, USA.

Acanthamoeba encephalitis is a rare, often fatal condition, particularly after HSCT, with 9 reported cases to date in the world literature. Our case was originally diagnosed with ALL at age 3 years, and after several relapses underwent HSCT at age 9 years. At 17 years of age, he was diagnosed with secondary AML for which he underwent a second allogeneic HSCT. He presented with acute-onset worsening neurological deficits on day +226 after the second transplant and a post-mortem diagnosis of Acanthamoeba encephalitis was established, with the aid of the CDC.
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http://dx.doi.org/10.1111/petr.13060DOI Listing
December 2017

Successful Treatment of Bloodstream Infection Due to Metallo-β-Lactamase-Producing Stenotrophomonas maltophilia in a Renal Transplant Patient.

Antimicrob Agents Chemother 2016 09 22;60(9):5130-4. Epub 2016 Aug 22.

Department of Infectious Diseases, Infection Control, and Employee Health, and Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

Stenotrophomonas maltophilia is an emerging multidrug-resistant (MDR) opportunistic pathogen for which new antibiotic options are urgently needed. We report our clinical experience treating a 19-year-old renal transplant recipient who developed prolonged bacteremia due to metallo-β-lactamase-producing S. maltophilia refractory to conventional treatment. The infection recurred despite a prolonged course of colistimethate sodium (colistin) but resolved with the use of a novel drug combination with clinical efficacy against the patient's S. maltophilia isolate.
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http://dx.doi.org/10.1128/AAC.00264-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997835PMC
September 2016

A protracted course of Pneumocystis pneumonia in the setting of an immunosuppressed child with GMS-negative bronchoalveolar lavage.

Med Mycol Case Rep 2016 Mar 25;11:48-52. Epub 2016 Apr 25.

University of Pittsburgh, RK Mellon Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, United States.

We report a case of Pneumocystis pneumonia in a 5-year-old male with Trisomy 21 and acute lymphoblastic leukemia. The lack of response to trimethoprim-sulfamethoxazole raised concerns for antimicrobial resistance. Further, diagnosis of Pneumocystis in this patient was complicated by a GMS-negative bronchoalveolar lavage despite molecular evidence of Pneumocystis infection.
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http://dx.doi.org/10.1016/j.mmcr.2016.04.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4857217PMC
March 2016

NASPGHAN Clinical Report: Surveillance, Diagnosis, and Prevention of Infectious Diseases in Pediatric Patients With Inflammatory Bowel Disease Receiving Tumor Necrosis Factor-α Inhibitors.

J Pediatr Gastroenterol Nutr 2016 07;63(1):130-55

*Infectious Diseases and Immunology, Host Defense Program, Nationwide Children's Hospital, The Ohio State University, Columbus, OH†Pediatric Infectious Diseases, Weill Cornell Medical Center, New York, NY‡Pediatric Infectious Diseases, Children's Medical Center Dallas, University of Texas Southwestern, Dallas, TX§Cohen Children's Medical Center, Hofstra North Shore-LIJ School of Medicine, Lake Success, NY||Pediatric Gastroenterology, Boston Children's Hospital, Harvard Medical School, Boston, MA#Division of Gastroenterology, Hepatology, and Nutrition, Nationwide Children's Hospital, The Ohio State University, Columbus, OH.

Children and adolescents with inflammatory bowel disease (IBD) receiving therapy with tumor necrosis factor α inhibitors (anti-TNFα) pose a unique challenge to health care providers in regard to the associated risk of infection. Published experience in adult populations with distinct autoinflammatory and autoimmune diseases treated with anti-TNFα therapies demonstrates an increased risk of serious infections with intracellular bacteria, mycobacteria, fungi, and some viruses; however, there is a paucity of robust pediatric data. With a rising incidence of pediatric IBD and increasing use of biologic therapies, heightened knowledge and awareness of infections in this population is important for primary care pediatricians, pediatric gastroenterologists, and infectious disease (ID) physicians. This clinical report is the result of a consensus review performed by pediatric ID and gastroenterology physicians detailing relevant published literature regarding infections in pediatric patients with IBD receiving anti-TNFα therapies. The objective of this document is to provide comprehensive information for prevention, surveillance, and diagnosis of infections based on current knowledge, until additional pediatric data are available to inform evidence-based recommendations.
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http://dx.doi.org/10.1097/MPG.0000000000001188DOI Listing
July 2016

Cytomegalovirus Meningitis in an Infant with Severe Combined Immunodeficiency.

J Pediatr 2016 Jun 17;173:235-7. Epub 2016 Mar 17.

Division of Pediatric Infectious Diseases, Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH; Center for Perinatal Research, Division of Neonatology, Department of Pediatrics, Nationwide Children's Hospital and The Ohio State University, Columbus, OH.

A 35-day-old female with severe combined immunodeficiency developed cytomegalovirus (CMV) meningitis before undergoing hematopoietic stem cell transplantation. Strategies for timely diagnosis of neonates with congenital or acquired CMV infection and prevention of CMV acquisition in the era of universal newborn severe combined immunodeficiency screening are needed.
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http://dx.doi.org/10.1016/j.jpeds.2016.02.054DOI Listing
June 2016

Recurrent Streptococcus equi subsp. zooepidemicus Bacteremia in an Infant.

J Clin Microbiol 2015 Sep 15;53(9):3096-9. Epub 2015 Jul 15.

Department of Pediatrics, Infectious Diseases and Immunology, Nationwide Children's Hospital, and The Ohio State University, Columbus, Ohio, USA

We describe a case of an infant with recurrent bacteremia caused by Streptococcus equi subsp. zooepidemicus, likely transmitted from mother to infant. Our case highlights the importance of an epidemiological history and molecular diagnostics in ascertaining insights into transmission, pathogenesis, and optimal management.
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http://dx.doi.org/10.1128/JCM.01306-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4540932PMC
September 2015

Central catheter-associated bloodstream infection reduction with ethanol lock prophylaxis in pediatric intestinal failure: broadening quality improvement initiatives from hospital to home.

JAMA Pediatr 2015 Apr;169(4):324-31

Gastroenterology, Hepatology, and Nutrition, Nationwide Children's Hospital and The Ohio State University, Columbus.

Importance: Children with intestinal failure are at high risk for developing central catheter-associated bloodstream infections (CCABSIs) owing to children's chronic dependence on central venous catheters for parenteral nutrition.

Objective: To evaluate the effectiveness and safety of the addition of ethanol lock prophylaxis to a best-practice CCABSI prevention bundle on hospital and ambulatory CCABSI rates in children with intestinal failure.

Design, Setting, And Participants: Quality improvement and statistical process control analysis that took place at a tertiary care pediatric hospital and patient homes. Participants included children who were 18 years or younger with intestinal failure requiring a central venous catheter.

Interventions: Central catheter-associated bloodstream infection prevention bundle that included daily ethanol lock prophylaxis.

Main Outcomes And Measures: Central catheter-associated bloodstream infection rates and safety outcomes (central catheter insertions, repairs, and hospitalizations) before (January 1, 2011-January 31, 2012) and after (February 1, 2012-December 31, 2013) ethanol lock prophylaxis bundle implementation.

Results: Twenty-four children with intestinal failure received the ethanol lock prophylaxis CCABSI prevention bundle for a median of 266 days (range, 12-635 days). Rates of CCABSI decreased from 6.99 CCABSIs per 1000 catheter days at baseline to 0.42 CCABSI per 1000 catheter days after ethanol lock prophylaxis bundle implementation, despite an increase in the total number of catheter days. A subset of 14 children who received prolonged ethanol lock prophylaxis (≥3 months) had fewer median (range) central catheter insertions 0 (0-2) vs 3 (0-6); P = .001. The pre-ELP intervention CCABSI rates in this subset was 7.01 per 1000 catheter days vs 0.64 per 1000 catheter days for post-ELP intervention (P = .004). There were no significant differences in the total number of hospital admissions; however, there were fewer hospitalizations for fever and CCABSI (P = .003).

Conclusions And Relevance: A best-practice CCABSI prevention bundle that included ethanol lock prophylaxis in both the hospital and home was successfully implemented, well tolerated, and demonstrated a significant and sustained reduction in preventable harm in the form of CCABSIs in children with intestinal failure.
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http://dx.doi.org/10.1001/jamapediatrics.2014.3291DOI Listing
April 2015

Whole blood gene expression profiles to assess pathogenesis and disease severity in infants with respiratory syncytial virus infection.

PLoS Med 2013 Nov 12;10(11):e1001549. Epub 2013 Nov 12.

Division of Pediatric Infectious Disease, The Research Institute at Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, Ohio, United States of America ; Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, Ohio, United States of America.

Background: Respiratory syncytial virus (RSV) is the leading cause of viral lower respiratory tract infection (LRTI) and hospitalization in infants. Mostly because of the incomplete understanding of the disease pathogenesis, there is no licensed vaccine, and treatment remains symptomatic. We analyzed whole blood transcriptional profiles to characterize the global host immune response to acute RSV LRTI in infants, to characterize its specificity compared with influenza and human rhinovirus (HRV) LRTI, and to identify biomarkers that can objectively assess RSV disease severity.

Methods And Findings: This was a prospective observational study over six respiratory seasons including a cohort of infants hospitalized with RSV (n = 135), HRV (n = 30), and influenza (n = 16) LRTI, and healthy age- and sex-matched controls (n = 39). A specific RSV transcriptional profile was identified in whole blood (training cohort, n = 45 infants; Dallas, Texas, US) and validated in three different cohorts (test cohort, n = 46, Dallas, Texas, US; validation cohort A, n = 16, Turku, Finland; validation cohort B, n = 28, Columbus, Ohio, US) with high sensitivity (94% [95% CI 87%-98%]) and specificity (98% [95% CI 88%-99%]). It classified infants with RSV LRTI versus HRV or influenza LRTI with 95% accuracy. The immune dysregulation induced by RSV (overexpression of neutrophil, inflammation, and interferon genes, and suppression of T and B cell genes) persisted beyond the acute disease, and immune dysregulation was greatly impaired in younger infants (<6 mo). We identified a genomic score that significantly correlated with outcomes of care including a clinical disease severity score and, more importantly, length of hospitalization and duration of supplemental O2.

Conclusions: Blood RNA profiles of infants with RSV LRTI allow specific diagnosis, better understanding of disease pathogenesis, and assessment of disease severity. This study opens new avenues for biomarker discovery and identification of potential therapeutic or preventive targets, and demonstrates that large microarray datasets can be translated into a biologically meaningful context and applied to the clinical setting. Please see later in the article for the Editors' Summary.
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http://dx.doi.org/10.1371/journal.pmed.1001549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3825655PMC
November 2013

Intraventricular rituximab and systemic chemotherapy for treatment of central nervous system post-transplant lymphoproliferative disorder after kidney transplantation.

Pediatr Transplant 2012 Sep 30;16(6):E201-9. Epub 2012 May 30.

Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA.

PTLD of the CNS is a rare complication of solid organ transplantation, and there are only case reports/series available in the literature. Current literature suggests that CNS PTLD carries a worse prognosis than PTLD outside the CNS, and most are of B-cell lineage, predominantly monomorphic, and are associated with EBV infection. Because this disorder is so rare, there is no standard chemotherapy for pediatric patients with CNS PTLD and reported therapies for EBV-associated CNS PTLD are heterogeneous with mixed results. Since outcomes of CNS PTLD are historically poor, we attempted to develop a novel therapeutic treatment regimen. Based on a review of the literature and with the help of a multidisciplinary team, we created a regimen of chemotherapy that included dexamethasone and high-dose methotrexate in addition to intravenous and intraventricular Rituximab in two pediatric patients. The intraventricular chemotherapy succeeded in shrinking the tumor in both of our patients; however, as shown in the second case, the clinical outcome depends on the location of the tumor. Systemic and intraventricular therapies hold promise in the management of EBV-associated CNS PTLD; however the rarity of this entity prevents the development of well-designed studies necessary for the establishment of an evidence-based treatment standard.
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http://dx.doi.org/10.1111/j.1399-3046.2012.01699.xDOI Listing
September 2012

2009 influenza A in infants hospitalized at younger than 6 months.

J Pediatr 2012 Apr 17;160(4):626-631.e1. Epub 2011 Nov 17.

Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 95390-9063, USA.

Objective: To describe the clinical characteristics and outcomes of infants hospitalized at <6 months of age with 2009 influenza A infection.

Study Design: Prospective laboratory surveillance and discharge International Classification of Disease, 9th edition codes for influenza infection were used to identify all infants hospitalized at <6 months of age with positive influenza A tests at Children's Medical Center Dallas from April 27, 2009 to March 23, 2010. Retrospective chart review then was performed.

Results: Seventy-three infants aged <6 months were hospitalized with laboratory-confirmed influenza A infection at a median age of 48 days (range, 3-179 days). The most common clinical characteristics were fever and respiratory signs, and 53% were given a bolus of intravenous fluid. Median length of hospitalization was 2 days (range, 1-162 days). Twenty (27%) infants developed influenza-related complications, including pneumonia (n = 3), hypoxia (n = 18), seizures (n = 2), need for intensive care (n = 8), or death (n = 2). Oseltamivir was administered to 60 (82%) infants and was well tolerated.

Conclusions: The majority of infants hospitalized with 2009 influenza A had community-acquired infection that was associated with short hospital stays and favorable short-term outcomes. Complications including death occurred, emphasizing the need for preventive strategies.
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http://dx.doi.org/10.1016/j.jpeds.2011.09.060DOI Listing
April 2012

2009 pandemic influenza A (H1N1) virus infection in pediatric oncology and hematopoietic stem cell transplantation patients.

Pediatr Blood Cancer 2011 Jan;56(1):127-33

Department of Pediatrics, Division of Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

Background: Pediatric oncology and hematopoietic stem cell transplantation (HSCT) patients are at high risk for influenza infection and its associated complications. Little is known about infection with novel 2009 influenza A (H1N1) in this population.

Procedure: Prospective laboratory surveillance identified all children with positive influenza test results from 4/27/09-12/5/09. 2009 H1N1 infection was confirmed by PCR subtyping; cases in which subtyping was not performed were considered probable. Medical records of all pediatric oncology and HSCT cases were reviewed.

Results: Thirty children with cancer or HSCT had laboratory-confirmed influenza A. Patients with ALL (18), CNS tumors (4), CML (1), Ewing sarcoma (1), Hodgkin lymphoma (1), LCH (1), severe aplastic anemia (1), and HSCT (3), had confirmed (5) and probable (25) H1N1 by rapid (22; 73%), DFA (4; 13%), or RVP (4; 13%) assays. Most frequent presenting signs and symptoms were fever (93%; median 38.6°C), cough (97%), and rhinorrhea (83%). Ten patients required hospitalization for a median of 5 days, most commonly for fever and neutropenia (8). Imaging demonstrated lower respiratory tract involvement in three patients. There were no concomitant bacteremias; one patient had rhinovirus co-infection. Three patients required ICU care; 1 developed ARDS, multi-organ failure, and died after 5 days. Chemotherapy was delayed in five patients. Oseltamivir was administered to 28 patients; 1 patient developed an oseltamivir-resistant strain and was treated with zanamivir.

Conclusions: 2009 influenza A H1N1 infection in children with cancer and HSCT is mild in most patients, but can lead to serious complications.
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http://dx.doi.org/10.1002/pbc.22771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2992087PMC
January 2011