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Adverse events (AEs) experienced by children and adults with congenital heart disease (CHD) on ventricular assist devices (VADs) are sometimes unique to these populations. The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) and the Academic Research Consortium (ARC) aimed to harmonize definitions of pediatric and CHD AEs for use in clinical trials, registries, and regulatory evaluation. Data from the ACTION registry and adjudication committee were used to adapt general mechanical circulatory support ARC definitions. This ACTION-ARC international expert panel of trialists, clinicians, patients, families, statisticians, biomedical engineers, device developers, and regulatory agencies drafted and iterated definitions harmonized to ACTION data and existing literature during sessions conducted between December 2022 and May 2023, followed by dissemination across clinical/research audiences and professional organizations and further revision. Both email-linked, internet-based surveys and in-person discussions were used as a modified Delphi process. Nineteen AE types were identified and defined, including seven new event types and six event types that were deleted and will no longer be collected, achieving consensus. ACTION-ARC paired rigorous development with methodical stakeholder involvement and dissemination to define pediatric VAD AEs to facilitate assimilation of data across future clinical trials and evaluation of devices for VAD-supported children and adults with CHD., Competing Interests: Disclosure: A.L. is a consultant for Bayer, Abbott, Abiomed, Berlin Heart, and Syncardia and is the primary investigator for the Berlin ACTIVE driver trial. I.A. is a consultant for Abbott, Abiomed, Bivacor, and Berlin Heart. P.M.A.A. is Treasurer of the Board of Directors of the Extracorporeal Life Support Organization (ELSO) and immediate past-chair of PediECMO, a research collaborative between ELSO and the Pediatric Acute Lung Injury and Sepsis Investigators. P. Alexander’s institution received funding from the National Institutes of Health (NICHD R13HD104432) and the U.S. Department of Defense (U.S. DoD PRMRP Clinical Trial Award #W81XWH2210301). R.P.B. reports grants from the National Institutes of Health (NIH) R01 HL153519 and is a member of the Extracorporeal Life Support Organization (ELSO) Board of Directors. S.B. is a full-time employee of Abiomed, Inc. a part of Johnson and Johnson. K.B. is an Abbott employee. J.C. receives an unrestricted education grant—from Abbott and is a medical monitor for Pumpkin Trial. R.R.D. is a paid consultant for Abbott, Inc. and Abiomed, Inc. R.L.K. is an employee at Abbott, Inc. R.K. is an employee at Berlin Heart Inc. M.K. is involved in Grants & Consulting for Medtronic, Abbott Vascular, Johnson & Johnson, Boston Scientific, and Getinge. J.L. is a consultant for Abbott. D.L.S.M. is a consultant for Abbott Inc., Syncardia Inc., and Berlin Heart Inc. R.A.N. uses Berlin Heart of North America travel funds to attend the annual user’s group meeting. F.D.P. is a non-compensated ad-hoc scientific advisor for Abbott, BrioHealth Solutions, FineHeart, and Medtronic, a non-compensated medical monitor for Abiomed, a member—Data Safety Monitoring Board for Carmat, receives grant funding from the National Heart, Lung, and Blood Institute and the Agency for Healthcare Research and Quality, and receives partial salary support from Blue Cross/Blue Shield of Michigan as Associate Director of the Michigan Society of Thoracic and Cardiovascular Surgeons Quality Collaborative. D.M.P. is on the Data Safety Monitoring Board for the Berlin Active Driver Trial. D.R. is associated with ACTION, DSMB for Parexel (unrelated to topic of AE manuscript), and Medicolegal consultation (unrelated to topic of AE manuscript). J.W.R. is a consultant for American Regent, AskBio, BioMarin, Bayer, Merck, Bristol Myers Squibb, and Enzyvant. E.S. reports institutional contracts for which he receives no direct compensation with Boston Scientific, Cardiawave, Edwards Lifesciences, Medtronic, Shanghai Microport Medical Co. Ltd., NVT GmBH, Pie Medical Imaging, Siemens Healthcare GmBH. M.E.S. is involved in a Medtronic educational contract, Octapharma advisory panel, and NIH DSMB for PumpKIN trial (completed). J.M.T. is a Berlin Heart CEC member. C.V. is on the Merck scientific advisory committee and a consultant for Abiomed. C.R.V. is a consultant for PTC therapeutics (previous), Antisense (current), and Capricor (current). The other authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Background: Norovirus (NoV) can cause chronic relapsing and remitting diarrhea in immunocompromised patients.  Few multicenter studies have described the clinical course, outcomes, and complications of chronic NoV in transplant recipients., Methods: A multicenter retrospective study of adult and pediatric SOT and HSCT recipients diagnosed with NoV between November 1, 2017, and February 28, 2021. Data were obtained from electronic medical records (EMR) and entered into a central REDCap database. Descriptive statistics were calculated., Results: A total of 280 NoV+ patients were identified across eight sites. The majority were adults (74.1%) and SOT recipients (91.4%). Initial diagnosis of NoV occurred a median of 36 months post-Tx (IQR [15.0, 90.0]). Most NoV cases had >3 diarrheal episodes daily (66.0%), nausea and vomiting (60.1%). Duration of diarrhea varied greatly (median = 10 days, mean = 85.9 days, range (1, 2100)). 71.3% were hospitalized. Adjustment of immunosuppression, including reduction and discontinuation of mToR inhibitor, CNI, and/or MMF, was the most common management intervention for NoV. Other therapies resulted only in temporary improvement. Four patients died within 30 days and three others died by 180 days postdiagnosis. Clinically significant renal dysfunction was observed in 12.5% by 30 days and 21.4% by 180 days post-NoV diagnosis., Conclusion: In HSCT and SOT patients, NoV frequently resulted in severe symptoms, prolonged diarrhea (30% persistent with diarrhea for >30 days), and clinically significant renal dysfunction (up to 21% of patients). Utilized therapies did not reliably result in the resolution of infection demonstrating the need for more effective treatment., (© 2024 The Authors. Transplant Infectious Disease published by Wiley Periodicals LLC.)

Despite current prophylaxis regimens, cytomegalovirus (CMV) is common in hematopoietic cell transplantation (HCT) and solid organ transplantation (SOT) and remains a significant cause of morbidity and mortality. Newer antiviral medications are reshaping the landscape for prevention and treatment of CMV DNAemia, infection, and disease. Letermovir is approved for CMV prevention in adult HCT patients and is attractive due to the absence of marrow suppression seen with ganciclovir/valganciclovir. Letermovir should not be routinely used for CMV treatment due to its low threshold for resistance. Maribavir is approved for the treatment of refractory or resistant CMV disease in HCT and SOT recipients ≥12 years of age, though it has no current role in CMV prevention. More research is needed to fully elucidate the roles, efficacy, and safety of these newer agents in prevention and treatment of CMV in pediatric transplant recipients., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

SARS-CoV-2 infection during the Omicron period was frequent amongst a cohort of vaccinated pediatric solid organ transplant recipients (pSOTRs) despite robust anti-receptor-binding domain (anti-RBD) antibody response, suggesting poor neutralizing capacity against Omicron subvariants. Breakthrough infections among pSOTRs were overall limited in severity., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Adolescent solid organ transplant recipients (aSOTRs) who received three doses of the COVID-19 mRNA vaccine experience high seroconversion rates and antibody persistence for up to 3 months. Long-term antibody durability beyond this timeframe following three doses of the SARS-CoV-2 mRNA vaccine remains unknown. We describe antibody responses 6 months following the third vaccine dose (D3) of the BNT162b2 mRNA vaccination among aSOTRs., Methods: Participants in a multi-center, observational cohort who received the third dose of the vaccine were analyzed for antibodies to the SARS-CoV-2 spike protein receptor-binding domain (Roche Elecsys anti-SARS-CoV-2-S positive: ≥0.8, maximum: >2500 U/mL). Samples were collected at 1-, 3-, and 6-months post-D3. Participants were surveyed at each timepoint and at 12-months post-D3., Results: All 34 participants had positive anti-RBD antibody titers 6 months post-D3. Variations in titers occurred between 3 and 6 months post-D3, with 8/28 (29%) having decreased antibody levels at 6 months compared to 3 months and 2/28 (7%) reporting increased titers at 6 months. The remaining 18/28 (64%) had unchanged antibody titers compared to 3-month post-D3 levels. A total of 4/34 (12%) reported breakthrough infection within 6 months and 3/32 (9%) reported infection after 6-12 months following the third dose of the SARS-CoV-2 mRNA vaccine., Conclusions: The results suggest that antibody durability persists up to 6 months following three doses of the SARS-CoV-2 mRNA in aSOTRs. Demography and transplant characteristics did not differ for those who experienced antibody weaning. Breakthrough infections did occur, reflecting immune-evasive nature of novel variants such as Omicron., (© 2024 Wiley Periodicals LLC.)

Importance: Live vaccines (measles-mumps-rubella [MMR] and varicella-zoster virus [VZV]) have not been recommended after solid organ transplant due to concern for inciting vaccine strain infection in an immunocompromised host. However, the rates of measles, mumps, and varicella are rising nationally and internationally, leaving susceptible immunocompromised children at risk for life-threating conditions., Objective: To determine the safety and immunogenicity of live vaccines in pediatric liver and kidney transplant recipients., Design, Setting, and Participants: This cohort study included select pediatric liver and kidney transplant recipients who had not completed their primary MMR and VZV vaccine series and/or who displayed nonprotective serum antibody levels at enrollment between January 1, 2002, and February 28, 2023. Eligibility for live vaccine was determined by individual US pediatric solid organ transplant center protocols., Exposures: Exposure was defined as receipt of a posttransplant live vaccine. Transplant recipients received 1 to 3 doses of MMR vaccine and/or 1 to 3 doses of VZV vaccine., Main Outcome and Measure: Safety data were collected following each vaccination, and antibody levels were obtained at 0 to 3 months and 1 year following vaccination. Comparisons were performed using Mann-Whitney U test, and factors associated with development of postvaccination protective antibodies were explored using univariate analysis., Results: The cohort included 281 children (270 [96%] liver, 9 [3%] kidney, 2 [1%] liver-kidney recipients) from 18 centers. The median time from transplant to enrollment was 6.3 years (IQR, 3.4-11.1 years). The median age at first posttransplant vaccine was 8.9 years (IQR, 4.7-13.8 years). A total of 202 of 275 (73%) children were receiving low-level monotherapy immunosuppression at the time of vaccination. The majority of children developed protective antibodies following vaccination (107 of 149 [72%] varicella, 130 of 152 [86%] measles, 100 of 120 [83%] mumps, and 124 of 125 [99%] rubella). One year post vaccination, the majority of children who initially mounted protective antibodies maintained this protection (34 of 44 [77%] varicella, 45 of 49 [92%] measles, 35 of 42 [83%] mumps, 51 of 54 [94%] rubella). Five children developed clinical varicella, all of which resolved within 1 week. There were no cases of measles or rubella and no episodes of graft rejection within 1 month of vaccination. There was no association between antibody response and immunosuppression level at the time of vaccination., Conclusions and Relevance: The findings suggest that live vaccinations may be safe and immunogenic after solid organ transplant in select pediatric recipients and can offer protection against circulating measles, mumps, and varicella.

Background: COVID-19 vaccine is recommended for individuals ages ≥6 months; however, whether vaccination should be mandated for transplant candidates and living donors remains controversial. This study assessed COVID-19 policies at US pediatric solid organ transplant centers., Methods: A 79-item survey was emailed between March and April 2022 to 200 UNOS Medical Directors detailing center COVID-19 vaccine policies for transplant candidates and living donors and use of grafts from COVID-19-positive deceased donors., Results: The response rate was 77% (154/200). For children aged 5-15 years, 23% (35/154 centers) have a COVID-19 vaccine mandate, 27% (42/154) anticipate implementing a future mandate, and 47% (72/154) have not considered or do not anticipate implementing a mandate. For children ≥16 years, 32% (50/154 centers) have a COVID-19 vaccine mandate, 25% (39/154) anticipate implementing a future mandate, and 40% (62/154) have not considered or do not anticipate implementing a mandate. The top two reasons for not implementing a COVID-19 vaccine mandate were concerns about penalizing a child for their parent's decision and worsening inequities in transplant. Of 85 kidney and liver living donor centers, 32% (27/85) require vaccination of donors. Twenty percent (31/154) of centers accept organs from COVID-19-positive deceased donors., Conclusions: There is great variation among pediatric SOT centers in both the implementation and details of COVID-19 vaccine mandates for candidates and living donors. To guide more uniform policies, further data are needed on COVID-19 disease, vaccine efficacy, and use of grafts from donors positive for COVID-19 in the pediatric transplant population., (© 2023 Wiley Periodicals LLC.)

Background: There is no practice standard regarding antibiotic duration in children with cancer and unexplained febrile neutropenia (FN). We hypothesized that absolute monocyte count (AMC) and absolute phagocyte count (APC= ANC + AMC + bands) are more sensitive, earlier, and safe markers of antibiotic cessation compared with absolute neutrophil count (ANC)., Methods: A retrospective review of FN episodes (FNEs) in pediatric oncology patients was conducted between 2009 and 2016. Included patients were afebrile for 24 hours and without an identified infectious source at antibiotic cessation. Primary endpoints, including recurrent fever, readmission, bloodstream infection, microbiologically documented infection, and adverse outcomes, were assessed 10 days after antibiotic cessation and compared among different bone marrow recovery parameters (ANC, AMC, APC). Secondary endpoints included length of FN stay, antibiotic-free days, and cost., Results: Three hundred ninety-one FNEs in 235 patients were included. Three groups were compared based on ANC (cells/μL) at the time of antibiotic cessation: < 200 in 102 (26%), 200 to 500 in 111 (28%), and >500 in 178 (46%). No statistically significant differences in primary endpoints were identified among the 3 ANC groups; however, a trend toward unfavorable outcomes in the ANC ≤200 cells/μL group compared with the ANC >200 cells/μL was observed. Primary endpoints based on AMC >100 cells/μL at the time of antibiotic cessation showed statistically significant favorable outcomes compared AMC ≤100 cells/μL (80%, 88%, 90%, 89%, and 93% risk reduction in recurrent fever, readmission, new bloodstream infection, new microbiologically documented infection, and adverse events, respectively). Similar favorable results were seen when APC >300 cells/μL was used as a threshold for antibiotic cessation. The median length of stay for FN if discharged when AMC >100 cells/μL was 3 days shorter and associated with fewer unfavorable outcomes, thus resulting in fewer hospital days, fewer antibiotic days, and decreased cost., Conclusion: Our results suggest that AMC >100 cells/μL (regardless of ANC) or APC >300 cells/μL may be safe thresholds for empiric antibiotic cessation and result in reduced unfavorable clinical outcomes within 10 days postdischarge, reduced antibiotic days of therapy and reduced health care costs. Further prospective studies are needed to validate AMC as an accurate surrogate marker for antibiotic cessation in FNEs in children with cancer., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has significantly impacted all aspects of healthcare including solid organ transplantation. In this review, we discuss the specific impact of COVID-19 on the pediatric solid organ transplant population including access to grafts for pediatric transplant candidates as well as COVID-19 disease manifestations in pediatric transplant recipients. We address the current knowledge of prevention and management of COVID-19 in pediatric transplant recipients and provide additional information regarding social distancing, infection prevention and return to school., (Copyright © 2022. Published by Elsevier Inc.)

The COVID-19 pandemic continues to generate challenges for pediatric solid organ transplant (SOT) recipients and their families. As rates of COVID-19 fluctuate, new SARS-CoV-2 variants emerge, and adherence to and implementation of mitigation strategies vary from community to community, questions remain about the best and safest practices to prevent COVID-19 in vulnerable patients. Notably, decisions about returning to school remain difficult. We assembled a team of specialists in pediatric infectious diseases, transplant infectious diseases, public health, transplant psychology, and infection prevention and control to re-address concerns about school re-entry, as well as COVID-19 vaccines, for pediatric SOT recipients in the United States in 2021. Based on available literature and guidance from national organizations, we generated expert statements specific to pediatric SOT recipients focused on school attendance in 2021., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The contribution of the gastrointestinal tract microbiome to outcomes after allogeneic hematopoietic cell transplantation (HCT) is increasingly recognized. Investigations of larger pediatric cohorts aimed at defining the microbiome state and associated metabolic patterns pretransplant are needed., Methods: We sought to describe the pretransplant stool microbiome in pediatric allogenic HCT patients at four centers. We performed shotgun metagenomic sequencing and untargeted metabolic profiling on pretransplant stool samples. Samples were compared with normal age-matched controls and by clinical characteristics. We then explored associations between stool microbiome measurements and metabolite concentrations., Results: We profiled stool samples from 88 pediatric allogeneic HCT patients, a median of 4 days before transplant. Pretransplant stool samples differed from healthy controls based on indices of alpha diversity and in the proportional abundance of specific taxa and bacterial genes. Relative to stool from healthy patients, samples from HCT patients had decreased proportion of Bacteroides, Ruminococcaeae, and genes involved in butyrate production, but were enriched for gammaproteobacterial species. No systematic differences in stool microbiome or metabolomic profiles by age, transplant indication, or hospital were noted. Stool metabolites demonstrated strong correlations with microbiome composition., Discussion: Stool samples from pediatric allogeneic HCT patients demonstrate substantial dysbiosis early in the transplant course. As microbiome disruptions associate with adverse transplant outcomes, pediatric-specific analyses examining longitudinal microbiome and metabolome changes are imperative to identify causal associations and to inform rational design of interventions., (© 2021 Wiley Periodicals LLC.)

Objective: Hepatitis B virus (HBV) infection remains a significant public health challenge, particularly for immunocompromised patients. Our aim was to evaluate the serologic immunity in immunocompromised rheumatology and inflammatory bowel disease (IBD) patients, assess factors for serologic nonimmunity, and evaluate their response to 1 HBV booster dose., Methods: Immunocompromised rheumatology and IBD patients with completed HBV screening were identified. A chart review was performed to collect demographics, clinical information, baseline HBV serology results, and serologic response to booster vaccination. Serologic nonimmunity was defined as a negative/indeterminate hepatitis B surface antibody (anti-HBs) level., Results: Among 580 patients, 71% were nonimmune. The highest portion of nonimmune patients were 11-18 years old ( P = 0.004). There was no significant difference between immune and nonimmune patients with regards to diagnosis ( P = 0.34), age at diagnosis ( P = 0.64), duration of treatment ( P = 0.07), or type of medications ( P = 0.08). Sixty-two percent of those who received a booster vaccine were rescreened, and most (68%) seroconverted. In those 18 years or older, only half seroconverted., Conclusion: Results of this study support the benefit of HBV screening in immunosuppressed patients. Beginning at age 11 years, most patients lacked serologic immunity to HBV. Seroconversion for most patients 11-18 years occurred after 1 booster vaccine. Thus, for immunocompromised patients without recent HBV serologic data, obtaining the HBV serology beginning at age 11 years might be considered. Those 18 years and older were least likely to seroconvert after 1 booster, indicating that they may benefit from receiving the 3-dose HBV vaccine series., (© 2021 The Journal of Rheumatology.)

Vaccine-preventable viral infections are associated with increased risk of morbidity and mortality in post-transplant patients on immunosuppression regimens. Therefore, we studied rates of immunity against vaccine-preventable viruses in lung transplantation (LTx) candidates and their associations with underlying lung disease and clinical characteristics. We retrospectively studied 1025 consecutive adult patients who underwent first-time evaluation for LTx at a single center between January 2016 and October 2018. Viruses studied included varicella zoster (VZV), measles, and mumps. Young age (17-48 years old) was negatively associated with immunity for VZV (OR 4.54, p < .001), measles (OR 15.45, p < .001) and mumps (OR 3.1, p < .001), as compared to those 65+. Many LTx candidates with cystic fibrosis (CF) had undetectable virus-specific antibody titers including: 13.5% for VZV, 19.1% for measles, and 15.7% for mumps with significant odds of undetectable titers for VZV (OR 4.54, p < .001) and measles (OR 2.32, p = .010) as compared to those without CF. Therefore, a substantial number of patients undergoing LTx evaluation had undetectable virus-specific antibody titers. Our results emphasize the importance of screening for immunity to vaccine-preventable infections in this population and the need for revaccination in selected patients to boost their humoral immunity prior to transplantation., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Isavuconazole, administered as the water-soluble prodrug isavuconazonium sulfate, is a new triazole agent used to treat invasive fungal infections. This phase 1 study evaluated the pharmacokinetics (PK), safety, and tolerability of isavuconazole in 46 immunocompromised pediatric patients, stratified by age (1 to <6 [intravenous (i.v.) only], 6 to <12, and 12 to <18 years), receiving 10 mg/kg body weight (maximum, 372 mg) isavuconazonium sulfate either i.v. or orally. A population PK model using weight-based allometric scaling was constructed with the pediatric i.v. and oral data plus i.v. data from a phase 1 study in adults. The best model was a 3-compartment model with combined zero-order and first-order input, with linear elimination. Stepwise covariate modeling was performed in Perl-speaks-NONMEM version 4.7.0. None of the covariates examined, including age, sex, race, and body mass index, were statistically significant for any of the PK parameters. The area under the concentration-time curve at steady state (AUC SS ) was predicted for pediatric patients using 1,000 Monte Carlo simulations per age cohort for each administration route. The probability of target attainment (AUC SS range, 60 to 233 μg · h/ml) was estimated; this target range was derived from plasma drug exposures in adults receiving the recommended clinical dose. Predicted plasma drug exposures were within the target range for >80% and >76% of simulated pediatric patients following i.v. or oral administration, respectively. Intravenous and oral administration of isavuconazonium sulfate at the studied dosage of 10 mg/kg was well tolerated and resulted in exposure in pediatric patients similar to that in adults. (This study has been registered at ClinicalTrials.gov under identifier NCT03241550).

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Pancreatectomy with islet autotransplantation (IAT) is a treatment option for children with debilitating chronic pancreatitis. Sterility cultures from preservation solutions are often positive, yet their impact has not been well studied in children., Methods: A retrospective review of all patients who underwent IAT from 2015 to 2018 at a single institution was performed. Sterility culture data were obtained from both the pancreas transport and islet transplant media. All patients received prophylactic perioperative meropenem and vancomycin for 72 h per our protocol. If cultures resulted positive, antibiotics were extended for a total of 7 days. Primary outcomes were postoperative fever and 30-day infectious complications., Results: Forty-one patients underwent IAT during the study period. Seventeen (41.5 %) patients had negative cultures of both the transport and transplant media, while 24 (58.5 %) patients had a positive culture from either sample. Of these patients, 13 (31.7 %) were positive in both, 10 (24.4 %) were positive in only the transport media, and 1 (2.4 %) was positive in only the transplant media. Patients with positive transplant media were similar with regard to age, gender, etiology, and disease duration compared to those with negative transplant media (all p > 0.05), but the positive group was more likely to have a pancreatic stent in place at the time of surgery (38.5 % vs. 4.2 %, p = 0.01). The overall postoperative infectious complication rate was 31.2 % (n = 13). No difference was detected between the transplant positive and negative culture groups in postoperative fever or 30-day infectious complications (p > 0.05 for each)., Conclusion: An existing pancreatic stent at the time of pancreatectomy with IAT is a risk factor for positive sterility cultures. However, positive islet transplant media culture was not associated with increased risk of post-IAT infection or morbidity in the setting of an empiric antibiotic protocol. Future work is necessary to study the optimal perioperative antibiotic regimen in pediatric IAT.

Background: The optimal choice of initial antibiotic therapy for patients with high-risk febrile neutropenia (FN) in children is unclear and varies by the institution on the basis of local antibiograms and epidemiology of specific pathogens. The authors evaluated the appropriateness of antibiotics for the empiric treatment of FN in pediatric patients with cancer in our institution on the basis of changes in the epidemiology of organisms isolated from blood cultures (BCx)., Methods: The authors conducted a retrospective medical record review of pediatric patients who received any oncology care (including patients with cancer and patients who had stem cell transplant) at University of Chicago Medicine Comer Children's Hospitals (March 2009 to December 2016) with a diagnosis of FN who had at least 1 BCx obtained. They reviewed pathogens isolated from BCx and determined whether they were pathogens or contaminants using the Infectious Diseases Society of America (IDSA) guidelines and the team's decision to treat. They investigated the microbiologic spectrum and susceptibility patterns of pathogens causing bacteremia in pediatric FN and whether the empiric therapy chosen may have affected clinical outcomes., Results: A total of 667 FN episodes were identified in 268 patients. BCx were negative in 497 (74.5%) and were determined to be contaminants in 27 (4%). In 143 episodes (21.5%), the BCx were positive for a pathogenic species. Polymicrobial bacteremia was identified in 25 episodes; a total of 176 pathogens were isolated. The majority of pathogens (95/176, 54%) were Gram-positive (GP), whereas 64 of 162 (36%) were Gram-negative (GN), 5 were fungal, and 4 were mycobacterial. The most common GP pathogens were viridans group streptococci (VGS) (n=34, 19.3%), coagulase-negative staphylococci (n=25, 14%), and methicillin-susceptible Staphylococcus aureus (n=12, 6.8%). Of aerobic GN bacilli, 15 (8.5%) were AmpC producers and 3 (1.7%) carried extended-spectrum beta-lactamases. There was no increase in the prevalence of multidrug-resistant GN isolates during the study period. Patients with VGS and multidrug-resistant GN bacteremia were more likely to be admitted to the pediatric intensive care unit [odds ratio (OR), 3.24; P=0.017; and OR, 2.8; P=0.07, respectively]. There were trends toward a higher prevalence of GP pathogens causing bacteremia and the emergence of VGS with decreased penicillin sensitivity. The prevalence of bacteremia with VGS was higher in acute myelogenous leukemia and neuroblastoma (OR, 2.3; P<0.01) than in patients with other solid tumors., Conclusions: Empiric antibiotic treatment should be tailored to patients' risk for VGS and multidrug-resistant organisms. Individual hospitals should monitor the pathogens causing FN among patients with cancer to guide choice of empiric therapy.

Background: Infectious Diseases Society of America guidelines defines febrile neutropenia (FN) patients as high risk, if they have an absolute neutrophil count (ANC) ≤100 cells/µL anticipated to last >7 days. However, data evaluating the clinical significance of the depth and duration of neutropenia are limited., Methods: We conducted a retrospective cohort study of pediatric oncology patients presenting with FN to examine whether the effects of the depth and duration of neutropenia prior to presentation were predictive of blood stream infection (BSI), invasive fungal disease (IFD), pediatric intensive care unit (PICU) admission or length of stay., Results: A total of 585 FN episodes (FNEs) were identified in 265 patients. ANC at the time of presentation was <100 in 411 (70%), 100-500 in 119 (20%), and >500 cells/μL with subsequent decline to <500 cells/μL in the next 48 hours in 55 (10%) of FNEs. In the group with ANC > 500 with subsequent decline in 48 hours, rates of IFD and BSI were higher when compared with ANC < 100 cells/μL [odds ratio (OR) = 5.9, 95% confidence interval (CI): 0.7-29.6] and (OR = 2.35, 95% CI: 01.02-5.4), and patients in this group were more likely to be admitted to the PICU (OR= 5.1, 95% CI: 1.134-19.46). No difference in outcomes was identified when the groups of ANC < 100 and ANC of 100-500 cells/μL were compared. Neutropenia >7 days prior to FNE was an independent risk factor for BSI (OR = 2.88, 95% CI: 1.55-5.35 and increased length of stay., Conclusions: Clinicians should not be reassured when patients present with FN and initial ANC >500 cells/mL after recent chemotherapy if continued decline is expected as patients in this group are at high risk of IFD, BSI and PICU admission.

Background: Chronic lung allograft dysfunction (CLAD) is the main limitation to long-term survival after lung transplantation. Because effective therapies are lacking, early identification and mitigation of risk factors is a pragmatic approach to improve outcomes. Acute cellular rejection (ACR) is the most pervasive risk factor for CLAD, but diagnosis requires transbronchial biopsy, which carries risks. We hypothesized that gene expression in the bronchoalveolar lavage (BAL) cell pellet (CP) could replace biopsy and inform on mechanisms of CLAD., Methods: We performed RNA sequencing on BAL CPs from 219 lung transplant recipients with A-grade ACR (n = 61), lymphocytic bronchiolitis (n = 58), infection (n = 41), or no rejection/infection (n = 59). Differential gene expression was based on absolute fold difference >2.0 and Benjamini-adjusted p-value ≤0.05. We used the Database for Annotation, Visualization and Integrated Discovery Bioinformatics Resource for pathway analyses. For classifier modeling, samples were randomly split into training (n = 154) and testing sets (n = 65). A logistic regression model using recursive feature elimination and 5-fold cross-validation was trained to optimize area under the curve (AUC)., Results: Differential gene expression identified 72 genes. Enriched pathways included T-cell receptor signaling, natural killer cell-mediated cytotoxicity, and cytokine-cytokine receptor interaction. A 4-gene model (AUC = 0.72) and classification threshold defined in the training set exhibited fair performance in the testing set; accuracy was 76%, specificity 82%, and sensitivity 60%. In addition, classification as ACR was associated with worse CLAD-free survival (hazard ratio = 2.42; 95% confidence interval = 1.29-4.53)., Conclusions: BAL CP gene expression during ACR is enriched for immune response pathways and shows promise as a diagnostic tool for ACR, especially ACR that is a precursor of CLAD., (Copyright © 2019 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Infectious diseases (ID) specialists with experience in managing infections in transplant recipients and other immunocompromised hosts are increasingly needed as these fields expand., Methods: To evaluate experiences and identify trainee-described needs in transplant infectious diseases (TID) training, the American Society of Transplantation, Infectious Diseases Community of Practice (AST IDCOP) surveyed ID fellows across the United States and TID fellows in the United States and Canada and received responses from 203 ID fellows and 13 TID fellows., Results: Among ID fellows, the amount of TID training during ID fellowship was rated between less than ideal and adequate. Reasons cited included limited frequency of didactic activities and limited exposure to transplant patients during training. In particular, ID fellows at low-volume transplantation centers expressed interest in more TID training time, away training opportunities, and specific TID didactics. Educational resources of high interest among trainees were case-based interactive websites, mobile phone applications with TID guidelines, and a centralized collection of relevant articles. Pediatric ID fellows reported lower satisfaction scores with TID training, while TID fellows were overall satisfied or more than satisfied with their training experience., Conclusion: Findings from this survey will inform local and national TID educational initiatives., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Anelloviruses are DNA viruses ubiquitously present in human blood. Due to their elevated levels in immunosuppressed patients, anellovirus levels have been proposed as a marker of immune status. We hypothesized that low anellovirus levels, reflecting relative immunocompetence, would be associated with adverse outcomes in pediatric lung transplantation. We assayed blood samples from 57 patients in a multicenter study for alpha- and betatorquevirus, two anellovirus genera. The primary short-term outcome of interest was acute rejection, and longer-term outcomes were analyzed individually and as "composite" (death, chronic rejection, or retransplant within 2 years). Patients with low alphatorquevirus levels at 2 weeks post-transplantation were more likely to develop acute rejection within 3 months after transplant (P = .013). Low betatorquevirus levels at 6 weeks and 6 months after transplant were associated with death (P = .047) and the composite outcome (P = .017), respectively. There was an association between low anellovirus levels and adverse outcomes in pediatric lung transplantation. Alphatorquevirus levels were associated with short-term outcomes (ie, acute rejection), while betatorquevirus levels were associated with longer-term outcomes (ie, death, or composite outcome within 2 years). These observations suggest that anelloviruses may serve as useful biomarkers of immune status and predictors of adverse outcomes., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Solid organ transplantation is a life-saving procedure that has changed the prognosis for infants and children with end-stage organ disease. Cytomegalovirus (CMV) is one of the most common infections that occur after organ transplantation in pediatric patients, yet the standard of care for CMV prevention remains unclear. We review the literature regarding CMV disease effects, risk factors, diagnostics, prevention strategies, and antiviral treatment in pediatric solid organ transplantation. This discussion focuses on the current prevention strategies: prophylaxis, preemptive, and hybrid therapy, as well as novel strategies that may help better prevent the CMV disease in the pediatric solid organ transplant population.

Fungal infections create a significant risk to pediatric lung transplant recipients. However, no international consensus guidelines exist for fungal infection prevention strategies. It was the aim to describe the current strategies of antifungal prophylaxis in pediatric lung transplant centers. A self-administered, web-based survey on current practices to prevent fungal infection was circulated to centers within the IPLTC. Twenty-one (88%) IPLTC centers participated, predominantly from Europe and the US. More than 50% of respondents perform adult and pediatric lung transplant operations. Twenty-four percent use universal prophylaxis, 28% give prophylaxis to all patients but stratify the antifungal coverage based on pretransplant risk, and 48% target prophylaxis to only the children with CF or pretransplantation fungal colonization. Commonly, centers aim to target Aspergillus and Candida infection. Monotherapy with either voriconazole or inhaled amphotericin B is used in the majority of centers. Institutions utilize prophylactic therapy for variable time periods (40% 3-6 months; 30% ≥12 months). Alternative drugs were prescribed for lack of tolerance, toxicity, or positive surveillance culture. TDM (itraconazole/voriconazole) was used in 86% of centers. The survey revealed a wide range of antifungal prophylaxis strategies as current international practice in pediatric lung transplant recipients., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Prevention strategies for cytomegalovirus (CMV) in pediatric transplant recipients are sparsely reported. A hybrid strategy that combines prophylaxis with preemptive therapy using serial CMV viral load monitoring is an emerging option. We report our clinical outcomes with a hybrid strategy in pediatric heart transplant recipients., Methods: A retrospective chart review was performed for pediatric heart transplant recipients who received a hybrid strategy of 2-4 weeks intravenous ganciclovir followed by serial whole blood CMV monitoring from 2002 to 2010. Subject demographics, medications, drug levels, serial CMV viral loads, intravascular ultrasound and angiography reports, and histopathology were collected. Descriptive statistics and patient groups were compared using χ(2), Fisher's exact, and Wilcoxon rank-sum tests., Results: Twelve females and 13 males, ranging from 4 months to 19 years of age, underwent 26 heart transplants. Mean follow-up was 39 months (range, 5-94 months). Fourteen (54%) subjects were CMV donor (D) + /recipient (R) - , 8 (31%) were D + /R + , and 4 (15%) were D - /R + . Six subjects (23%) died of complications unrelated to CMV. Median prophylaxis duration was 25 days (range, 7-70 days). Ten (38%) subjects developed CMV infection: 1 subject had 2 episodes of CMV syndrome, and 1 subject had 2 episodes CMV. Although 6 of 14 patients with coronary artery vasculopathy had prior CMV, no association was found (P = .81). Median time to first CMV DNAemia was 2.3 months (range, 9 days to 24.8 months). Median time to viral load clearance was 29 days (range, 4-233 days). In addition, 25 D - /R- patients were transplanted and received no prophylaxis; 2 (8%) patients developed CMV infection., Conclusions: Pediatric heart transplant recipients who were at risk for CMV and treated with a novel preventative hybrid strategy developed CMV infection, syndrome, and disease at rates similar to those reported in literature for prophylactic strategies., (© The Author 2012. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

RSV infection can be severe after pediatric lung transplantation. Strategies to prevent and treat RSV in this population are underreported. To assess the current practices, we surveyed the members of the IPLTC regarding RSV prevention and treatment strategies. Twenty-eight programs were surveyed; 18 (64.3%) responded at least partially. A median of 53 transplants (range, 8-355) occurred since inception. RSV testing occurs in asymptomatic (6/17) and symptomatic (17/17) patients. Diagnostic method is polymerase chain reaction at 13 sites and DFA at 8. Transplant candidates were received prophylaxis at 10 sites, with nine following national (5) or local (4) guidelines. All use palivizumab IM and/or IV. Recipients were received prophylaxis with palivizumab at eight centers (eight IM, one IV). Fourteen were treated for RSV (seven all patients; seven age-related). Medications include inhaled (6), oral (4), or IV (4) ribavirin, plus IVIG (9), steroids (8), and IV (2) or IM (3) palivizumab. Prevention and treatment barriers include insurance/hospital concerns, such as institutional reluctance to use inhaled ribavirin. RSV prevention and treatment strategies are diverse at pediatric lung transplant programs. Many centers offer prophylaxis (9/17) and treatments (14/17), but strategies are not uniform., (© 2012 John Wiley & Sons A/S.)

Cytomegalovirus (CMV) is an important cause of morbidity and mortality in children who have received organ transplants. Patients have been reported to be at differential risk for CMV disease based on the serostatus of the donor and recipient with highest risk reported for CMV seronegative recipients who receive an organ from a CMV seropositive donor. Prophylaxis with ganciclovir and/or oral valganciclovir is reasonable to attempt to prevent CMV infections. A hybrid strategy bridging prophylaxis and pre-emptive therapy appears to be emerging as an additional method to prevent CMV disease. However, there is no agreement on the optimal schedule of testing, duration and dosing of antiviral medications or the role of immunoglobulin therapy. This manuscript will review the most recent literature and recommendations for the prophylaxis and treatment of CMV infections and disease in pediatric transplant recipients. Multicenter, randomized, clinical studies involving several pediatric transplant centers are needed to determine the best strategies to prevent and treat CMV infections in these patients., (© 2010 John Wiley & Sons A/S.)

In adult lung transplantation, a single minimal AR episode is a significant predictor of BOS independent of other factors. However, the significance of single minimal AR episodes in children is unknown. A retrospective, multi-center analysis was performed to determine whether isolated single AR episodes are associated with an increased BOS risk in children. Risk factors for BOS, death, or re-transplantation, and a combined outcome of BOS, death, or re-transplantation were assessed. Original data included 577 patients (<21 yr of age). A total of 383 subjects were eligible for the study. Fifteen percent of patients developed BOS, and 13% of patients either died or underwent re-transplant within one-yr post-transplant. In the multivariable survival model for time to BOS, there was no significant risk to developing BOS after a single minimal AR (A1) episode (HR 1.7, 95% CI 0.64-4.8; p=0.28). Even after a second minimal AR episode, no significant risk for BOS was appreciated. However, a single episode of mild AR (A2) was associated with twice the risk of BOS within one-yr post-transplant. In this select cohort, a single minimal AR episode was not associated with an increased risk for BOS within one yr following lung transplantation, in contrast to previous reports in adults., (Copyright (c) 2010 John Wiley & Sons A/S.)

To evaluate the epidemiology and to investigate the impact of RVI on chronic allograft rejection after pediatric lung transplantation, a retrospective study of pediatric lung transplant recipients from 2002 to 2007 was conducted. Association between RVI and continuous and categorical risk factors was assessed using Wilcoxon rank-sum tests and Fisher's exact tests, respectively. Association between risk factors and outcomes were assessed using Cox proportional hazards models. Fifty-five subjects were followed for a mean of 674 days (range 14-1790). Twenty-eight (51%) developed 51 RVI at a median of 144 days post-transplant (mean 246; range 1-1276); 41% of infections were diagnosed within 90 days. Twenty-five subjects developed 39 LRI, and eight subjects had 11 URI. Organisms recovered included rhinovirus (n = 14), adenovirus (n = 10), parainfluenza (n = 10), influenza (n = 5), and RSV (n = 4). Three subjects expired secondary to their RVI (two adenovirus, one RSV). Younger age and prior CMV infection were risks for RVI (HR 2.4 95% CI 1.1-5.3 and 17.0; 3.0-96.2, respectively). RVI was not associated with the development of chronic allograft rejection (p = 0.25) or death during the study period. RVI occurs in the majority of pediatric lung transplant recipients, but was not associated with mortality or chronic allograft rejection.

The emergence of the novel 2009 H1N1 influenza virus highlights unique aspects of transplant care that will require heightened vigilance in coming months. Recognition of the syndrome, aggressive diagnosis and early treatment should be paired with active preventative measures to stem the impact of infection in the transplant population. This special advisory addresses issues relevant to cardiothoracic transplant candidates, selection of donors, recipient management and those patients with mechanical circulatory support devices.

Background: The purpose of this study was to evaluate the epidemiology and investigate the impact of colonization and pulmonary fungal infections (PFIs)., Methods: In this investigation we performed a retrospective analysis of 55 pediatric lung transplant recipients from 2002 to 2007 at a single institution. Associations between risk factors and time to post-transplant colonization, PFI, and other outcomes were assessed using Cox proportional hazard models., Results: Although 29 patients had positive pre-transplant colonization, 33 (60%) were colonized post-transplant and 20% (11 subjects) developed proven or probable PFI. In a multivariate model, post-transplant fungal colonization was associated with older age (hazard ratio [HR] 2.9, 95% confidence interval [CI] 1.1 to 7.6), cytomegalovirus (CMV) prophylaxis (HR 5.6, 95% CI 1.3 to 24.6) and respiratory viral infection prior to fungal colonization (HR 2.9, 95% CI 1.0 to 8.3)., Conclusion: Neither fungal colonization nor PFI was associated with the development of chronic allograft rejection or death.

To characterize epidemiology and risk factors for respiratory viral infections (RVI) in pediatric lung transplant recipients within the first post-transplant year, a retrospective multicenter study of pediatric lung transplant recipients from 1988 to 2005 was conducted at 14 centers in the United States and Europe. Data were recorded for 1 year post transplant. Associations between RVI and continuous and categorical risk factors were assessed using Wilcoxon's rank-sum and chi(2) tests, respectively. Associations between time to RVI and risk factors or survival were assessed by multivariable Cox proportional hazards models. Of 576 subjects, 79 subjects (14%) had 101 RVI in the first year post transplant. Subjects with RVI were younger than those without RVI (median ages 9.7, 13; P<0.01). Viruses detected included adenovirus (n=25), influenza (n=9), respiratory syncytial virus (n=21), parainfluenza virus (n=19), enterovirus (n=4), and rhinovirus (n=22). In a multivariable model for time to first RVI, etiology other than cystic fibrosis (CF), younger age, and no induction therapy were independently associated with risk of RVI. Cytomegalovirus serostatus and acute rejection were not associated with RVI. RVI was independently associated with decreased 12-month survival (hazard ratio 2.6, 95% confidence interval 1.6-4.4). RVI commonly occurs after pediatric lung transplantation with risk factors including younger age and non-CF diagnosis. RVI is associated with decreased 1-year survival.

Background: A retrospective review of pediatric lung transplant recipients at 14 centers in North America and Europe was conducted to characterize the epidemiology and the risk factors for cytomegalovirus (CMV) and to explore the impact of preventative antiviral therapy., Methods: Data were recorded for 1 year posttransplant. Associations between CMV and continuous and categorical risk factors were assessed using Wilcoxon rank sum and chi-square tests, respectively. Associations between time to CMV and risk factors or survival were assessed by multivariable Cox proportional hazards models., Results: Within 12 months posttransplant, 172 of 577 subjects (29.8%) developed 218 CMV episodes (90 asymptomatic infection, 25 syndrome, and 103 disease). Forty-one subjects developed more than one episode of CMV. Donor or recipient CMV seropositivity was associated with increased risk of CMV episodes. Except for decreased prophylaxis in CMV D-/R- subjects, duration of prophylaxis did not vary by D/R serostatus. For CMV D+ subjects, not being on prophylaxis at the time of CMV episode increased the risk of CMV (D+/R+ hazard ratio 3.5, 95% confidence interval 1.4-8.4; D+/R- 1.9, 1.02-3.7). CMV was associated with increased mortality within the first posttransplant year among those with donor or recipient CMV seropositivity (hazard ratio 2.0: 95% confidence interval 1.1-3.6; P=0.024)., Conclusions: CMV remains a serious complication after pediatric lung transplant, and the impact of prophylaxis is complex.

Background: Risk factors, morbidity and mortality from pulmonary fungal infections (PFIs) within the first year after pediatric lung transplant have not previously been characterized., Methods: A retrospective, multicenter study from 1988 to 2005 was conducted with institutional approval from the 12 participating centers in North America and Europe. Data were recorded for the first post-transplant year. The log-rank test assessed for the association between PFI and survival. Associations between time to PFI and risk factors were assessed by Cox proportional hazards models., Results: Of the 555 subjects transplanted, 58 (10.5%) had 62 proven (Candida, Aspergillus or other) or probable (Aspergillus or other) PFIs within the first year post-transplant. The mean age for PFI subjects was 14.0 years vs 11.4 years for non-PFI subjects (p < 0.01). Candida and Aspergillus species were recovered equally for proven disease. Comparing subjects with PFI (n = 58) vs those without (n = 404), pre-transplant colonization was associated with PFI (hazard ratio [HR] 2.0; 95% CI 0.95 to 4.3, p = 0.067). Cytomegalovirus (CMV) mismatch, tacrolimus-based regimen and age >15 years were associated with PFI (p < 0.05). PFI was associated with any prior rejection higher than Grade A2 (HR 2.1; 95% CI 1.2 to 3.6). Cystic fibrosis, induction therapy, transplant era and type of transplant were not associated with PFI. PFI was independently associated with decreased 12-month survival (HR 3.9, 95% CI 2.2 to 6.8)., Conclusions: Risk factors for PFI include Grade A2 rejection, repeated acute rejection, CMV-positive donor, tacrolimus-based regimen and pre-transplant colonization.

Lung transplant candidates and recipients are at high risk of infections from vaccine-preventable diseases. However, well-established guidelines neither exist for pre- and post-transplant vaccination nor do monitoring guidelines for pediatric lung transplant recipients. To ascertain the current vaccination and monitoring practices of pediatric lung transplant centers, a self-administered questionnaire was distributed to the 18 pediatric lung transplant centers within the International Pediatric Lung Transplant Collaborative in April 2006. Sixteen of 18 centers (89%) surveyed responded. Pretransplant, national vaccination guidelines are followed. Eleven centers reported following standardized vaccination guidelines post-transplant. Vaccines were more commonly provided by the primary-care physician pretransplant (69%) rather than post-transplant (38%). Post-transplant, 50% of the centers recommend live vaccines for household contacts but not for the transplant recipient. Pretransplant monitoring of response to prior vaccination was performed inconsistently except for varicella (88%). Only 44% of the transplant centers measure for response to vaccination post-transplant, mostly hepatitis B. Current vaccination practices of pediatric lung transplant centers are heterogeneous. The lung transplant community would be well served by studies designed to evaluate the efficacy of vaccinations in this population.

CMV infection causes morbidity and mortality after transplantation. Despite a wide range of prevention strategies among pediatric lung transplant programs, the optimal duration of prophylactic therapy against CMV infection in pediatric lung transplantation is unknown. To assess the feasibility, safety, and short-term efficacy of extending intravenous ganciclovir administration from six wk duration to 12 wk duration in pediatric lung transplant recipients. An open-label pilot study was performed in primary pediatric lung transplant recipients with donor and/or recipient CMV seropositivity. Intravenous ganciclovir was given for 12 wk post-transplantation. Subjects were tracked for protocol completion. Toxicities monitored included renal dysfunction, myelosuppression, gastrointestinal and neurological complications, as well as infection related to indwelling catheter placement. Serial CMV levels were measured to determine short-term efficacy of the intervention. Nine of nine subjects enrolled completed the pilot study. Subjects' ages ranged from six to 18 yr. Indications for lung transplantation included cystic fibrosis (n = 7), idiopathic pulmonary hypertension (n = 1), and complex congenital heart disease with pulmonary hypertension (n = 1). Seven subjects underwent deceased donor bilateral lung transplantation and two subjects underwent heart-lung transplantation. No subjects had protocol-defined drug toxicity. No episodes of neutropenia, thrombocytopenia, or renal toxicity occurred. Five subjects had catheter-related infections (three after week 12 of ganciclovir). Seven of nine subjects had CMV detected by PCR (four prior to ganciclovir completion) with only one subject having a positive viral culture for CMV viremia (prior to ganciclovir completion). No subjects had UL-97 mutation for ganciclovir resistance detected. The use of prolonged prophylactic administration of ganciclovir for 12 wk duration is a feasible, safe, and effective treatment to prevent CMV viremia based on viral culture in at risk pediatric lung transplant recipients. Further clinical studies are underway to determine optimal CMV prevention strategies.

Procalcitonin appears to be an early and sensitive marker of bacterial infection in a variety of clinical settings. The use of levels of procalcitonin to predict infection in children undergoing cardiac surgery, however, may be complicated by the systemic inflammatory response that normally accompanies cardiopulmonary bypass. The aim of our study was to estimate peri-operative concentrations of procalcitonin in non-infected children undergoing cardiac surgery. Samples of serum for assay of procalcitonin were obtained in 53 patients at baseline, 24, 48, and 72 hours following cardiac surgery. Concentrations were assessed using an immunoluminetric technique. Median concentrations were lowest at baseline at less than 0.5 nanograms per millilitre, increased at 24 hours to 1.8 nanograms per millilitre, maximized at 48 hours at 2.1 nanograms per millilitre, and decreased at 72 hours to 1.3 nanograms per millilitre, but did not return to baseline levels. Ratios of concentrations between 24, 48 and 72 hours after surgery as compared to baseline were 6.15, with 95 percent confidence intervals between 4.60 and 8.23, 6.49, with 95 percent confidence intervals from 4.55 to 9.27, and 4.26, with 95 percent confidence intervals between 2.78 and 6.51, respectively, with a p value less than 0.001. In 8 patients, who had no evidence of infection, concentrations during the period from 24 to 72 hours were well above the median for the group. We conclude that concentrations of procalcitonin in the serum increase significantly in children following cardiac surgery, with a peak at 48 hours, and do not return to baseline within 72 hours of surgery. A proportion of patients, in the absence of infection, had exaggerated elevations post-operatively.

Background: Substantial morbidity and mortality rates are associated with infections in the first year after pediatric lung transplantation. To understand better the clinical significance of bloodstream infections (BSIs), we evaluated systematically the epidemiologic features of BSIs in the first year after transplantation., Methods: A retrospective case-cohort study of pediatric primary lung transplant recipients was performed. The frequency of BSIs and the organisms isolated were determined through medical and laboratory record review. We assessed variations in causative organisms and rates of BSIs in 3 time periods after transplantation, ie, early (0-30 days), intermediate (31-90 days) and late (91-365 days)., Results: Between July 1990 and November 2000, 190 pediatric patients received primary lung transplants. Twenty-six percent (49 of 190) of recipients had at least 1 BSI. The most commonly isolated organisms were coagulase-negative Staphylococcus (n = 25, 28.4%), Pseudomonas aeruginosa (n = 14, 16.0%) and Candida spp. (n = 9, 10.2%). The overall rate of BSIs was 2.1 episodes per 1000 catheter-days. The highest rate of BSIs occurred in the early period, compared with the intermediate and late periods (5.5, 1.3 and 1.6 episodes per 1000 catheter-days, respectively; P = 0.21). Early BSIs were associated with death in the first year after transplantation (relative risk, 3.9; 95% confidence interval, 1.6-9.4; P = 0.002)., Conclusions: BSIs occur frequently after primary pediatric lung transplantation, with the highest rate being in the first 30 days after transplantation. Early BSIs are associated with death in the first year after transplantation.

Cytomegalovirus (CMV) infection after pediatric lung transplantation is a significant risk factor for morbidity and mortality in the first year after transplantation. Multiple strategies have been reported for CMV prevention among adult lung transplant programs. In contrast, little information has been reported regarding protocols for prevention and detection of CMV from pediatric programs. We conducted a survey to better understand the range of practice patterns for CMV prevention and detection at pediatric lung transplant centers. A self-administered questionnaire was distributed to 11 pediatric lung transplant centers identified through the International Pediatric Lung Transplant Collaborative in September 2002. A member of the lung transplant team from each institution was asked to provide the methods of CMV prevention and surveillance. Eight of 11 centers surveyed responded to the questionnaire accounting for 45.6% (26 of 57) and 100% (three of three) of the pediatric lung transplants performed in the US and UK in 2001, respectively. All centers used prophylactic therapy against CMV with either ganciclovir or valganciclovir with duration ranging from 3.5 wk to indefinitely. Most centers (six of eight) prescribed a prophylactic regimen based on donor and recipient CMV serostatus. Half (four of eight) of the centers report using CMV hyperimmune globulin in addition to an antiviral agent. Method for CMV detection varied widely, including use of conventional viral culture (n = 1), antigenemia (n = 7), and polymerase chain reaction (n = 2). A wide range of strategies is used to prevent and detect CMV in pediatric lung transplant recipients with little empiric evidence demonstrating the optimal approach. A retrospective analysis among these centers is being conducted to evaluate the efficacy of these approaches.

Background: Cytomegalovirus (CMV) infection is a frequent complication of lung transplantation. However, there is limited information regarding the incidence and sequelae of CMV infections in pediatric lung-transplant recipients. On the basis of case series suggesting that CMV infection was associated with excess morbidity and mortality in lung-transplant recipients, we hypothesize that CMV viremia increases the risk of bronchiolitis obliterans (BOS) or death and retransplantation in the first year following transplantation., Methods: A case-cohort study of pediatric primary lung-transplant recipients was performed. Univariate analysis was used to assess whether CMV viremia was associated with BOS or death and retransplantation within 1 year after transplantation. Patients at high risk for CMV infection received ganciclovir prophylaxis for 42 days posttransplantation., Results: From July 1990 to November 2000, 194 pediatric patients received primary lung transplants. Twenty-three percent of patients developed CMV viremia. Eighty percent of CMV viremia episodes occurred before 120 days posttransplant. A first episode of CMV viremia was associated with retransplantation or death between days 90 and 365 (RR=4.1, 95% confidence interval [CI] 1.1-14.5) and was not associated with BOS (RR=1.3, 95% CI 0.5-3.3)., Conclusions: CMV viremia in the first year after pediatric primary lung transplantation is associated with increased risk of death or retransplantation between 90 and 365 days posttransplant, when CMV prophylaxis has stopped. A phase II pilot trial is warranted to assess safety and short-term efficacy of increasing the duration of CMV prophylaxis from 42 to 120 days.