Mortality In Immunocompromised Children Research Articles

Conference Report 33rd European Congress on Clinical Microbiology and Infectious Diseases (ECCMID): New developments in pediatric oncology infectious disease supportive care.

Infections continue to be major causes of morbidity and mortality in immunocompromised children and adolescents with cancer or undergoing allogeneic hematopoietic cell transplantation. This report summarizes new clinical research data presented at the 33rd European Congress on Clinical Microbiology and Infectious Diseases on infections in this vulnerable population, with a focus on the epidemiology, diagnosis, and prevention of invasive fungal diseases and de-escalation strategies in neutropenic patients with fever of unknown origin.

Healthcare-associated infections and drug resistance in immunocompromised children with cancer in a low income country

Aim: It was a clinical audit conducted over 6 monthsperiod in order to determine the clinical characteristics of healthcare-associated infections (HAIs) in immunocompromised children with cancer in a developing country. Methods: It was a descriptive, cohort study conducted in the department of Pediatric Hematology/Oncology, University of Child Health Sciences, The Children’s Hospital Lahore. All patients age less than 16 years, admitted in the pediatric oncology unit, having neutropenia and any culture-proven HAI were included. Data was analyzed in SPSS 16.0. Results: The total number ofHAIs was 101 while the total number of infected patients was 83. The number of infections per 1000 patient days was 6.66. The most common HAI was bloodstream infection (BSI). Sixty-nine percent of HAIs were gram-negative while 31% were gram-positive. Klebsiella species was the most common gram-negative and Staphylococcal Aureus was the most common gram-positive organism. Pan-resistance was encountered in 25.74%, Carbepenam-resistant Enterobacteriaceae in 16%, Vancomycin-resistant Enterococci in 3%, and Methicillin-resistant Staphylococcus Aureus in 2%. Mean hospital stay was 20.22 days, 60.25% of patients were discharged, and 39.75% expired. Conclusion: Drug resistance is seen in about half of the HAIs. Gram-negative infections are the most common cause of HAIs in our setup.HAI and drug resistance areassociated with significant morbidity and mortality in immunocompromised children with cancer and a pose major challenge in their management especially in a resource-limited setting. Keywords: Childhood cancer, Drug resistance, Healthcare-associated infections, Low-middle-income country

249.2: Impact of COVID-19 Infection on Children and Adolescents After Liver Transplantation in a Latin American Reference Center

Background & Aims: Published studies suggest that children (<18 years) infected with COVID-19 are less likely to progress to the severe form of disease when compared to adults, however, scarce data are available on morbidity and mortality in immunocompromised children and adolescents. The aim of this study was to evaluate the outcomes of Pediatric Liver Transplant Recipients (PLTR) who were infected with COVID-19. Methods: Prospective longitudinal cohort study. Between 1st March 2020 and 31st October 2021 clinical, laboratory and evolution data from PLTR (<18 years) were collected in person or by remote telemedicine, who tested positive for COVID-19, for presenting symptoms suggestive of COVID-19 infection or positive epidemiological screening or for presenting positive in laboratory screening before procedure – incidental positive. Results: A total of 74 PLTR were diagnosed with COVID-19. The mean age was 8.2 years (SD 4.49) and 51.4% were girls. The prevalent indication for liver transplantation (LT) was biliary atresia 48 (64.8%) and in 69 (93.2%) patients LT was performed with a living donor. The mean time between LT and COVID-19 infection was 60 months (SD 57.7) and 5 (6.7%) patients became infected up to 3 months after LT, 2 in the early postoperative period. Most patients developed mild symptoms (66%) such as fever (25%), cough (20.2%) and runny nose (20.2%). Hospitalization of outpatients was necessary in 6 children (8.1%), all in hospital ward for suspected sepsis (1), respiratory distress (2), periorbital cellulitis requiring parenteral antibiotics (1), vomiting (1) and gum-stomatitis (1) both requiring hydroeletrolitic replacement. Only 1 child, previously admitted to hospital ward, required transfer to the ICU for respiratory support. The main comorbidities were atopic dermatitis in 5 patients (6.7%), asthma in 4 (5.4%), heart disease, neurological diseases and food allergy in 3(4%), none of which was related to the severity of presentation of COVID-19 infection. Baseline immunosuppression was based on tacrolimus, being associated with prednisone and mycophenolate in 28% and 13.7% respectively. Change in immunosuppression was required with mycophenolate discontinuation in 3 (4%) and a decrease tacrolimus level in 1 patient. Most patients had a good recovery, and only 1 child developed Multisystem Inflammatory Syndrome associated with COVID-19 infection. No child died in this study cohort. Conclusion: In pediatric population LT and immunosuppression cannot be considered independently as factors associated with the risk of severity and death due to COVID-19.

Predictors of mortality in immunocompromised children with respiratory infections

Background Respiratory infection is a common morbidity and a major cause of mortality in immunocompromised children. Hence, identification of clinical parameters that predict mortality among immunocompromised children with respiratory infections is of importance to provide timely and appropriate intervention.&#x0D; Objective To determine predictors of mortality in immunocompromised children with respiratory infections.&#x0D; Methods We conducted a prospective cohort study of immunocompromised children aged 18 years or younger with respiratory tract infections who were admitted to Dr. Sardjito Hospital, Yogyakarta, Indonesia. All eligible children were prospectively followed up until hospital discharge. Clinical and laboratory parameters during the first 24 hours of hospitalization were collected.&#x0D; Results Of 79 eligible children, the overall mortality was 11 subjects (13.9%). Fever, tachycardia, tachypnea, cyanosis, leukopenia, neutropenia, thrombocytopenia, and pleural effusion were predictive factors of mortality in bivariate analysis (P&lt;0.25). A logistic regression model showed that neutropenia (absolute neutrophil count &lt;125/mm3) and tachycardia were the best independent predictors of mortality in immunocompromised children with respiratory infections. The children with tachycardia had 15.8 times higher probability of mortality (95%CI 5.0 to 4.4) and those with neutropenia had 8.24 times higher probability of mortality. Cyanosis and pleural effusion were also independent mortality predictors.&#x0D; Conclusion The risk of mortality is significantly increased in immunocompromised children with respiratory infection when tachycardia and neutropenia are also present.

The Use and Duration of Preintubation Respiratory Support Is Associated With Increased Mortality in Immunocompromised Children With Acute Respiratory Failure.

To determine the association between preintubation respiratory support and outcomes in patients with acute respiratory failure and to determine the impact of immunocompromised (IC) diagnoses on outcomes after adjustment for illness severity. Retrospective multicenter cohort study. Eighty-two centers in the Virtual Pediatric Systems database. Children 1 month to 17 years old intubated in the PICU who received invasive mechanical ventilation (IMV) for greater than or equal to 24 hours. None. High-flow nasal cannula (HFNC) or noninvasive positive-pressure ventilation (NIPPV) or both were used prior to intubation in 1,825 (34%) of 5,348 PICU intubations across 82 centers. When stratified by IC status, 50% of patients had no IC diagnosis, whereas 41% were IC without prior hematopoietic cell transplant (HCT) and 9% had prior HCT. Compared with patients intubated without prior support, preintubation exposure to HFNC (adjusted odds ratio [aOR], 1.33; 95% CI, 1.10-1.62) or NIPPV (aOR, 1.44; 95% CI, 1.20-1.74) was associated with increased odds of PICU mortality. Within subgroups of IC status, preintubation respiratory support was associated with increased odds of PICU mortality in IC patients (HFNC: aOR, 1.50; 95% CI, 1.11-2.03; NIPPV: aOR, 1.76; 95% CI, 1.31-2.35) and HCT patients (HFNC: aOR, 1.75; 95% CI, 1.07-2.86; NIPPV: aOR, 1.85; 95% CI, 1.12-3.02) compared with IC/HCT patients intubated without prior respiratory support. Preintubation exposure to HFNC/NIPPV was not associated with mortality in patients without an IC diagnosis. Duration of HFNC/NIPPV greater than 6 hours was associated with increased mortality in IC HCT patients (HFNC: aOR, 2.41; 95% CI, 1.05-5.55; NIPPV: aOR, 2.53; 95% CI, 1.04-6.15) and patients compared HCT patients with less than 6-hour HFNC/NIPPV exposure. After adjustment for patient and center characteristics, both preintubation HFNC/NIPPV use (median, 15%; range, 0-63%) and PICU mortality varied by center. In IC pediatric patients, preintubation exposure to HFNC and/or NIPPV is associated with increased odds of PICU mortality, independent of illness severity. Longer duration of exposure to HFNC/NIPPV prior to IMV is associated with increased mortality in HCT patients.

Cytomegalovirus Infections in Children with Primary and Secondary Immune Deficiencies.

Cytomegalovirus (CMV) is a human herpes virus that causes significant morbidity and mortality in immunosuppressed children. CMV primary infection causes a clinically mild disease in healthy children, usually in early childhood; the virus then utilises several mechanisms to establish host latency, which allows for periodic reactivation, particularly when the host is immunocompromised. It is this reactivation that is responsible for the significant morbidity and mortality in immunocompromised children. We review CMV infection in the primary immunodeficient host, including early identification of these infants by newborn screening to allow for CMV infection prevention strategies. Furthermore, clinical CMV is discussed in the context of children treated with secondary immunodeficiency, particularly paediatric cancer patients and children undergoing haematopoietic stem cell transplant (HSCT). Treatments for CMV are highlighted and include CMV immunotherapy.

Trends in bacterial bloodstream infections and resistance in immuno-compromised patients with febrile neutropenia: a retrospective analysis.

Bacterial infections remain a major cause of morbidity and mortality in immunocompromised children. From the onset of fever, an early administration of broad-spectrum antibiotics is begun; this strategy could induce emergence of multi-drug resistant bacteria (MDR). We describe the incidence and microbiological spectrum, including MDR bacteria of bacterial documented blood-stream infections (BSI) in immunocompromised children. A retrospective, descriptive study was conducted in a tertiary referral centre in France from January 2014 to December 2017. Our cohort included a large scale of patients with febrile neutropenia: haematological and oncological malignancies, haematopoietic stem cell transplantations, severe combined immunodeficiency syndromes. BSI were defined by positive blood culture samples associated with fever. Among 760 febrile neutropenia episodes in 7301 admitted patients, we identified 310 documented BSI with a mean of 7.4 BSI/1000 patient bed days. Only 2.9% BSIs were caused by MDR bacteria, none vancomycin resistant. Coagulase-negative staphylococci were identified in 49.7% BSI and Staphylococcus aureus caused 6.5% infections. Gram-negative bacilli accounted for 21.6% of isolated bacteria, Pseudomonas for 4.8%. The incidence of BSI annually decreased by 0.75% (p = 0.002).Conclusion: With a step-down strategy at 48h of initial broad-spectrum antibiotic therapy, we reported a low number of MDR bacteria, no deaths related to BSI. What is Known: • Bacterial bloodstream infections are a leading cause of morbidity and mortality in immunocompromised children • Multi-drug resistant bacteria are emerging worldwide. What is New: • Initial broad-spectrum antibiotic therapy with a step-down strategy at 48h: no deaths related to bloodstream infections with a low number of resistant bacteria. • Parental and nurse stewardship to decrease bloodstream infections incidence with a drop of staphylococcal infections.

1356. Ribavirin Use in Hospitalized Children

BackgroundRespiratory syncytial virus (RSV) infection is a significant cause of morbidity and mortality in immunocompromised children. Aerosolized ribavirin is approved for treatment of RSV lower respiratory tract infections. However, due to high cost, challenges to administration and uncertainty about benefit, use is limited. Recent studies in adult patients have reported similar outcomes between patients treated with aerosolized and oral ribavirin. We sought to characterize trends in use of ribavirin for hospitalized children.MethodsWe used the Pediatric Health Information System (PHIS), an administrative database which contains resource utilization data from 52 children’s hospitals, to perform a retrospective analysis of children hospitalized between January 1, 2010 through December 31, 2019 who were billed for ribavirin treatment. Data related to ribavirin use (number of courses, route of administration) and clinical characteristics were abstracted. International Classification of Diseases, 9th Revision (ICD-9) or 10th Revision (ICD-10) codes and All Patients Refined Diagnosis Related Groups (APR DRG) classifications were used to define underlying clinical conditions and illness severity. Summary statistics were used to describe patient characteristics and the use of ribavirin.ResultsThirty-eight hospitals reported ribavirin use; 1 hospital was excluded due to inaccuracies in charge coding. We identified 837 children who received 937 courses of ribavirin (Table 1). The overall frequency of ribavirin use was unchanged over the study period, and the number of ribavirin treatment courses per hospital ranged from 1 to 228 (Figure 1). The most frequent routes of administration were inhalation (603/937, 64%) and oral (322/937, 34%). There was a decrease in the use of aerosolized ribavirin over time, with a corresponding increase in the use of oral ribavirin (Figure 2).Table 1: Patient demographics (N=837) Figure 1: Total ribavirin treatment courses over the study period (a) by year and (b) by treating hospital Figure 2: (a) Route of administration (inhalation versus oral), by year during the study period and (b) use of oral ribavirin over time during the study period ConclusionAlthough overall prescribing rates of ribavirin in hospitalized children have remained stable, use varies widely across centers and the proportion of oral ribavirin use has increased over time. Comparative effectiveness studies are needed in the pediatric population to evaluate outcomes of children treated with aerosolized vs. oral ribavirin.Disclosures All Authors: No reported disclosures

COVID-19 in Children With Cancer: A Single Low-Middle Income Center Experience.

Coronavirus disease-2019 (COVID-19) could be associated with morbidity and mortality in immunocompromised children. The objective of this study was to measure the frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among hospitalized children with cancer and to detect the associated clinical manifestations and outcomes. A prospective noninterventional study including all hospitalized children with cancer conducted between mid-April and mid-June 2020 in Ain Shams University Hospital, Egypt. Clinical, laboratory, and radiologic data were collected. SARS-CoV-2 infection was diagnosed by reverse transcription polymerase chain reaction tests in nasopharyngeal swabs. Fifteen of 61 hospitalized children with cancer were diagnosed with SARS-CoV-2. Their mean age was 8.3±3.5 years. Initially, 10 (66.7%) were asymptomatic and 5 (33.3%) were symptomatic with fever and/or cough. Baseline laboratory tests other than SARS-CoV-2 reverse transcription polymerase chain reaction were not diagnostic; the mean absolute lymphocyte count was 8.7±2.4×109/L. C-reactive protein was mildly elevated in most of the patients. Imaging was performed in 10 (66.7%) patients with significant radiologic findings detected in 4 (40%) patients. Treatment was mainly supportive with antibiotics as per the febrile neutropenia protocol and local Children Hospital guidance for management of COVID-19 in children. Pediatric cancer patients with COVID-19 were mainly asymptomatic or with mild symptoms. A high index of suspicion and regular screening with nasopharyngeal swab in asymptomatic hospitalized cancer patients is recommended.

Invasive fungal infections in a pediatric hematology-oncology department: A 16-year retrospective study

Background and Purpose: Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in immunocompromised children. The purpose of our study was to evaluate the incidence of IFIs in pediatric patients with underlying hematologic malignancies and determine the patient characteristics, predisposing factors, diagnosis, treatment efficacy, and outcome of IFIs.Materials and Methods: For the purpose of the study, a retrospective analysis was performed on cases with proven and probable fungal infections from January 2001 to December 2016 (16 years)Results: During this period, 297 children with hematologic malignancies were admitted to the 2nd Pediatric Department of Aristotle University of Thessaloniki, Greece, and 24 cases of IFIs were registered. The most common underlying diseases were acute lymphoblastic leukemia (ALL; n=19,79%), followed by acute myeloid leukemia (AML; n=4, 17%) and non-Hodgkin lymphoma (NHL; n=1,4%). The crude incidence rates of IFIs in ALL, AML, and NHL were 10.5%, 18.2%, and 2.8% respectively. Based on the results, 25% (n=6) and 75% (n=18) of the patients were diagnosed as proven and probable IFI cases, respectively. The lung was the most common site of involvement in 16 (66.7%) cases. Furthermore, Aspergillus and Candida species represented 58.3% and 29.1% of the identified species, respectively. Regarding antifungal treatment, liposomal amphotericin B was the most commonly prescribed therapeutic agent (n=21), followed by voriconazole (n=9), caspofungin (n=3), posaconazole (n=3), micafungin (n=1), and fluconazole (n=1). In addition, 12 children received combined antifungal treatment. The crude mortality rate was obtained as 33.3%.Conclusion: As the findings of the present study indicated, despite the progress in the diagnosis and treatment of IFIs with the use of new antifungal agents, the mortality rate of these infections still remains high.

Risk of Mortality in Immunocompromised Children With Severe Sepsis and Septic Shock.

To assess the prevalence of immunocompromised diagnoses among children with severe sepsis and septic shock, and to determine the association between immunocompromised diagnoses and clinical outcomes after adjustment for demographics and illness severity. Retrospective multicenter cohort study. Eighty-three centers in the Virtual Pediatric Systems database. Children with severe sepsis or septic shock admitted to a participating PICU between January 1, 2012, and December 31, 2016. None. Across 83 centers, we identified 10,768 PICU admissions with an International Classification of Diseases, 9th Revision, Clinical Modification code for severe sepsis or septic shock; 3,021 of these patients (28%) had an immunocompromised diagnosis. To evaluate variation across centers and determine factors associated with PICU mortality, we used mixed-effect logistic regression models. Among patients without hematopoietic cell transplant, congenital immunodeficiency (adjusted odds ratio, 1.90; 95% CI, 1.24-2.92), multiple prior malignancies (adjusted odds ratio, 1.86; 95% CI, 1.15-2.99), and hemophagocytic lymphohistiocytosis (adjusted odds ratio, 3.09; 95% CI, 1.91-4.98) were associated with an increased odds of PICU mortality. Among patients with prior hematopoietic cell transplant, liquid malignancy (adjusted odds ratio, 3.15; 95% CI, 2.09-4.74), congenital immunodeficiency (adjusted odds ratio, 6.94; 95% CI, 3.84-12.53), multiple prior malignancies (adjusted odds ratio, 3.54; 95% CI, 1.80-6.95), and hemophagocytic lymphohistiocytosis (adjusted odds ratio, 2.79; 95% CI, 1.36-5.71) were associated with an increased odds of PICU mortality. PICU mortality varied significantly by center, and a higher mean number of sepsis patients per month in a center was associated with lower PICU mortality (adjusted odds ratio, 0.94; 95% CI, 0.90-0.98). PICU resource utilization varied by immunocompromised diagnosis and history of hematopoietic cell transplant, and among survivors immunocompromised patients have shorter median PICU length of stay compared with patients without immunocompromised diagnoses (p < 0.001). Immunocompromised diagnoses are present in 28% of children with severe sepsis or septic shock. Multiple prior malignancies, hemophagocytic lymphohistiocytosis, congenital immunodeficiency, and hematopoietic cell transplant are independently associated with an increased odds of PICU mortality in children with severe sepsis or septic shock. Significant variation exists in PICU mortality among centers despite adjustment for immunocompromised diagnoses, known risk factors for sepsis-related mortality, and center-level sepsis volume.

269. Epidemiology and Outcomes of Invasive Aspergillosis (IA) Among Pediatric Immunocompromised Patients: A 12-Year, Single-Center Experience

BackgroundIA remains a leading cause of morbidity and mortality in immunocompromised children, and our understanding regarding epidemiology and outcomes of IA are limited and based on adult studies.MethodsWe conducted a retrospective evaluation of cases of proven or probable IA according to the 2008 EORTC/MSG criteria cared for at Boston Children’s Hospital from 2007 to 2019. We collected data including demographics, clinical characteristics, diagnosis modality, antifungal treatment, and survival. Survival curves over one year were estimated using the Kaplan–Meier method and univariate and multivariate Cox modeling was used to evaluate for risk factors for mortality.Results67 patient cases were identified, 20 (30%) with proven IA and 47 (70%) with probable IA. The mean age at diagnosis was 11.9 years (6 months–28 years). Underlying conditions included hematopoietic-cell transplantation (HCT) in 45%, cancer in 21%, and solid-organ transplantation in 18%. Pulmonary IA was the most common (70.1%) presentation. Diagnostic modalities included positive microbiology alone (18%), fungal PCR alone (1.5%), galactomannan alone (28%), and multiple modalities for the remaining cases (52.5%). 44.8% of patients were neutropenic at diagnosis and 78.5% of patients with malignancies were receiving chemotherapy. Immunosuppressive drugs included glucocorticoids in 34.3%, calcineurin inhibitors in 31.3%, and IMDH inhibitors in 25.3%. Voriconazole was the most common treatment used (72%). Twenty-two (33%) deaths occurred in the cohort attributable to IA (6 of which underwent autopsies and 4 had histopathological confirmation) Most deaths occurred in the BMT patients (15 patients, 45% of deaths). The 6 week mortality was 18% while the 12 week mortality was 25.4%. No antifungal or immunosuppressive regimen had a statistically significant impact on mortality.ConclusionWe demonstrate in our >10-year retrospective cohort analysis of immunocompromised hosts that IA is associated with 49% all-cause mortality with particular impact on the BMT population. No protective nor harmful association was also noted with a particular antifungal or immunosuppressive regimen. Disclosures All authors: No reported disclosures.

Frequency of the CYP2C19*17 polymorphism in a Chilean population and its effect on voriconazole plasma concentration in immunocompromised children

Invasive fungal infections (IFIs) are the most frequent cause of morbidity and mortality in immunocompromised children. Voriconazole is the first-line antifungal choice in the treatment of IFIs like aspergillosis. Voriconazole pharmacokinetics vary widely among patients and voriconazole is metabolized mainly in the liver by the CYP2C19 enzyme, which is highly polymorphic. The CYP2C19*17 allele is characterized by the presence of four single nucleotide polymorphisms expressing an ultra-rapid enzyme phenotype with an accelerated voriconazole metabolism, is associated with low (sub-therapeutic) plasma levels in patients treated with the standard dose. Considering that in our center a high percentage of children have sub-therapeutic levels of voriconazole when treated with standard doses, we sought to determine the frequency of the CYP2C19*17 polymorphism (rs12248560) in a Chilean population and determine the association between voriconazole concentrations and the rs12248560 variant in immunocompromised children. First, we evaluated the frequency of the rs12248560 variant in a group of 232 healthy Chilean children, and we found that 180 children (77.6%) were non-carriers of the rs12248560 variant, 49 children (21.1%) were heterozygous carriers for rs12248560 variant and only 3 children (1.3%) were homozygous carriers for rs12248560 variant, obtaining an allelic frequency of 12% for variant in a Chilean population. To determine the association between voriconazole concentrations and the rs12248560 variant, we analyzed voriconazole plasma concentrations in a second group of 33 children treated with voriconazole. In these patients, carriers of the rs12248560 variant presented significantly lower voriconazole plasma concentrations than non-carriers (p = 0,011). In this study, we show the presence of the rs12248560 variant in a Chilean population and its accelerating effect on the pharmacokinetics of voriconazole in pediatric patients. From these data, it would be advisable to consider the variant of the patient prior to calculating the dosage of voriconazole.

The Pediatric Sepsis Biomarker Risk Model (PERSEVERE) Biomarkers Predict Clinical Deterioration and Mortality in Immunocompromised Children Evaluated for Infection

Pediatric sepsis and bacterial infection cause significant morbidity and mortality worldwide, with immunocompromised patients being at particularly high risk of rapid deterioration and death. This study evaluated if PERSEVERE, PERSEVERE-II, or the PERSEVERE biomarkers, can reliably estimate the risk of clinical deterioration and 28-day mortality among immunocompromised pediatric patients. This is a single-center prospective cohort study conducted from July 2016 through September 2017 incorporating 400 episodes of suspected bacterial infection from the inpatient units at Cincinnati Children’s Hospital Medical Center, a large, tertiary care children’s hospital. The primary analysis assessed clinical deterioration within 72 hours of evaluation for infection. Secondarily, we assessed 28-day mortality. Clinical deterioration was seen in 15% of subjects. Twenty-eight day mortality was 5%, but significantly higher among critically ill patients. Neither PERSEVERE nor PERSEVERE-II performed well to predict clinical deterioration or 28-day mortality, thus we derived new stratification models using the PERSEVERE biomarkers with both high sensitivity and negative predictive value. In conclusion, we evaluated previously validated biomarker risk models in a novel population of largely non-critically ill immunocompromised pediatric patients, and attempted to stratify patients based on a new outcome metric, clinical deterioration. The new highly predictive models indicate common physiologic pathways to clinical deterioration or death from bacterial infection.

Does administration of broad-spectrum antibiotics in febrile neutropenic children trigger the emergence of BMR? A French experience

Background Blood stream infections (BSI) remain a major cause of morbidity and mortality in immunocompromised children and increase the length of hospitalisation as well as the cost of treatment. The difficulty of documenting bacteremia at the onset of fever in neutropenic patients led to an early administration of broad-spectrum antibiotics, without waiting for further clinical or microbiological evidence of infection. Furthermore, gut decontamination is performed in children with a high-risk of BSI. Does this practice trigger the emergence of multidrug resistant bacteria? Methods We performed a monocentric, retrospective and descriptive study between January 2014 and December 2017, using a large cohort of pediatric patients with hematological and oncological diseases in a tertiary care pediatric center in France, the Institute of Hematology and Oncology Pediatric (IHOPe) in Lyon. This includes patients with acute leukemia, lymphoma, children who underwent hematopoietic stem cell transplantation (HSCT) (allogenic and autogenic), children with severe combined immunodeficiency syndromes as well as children suffering from solid tumors. A bacteremia was defined by a positive blood culture sample, associated with fever. For coagulase-negative staphylococci (CoNS), two distinct positive blood cultures within 48 h were mandatory. The children were divided into 4 infectious risk groups regarding their immunosuppression level. Groups 3 and 4 received non-absorbable antibiotics for gut and oral decontamination. The empirical antibacterial therapy was adjusted to the risk group, as well as a prior identified bacteria colonisation: all patients with a central venous access received vancomycin (stopped after 48 hours in the absence of bacterial identification), amikacin and a broad-spectrum penicillin. Results During these 4 years, our institution recorded more than 8000 hospitalisations distributed within 3 units: 2 conventional hospitalisation wards and the HSCT unit. Our protected unit is equipped with spacious positive air pressure rooms, for child and parent, with high-efficiency particulate air (HEPA) filters where only a clean non-sterile outfit (gown and mask) are required. We identified 350 cases of BSI, thus an overall incidence of 4,5%. Fifteen to twenty per cent of these children suffered from a second or more re-infection. The incidence of BSI was stable throughout the four years of our study. Gram-positive bacteria represented more than 50% of BSI and CoNS was the most frequent pathogen agent found. Among the others gram-positive isolates, we counted around 5 to 6 cases/year of Streptococcus and Staphylococcus aureus. Among Gram-negative bacteria, enterobacteries accounted for 14 to 20 BSI per year and Pseudomonas aeruginosa for 2 to 4 cases per year. Among the identified bacteria, only 6.5% were multidrug resistant for all our study time. Three highly resistant bacteria were identified in 2 children priorly treated in Romania and Tunisia: 2 Klebsiella pneumoniae producing Carbapenemase (KPC), 1 Enterococcus faecium resistant to glycopeptides. Interestingly, 35% of the BSI occurred in the less immunocompromised group. The other cases were evenly distributed between the 3 more severely immunocompromised groups. Conclusion Our empirical initial broad-spectrum antimicrobial coverage is well adapted to the epidemiology of our bacterial agents and shortens hospitalisations. Furthermore, it is not associated with the emergence of antibiotic resistance patterns. The microbiological spectrum of incriminated bacteria is relatively stable over time and we do not observe the emergence of multidrug resistant gram-negative bacteria as well as the absence of vancomycin-resistant enterococci (VRE) in our tertiary center.

Human metapneumovirus (hMPV) infection in immunocompromised children

BackgroundHuman metapneumovirus (hMPV) is a major cause of upper and lower respiratory tract infection (URTI, LRTI) in children. The prognosis of hMPV is unclear in immunocompromised patients. ObjectivesTo describe the characteristics of hMPV infection in immunocompromised pediatric patients and to review the literature. Study designThis retrospective study included 39 immunocompromised children (age 0–18 years) with proven hMPV infection attending two tertiary pediatric medical centers in 2004–2014. Demographic, clinical, laboratory, and radiological data were collected from the medical files. ResultsMedian age was 6 years. Seven patients had primary immune deficiency and 32, secondary immune deficiency, including 9 patients who underwent hematopoietic stem cell transplantation (HSCT). Most cases (92%) occurred in January–May. Twenty patients (51%) had lower respiratory tract infection and 17 (44%), upper respiratory tract infection; 2 patients (5%) had fever only. Presenting symptoms were fever (70%), cough (54%), and rhinorrhea (35%). Severe lymphopenia (<1000lymphocytes/mL) was noted in 64% of patients and elevated liver enzyme levels in 49%. Seventeen patients had pneumonia: bilateral and alveolar in 13 patients, each. HSCT was not associated with more severe disease. Respiratory failure occurred in 6 patients, of whom 4 died (10% of cohort). All children who died had severe lymphopenia. On multivariate analysis, bacterial or fungal co-infection was the only major risk factor for death. Review of the literature showed variable clinical presentations and severity in pediatric patients with hMPV infection. ConclusionsInfection with hMPV may be associated with relatively high morbidity and mortality in immunocompromised children. Death was associated with bacterial and fungal co-infection.

G415(P) Cytomegalovirus infection presenting as recurrent fever in a child receiving standard chemotherapy for acute lymphoblastic leukaemia

<h3>Introduction</h3> Infection presenting with fever is a common cause for hospital admission of immunocompromised children. Initial management is aimed at the treatment and identification of bacterial and fungal infection. Cytomegalovirus (CMV) is well recognised as causing increased morbidity and mortality in immunocompromised children who have undergone stem cell transplants but less so in children receiving standard chemotherapy in acute lymphoblastic leukaemia. <h3>Case description</h3> Our patient is a 7 year old girl receiving standard chemotherapy for acute lymphoblastic leukaemia. Post induction she was admitted with significant fever but no other clinical signs or symptoms. She was not neutropenic, CRP was unremarkable and cultures negative. A chest X-ray showed right middle lobe changes and CT chest showed consolidation and atelectasis but no ground glass appearance or nodules. Candida PCR and beta-D-glucan test were negative. She received a course of empiric antibiotics, including macrolides, and antifungal treatment. Her fever settled. Following cessation of treatment she was readmitted with fever and a dry cough and intravenous antibiotic and antifungal therapy was recommenced. Repeat investigative workup was unremarkable. She settled. A further brief admission with fever settled without intervention following which she was readmitted for the fourth time with fever and cough. She became unwell, developing an oxygen requirement with respiratory signs on chest auscultation. Blood viral PCRs were sent. CMV PCR was significantly elevated at 142,000 copies/ml. BAL fluid was CMV positive and negative for fungi. Intravenous foscarnet was added to the treatment regime. She improved with this and empirical antifungal treatment. <h3>Results and conclusion</h3> This patient presented with recurrent fevers resulting in prolonged admissions impacting on quality of life and interruption of treatment. No other positive pathogens for the fever were identified apart from CMV. A literature review confirms that CMV is an opportunistic infection that can cause serious, sometimes life-threatening, illness even during conventional anticancer infection due to profound immunosuppression. This is less recognised in clinical practice. We would highlight the importance of considering CMV infection in cases of recurrent and prolonged fever in these children.

A Prospective, International Cohort Study of Invasive Mold Infections in Children.

Invasive mold infections (IMIs) are a leading cause of mortality in immunocompromised children, yet there has never been an international epidemiologic investigation of pediatric IMIs. This international, prospective cohort study was performed to characterize the epidemiology, antifungal therapy, and outcomes of pediatric IMIs. Children (≤18 years) with proven or probable IMIs were enrolled between August 2007 and May 2011 at 22 sites. Risk factors, underlying diagnoses, and treatments were recorded. Outcomes were assessed at 12 weeks after diagnosis using European Organization for Research and Treatment of Cancer/Mycoses Study Group response criteria. One hundred thirty-one pediatric patients with IMIs were enrolled; the most common IMI was invasive aspergillosis ([IA] 75%). Children with IA and those with other types of IMIs had similar underlying risk factors, except that children with IMIs caused by non-Aspergillus species were more likely to have received mold-active antifungal agents preceding diagnosis. The most commonly used antifungal classes after diagnosis were triazoles (82%) and polyenes (63%). Combination therapy was used in 53% of patients. Use of combination therapy was associated with an increased risk of adverse events (risk ratio, 1.98; 95% confidence interval, 1.06-3.68; P = .031), although there was no detectable difference in outcome. Although risk factors for IMIs are similar across specific subtypes, preceding antifungal therapy may be an important modifier. Combination antifungal therapy requires further study to determine its true risks and benefits.

Invasive Fusariosis: A Single Pediatric Center 15-Year Experience.

Invasive fungal infection (IFI) is an important cause of mortality in immunocompromised children, particularly after hematopoietic stem cell transplantation. We describe 5 cases of Fusarium IFI in immunocompromised children seen at our institution over a 15-year period. A summary of all published pediatric cases of invasive Fusarium infection is presented. A focus on antifungal management challenges in these patients will be discussed.

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Introduction: We report the case of a 3 y/o boy with fever, headache, abdominal pain, decreased appetite who was being treated for presumed pneumonia and was found to have hepatomegaly, lymphadenopathy, hyperleukocytosis of 234,000 cells with 91% blasts, hemoglobin of 4.2 and platelets less than 5000. On transfer to our PICU, he was mechanically ventilated for respiratory failure and had plasmapheresis to prevent hyperviscocity syndrome. He was diagnosed with Pre B cell ALL and received chemotherapy per AALL1123 protocol. He was treated with piperacillin/tazobactam and azithromycin for pneumonia and bactrim and fluconazole for prophylaxis against opportunistic infections. He was extubated after 7days. On day 12 of induction chemotherapy, he had decreased responsiveness when CT brain revealed multiple areas of low density with surrounding vasogenic edema suspicious for fungal abscess or hemorrhage. MR spectroscopy result was suspicious for angioinvasive aspergillosis with associated abscesses. Amphotericin and voriconazole were used to treat presumed aspergillus infection. Stereotaxic guided craniotomy was done for biopsy of the brain lesion, which grew Aspergillus Fumigatus. Repeat CT scan of brain 4 and 6days after MRI showed worsening lesions and no improvement despite aggressive antifungal therapy. He died one month after his admission due to aspergillus brain abscess involving multiple areas of the brain including brain stem. Invasive aspergillosis(IA) is an important cause of morbidity and mortality in immunocompromised children with highest incidence found in children with Wiskott-Aldrich syndrome and a very low incidence of 0.6% in children with ALL. Aspergillus fumigatus is the most common cause of IA followed by aspergillus flavus, aspergillus niger, aspergillus terreus. Clinical practice guidelines of the Infectious disease society of America does not recommend empirical therapy in shorter duration of neutropenia <10days unless there are findings of invasive fungal infections. Our patient presented with hyperleukocytosis and likely had dysfunctional neutrophil function thus predisposing him to IA. He also progressed to absolute neutropenia in rapid fashion within 3days of initiation of chemotherapy. The most significant risk factor contributing to his development of IA may have been his home environment. The family lived and worked in Avondale Pennsylvania, a suburb of Philadelphia in chester County with close proximity to Kennet Square and its large mushroom farming industry. Kennet Square is noted as "The Mushroom Capital of the World" supplying over 51% of the nation's mushroom crop. Mushrooms as with other fungi, thrive in warm moist dark environment and are frequently fertilized with a soil/manure compost that is frequently rotated by heavy equipment. This compost rotation releases spores into the air that are harmless when inhaled by immunocompetent individuals. Our patient living in this endemic area was likely exposed to high spore content of pathogenic Aspergillus species environmentally and so rapidly developed brain abscess when chemotherapy was initiated. Our case is unique as he had very rapid onset of CNS aspergillosis, with history of agricultural exposure in the setting of Pre B cell ALL. Given our hospital's geographic location, questions remain whether consideration should be given to initiate empirical antifungal therapy at treatment doses with initiation of chemotherapy.