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Epidemiology of Clostridioides difficile infection (CDI) in paediatric cancer patients is uncertain. The primary objective was to describe the prevalence of CDI outcomes among paediatric patients receiving cancer treatments. Secondary objectives were to describe clinical features of CDI, propose a definition of severe CDI and to determine risk factors for CDI clinical outcomes. A multi-centre retrospective cohort study that included paediatric patients (1–18 years of age) receiving cancer treatments with CDI. Severe CDI definition was achieved by consensus. Univariable and multivariable regression was conducted to evaluate risk factors for CDI outcomes. There were 627 eligible patients who experienced 721 CDI episodes. The prevalence of clinical cure was 82.9%, recurrence was 9.6%, global cure was 75.0% and repeated new CDI episode was 12.8%. The proposed definition of severe CDI was the presence of colitis, pneumatosis intestinalis, pseudomembranous colitis, ileus or surgery for CDI, occurring in 70 (9.7%) episodes. In univariable regression, initial oral metronidazole or initial oral vancomycin were not significantly associated with failure to achieve clinical cure or CDI recurrence. In multiple regression, oral metronidazole was significantly associated with higher odds (odds ratio (OR) 1.7, 95% confidence interval (CI) 1.0–2.7) and oral vancomycin was significantly associated with lower odds (OR 0.4, 95% CI 0.2–0.8) of repeated new episodes. The prevalence of clinical cure was 82.9% and recurrence was 9.6% in pediatric patients receiving cancer treatments. Severe CDI, as per our proposed definition, occurred in 9.7% episodes. Initial oral vancomycin was significantly associated with a reduction in repeated new CDI episodes. • In children with cancer and C. difficile infection (CDI), 82.9% had clinical cure. • Recurrence of CDI occurred in 9.6%. • A definition for severe CDI was derived and occurred in 9.7%. • Oral vancomycin was significantly associated with reduced repeated CDI episodes. [ABSTRACT FROM AUTHOR]

Invasive fungal disease (IFD) remains a common and serious complication in children treated for leukaemia. Antifungal prescription in children with leukaemia presents unique challenges, particularly due to variation in IFD risk between and within leukaemia treatment protocols, drug toxicities and interactions between antifungals and chemotherapeutic agents. With recent advances in the understanding of IFD epidemiology and large clinical trials in adults assessing antifungals for IFD treatment and prophylaxis, together with paediatric clinical and pharmacokinetic studies, there is a growing body of data to inform optimal antifungal use in children. A panel of infectious diseases and haematology-oncology clinicians with expertise in IFD management compiled a list of 10 key clinical questions following development of the 2021 Australia and New Zealand Mycology Antifungal Consensus Guidelines. A focused literature review was conducted to explore available evidence and identify gaps in knowledge to direct future research. With the changing epidemiology of IFD globally, the ongoing evolution of paediatric leukaemia treatment and the increasing availability of novel antifungal agents, advocacy for paediatric clinical studies will remain vital to optimize IFD prevention and treatment in children with leukaemia. [ABSTRACT FROM AUTHOR]

Objectives: Febrile neutropenia (FN) is a major cause of treatment disruption and unplanned hospitalization in childhood cancer patients. This study investigated the transcriptome of peripheral blood mononuclear cells (PBMCs) in children with cancer and FN to identify potential predictors of serious infection. Methods: Whole‐genome transcriptional profiling was conducted on PBMCs collected during episodes of FN in children with cancer at presentation to the hospital (Day 1; n = 73) and within 8–24 h (Day 2; n = 28) after admission. Differentially expressed genes as well as gene pathways that correlated with clinical outcomes were defined for different infectious outcomes. Results: Global differences in gene expression associated with specific immune responses in children with FN and documented infection, compared to episodes without documented infection, were identified at admission. These differences resolved over the subsequent 8–24 h. Distinct gene signatures specific for bacteraemia were identified both at admission and on Day 2. Differences in gene signatures between episodes with bacteraemia and episodes with bacterial infection, viral infection and clinically defined infection were also observed. Only subtle differences in gene expression profiles between non‐bloodstream bacterial and viral infections were identified. Conclusion: Blood transcriptome immune profiling analysis during FN episodes may inform monitoring and aid in defining adequate treatment for different infectious aetiologies in children with cancer. [ABSTRACT FROM AUTHOR]

This article discusses the shifting landscape of infectious diseases in hematologic malignancies, specifically focusing on hematopoietic cell transplantation (HCT) and cellular therapy. The advancements in genetic characterization of hematologic malignancies have led to targeted treatments and increased eligibility for HCT. The availability of chimeric antigen receptor (CAR) T-cell therapy is also changing the treatment landscape for certain types of cancer. However, as cancer treatments evolve, so do the associated risks and spectrum of infections. The article emphasizes the importance of anticipating and responding to unintended infectious consequences and discusses the latest updates in the prevention, diagnosis, and treatment of infections in patients receiving HCT and cellular therapies. The article also includes personal accounts from patients and their loved ones, highlighting the impact of infectious diseases on their lives. The authors express their appreciation to the contributors and emphasize the importance of global, collaborative research efforts in advancing the field of transplant infectious diseases. [Extracted from the article]

There are limited data on SARS-CoV-2 (COVID-19) infection in children with cancer or after haematopoietic stem cell transplant (HSCT). We describe the severity and outcomes of SARS-COV-2 in these patients and identify factors associated with severe disease. This was a multinational, observational study of children (aged <19 years) with cancer or HSCT and SARS-CoV-2 confirmed by polymerase chain reaction. COVID-19 was classified as asymptomatic, mild, moderate, severe or critical (≥1 organ support). Exact polytomous regression was used to determine the relationship between clinical variables and disease severity. One hundred and thirty-one patients with COVID-19 across 10 countries were identified (median age 8 years). Seventy-eight (60%) had leukaemia/lymphoma, 48 (37%) had solid tumour and five had primary immunodeficiency and HSCT. Fever (71%), cough (47%) and coryza (29%) were the most frequent symptoms. The median duration of detectable virus was 16 days (range, 1–79 days). Forty-nine patients (37%) were hospitalised for COVID-19 symptoms, and 15 (11%) required intensive care unit–level care. Chemotherapy was delayed/modified in 35% of patients. COVID-19 was asymptomatic in 32% of patients, mild in 47%, moderate in 8%, severe in 4% and critical in 9%. In 124 patients (95%), a full recovery was documented, and four (3%) died due to COVID-19. Any comorbidity (odds ratio, 2.94; 95% confidence interval [CI], 1.81–5.21), any coinfection (1.74; 95% CI 1.03–3.03) and severe baseline neutropenia (1.82; 95% CI 1.13–3.09) were independently and significantly associated with increasing disease severity. Although most children with cancer had asymptomatic/mild disease, 13% had severe COVID-19 and 3% died. Comorbidity, coinfection and neutropenia may increase the risk of severe disease. Our data may help management decisions in this vulnerable population. • Data on COVID-19 infection in children with cancer are limited. • In this multinational study, 11% of children with cancer and COVID-19 required intensive care unit admission. • There were 4 of 131 children who died due to infection. • The median duration of detectable SARS-CoV-2 virus was 16 days. • Comorbidity, coinfection and neutropenia were significantly associated with severe COVID-19. [ABSTRACT FROM AUTHOR]

Purpose: Contention surrounds how best to screen patients for latent and undiagnosed infection prior to cancer treatment. Early treatment and prophylaxis against reactivation may improve infection-associated morbidity. This study sought to examine rates of screening and prevalence of latent infection in overseas-born patients receiving cancer therapies. Methods: A single-centre retrospective audit of 952 overseas-born patients receiving chemotherapy, targeted agents and immunotherapy between January 1 and December 31 2019 was undertaken at Peter MacCallum Cancer Centre. Pre-treatment screening for hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV), latent tuberculosis (LTBI), toxoplasmosis and strongyloidiasis was audited. Results: Approximately half of our overseas-born patients were screened for HBV (58.9%) and HCV (50.7%). Fewer patients were screened for HIV (30.5%), LTBI (18.3%), strongyloidiasis (8.6%) or toxoplasmosis (8.1%). Although 59.7% of our patients were born in countries with high epidemiological risk for latent infection, according to World Health Organization data, 35% were not screened for any infection prior to commencement of therapy. Conclusion: The prevalence of latent infections amongst overseas-born patients with cancer, and complexities associated with risk-based screening, likely supports universal latent infection screening amongst this higher-risk cohort. [ABSTRACT FROM AUTHOR]

Aim: The Australian 'There is no place like home' project is implementing a paediatric low‐risk febrile neutropenia (FN) programme across eight paediatric hospitals. We sought to identify the impact of the coronavirus disease 2019 (COVID‐19) pandemic on programme implementation. Methods: Paediatric oncology, infectious diseases and emergency medicine health‐care workers and parent/carers were surveyed to explore the impact of the COVID‐19 pandemic on home‐based FN care. Online surveys were distributed nationally to health‐care workers involved in care of children with FN and to parents or carers of children with cancer. Results: Surveys were completed by 78 health‐care workers and 32 parents/carers. Overall, 95% of health‐care workers had confidence in the safety of home‐based FN care, with 35% reporting changes at their own hospitals in response to the pandemic that made them more comfortable with this model. Compared to pre‐pandemic, >50% of parent/carers were now more worried about attending the hospital with their child and >80% were interested in receiving home‐based FN care. Among both groups, increased telehealth access and acceptance of home‐based care, improved patient quality of life and reduced risk of nosocomial infection were identified as programme enablers, while re‐direction of resources due to COVID‐19 and challenges in implementing change during a crisis were potential barriers. Conclusion: There is strong clinician and parent/carer support for home‐based management of low‐risk FN across Australia. Changes made to the delivery of cancer care in response to the pandemic have generally increased acceptance for home‐based treatments and opportunities exist to leverage these to refine the low‐risk FN programme. [ABSTRACT FROM AUTHOR]

Background: Home-based management of low-risk febrile neutropenia (FN) is safe, improves quality of life and reduces healthcare expenditure. A formal low-risk paediatric program has not been implemented in Australia. We aimed to describe the implementation process and evaluate the clinical impact. Method: This prospective study incorporated three phases: implementation, intervention and evaluation. A low-risk FN implementation toolkit was developed, including a care-pathway, patient information, home-based assessment and educational resources. The program had executive-level endorsement, a multidisciplinary committee and a nurse specialist. Children with cancer and low-risk FN were eligible to be transferred home with a nurse visiting daily after an overnight period of observation for intravenous antibiotics. Low-risk patients were identified using a validated decision rule, and suitability for home-based care was determined using disease, chemotherapy and patient-level criteria. Plan-Do-Study-Act methodology was used to evaluate clinical impact and safety. Results: Over 18 months, 292 children with FN were screened: 132 (45%) were low-risk and 63 (22%) were transferred to home-based care. Compared with pre-implementation there was a significant reduction in in-hospital median LOS (4.0 to 1.5 days, p < 0.001) and 291 in-hospital bed days were saved. Eight (13%) patients needed readmission and there were no adverse outcomes. A key barrier was timely screening of all patients and program improvements, including utilising the electronic medical record for patient identification, are planned. Conclusion: This program significantly reduces in-hospital LOS for children with low-risk FN. Ongoing evaluation will inform sustainability, identify areas for improvement and support national scale-up of the program. [ABSTRACT FROM AUTHOR]

Background The timing and necessity of repeated blood cultures (BCs) in children with cancer and febrile neutropenia (FN) are unknown. We evaluated the diagnostic yield of BCs collected pre- and post-empiric FN antibiotics. Methods Data collected prospectively from the Australian Predicting Infectious ComplicatioNs in Children with Cancer (PICNICC) study were used. Diagnostic yield was calculated as the number of FN episodes with a true bloodstream infection (BSI) detected divided by the number of FN episodes that had a BC taken. Results A BSI was identified in 13% of 858 FN episodes. The diagnostic yield of pre-antibiotic BCs was higher than of post-antibiotic cultures (12.3% vs 4.4%, P <.001). Two-thirds of the post-antibiotic BSIs were associated with a new episode of fever or clinical instability, and only 2 new BSIs were identified after 48 hours of empiric antibiotics and persistent fever. A contaminated BC was identified more frequently in post-antibiotic cultures. Conclusions In the absence of new fever or clinical instability, BCs beyond 48 hours of persistent fever have limited yield. Opportunity exists to optimize BC collection in this population and reduce the burden of unnecessary tests on patients, healthcare workers, and hospitals. [ABSTRACT FROM AUTHOR]

Aminoglycosides are commonly prescribed to children with febrile neutropenia (FN) but their impact on clinical outcomes is uncertain and extent of guideline compliance is unknown. We aimed to review aminoglycoside prescription and additional antibiotic prescribing, guideline compliance and outcomes for children with FN. We analysed data from the Australian Predicting Infectious ComplicatioNs in Children with Cancer (PICNICC) prospective multicentre cohort study, in children <18 years with FN between November 2016 and January 2018. Impact of aminoglycoside use in the first 12 hours of FN on composite unfavourable outcome of death, ICU admission, relapse of infection or late-onset sepsis was assessed using multivariable Cox regression. The study was conducted in Australia where antimicrobial resistance among gram negative organisms is relatively low. Data from 858 episodes of FN in 462 children from 8 centres were assessed, median age 5.8 years (IQR 3.5–10.8 years). Early empiric aminoglycosides were prescribed in 255 episodes (29.7%). Guideline non-compliance was common: in 46% (184/400) of eligible episodes, patients did not receive aminoglycosides, while aminoglycosides were prescribed in 9% (39/458) of guideline-ineligible episodes. Adjusted hazard of the composite unfavourable outcome was 3.81 times higher among patients prescribed empiric aminoglycosides than among those who weren't (95% confidence interval, 1.89–7.67), with no increased risk of unfavourable outcome in eligible patients who did not receive aminoglycosides. In a large paediatric FN cohort, aminoglycoside prescription was common and was often non-compliant with guidelines. There was no evidence for improved outcome with aminoglycosides, even in those who met guideline criteria, within a low-resistance setting. Empiric aminoglycoside prescription for children with FN requires urgent review in guidelines and in national practice. [ABSTRACT FROM AUTHOR]

Aim: Variation in the management of fever and neutropenia (FN) in children is well described. The aim of this study was to explore the current management of FN across Australia and New Zealand and highlight areas for improvement.Methods: A practice survey was administered to paediatric health-care providers via four clinical and research networks. Using three clinical case vignettes, we explored risk stratification, empiric antibiotics, initial investigations, intravenous-oral switch, ambulatory management and antibiotic duration in children with cancer and FN.Results: A response was received from 104 participants from 16 different hospitals. FN guideline compliance was rated as moderate or poor by 24% of respondents, and seven different fever definitions were described. There was little variation in the selected empiric monotherapy and dual-therapy regimens, and almost all respondents recommended first-dose antibiotics within 1 h. However, 27 different empiric antibiotic combinations were selected for beta-lactam allergy. An incorrect risk status was assigned to the low-risk case by 27% of respondents and to the high-risk case by 41%. Compared to current practice, significantly more respondents would manage the low-risk case in the ambulatory setting provided adequate resources were in place (43 vs. 85%, P < 0.0001). There was variation in the use of empiric glycopeptides as well as use of aminoglycosides beyond 48 h.Conclusion: Although the antibiotics selected for empiric management of FN are appropriate and consistent, variation and inaccuracies exist in risk stratification, the selection of monotherapy over dual therapy, empiric antibiotics chosen for beta-lactam allergy, use of glycopeptides and duration of aminoglycosides. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to validate the 'Predicting Infectious ComplicatioNs in Children with Cancer' (PICNICC) clinical decision rule (CDR) that predicts microbiologically documented infection (MDI) in children with cancer and fever and neutropenia (FN). We also investigated costs associated with current FN management strategies in Australia.Methods: Demographic, episode, outcome and cost data were retrospectively collected on 650 episodes of FN. We assessed the discrimination, calibration, sensitivity and specificity of the PICNICC CDR in our cohort compared with the derivation data set.Results: Using the original variable coefficients, the CDR performed poorly. After recalibration the PICNICC CDR had an area under the receiver operating characteristic (AUC-ROC) curve of 0.638 (95% CI 0.590-0.685) and calibration slope of 0.24. The sensitivity, specificity, positive predictive value and negative predictive value of the PICNICC CDR at presentation was 78.4%, 39.8%, 28.6% and 85.7%, respectively. For bacteraemia, the sensitivity improved to 85.2% and AUC-ROC to 0.71. Application at day 2, taking into consideration the proportion of MDI known (43%), further improved the sensitivity to 87.7%. Length of stay is the main contributor to cost of FN treatment, with an average cost per day of AUD 2183 in the low-risk group.Conclusions: For prediction of any MDI, the PICNICC rule did not perform as well at presentation in our cohort as compared with the derivation study. However, for bacteraemia, the predictive ability was similar to that of the derivation study, highlighting the importance of recalibration using local data. Performance also improved after an overnight period of observation. Implementation of a low-risk pathway, using the PICNICC CDR after a short period of inpatient observation, is likely to be safe and has the potential to reduce health-care expenditure. [ABSTRACT FROM AUTHOR]

The article presents case study of a five-year-old girl with acute lymphoblastic leukaemia, who has been receiving empirical intravenous antibiotic treatment for febrile neutropenia. Blood test of the patient revealed presence of gram-negative bacillus. Biomedical database Medline was searched for articles related to antibiotic resistant Gram-negative organism. Further analysis inferred that in hospitalization of children with cancer for 48 hours increases likelihood the resistant organisms.

Objective Fludarabine, cyclophosphamide and rituximab ( FCR) therapy for lymphoid malignancies has historically been associated with a low reported incidence of Pneumocystis jirovecii pneumonia ( PJP). However, prophylaxis was routinely used in early studies, and molecular diagnostic tools were not employed. The objective of this study was to review the incidence of PJP during and post- FCR in the era of highly sensitive molecular diagnostics and 18F-fluorodeoxyglucose ( FDG) positron emission tomography ( PET)-computerised tomography ( CT). Methods All patients treated with standard FCR at the Peter Mac Callum Cancer Centre ( March 2009 to June 2012) were identified from a medications management database. Laboratory-confirmed PJP cases during this time were identified from an electronic database. Results Overall, 66 patients were treated with a median of 5.5 FCR cycles. Eight PJP cases were identified, 6 of whom had received chemotherapy prior to FCR. In 5 cases, 18F- FDG PET demonstrated bilateral ground-glass infiltrates. Median CD4+ lymphocyte counts at time of PJP diagnosis and 9-12 months following FCR were 123 and 400 cells/μL, respectively. In patients receiving no prophylaxis, 9.1% developed PJP during FCR. The rate following FCR was 18.4%, with median onset at 6 months (2.4-24 months). Conclusion Given the high rate of late-onset PJP, consideration should be given for extended PJP prophylaxis for up to 12 months post- FCR, particularly in pretreated patients. Further evaluation of the role of CD4+ monitoring is warranted to quantify risk of disease development and to guide duration of prophylaxis. [ABSTRACT FROM AUTHOR]

The article provides an answer to a question of how do febrile convulsions cause cerebrospinal fluid (CSF) pleocytosis.

Objectives Posaconazole is increasingly used for the treatment and prophylaxis of invasive fungal infections in immunocompromised children. We aimed to review evidence for paediatric posaconazole dosing regimens focusing on attainment of target concentrations and frequency of adverse effects. Methods In May 2023, the Cochrane, Embase, MEDLINE and PubMed databases were searched for articles reporting posaconazole dosing in children with malignancy or post-haematopoietic stem cell transplantation. Studies reporting the attainment of target serum concentrations were included. Results Overall, 24 studies were included. Eighteen studies of the oral suspension consistently reported poor attainment of target concentrations for prophylaxis (≥0.7 µg/mL, 12%–78%) despite high daily doses of 14–23 mg/kg/day (max. 1200 mg/day). Target attainment was significantly affected by gastric pH and food intake. Six studies of the delayed-release tablet (DRT) reported 58%–94% achieved concentrations ≥0.7 µg/mL, with the majority using lower doses of 4–12 mg/kg/day (max. 300 mg/day). Similarly, one study of powder for oral suspension found 67%–100% achieved target concentrations with a dose of 6 mg/kg/day (max. 300 mg/day). As expected, the IV formulation had high attainment of prophylaxis targets (81%–90%) with 6–10 mg/kg/day (max. 400 mg/day). All formulations were well tolerated, and no relationship between adverse effects and posaconazole concentrations was identified. Conclusions The required posaconazole dose in immunocompromised children varies depending on the formulation. The IV infusion had the highest attainment of therapeutic concentration followed by the DRT and powder for suspension. By contrast, the oral suspension had low attainment of target concentrations despite higher daily doses. [ABSTRACT FROM AUTHOR]

Community Pharmacists (CPs) are easily accessible and can advocate for the appropriate use of antibiotics in children. Semi-structured interviews were conducted with 47 CPs and 46 parents/caregivers. Both groups expressed challenges to intervening when antibiotics have already been prescribed and highlighted the need for more support for CPs to make informed decisions. [ABSTRACT FROM AUTHOR]

Antifungal prophylaxis can reduce morbidity and mortality from invasive fungal disease (IFD). However, its use needs to be optimised and appropriately targeted to patients at highest risk to derive the most benefit. In addition to established risks for IFD, considerable recent progress in the treatment of malignancies has resulted in the development of new 'at‐risk' groups. The changing epidemiology of IFD and emergence of drug resistance continue to impact choice of prophylaxis, highlighting the importance of active surveillance and knowledge of local epidemiology. These guidelines aim to highlight emerging risk groups and review the evidence and limitations around new formulations of established agents and new antifungal drugs. It provides recommendations around use and choice of antifungal prophylaxis, discusses the potential impact of the changing epidemiology of IFD and emergence of drug resistance, and future directions for risk stratification to assist optimal management of highly vulnerable patients. [ABSTRACT FROM AUTHOR]

Background Neutropenic fever (NF) is a common complication in patients receiving chemotherapy. Judicious antimicrobial use is paramount to minimize morbidity and mortality and to avoid antimicrobial-related harms. Objectives To use an Australian national dataset of antimicrobial prescriptions for the treatment of NF to describe antimicrobial use, prescription guideline compliance and appropriateness; and to compare these findings across different healthcare settings and patient demographics. We also aimed to identify trends and practice changes over time. Methods Data were extracted from the Hospital National Antimicrobial Prescribing Survey (Hospital NAPS) database from August 2013 to May 2022. Antimicrobial prescriptions with a NF indication were analysed for antimicrobial use, guideline compliance and appropriateness according to the Hospital NAPS methodology. Demographic factors, hospital classifications and disease characteristics were compared. Results A total of 2887 (n = 2441 adults, n = 441 paediatric) NF prescriptions from 254 health facilities were included. Piperacillin-tazobactam was the most prescribed antimicrobial. Overall, 87.4% of prescriptions were appropriate. Piperacillin-tazobactam and cefepime had the highest appropriateness though incorrect piperacillin-tazobactam dosing was observed. Lower appropriateness was identified for meropenem, vancomycin, and gentamicin prescribing particularly in the private hospital and paediatric cohorts. The most common reasons for inappropriate prescribing were spectrum too broad, incorrect dosing or frequency, and incorrect duration. Conclusions This study provides insights into antimicrobial prescribing practices for NF in Australia. We have identified three key areas for improvement: piperacillin-tazobactam dosing, paediatric NF prescribing and private hospital NF prescribing. Findings from this study will inform the updated Australian and New Zealand consensus guidelines for the management of neutropenic fever in patients with cancer. [ABSTRACT FROM AUTHOR]

Background: CD19‐directed chimeric antigen receptor T‐cell (CAR‐T) therapy is transforming care for pediatric patients with relapsed or refractory B‐cell acute lymphoblastic leukemia (B‐ALL). There are limited pediatric‐specific data concerning the infection risks associated with CD19 CAR‐T therapy and the adequacy of current antimicrobial prophylaxis guidelines for these patients. Methods: We describe the antimicrobial prophylaxis used and the types of infectious occurring in the first 100 days following CAR‐T therapy for relapsed or refractory B‐cell ALL in children and adolescents (≤18 years) at our centre. Results: Twenty‐seven patients received their first CAR‐T infusion (CTI) during the study period. Almost all patients (96%) had a comprehensive Infectious Diseases review prior to CTI, which informed a personalised prophylaxis or fever/sepsis plan in six (22%). Overall, six (22%) patients had one or more infections during the study period including five (19%, 0.9 per 100 days‐at‐risk) from days 0–30 and three (n = 20, 15%, 0.6 per 100 days‐at‐risk) from days 31–100. Bacterial blood stream infections were the most common type of infection encountered during both time periods, and one patient had probable pulmonary aspergillosis. There were no infection‐related deaths. Conclusion: Our study contributes important information on the spectrum of infections encountered in pediatric patients with B‐ALL post CAR‐T therapy. Overall, the burden of infectious complications post CAR‐T therapy in our cohort is lower than previously reported in the literature. Results suggest that our prophylaxis recommendations are effective in this population. [ABSTRACT FROM AUTHOR]

The authors discuss research on the effectiveness of moxifloxacin in reducing febrile neutropenia episodes in patients with hematological malignancies, conducted by A. Shinohara and colleagues, published within the issue. Topics explored include the necessity of antibiotic prophylaxis in the prevention of infectious complications, the European Conference on Infections in Leukaemia (ECIL)-issued guidelines for addressing febrile neutropenia, and the monitoring of bacterial resistance patterns.

Background: Antibiotics, while an essential component of supportive care in allogeneic hematopoietic cell transplantation (allo‐HCT), can have adverse effects and select for antibiotic resistance. Understanding of patterns of use will inform antimicrobial stewardship (AMS) interventions. Methods: Retrospective, single‐center cohort of children undergoing first allo‐HCT (n = 125). Antibiotic prescription and infection data were included from the date conditioning was commenced until 30 days post allo‐HCT. Antibiotic use was reported as length of therapy (LOT) (number of days a patient received an antibiotic) and days of therapy DOT (aggregating all antibiotics prescribed per day). Infections were classified as microbiologically documented infection (MDI) or clinically documented infections. Results: At least one course of antibiotics was administered to 124 (99%) patients. The LOT was 636 per 1000 patient days and DOT was 959 per 1000 patient days. The median duration of cumulative antibiotic exposure per patient was 24 days (interquartile range [IQR] 20–30 days). There were 131 days of fever per 1000 patient days with patients febrile for a median of 4 days (IQR 1–7 days). Piperacillin–tazobactam was used for 116 (94%) of patients with an LOT of 532 per 1000 patient days. A total of 119 MDI episodes occurred in 74 (59%) patients, including blood stream infection in 30 (24%) and a proven/probable invasive fungal infection in 4 (3%). Conclusion: Pediatric HCT patients receive prolonged courses of broad‐spectrum antibiotics relative to the frequency of fever and bacterial infections. This study has identified opportunities for AMS intervention to improve outcomes for our HCT patients. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 13 year old girl who was taken to the hospital with a seven month old left hip pain, night sweats and weight loss. After going through several examinations she was pronounced with a bruised left sacroiliac joint and small premembranous ventricular septal defect. Her blood was found infected with abiotrophia defectiva, a bacterium.

Purpose: Clostridium difficile infection (CDI) is the leading cause of diarrhoea in hospitalised patients. Cancer populations are at high-risk for infection, but comprehensive evaluation in the current era of cancer care has not been performed. The objective of this study was to describe characteristics, risk factors, and outcomes of CDI in cancer patients.Methods: Fifty consecutive patients with CDI at a large Australian cancer centre (2013-2015) were identified from the hospital pathology database. Each case was matched by ward and hospital admission date to three controls without toxigenic CDI. Treatment and outcomes of infection were evaluated and potential risk factors were analysed using conditional logistic regression.Results: Patients with CDI had a mean age of 59.7 years and 74% had an underlying solid tumour. Healthcare-associated infection comprised 80% of cases. Recurrence occurred in 10, and 12% of cases were admitted to ICU within 30 days. Severe or severe-complicated infection was observed in 32%. Independent risk factors for infection included chemotherapy (odds ratio (OR) 3.82, 95% CI 1.67-8.75; p = 0.002), gastro-intestinal/abdominal surgery (OR 4.64, 95% CI 1.20-17.91; p = 0.03), proton pump inhibitor (PPI) therapy (OR 2.47, 95% CI 1.05-5.80; p = 0.04), and days of antibiotic therapy (OR 1.04, 95% CI 1.01-1.08; p = 0.02).Conclusions: Severe or complicated infections are frequent in patients with cancer who develop CDI. Receipt of chemotherapy, gastro-intestinal/abdominal surgery, PPI therapy, and antibiotic exposure contribute to infection risk. More effective CDI therapy for cancer patients is required and dedicated antibiotic stewardship programs in high-risk cancer populations are needed to ameliorate infection risk. [ABSTRACT FROM AUTHOR]

Objective: Children with acquired neutropaenia due to cancer chemotherapy are at high risk of severe infection. The present study aims to describe the prevalence and predictors of poor outcomes in children with febrile neutropaenia (FN). Methods: This is a multicentre, prospective observational study in tertiary Australian EDs. Cancer patients with FN were included. Fever was defined as a single temperature ≥38°C, and neutropaenia was defined as an absolute neutrophil count <1000/mm3. The primary outcome was the ICU admission for organ support therapy (inotropic support, mechanical ventilation, renal replacement therapy, extracorporeal life support). Secondary outcomes were: ICU admission, ICU length of stay (LOS) ≥3 days, proven or probable bacterial infection, hospital LOS ≥7 days and 28‐day mortality. Initial vital signs, biomarkers (including lactate) and clinical sepsis scores, including Systemic Inflammatory Response Syndrome, quick Sequential Organ Failure Assessment and quick Paediatric Logistic Organ Dysfunction‐2 were evaluated as predictors of poor outcomes. Results: Between December 2016 and January 2018, 2124 episodes of fever in children with cancer were screened, 547 episodes in 334 children met inclusion criteria. Four episodes resulted in ICU admission for organ support therapy, nine episodes required ICU admission, ICU LOS was ≥3 days in four, hospital LOS was ≥7 days in 153 and two patients died within 28 days. Vital signs, blood tests and clinical sepsis scores, including Systemic Inflammatory Response Syndrome, quick Sequential Organ Failure Assessment and quick Paediatric Logistic Organ Dysfunction‐2, performed poorly as predictors of these outcomes (area under the receiver operating characteristic curve <0.6). Conclusions: Very few patients with FN required ICU‐level care. Vital signs, biomarkers and clinical sepsis scores for the prediction of poor outcomes are of limited utility in children with FN. [ABSTRACT FROM AUTHOR]

Paradoxical reactions in central nervous system tuberculosis (CNS-TB) are associated with significant morbidity and mortality. We describe 4 HIV-uninfected children treated for CNS-TB with severe paradoxical reactions unresponsive to corticosteroids. All made recovery after treatment with infliximab, highlighting the safety and effectiveness of infliximab for this complication, and need for prospective trials. [ABSTRACT FROM AUTHOR]

Human herpesvirus 6 (HHV6) is the major cause of posttransplant acute limbic encephalitis (PALE) in immunosuppressed patients following hematopoietic stem cell transplant. Memory impairment and temporal lobe epilepsy following PALE are reported in adults, but sequelae in young children are unknown. We report three children with HHV6-associated PALE 20-23 days after cord blood transplantation for leukemias who developed symptomatic generalized epilepsy. Patients were followed for 2-8 years and underwent magnetic resonance imaging (MRI) and video-electroencephalography (EEG). Two patients underwent viral and autoimmune testing and immunotherapies. Generalized seizures, including tonic seizures, developed 11-18 months after HHV6-associated PALE. Seizures were frequent and resistant to multiple antiepileptic drugs (AEDs). Generalized slow spike-wave and low-voltage fast activity were recorded on interictal and ictal EEGs. The two younger patients regressed in their general abilities, synchronous with seizure evolution, whereas the older patient developed a severe amnestic syndrome that halted intellectual development. Serial MRI studies revealed bilateral signal change and atrophy in the medial temporal structures of all patients. In the two investigated patients, there was no evidence of chronic HHV6 infection, minimal evidence of cerebral inflammation, and no significant improvement with pulse with intravenous methylprednisolone and immunoglobulin. The severe and generalized seizure, cognitive, and EEG sequelae of HHV6-related PALE in these children may be due to a chronic, viral, or immune-mediated inflammatory process or developmental epileptogenesis resulting from bilateral hippocampal injury at an early age, although there was a paucity of evidence for either. [ABSTRACT FROM AUTHOR]

Background: Invasive fungal infection (IFI) detection requires application of complex case definitions by trained staff. Administrative coding data (ICD-10-AM) may provide a simplified method for IFI surveillance, but accuracy of case ascertainment in children with cancer is unknown. Objective: To determine the classification performance of ICD-10-AM codes for detecting IFI using a gold-standard dataset (r-TERIFIC) of confirmed IFIs in paediatric cancer patients at a quaternary referral centre (Royal Children's Hospital) in Victoria, Australia from 1st April 2004 to 31st December 2013. Methods: ICD-10-AM codes denoting IFI in paediatric patients (<18-years) with haematologic or solid tumour malignancies were extracted from the Victorian Admitted Episodes Dataset and linked to the r-TERIFIC dataset. Sensitivity, positive predictive value (PPV) and the F1 scores of the ICD-10-AM codes were calculated. Results: Of 1,671 evaluable patients, 113 (6.76%) had confirmed IFI diagnoses according to gold-standard criteria, while 114 (6.82%) cases were identified using the codes. Of the clinical IFI cases, 68 were in receipt of ≥1 ICD-10-AM code(s) for IFI, corresponding to an overall sensitivity, PPV and F1 score of 60%, respectively. Sensitivity was highest for proven IFI (77% [95% CI: 58–90]; F1 = 47%) and invasive candidiasis (83% [95% CI: 61–95]; F1 = 76%) and lowest for other/unspecified IFI (20% [95% CI: 5.05–72%]; F1 = 5.00%). The most frequent misclassification was coding of invasive aspergillosis as invasive candidiasis. Conclusion: ICD-10-AM codes demonstrate moderate sensitivity and PPV to detect IFI in children with cancer. However, specific subsets of proven IFI and invasive candidiasis (codes B37.x) are more accurately coded. [ABSTRACT FROM AUTHOR]

Background Bacteremia and other invasive bacterial infections are common among children with cancer receiving intensive chemotherapy and in pediatric recipients of hematopoietic stem cell transplantation (HSCT). Systemic antibacterial prophylaxis is one approach that can be used to reduce the risk of these infections. Our purpose was to develop a clinical practice guideline (CPG) for systemic antibacterial prophylaxis administration in pediatric patients with cancer and those undergoing HSCT. Methods An international and multidisciplinary panel was convened with representation from pediatric hematology/oncology and HSCT, pediatric infectious diseases (including antibiotic stewardship), nursing, pharmacy, a patient advocate, and a CPG methodologist. The panel used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to generate recommendations based on the results of a systematic review of the literature. Results The systematic review identified 114 eligible randomized trials of antibiotic prophylaxis. The panel made a weak recommendation for systemic antibacterial prophylaxis for children receiving intensive chemotherapy for acute myeloid leukemia and relapsed acute lymphoblastic leukemia (ALL). Weak recommendations against the routine use of systemic antibacterial prophylaxis were made for children undergoing induction chemotherapy for ALL, autologous HSCT and allogeneic HSCT. A strong recommendation against its routine use was made for children whose therapy is not expected to result in prolonged severe neutropenia. If used, prophylaxis with levofloxacin was recommended during severe neutropenia. Conclusions We present a CPG for systemic antibacterial prophylaxis administration in pediatric cancer and HSCT patients. Future research should evaluate the long-term effectiveness and adverse effects of prophylaxis. [ABSTRACT FROM AUTHOR]

Aim: Fever in immunocompromised children presents significant challenges. We aimed to determine the clinical impact of fluorodeoxyglucose-positron emission tomography (FDG-PET) in combination with computed tomography (CT) in children with malignancy or following haematopoietic stem cell transplantation with prolonged or recurrent fever.Methods: Immunocompromised children who underwent FDG-PET/CT for investigation of prolonged or recurrent fever were identified from hospital databases. The clinical impact of the FDG-PET/CT was considered 'high' if it contributed to any of the following: diagnosis of a new site infection/inflammation, change to antimicrobials or chemotherapy, or additional investigations or specialist consult contributing to final diagnosis.Results: Fourteen patients underwent an FDG-PET/CT for prolonged or recurrent fever. Median age was 11 years and 46% had diagnosis of acute lymphoblastic leukaemia. The median absolute neutrophil count on the day of FDG-PET/CT was 0.47 cells/μL. The clinical impact of FDG-PET/CT was 'high' in 11 (79%) patients, contributing to rationalisation of antimicrobials in three, and cessation of antimicrobials in five. Compared to conventional imaging, FDG PET/CT identified seven additional sites of clinically significant infection/inflammation in seven patients. Of the 10 patients who had a cause of fever identified, FDG-PET/CT contributed to the final diagnosis in six (60%).Conclusion: This study has identified potential utility for FDG-PET/CT in immunocompromised children with prolonged or recurrent fever. Further prospective studies are needed to compare FDG-PET/CT versus conventional imaging, to identify the optimal timing of FDG-PET/CT and to study the role of subsequent scans to monitor response to therapy. [ABSTRACT FROM AUTHOR]

Background: Risk-stratified management of fever with neutropenia (FN), allows intensive management of high-risk cases and early discharge of low-risk cases. No single, internationally validated, prediction model of the risk of adverse outcomes exists for children and young people. An individual patient data (IPD) meta-analysis was undertaken to devise one.Methods: The 'Predicting Infectious Complications in Children with Cancer' (PICNICC) collaboration was formed by parent representatives, international clinical and methodological experts. Univariable and multivariable analyses, using random effects logistic regression, were undertaken to derive and internally validate a risk-prediction model for outcomes of episodes of FN based on clinical and laboratory data at presentation.Results: Data came from 22 different study groups from 15 countries, of 5127 episodes of FN in 3504 patients. There were 1070 episodes in 616 patients from seven studies available for multivariable analysis. Univariable analyses showed associations with microbiologically defined infection (MDI) in many items, including higher temperature, lower white cell counts and acute myeloid leukaemia, but not age. Patients with osteosarcoma/Ewings sarcoma and those with more severe mucositis were associated with a decreased risk of MDI. The predictive model included: malignancy type, temperature, clinically 'severely unwell', haemoglobin, white cell count and absolute monocyte count. It showed moderate discrimination (AUROC 0.723, 95% confidence interval 0.711-0.759) and good calibration (calibration slope 0.95). The model was robust to bootstrap and cross-validation sensitivity analyses.Conclusions: This new prediction model for risk of MDI appears accurate. It requires prospective studies assessing implementation to assist clinicians and parents/patients in individualised decision making. [ABSTRACT FROM AUTHOR]

Pneumocystis jirovecii pneumonia (PJP) is seen increasingly in non-human immunodeficiency virus (HIV) infected immunocompromised populations, but few cases have previously been reported in association with gemcitabine therapy. We identified all patients administered gemcitabine between March 2009 and December 2012 at the Peter MacCallum Cancer Centre. Cases of PJP were identified using accepted definitions. Overall, 288 gemcitabine-treated patients were identified. Nine cases of PJP were detected, corresponding to an overall rate of 3.1% (95% confidence interval [Cl] 1.5-5.7%). PJP was diagnosed during gemcitabine therapy in seven patients, a median of 67 (range 31-109) days from commencement. Among patients with lymphoma, 4/22 developed PJP, corresponding to a rate of 18.2% (95% Cl 6.1-38.2%). Fewer infections were associated with breast, lung and gastrointestinal malignancies (1/24 [4.2%], 3/118 [2.5%] and 1/61 [1.6%], respectively). A risk-based tool incorporating concomitant steroid therapy can be applied to target high-risk populations who would benefit from PJP prophylaxis during gemcitabine therapy. [ABSTRACT FROM AUTHOR]

Abstract: Bacille Calmette-Guérin (BCG) vaccine is one of the most commonly administered vaccines worldwide. In countries with high tuberculosis (TB) prevalence, it is generally given shortly after birth. In a number of low TB prevalence countries, BCG is used as a travel vaccine, typically given to children outside the neonatal period prior to visiting regions where TB is common. In this setting, it is recommended that latent TB infection (LTBI) resulting from prior exposure to Mycobacterium tuberculosis is excluded by a tuberculin skin test (TST) before BCG immunisation. This is to avoid the risk of an accelerated local reaction that is more common in individuals who have LTBI. In addition, BCG immunisation in individuals with LTBI is unnecessary, as it does not provide protection against progression to active TB disease. We review and discuss current international guidelines and recommendations on the need to screen children for LTBI prior to BCG immunisation. Guidelines vary significantly regarding age-related cut-offs and additional selection criteria. This variation primarily reflects the lack of evidence on which to base recommendations. We suggest an alternative strategy using a risk assessment questionnaire to identify children who should have a TST before BCG immunisation. This targeted approach will reduce the number of children unnecessarily screened, whilst allowing the identification of those with LTBI, who need further evaluation and treatment. [Copyright &y& Elsevier]

Purpose: Sepsis is a significant complication following cancer surgery. Although standardised care bundles improve sepsis outcomes in other populations, the benefits in cancer patients are unclear. The objectives of this study were to describe the epidemiology of sepsis in cancer patients post‐surgery, and to evaluate the impact of a clinical sepsis pathway on management and clinical outcomes. Methods: A standardised hospital‐wide sepsis pathway was developed in 2013, and all cases of sepsis at the Peter MacCallum Cancer Centre in 2014 were retrospectively evaluated. Inclusion criteria were sepsis onset during the 100‐day period following a surgical procedure for cancer diagnosis. Patients were identified using ICD‐10‐AM sepsis discharge codes, audit documentation and the hospital's antimicrobial approval system. Sepsis episodes were classified as managed on‐ or off‐pathway. Results: A total of 119 sepsis episodes were identified. Of these, 71 (59.7%) were managed on the sepsis pathway. Episodes managed on‐pathway resulted more frequently in administration of appropriate antibiotics compared to those off‐pathway (94.4% vs. 66.7%, p < 0.001), and had shorter time to first‐dose antibiotics (median 85 vs. 315 min, p < 0.001). Pathway utilisation was associated with significant reductions in need for inotropes (7% vs. 13%, p = 0.023), ventilation (3% vs. 10%, p = 0.006) and length of hospitalisation (median 15 vs. 30 days, p = 0.008). The most frequent source of infection was organ‐space surgical site infection (24.4% of instances). Conclusions: A dedicated hospital‐wide sepsis pathway had significant impact on the quality of care and clinical outcomes of sepsis in cancer surgery patients. Cost‐benefit analysis of sepsis pathways for cancer patients is required. [ABSTRACT FROM AUTHOR]

Few studies are available to inform duration of intravenous antibiotics for children and when it is safe and appropriate to switch to oral antibiotics. We have systematically reviewed antibiotic duration and timing of intravenous to oral switch for 36 paediatric infectious diseases and developed evidence-graded recommendations on the basis of the review, guidelines, and expert consensus. We searched databases and obtained information from references identified and relevant guidelines. All eligible studies were assessed for quality. 4090 articles were identified and 170 studies were included. Evidence relating antibiotic duration to outcomes in children for some infections was supported by meta-analyses or randomised controlled trials; in other infections data were from retrospective series only. Criteria for intravenous to oral switch commonly included defervescence and clinical improvement with or without improvement in laboratory markers. Evidence suggests that intravenous to oral switch can occur earlier than previously recommended for some infections. We have synthesised recommendations for antibiotic duration and intravenous to oral switch to support clinical decision making and prospective research. [ABSTRACT FROM AUTHOR]