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Background Point-of-care-tests (POCTs) have been advocated to optimise care in patients with infections but their actual use varies. This study aimed to estimate the variability in the adoption of current POCTs by paediatricians across Europe, and to explore the determinants of variability. Methods and findings A cross-sectional survey was conducted of hospital and primary care paediatricians, recruited through professional networks. Questions focused on the availability and use of currently available POCTs. Data were analysed descriptively and using Median Odds Ratio (MOR) to measure variation between countries. Multilevel regression modelling using changes in the area under the receiver operating characteristic curve of models were used to assess the contribution of individual or workplace versus country level factors, to the observed variation. The commonest POCT was urine dipsticks (UD) which were available to >80% of primary care and hospital paediatricians in 68% (13/19) and 79% (23/29) countries, respectively. Availability of all POCTs varied between countries. In primary care, the country (MOR) varied from 1.61 (95%CI: 1.04–2.58) for lactate to 7.28 (95%CI: 3.04–24.35) for UD. In hospitals, the country MOR varied from 1.37 (95%CI:1.04–1.80) for lactate to 11.93 (95%CI:3.35–72.23) for UD. Most paediatricians in primary care (69%, 795/1154) and hospital (81%, 962/1188) would use a diagnostic test in the case scenario of an infant with undifferentiated fever. Multilevel regression modelling showed that the country of work was more important in predicting both the availability and use of POCTs than individual or workplace characteristics. Conclusion There is substantial variability in the adoption of POCTs for the management of acute infections in children across Europe. To inform future implementation of both existing and innovative tests, further research is needed to understand what drives the variation between countries, the needs of frontline clinicians, and the role of diagnostic tests in the management of acute childhood infections.

OBJECTIVE: The need for pediatric antifungal stewardship programs has been driven by an increasing consumption of antifungals for prophylactic and empirical use. Drivers and rational of antifungal prescribing need to be identified to optimize prescription behaviors. METHODS: A prospective modified weekly Point Prevalence Survey capturing antifungal prescriptions for children (> 90 days to < 18 years of age) in 12 centers in England during 26 consecutive weeks was performed. Demographic, diagnostic and treatment information was collected for each patient. Data were entered into an online REDCap database. RESULTS: One thousand two hundred fifty-eight prescriptions were included for 656 pediatric patients, 44.9% were girls, with a median age of 6.4 years (interquartile range, 2.5-11.3). Most common underlying condition was malignancy (55.5%). Four hundred nineteen (63.9%) received antifungals for prophylaxis, and 237 (36.1%) for treatment. Among patients receiving antifungal prophylaxis, 40.2% did not belong to a high-risk group. In those receiving antifungal treatment, 45.9%, 29.4%, 5.1% and 19.6% had a diagnosis of suspected, possible, probable of proven invasive fungal disease (IFD), respectively. Proven IFD was diagnosed in 78 patients, 84.6% (n = 66) suffered from invasive candidiasis and 15.4% (n = 12) from an invasive mold infection. Liposomal amphotericin B was the most commonly prescribed antifungal for both prophylaxis (36.6%) and empiric and preemptive treatment (47.9%). Throughout the duration of the study, 72 (11.0%) patients received combination antifungal therapy. CONCLUSIONS: Antifungal use in pediatric patients is dominated by liposomal amphotericin B and often without evidence for the presence of IFD. A significant proportion of prophylactic and empiric antifungal use was seen in pediatric patients not at high risk for IFD.

Sepsis, defined as life-threatening organ dysfunction caused by infection is difficult to distinguish clinically from infection or post-operative inflammation. We hypothesized that in a heterogeneous group of critically ill children, there would be different metabolic profiles between post-operative inflammation, bacterial and viral infection and infection with or without organ dysfunction. 1D 1H nuclear magnetic resonance spectra were acquired in plasma samples from critically ill children. We included children with bacterial (n = 25) and viral infection (n = 30) and controls (n = 58) (elective cardiac surgery without infection). Principal component analysis was used for data exploration and partial least squares discriminant analysis models for the differences between groups. Area under receiver operating characteristic curve (AUC) values were used to evaluate the models. Univariate analysis demonstrated differences between controls and bacterial and viral infection. There was excellent discrimination between bacterial and control (AUC = 0.94), and viral and control (AUC = 0.83), with slightly more modest discrimination between bacterial and viral (AUC = 0.78). There was modest discrimination (AUC = 0.73) between sepsis with organ dysfunction and infection with no organ dysfunction. In critically ill children, NMR metabolomics differentiates well between those with a post-operative inflammation but no infection, and those with infection (bacterial and viral), and between sepsis and infection.

A survey was conducted in UK regional children's hospitals with paediatric intensive care and paediatric infectious disease (PID) departments to describe the characteristics of paediatric antimicrobial stewardship (PAS) programmes. A structured questionnaire was sent to PAS coordinators. 'Audit and feedback' was implemented in 13 out of 17 centres. Microbiology-led services were more likely to implement antimicrobial restriction (75% vs 33% in PID-led services), to focus on broad-spectrum antibiotics, and to review patients with positive blood cultures. PID-led services were more likely to identify patients from e-prescribing or drug charts and review all antimicrobials. A PAS network has been established.

IntroductionProcalcitonin (PCT) is a biomarker more specific for bacterial infection and responds quicker than other commonly used biomarkers such as C reactive protein, but is not routinely used in the National Health Service (NHS). Studies mainly in adults show that using PCT to guide clinicians may reduce antibiotic use, reduce hospital stay, with no associated adverse effects such as increased rates of hospital re-admission, incomplete treatment of infections, relapse or death. A review conducted for National Institute for Health and Care Excellence recommends further research on PCT testing to guide antibiotic use in children.Methods and analysisBiomarker-guided duration of Antibiotic Treatment in Children Hospitalised with confirmed or suspected bacterial infection is a multi-centre, prospective, two-arm, individually Randomised Controlled Trial (RCT) with a 28-day follow-up and internal pilot. The intervention is a PCT-guided algorithm used in conjunction with best practice. The control arm is best practice alone. We plan to recruit 1942 children, aged between 72 hours and up to 18 years old, who are admitted to the hospital and being treated with intravenous antibiotics for suspected or confirmed bacterial infection. Coprimary outcomes are duration of antibiotic use and a composite safety measure. Secondary outcomes include time to switch from broad to narrow spectrum antibiotics, time to discharge, adverse drug reactions, health utility and cost-effectiveness. We will also perform a qualitative process evaluation. Recruitment commenced in June 2018 and paused briefly between March and May 2020 due to the COVID-19 pandemic.Ethics and disseminationThe trial protocol was approved by the HRA and NHS REC (North West Liverpool East REC reference 18/NW/0100). We will publish the results in international peer-reviewed journals and present at scientific meetings.Trial registration numberISRCTN11369832.

Hepatitis B virus (HBV) is a potentially chronic infection that can be transmitted from mother-to-child with the risk of developing cirrhosis, liver failure, and hepatocellular carcinoma. There is a safe and effective vaccine to prevent vertical transmission that is recommended to be given as soon as possible after birth, and within 24 hours. When a woman with HBV refuses the birth dose of HBV vaccine for her baby, infectious diseases and safeguarding teams are asked to provide urgent opinions on whether this crosses the threshold for triggering child protection mechanisms. We consider a low-infectivity HBV vertical transmission scenario where there is parental refusal of HBV vaccination, and focus on ethical arguments for and against over-ruling parental refusal in the child’s best interests. We propose a dialogue process for managing scenarios where a pregnant woman with HBV has concerns about vaccinating her baby when born.

Paediatric common infection pathways have been developed in collaboration between the BSAC and national paediatric groups, addressing the management of cellulitis, lymphadenitis/lymph node abscess, pneumonia/pleural empyema, pyelonephritis, tonsillitis/peritonsillar abscess, otitis media/mastoiditis, pre-septal/post-septal (orbital) cellulitis, and meningitis. Guidance for the management of a child presenting with a petechial/purpuric rash and the infant under 3 months of age with fever is also provided. The aim of these pathways is to support the delivery of high-quality infection management in children presenting to a hospital. The pathways focus on diagnostic approaches, including the recognition of red flags suggesting complex or severe infection requiring urgent intervention, approaches to antimicrobial stewardship (AMS) principles and guidance on safe and timely ambulation aligned with good practice of outpatient parenteral antimicrobial therapy (OPAT).

Acute kidney injury (AKI), a common complication in paediatric intensive care units (PICU), is associated with increased morbidity and mortality. In this single centre, prospective, observational cohort study, neutrophil gelatinase-associated lipocalin in urine (uNGAL) and plasma (pNGAL) and renal angina index (RAI), and combinations of these markers, were assessed for their ability to predict severe (stage 2 or 3) AKI in children and young people admitted to PICU. In PICU children and young people had initial and serial uNGAL and pNGAL measurements, RAI calculation on day 1, and collection of clinical data, including serum creatinine measurements. Primary outcomes were severe AKI and renal replacement therapy (RRT). Secondary outcomes were length of stay, hospital acquired infection and mortality. The area under the Receiver Operating Characteristic (ROC) curves and Youden index was used to determine biomarker performance and identify optimum cut-off values. Of 657 children recruited, 104 met criteria for severe AKI (15∙8%) and 47 (7∙2%) required RRT. Severe AKI was associated with increased length of stay, hospital acquired infection, and mortality. The area under the curve (AUC) for severe AKI prediction for Day 1 uNGAL, Day 1 pNGAL and RAI were 0.75 (95% Confidence Interval [CI] 0∙69, 0∙81), 0∙64 (95% CI 0∙56, 0∙72), and 0.73 (95% CI 0∙65, 0∙80) respectively. The optimal combination of measures was RAI and day 1 uNGAL, giving an AUC of 0∙80 for severe AKI prediction (95% CI 0∙71, 0∙88). In this heterogenous PICU cohort, urine or plasma NGAL in isolation had poorer prediction accuracy for severe AKI than in previously reported homogeneous populations. However, when combined together with RAI, they produced good prediction for severe AKI.

Background: Paediatric antimicrobial stewardship (PAS) networks exist in the USA and Australia but not in the UK. We sought to capture a snapshot of the current PAS landscape across UK children’s hospitals. Methods: A survey of PAS activities was conducted in tertiary children’s hospitals. Results: Infectious disease or microbiology consultants responded to the survey (n=15). All hospitals had neonatal, paediatric intensive care and surgical patients.All centres provided a PAS education programme for doctors, 7 for nurses and 9 for pharmacists as well. All centres had empirical antimicrobial prescribing guidelines. All centres with a paediatric infectious diseases (PID) team (11/15) used “audit and feedback” rounds, although their frequency and coverage varied. The PAS teams mostly included a PID consultant and/or microbiology consultants and a pharmacist. Three centres also had a nurse covering also the paediatric out-patient antibiotic treatment programme. Funding for PAS were inconsistent: Great Ormond Street Hospital had secured a dedicated full-time paediatric microbiologist, antimicrobial pharmacist and PID consultant with a ratio of 1/453 in-patient beds. 9 centres did not have dedicated funding for a paediatric antimicrobial pharmacist, 7 did not have funding for a paediatric infectious disease consultant. Only 2 hospitals had microbiology consultant time for paediatric audit and feedback. Conclusion: PAS programmes in the UK are limited, funding is inconsistent and their set up is variable, even in tertiary children’s hospitals with a strong interest in infectious diseases. We propose a national PAS network to advocate for more consistency and research into the implementation of PAS programmes.

Diagnostic challenges combined with the vulnerability of neonates to develop invasive candidiasis (IC) may lead to antifungal administration in the absence of IC. A modified point-prevalence study was performed to obtain an improved insight and understanding of antifungal prescribing in this specific patient population.Neonates and infants ≤90 days of age receiving systemic antifungals from 12 centers in England were included. Data were collected prospectively during 26 consecutive weeks and entered into an online REDCap database.Two hundred eighty neonates and infants were included, the majority ≤1 month of age (68.2%). Prematurity was the commonest underlying condition (68.9%). Antifungals were prescribed for prophylactic reason in 79.6%; of those, 64.6% and 76.3% were extreme low birth weight infants and prematurely born neonates, respectively. Additional risk factors were present in almost all patients, but only 44.7% had ≥3 risk factors rendering them more susceptible to develop IC. Nonpremature and non extremely low birth weight premature infants only scored ≥3 risk factors in 32.6% and 15%, respectively. Fluconazole was the most common antifungal used (76.7% of all prescriptions), and commonly underdosed as treatment. The number of microbiologic proven IC was low, 5.4%.Neonatal antifungal prophylaxis is commonly prescribed outside the recommendations based on known risk profiles. Fluconazole is the main antifungal prescribed in neonates and infants, with underdosing frequently observed when prescribed for treatment. Number of proven IC was very low. These observations should be taken into consideration to develop a national pediatric Antifungal Stewardship program aiming to guide rational prescribing.

Fever is the most common reason that children present to Emergency Departments in the UK. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. As a result, many children are prescribed antibiotics often unnecessarily, while others with life-threatening bacterial infections can remain untreated. The ‘omics’ approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n=20) and confirmed viral infection (n=20). We show for the first time that bacterial and viral infection elicit distinct changes in the host lipidome. Glycerophosphoinositol, sphingomyelin, lysophosphotidylcholine and cholesterol sulfate were increased in the confirmed virus infected group, while fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were increased in cases with confirmed bacterial infection. A combination of three lipids achieved the area under the receiver operating characteristic (ROC) curve of 0.918 (95% CI 0.835 to 1). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics.

Objectives: Following surgery, it is difficult to distinguish a postoperative inflammatory reaction from infection. This study examined the predictive value of the biomarkers; procalcitonin, C-reactive protein, lactate, neutrophils, lymphocytes, platelets, and the biphasic activated partial thromboplastin time waveform in diagnosing bacterial infection following cardiac surgery. Design: Prospective, observational study. Setting: A regional, PICU in the United Kingdom. Patients: Three-hundred sixty-eight children under the age of 16 admitted to the PICU for elective cardiac surgery were enrolled in the study. Interventions: All biomarker measurements were determined daily until postoperative day 7. Children were assessed for postoperative infection until day 28 and divided into four groups: bacterial infection, culture-negative sepsis, viral infection, and no infection. We used the Kruskal-Wallis test, chi-square test, analysis of variance, and area under the curve in our analysis. Measurements and Main Results: In total, 71 of 368 children (19%) developed bacterial infection postoperatively, the majority being surgical site infections. In those with bacterial infection, procalcitonin was elevated on postoperative days 1–3 and the last measurement prior to event compared with those without bacterial infection. The most significant difference was the last measurement prior to event; 0.72 ng/mL in the bacterial infection group versus 0.13 ng/mL in the no infection group (for all groups; p < 0.001). Longitudinal profiles of all biomarkers were indistinct in the bacterial infection and nonbacterial infection groups except in those with culture-negative infections who had distinct procalcitonin kinetics on postoperative days 1–4. Children with culture-negative sepsis required longer ventilatory support and PICU stay and were more likely to develop complications than the other groups. Conclusions: None of the biomarkers studied within 3 days of infection distinguished between infection and postoperative inflammatory reaction. However, procalcitonin kinetics peaked on postoperative day 2 and fell more sharply than C-reactive protein kinetics, which peaked at postoperative day 3. The monitoring of procalcitonin kinetics following cardiac surgery may help guide rational antimicrobial use.

Objective Bacterial Infections remains a leading cause of death in the Paediatric Intensive Care Unit (PICU). In this era of rising antimicrobial resistance, new tools are needed to guide antimicrobial use. The aim of this study was to investigate the accuracy of procalcitonin (PCT), neutrophil gelatinase-associated lipocalin (NGAL), resistin, activated partial thromboplastin time (aPTT) waveform and C-reactive protein (CRP) for the diagnosis of serious bacterial infection (SBI) in children on admission to PICU and their use as prognostic indicators. Setting A regional PICU in the United Kingdom. Patients Consecutive PICU admissions between October 2010 and June 2012. Measurements Blood samples were collected daily for biomarker measurement. The primary outcome measure was performance of study biomarkers for diagnosis of SBI on admission to PICU based on clinical, radiological and microbiological criteria. Secondary outcomes included durations of PICU stay and invasive ventilation and 28-day mortality. Patients were followed up to day 28 post-admission. Main results A total of 657 patients were included in the study. 92 patients (14%) fulfilled criteria for SBI. 28-day mortality was 2.6% (17/657), but 8.7% (8/92) for patients with SBI. The combination of PCT, resistin, plasma NGAL and CRP resulted in the greatest net reclassification improvement compared to CRP alone (0.69, p Conclusion Combinations of biomarkers, including PCT, may improve accurate and timely identification of SBI on admission to PICU.

Background: Sepsis is one of the main reasons for non-elective admission to pediatric intensive care units (PICUs), but little is known about determinants influencing outcome. We characterized children admitted with community-acquired sepsis to European PICUs and studied risk factors for mortality and disability.Methods: Data were collected within the collaborative Seventh Framework Programme (FP7)-funded EUCLIDS study, which is a prospective multicenter cohort study aiming to evaluate genetic determinants of susceptibility and/or severity in sepsis. This report includes 795 children admitted with community-acquired sepsis to 52 PICUs from seven European countries between July 2012 and January 2016. The primary outcome measure was in-hospital death. Secondary outcome measures were PICU-free days censured at day 28, hospital length of stay, and disability. Independent predictors were identified by multivariate regression analysis.Results: Patients most commonly presented clinically with sepsis without a source (n = 278, 35%), meningitis/encephalitis (n = 182, 23%), or pneumonia (n = 149, 19%). Of 428 (54%) patients with confirmed bacterial infection, Neisseria meningitidis (n = 131, 31%) and Streptococcus pneumoniae (n = 78, 18%) were the main pathogens. Mortality was 6% (51/795), increasing to 10% in the presence of septic shock (45/466). Of the survivors, 31% were discharged with disability, including 24% of previously healthy children who survived with disability. Mortality and disability were independently associated with S. pneumoniae infections (mortality OR 4.1, 95% CI 1.1–16.0, P = 0.04; disability OR 5.4, 95% CI 1.8–15.8, P P P Conclusions: Despite widespread immunization campaigns, invasive bacterial disease remains responsible for substantial morbidity and mortality in critically ill children in high-income countries. Almost one third of sepsis survivors admitted to the PICU were discharged with some disability. More research is required to delineate the long-term outcome of pediatric sepsis and to identify interventional targets. Our findings emphasize the importance of improved early sepsis-recognition programs to address the high burden of disease.

Aims To describe the demographics of patients diagnosed with candidaemia, and to explore speciation and susceptibility trends in Candida organisms grown in blood cultures over 15 years in a single tertiary care paediatric hospital in the UK. Method Local laboratory records were accessed to obtain data about all positive blood cultures for Candida species between January 2001 and December 2015. A retrospective analysis of available electronic medical records was completed. Data was input and analysed using Microsoft Excel. Results There were 192 episodes of candidaemia, with 23 patients having multiple episodes of candidaemia (i.e. separated by >30 days). Patient’s ages ranged from 5 days to 18 years, with a mean of 5 years and 6 months. There were 85 females (44%) and 107 males (56%). The patient’s locations at the time of the candidaemia varied from the general paediatric wards (61, 32%), haematology/oncology wards (52, 27%), ICU (49, 26%), and paediatric surgical wards (30, 16%). The outcome of the patients after 30 days showed that 85 remained in hospital (44%), 81 had been discharged home (42%) and 26 had died (14%). The two most common candida species identified were Candida albicans (96, 50%) and Candida parapsilosis (56, 29%). There was a lower incidence of recognised resistant species such as Candida lusitaniae (9, 5%), Candida glabrata (7, 4%), and Candida krusei (3, 2%) with no increase in incidence of these species seen over time. The majority of samples (181, 94%) underwent sensitivity testing for a selection of seven common antifungal medications (amphotericin, caspofungin, fluconazole, flucytosine, itraconazole, micafungin and voriconazole). Eight samples of Candida albicans had resistance to a specific antifungal: 2 to fluconazole, 1 to flucytosine, 4 to itraconazole and 1 to voriconazole. No samples of Candida parapsilosis had resistance to any of the antifungals tested, however 16 had intermediate resistance to caspofungin. Conclusions This 15 year study of candidaemia in a tertiary paediatric hospital shows that almost 80% of the cases were due to Candida albicans or Candida parapsilosis. Resistant Candida species and overall resistance to antifungal medication was uncommon and did not show any increasing trend over time.

Background Sepsis and severe focal infections represent a substantial disease burden in children admitted to hospital. We aimed to understand the burden of disease and outcomes in children with life-threatening bacterial infections in Europe. Methods The European Union Childhood Life-threatening Infectious Disease Study (EUCLIDS) was a prospective, multicentre, cohort study done in six countries in Europe. Patients aged 1 month to 18 years with sepsis (or suspected sepsis) or severe focal infections, admitted to 98 participating hospitals in the UK, Austria, Germany, Lithuania, Spain, and the Netherlands were prospectively recruited between July 1, 2012, and Dec 31, 2015. To assess disease burden and outcomes, we collected demographic and clinical data using a secured web-based platform and obtained microbiological data using locally available clinical diagnostic procedures. Findings 2844 patients were recruited and included in the analysis. 1512 (53·2%) of 2841 patients were male and median age was 39·1 months (IQR 12·4–93·9). 1229 (43·2%) patients had sepsis and 1615 (56·8%) had severe focal infections. Patients diagnosed with sepsis had a median age of 27·6 months (IQR 9·0–80·2), whereas those diagnosed with severe focal infections had a median age of 46·5 months (15·8–100·4; pInterpretation Mortality in children admitted to hospital for sepsis or severe focal infections is low in Europe. The disease burden is mainly in children younger than 5 years and is largely due to vaccine-preventable meningococcal and pneumococcal infections. Despite the availability and application of clinical procedures for microbiological diagnosis, the causative organism remained unidentified in approximately 50% of patients.

Febrile neutropenia (FN) in children treated for malignancy is a common and direct sequela of chemotherapy. Episodes of FN can be life-threatening, and demand prompt recognition, assessment and treatment with broad spectrum antibiotics. While in the majority of episodes no causal infection is identified, 10-20% are secondary to a bloodstream infection (BSI). A reduction in episodes of BSI could be achieved through robust infection prevention strategies, such as CVL care bundles. Alongside good antimicrobial stewardship, these strategies could reduce the risk of emergent, multi-drug resistant (MDR) infections. Emerging bacterial pathogens in BSI include Viridans Group Streptococci (VGS) and Enterobacteriaceae such as Klebsiella spp. which are known for their ability to carry MDR genes. There is also increased recognition of the role of invasive fungal infection (IFI) in FN, in particular with Aspergillus spp. Novel diagnostics, including multiplex blood and respiratory polymerase chain reaction assays can identify infections early in FN, facilitating targeted therapy, and reducing unnecessary antimicrobial exposure. Given appropriate, and sensitive rapid diagnostics, potential also exists to safely inform the risk assessment of patients with FN, identifying those at low risk of complication, who could be treated in the out-patient setting. Several clinical decision rules (CDR) have now been developed and validated in defined populations, for the risk assessment of children being treated for cancer. Future research is needed to develop a universal CDR to improve the management of children with FN.

BACKGROUND: Improving the diagnosis of serious bacterial infections (SBIs) in the children’s emergency department is a clinical priority. Early recognition reduces morbidity and mortality, and supporting clinicians in ruling out SBIs may limit unnecessary admissions and antibiotic use. METHODS: A prospective, diagnostic accuracy study of clinical and biomarker variables in the diagnosis of SBIs (pneumonia or other SBI) in febrile children RESULTS: There were 1101 children studied, of whom 264 had an SBI. A diagnostic model discriminated well between pneumonia and no SBI (concordance statistic 0.84, 95% confidence interval 0.78–0.90) and between other SBIs and no SBI (0.77, 95% confidence interval 0.71–0.83) on internal validation. A published model discriminated well on external validation. Model updating yielded good calibration with good performance at both high-risk (positive likelihood ratios: 6.46 and 5.13 for pneumonia and other SBI, respectively) and low-risk (negative likelihood ratios: 0.16 and 0.13, respectively) thresholds. Extending the model with procalcitonin and resistin yielded improvements in discrimination. CONCLUSIONS: Diagnostic models discriminated well between pneumonia, other SBIs, and no SBI in febrile children in the emergency department. Improvements in the classification of nonevents have the potential to reduce unnecessary hospital admissions and improve antibiotic prescribing. The benefits of this improved risk prediction should be further evaluated in robust impact studies.

Aims The Systemic Inflammatory Response Syndrome (SIRS) is common after cardiac surgery and cardiopulmonary bypass (CPB), leading to difficulty in distinguishing between a bacterial infection or SIRS. Early diagnosis of post-operative infection is of fundamental importance in order to improve outcomes and reduce antibiotic over use. This study examined the predictive value of the biomarkers procalcitonin (PCT), lactate, neutrophil gelatinase associated lipocalin (NGAL) and the biphasic APTT waveform (bAPTT). Methods Consecutive children admitted for cardiac surgery at a tertiary paediatric intensive care unit (PICU) were enrolled in the study. None of our patients had a bacterial infection (BI) at admission. Receiver operating curves (ROC) were created to determine the predictive value of the biomarkers to diagnose BI. Results In total, 88/368 children (24%) developed BI. Median PCT in children with BI was 0.16 ng/ml (IQR 0.06–0.98) compared with 0.10 ng/ml (IQR 0.–0.36) in the non-infected group (p=0.03). Median lactate in children with BI was 1.42 mmol/L (IQR 0.93–2.37) compared with 1.20 mmol/L (0.93–1.79) in the non-infected group (p=0.03). The other biomarkers were not significantly different between BI and non-BI groups. The median inotrope score in first 12 hours was 10 (IQR 5–15) in those with BI compared with 7 (5–12) in the non-infected group (p=0.002). Prolonged hospital stay (p=0.001) and increased duration of mechanical ventilation (p=0.001) were more common in children with BI. CPB time was increased in children with BI (median 133 min, IQR 75–183) compared with those without BI (median 101 min, IQR 60–147) (p=0.005).Using ROC curves to predict BI, the AUC for PCT was 0.58, lactate 0.46, inotrope score in the first 12 hours 0.60, CPB 0.60, and circulatory arrest time 0.55 respectively. Conclusion None of the biomarkers studied demonstrated strong predictive value for BI. The increased health utilisation of postoperative infection is highlighted by increased PICU and hospital stay. Children at higher risk of developing post-operative infection can be identified as those with prolonged bypass and crossclamp times, and those with high inotrope scores in the first 12 hours of admission.

Of the 551 extended spectrum β-lactamase-producing isolates characterized, the MIC90 for Escherichia coli, Klebsiella spp., and Enterobacter spp. were in the susceptible range when tested against meropenem, but were in the resistant range for all other antimicrobials tested excluding E coli and Klebsiella spp. against ertapenem and ciprofloxacin, and for Enterobacter spp. against ciprofloxacin.

Susceptibility testing on 60 isolates of Staphylococcus epidermidis and 20 isolates of Staphylococcus hominis was performed using the Sensititre (Trek Diagnostics, Cleveland, OH, USA) method and compared with Vitek-2 automated susceptibility testing (bioMèrieux, Marcy l'Etoile, France), MICE strips for minimum inhibitory concentration determination (Oxoid, Basingstoke, UK), and disc diffusion (MAST, Bootle, UK). The categorical agreement between Vitek and Sensititre was greater than 90% for agents tested against S. epidermidis except for tetracycline (52%) and oxacillin (67%), and for S. hominis, the agreement was greater than 90% except for tetracycline (80%), gentamicin (65%), and oxacillin (75%). The categorical agreement between disc diffusion and Sensititre was greater than 90% for antimicrobials tested against S. epidermidis except for tetracycline (45%), moxifloxacin (70%), clindamycin (88%), and cefoxitin (80%), while against S. hominis, the categorical agreement was greater than 90% for antimicrobials tested except for gentamicin (65%), tetracycline (75%), moxifloxacin (80%), and ciprofloxacin (75%). Categorical agreement between MICE strips and Sensititre for S. epidermidis and S. hominis was greater than 95% for vancomycin and daptomycin. Sensititre method shows good categorical agreement with other standard methods for susceptibility testing of S. hominis and S. epidermidis.

BackgroundPiperacillin/Tazobactam is the first-line antibiotic for the treatment of febrile neutropenia in the UK. There is increasing interest in administration by continuous infusion in adult studies, but paediatric data is lacking. A continuous infusion, if given via an elastomeric pump could also facilitate earlier discharge from hospital.MethodsChildren with an oncology/haematology diagnosis admitted to Alder Hey Children’s Hospital with febrile neutropenia, normally treated with Piperacillin/Tazobactam via elastomeric device were considered eligible for the study. Patients received 24–36 hours of intermittent dosing before continuous dosing commenced via elastomeric pump. We analysed the data from 5 patients with double lumen central lines as a pilot phase to determine if expanded recruitment to include patients with single lumen lines was possible.ResultsFive patients were recruited, four of which had the continuous infusion. The mean Cmax following intermittent dosing of piperacillin and tazobactam from the lumen used for drug administration were 189.7 mg/L, 95% CI [71.7 - 307.9] and 18.5 mg/L, 95% CI [10.7, 26.3] respectively. The mean Cmax following intermittent dosing for the ‘empty’ lumen were 160.5 mg/L, 95% CI [121.6 - 199.4] for piperacillin and 13.7 mg/L, 95% CI [11.2 - 16.3] for tazobactam. The largest difference seen was on patient 002 with a concentration of piperacillin almost double that seen in the ‘empty’ lumen (429 mg/L vs 233 mg/L).ConclusionThe lumen used for drug administration has enough residual drug to influence the results, so expanding recruitment to include single lumen lines is not going to be undertaken. The study has been amended to recognise this, and recruitment will continue with double lumen central lines only.Disclosure(s)Nothing to disclose

The aim of this systematic review was to review studies that existed from 1993 to 2012 regarding antimicrobial treatment options of paediatric neurosurgical shunt.Studies were identified from MEDLINE, Scopus and Cochrane databases using a search strategy that was registered on the PROSPERO database. Studies were included if they had two or more patients, aged less than 18 years, and also specified the organism and antimicrobial treatment that was used.The search yielded 2,985 articles, and 76 articles were suitable for full review. In the final qualitative analysis, only eight studies were included, involving 86 participants. The most common antimicrobial regimens for Gram-positive infections was intravenous and intrathecal vancomycin (n = 7), followed by intravenous vancomycin monotherapy.This systematic review has shown that there are no prospective randomised studies of antimicrobial treatment options for paediatric neurosurgical patients in the last 20 years, and larger prospective studies are urgently required for this serious infection. There is some limited case series showing the benefits of certain antimicrobials such as vancomycin and ceftriaxone, but a larger case series or randomised controlled trial is required, particularly to establish the benefit, if any, of additional intraventricular antimicrobials.

Summary Background Carbapenem-resistant Enterobacteriaceae are an emerging global infection threat. However, there are few data describing their clinical importance in children. Aim This retrospective study reviewed the prevalence and resistance mechanisms of carbapenem-resistant Enterobacteriaceae grown from clinical and surveillance samples in a large tertiary referral children's hospital in the UK. Methods Carbapenem-resistant Enterobacteriaceae were sought in specimens submitted for diagnostic and surveillance purposes at Alder Hey Children's NHS Foundation Trust, Liverpool, between September 2011 and August 2012. Mechanisms of resistance were identified using phenotypic and/or molecular methods. Variable number tandem repeat profiling was used to type carbapenemase-producing strains. Findings During the 12-month study period, carbapenem-resistant Enterobacteriaceae were recovered from 24 patients. Five isolates were from clinical diagnostic specimens whereas 19 of 421 patients had positive rectal surveillance swabs (4.5%). Of the 24 isolates, seven (all Klebsiella spp.) harboured carbapenemases: three had bla KPC and four bla NDM , whereas 17 had resistance due to combinations of AmpC or extended-spectrum β-lactamase activity plus impermeability. Conclusion Carbapenem-resistant Enterobacteriaceae and, in particular, those with carbapenemases, are an emerging infection problem in a major paediatric hospital in the UK. Active surveillance is required to monitor and control their spread.

We compared the blood RNA transcriptome of children hospitalized with influenza A H1N1/09, respiratory syncytial virus (RSV) or bacterial infection, and healthy controls. Compared to controls, H1N1/09 patients showed increased expression of inflammatory pathway genes and reduced expression of adaptive immune pathway genes. This was validated on an independent cohort. The most significant function distinguishing H1N1/09 patients from controls was protein synthesis, with reduced gene expression. Reduced expression of protein synthesis genes also characterized the H1N1/09 expression profile compared to children with RSV and bacterial infection, suggesting that this is a key component of the pathophysiological response in children hospitalized with H1N1/09 infection.

There is uncertainty about the optimal teicoplanin regimens for neonates. The study aim was to determine the population pharmacokinetics (PK) of teicoplanin in neonates, evaluate currently recommended regimens and explore the exposure-effect relationships.An open-label PK study was conducted. Neonates from 26 to 44 weeks post-menstrual age were recruited (n = 18). The teicoplanin regimen was a 16 mg/kg loading dose, followed by 8 mg/kg once daily. Therapeutic drug monitoring and dose adjustment were not conducted. A standard two-compartment PK model was developed, followed by models that incorporated weight. A PK/pharmacodynamic (PD) model with C-reactive protein serial measurements as the PD input was fitted to the data. Monte Carlo simulations (n = 5000) were performed using Pmetrics. The AUCs at steady state and the proportion of patients achieving the recommended drug exposures (i.e. Cmin >15 mg/L) were determined. The study was registered in the European Clinical Trials Database Registry (EudraCT: 2012-005738-12).The PK allometric model best accounted for the observed data. The PK parameters medians were: clearance = 0.435 × (weight/70)(0.75) (L/h); volume = 0.765 (L); Kcp = 1.3 (h(-1)); and Kpc = 0.629 (h(-1)). The individual time-course of C-reactive protein was well described using the Bayesian posterior estimates for each patient. The simulated median AUC96-120 was 302.3 mg·h/L and the median Cmin at 120 h was 12.9 mg/L; 38.8% of patients attained a Cmin >15 mg/L by 120 h.Teicoplanin population PK is highly variable in neonates, weight being the best descriptor of PK variability. A low percentage of neonates were able to achieve Cmin >15 mg/L. The routine use of therapeutic drug monitoring and improved knowledge on the PD of teicoplanin is required.

Multi-drug resistance in Gram negative bacteria, particularly in Enterobacteriaceae, is a major clinical and public health challenge. The main mechanism of resistance in Enterobacteriaceae is linked to the production of beta-lactamase hydrolysing enzymes such as extended spectrum beta-lactamases (ESBL), AmpC beta-lactamases and carbapenemases (Carbapenemase Producing Enterobacteriaceae (CPE)). ESBL and CPE resistance genes are located on plasmids, which can be transmitted between Enterobacteriaceae, facilitating their spread in hospitals and communities. These plasmids usually harbour multiple additional co-resistance genes, including to trimethoprim-sulfamethoxazole, aminoglycosides, and fluoroquinolones, making these infections challenging to treat. Asymptomatic carriage in healthy children as well as community acquired infections are increasingly reported, particularly with ESBL. Therapeutic options are limited and previously little used antimicrobials such as fosfomycin and colistin have been re-introduced in clinical practice. Paediatric experience with these agents is limited hence there is a need to further examine their clinical efficacy, dosage and toxicity in children. Antimicrobial stewardship along with strict infection prevention and control practices need to be adopted widely in order to preserve currently available antimicrobials. The future development of novel agents effective against beta-lactamases producers and their applicability in children is urgently needed to address the challenge of multi-resistant Gram negative infections.

Viridans Group Streptococci (VGS) are associated with high mortality rates in febrile neutropenia; yet there are no recent European pediatric studies to inform antimicrobial therapy. The aim of this study was to describe the characteristics, outcome, and resistance patterns of children with VGS bacteremia (VGSB) undergoing treatment of malignancy or hematopoietic stem cell transplant. Patients aged 0 to 18 years, admitted to a tertiary pediatric hemato-oncology center with VGSB, from 2003 to 2013, were included in the study. All data were collected retrospectively from medical records. A total of 54 bacteremic episodes occurred in 46 patients. The most common underlying diagnosis was relapsed acute lymphoblastic leukemia. Streptococcus mitis was the most frequent organism. A total of 30% of isolates were resistant to penicillin and 100% sensitive to vancomycin. There were 8 episodes (14.8%) of Viridans Group Streptococcal Shock Syndrome; 6 resulted in admission to intensive care and 3 of these patients died of multiorgan failure. The potentially fatal nature of VGSB is confirmed. The high risk in relapsed acute lymphoblastic leukemia is of note. Research is needed to develop risk-stratification scores that identify children at risk of Viridans Group Streptococcal Shock Syndrome to guide empirical antimicrobial therapy in febrile neutropenia.

Central line associated bloodstream infection (CLABSI) reduction programmes in hospitalised children have been focused in the intensive care setting and little data is available on the efficacy and cost effectiveness of such programmes in other clinical areas. Prospective monitoring of hospital acquired CLABSI rates in all clinical areas was performed at Alder Hey Children’s Hospital for a period of three years following the implementation of a central venous line (CVL) care bundle. We observed a decrease in CLABSI rates from 220 in the first year following intervention to 108 per 100,000 patient days ( p=0.002) in the third year of the study, demonstrating a decrease of over 50% in CLABSI rates. Blood culture contamination rates were also significantly reduced. The introduction of a CVL care bundle produced a significant, sustainable reduction in hospital acquired CLABSI rates in a children’s hospital setting.

AimsContinuous intravenous infusion using an elastomeric pump is an alternative delivery method in paediatric patients who need intravenous antibiotics (IVAB) which would otherwise need to be administered three times daily, such as piperacillin/tazobactam or ceftazidime.1 We describe our experience using elastomeric pumps in the OPAT setting.MethodsA retrospective case series of 5 children (aged 5–17 years) discharged home on IVAB continuous infusion administered via an elastomeric pump. One child received this mode of delivery twice therefore 6 patient-episodes are described in this case series. Outcomes were assessed using the BSAC p-OPAT (British Society of Antimicrobial Chemotherapy Paediatric-OPAT) criteria. Ethics approval was not required because the information was gathered retrospectively and patient data has been anonymised.ResultsIn 5 of the episodes the indication was lower respiratory tract infection treated with continuous IV piperacillin/tazobactam. All patients had a background of neurodisability, recurrent respiratory tract infections and Pseudomonas aeruginosa carriage. The remaining patient was treated for an infective exacerbation of cystic fibrosis with a regimen that included continuous IV ceftazidime. All episodes had an outcome defined as ‘Success’ according to the BSAC p-OPAT criteria; having an infection outcome of ‘improved’ or ‘cured’ with no adverse events reported.ConclusionsThe successful outcomes in this case series suggest that elastomeric pumps are a safe and effective option for administering selected antibiotics by continuous IV infusion to children, although central venous access is a requirement. This option should be considered to facilitate the early discharge of patients to be treated with IVAB such as piperacillin/tazobactam under the guidance of an OPAT service.ReferencePatel S, Abrahamson E, Goldring S, Green H, Wickens H, Laundy M. Good practice recommendations for paediatric outpatient parenteral antibiotic therapy (p-OPAT) in the UK: A consensus statement. J Antimicrob Chemother2015;70(2):360–73.

Evidence suggests that Toll-like receptor 4 (TLR4) contributes to immune recognition of respiratory syncytial virus (RSV). The TLR4 gene harbours a polymorphism-Asp299Gly-previously associated with reduced TLR4 signalling. To understand of how host genetic variation influences the outcome of RSV infection in children, we examined the association between the TLR4 299Gly allele and severe RSV disease. By genotyping 236 children with RSV infection and 219 healthy controls we found no association between the risk of severe RSV infection and Asp299Gly polymorphisms (P>0.05), and we demonstrate that the TLR4 Asp299Gly genotype does not influence susceptibility to either RSV serotype A or B (P>0.05). Finally, examining the functional impact of the TLR4 Asp299Gly polymorphism (n=58), we demonstrate that proinflammatory cytokine production following TLR4 activation was indistinguishable between homozygous (Asp/Asp) and heterozygous (Asp/Gly) subjects. We conclude that the Asp299Gly TLR4 polymorphism does not alter receptor function and does not influence the risk of severe RSV infection.

Background: Healthcare-associated infections are costly and are increasingly viewed as an indicator of the quality of care. Although strategies to reduce infections have become widespread, few studies have formally investigated the role of undernutrition on the development of infection-related complications in children after surgery. \ud \ud Aim: To perform a systematic review of the literature to determine if undernutrition is prognostic of postoperative infection complications in children.\ud \ud Methods: Electronic bibliographic and research databases were searched from 1950 to 2014. Inclusion criteria were studies in children (age

Teicoplanin is frequently administered to treat Gram-positive infections in pediatric patients. However, not enough is known about the pharmacokinetics (PK) of teicoplanin in children to justify the optimal dosing regimen. The aim of this study was to determine the population PK of teicoplanin in children and evaluate the current dosage regimens. A PK hospital-based study was conducted. Current dosage recommendations were used for children up to 16 years of age. Thirty-nine children were recruited. Serum samples were collected at the first dose interval (1, 3, 6, and 24 h) and at steady state. A standard 2-compartment PK model was developed, followed by structural models that incorporated weight. Weight was allowed to affect clearance (CL) using linear and allometric scaling terms. The linear model best accounted for the observed data and was subsequently chosen for Monte Carlo simulations. The PK parameter medians/means (standard deviation [SD]) were as follows: CL, [0.019/0.023 (0.01)] × weight liters/h/kg of body weight; volume, 2.282/4.138 liters (4.14 liters); first-order rate constant from the central to peripheral compartment ( K cp ), 0.474/3.876 h −1 (8.16 h −1 ); and first-order rate constant from peripheral to central compartment ( K pc ), 0.292/3.994 h −1 (8.93 h −1 ). The percentage of patients with a minimum concentration of drug in serum ( C min ) of 10 mg/liter by day 4 of treatment. The teicoplanin population PK is highly variable in children, with a wider AUC distribution spread than for adults. Therapeutic drug monitoring should be a routine requirement to minimize suboptimal concentrations. IMPORTANCE (This trial has been registered in the European Clinical Trials Database Registry [EudraCT] under registration number 2012-005738-12.)

Ciprofloxacin is used in neonates with suspected or documented Gram-negative serious infections. Currently, its use is off-label partly because of lack of pharmacokinetic studies. Within the FP7 EU project TINN (Treat Infection in NeoNates), our aim was to evaluate the population pharmacokinetics of ciprofloxacin in neonates and young infants

Summary This report summarizes the establishment of the first national online registry of primary immune deficency in the United Kingdom, the United Kingdom Primary Immunodeficiency (UKPID Registry). This UKPID Registry is based on the European Society for Immune Deficiency (ESID) registry platform, hosted on servers at the Royal Free site of University College, London. It is accessible to users through the website of the United Kingdom Primary Immunodeficiency Network (http://www.ukpin.org.uk). Twenty-seven centres in the United Kingdom are actively contributing data, with an additional nine centres completing their ethical and governance approvals to participate. This indicates that 36 of 38 (95%) of recognized centres in the United Kingdom have engaged with this project. To date, 2229 patients have been enrolled, with a notable increasing rate of recruitment in the past 12 months. Data are presented on the range of diagnoses recorded, estimated minimum disease prevalence, geographical distribution of patients across the United Kingdom, age at presentation, diagnostic delay, treatment modalities used and evidence of their monitoring and effectiveness.

Aims Long-term tunnelled central venous catheters deliver potentially toxic medications such as chemotherapy and parenteral nutrition. Recurrent central line associated bloodstream infections (CLASBI) are a potentially serious complication. Introduction of central line care bundles can dramatically reduce paediatric CLABSI rates (Wheeler et al ., Paediatrics 2011), however despite these interventions some patients develop recurrent CLABSIs. This study reports the recurrent CLABSI rate and organisms found in two regional paediatric hospitals. Methods Paediatric patients diagnosed with a CLABSI between January 2012 and December 2012 were identified retrospectively in two regional paediatric institutions. All subsequent infection and line events were recorded for these patients. CLABSIs were classified according to the Centres for Disease Control and Prevention definition. Line event data was verified by comparing theatre records, clinic and discharge letters and radiology images. Results Eighty seven patients were included in the study (44 patients from centre 1, 43 patients from centre 2). 165 CLABSIs were diagnosed during the study period (87 first CLABSI and 78 subsequent CLABSIs). Forty three patients (50%) developed a second CLABSI. And 22 (25%) developed a third CLABSI. The median number of line days from 1 st CLABSI per patient was 389 days in centre 1 and 188 days in centre 2. 112 CLABSIs were due to a Gram negative pathogen (68%). 44 CLABSIs were due to a Gram positive (27%) pathogen. 9 CLABSIs were due to fungi (5%). The overall recurrent CLABSI rate after one CLABSI was 4.2 per 1000 catheter days (3.3 per 1000 catheter days in centre 1, 5.1 per 1000 catheter days in centre 2). Repeat infections with identical pathogens occurred on 16 occasions. The most commonly identified organisms were Enterococcus faecalis (29), Escherischia coli (27), Klebsiella pneumoniae (23), Staphylococcus epidermidis (21), Staphylococcus aureus (12). Conclusion Patients who develop one CLABSI are at high risk of recurrent catheter associated sepsis. Gram negative organisms are the most frequently identified group of pathogens.

Comparison of the clinical features of H1N1/09 and previous years' influenza A cases reveals that, in children presenting with severe disease, H1N1/09 influenza is associated with an increased prevalence of shock, duration of admission, and mortality. This was not attributable to demographic differences or underlying disease. H1N1/09 influenza is associated with more severe diseases than those with previous years' influenza A strains.

Viridans group Streptococcus (VGS) is a leading cause of bacteremia in pediatric oncology patients, primarily in children with acute myeloid leukemia or after hematopoietic stem cell transplantation. We retrospectively identified all positive blood cultures in oncology patients at the British Columbia Children's Hospital for a period of 54 months. VGS was the second most commonly isolated pathogen, present in 19% of all the positive blood cultures. Susceptibility analysis of 46 VGS isolates from that period was performed using the Etest method for penicillin, cefotaxime, ceftazidime, and piperacillin/tazobactam. The geometric mean minimal inhibitory concentration for ceftazidime was found to be 9 to 12-fold higher than for any other beta-lactam antibiotic. Penicillin resistance was of 13% with an additional 20% of samples with intermediate susceptibility. The study underscores the prevalence of VGS bacteremia in pediatric patients, especially with acute myeloid leukemia or postallogeneic hematopoietic stem cell transplantation, and the in vitro inferiority of ceftazidime compared with other beta-lactams in that context. We conclude that monotherapy with ceftazidime, or its use along with an aminoglycoside, is not an optimal therapy in pediatric oncology patients with febrile neutropenia.

INTRODUCTION: The incidence of bloodstream infection (BSI) in extracorporeal life support (ECLS) is reported between 0.9 and 19.5%. In January 2006, the Extracorporeal Life Support Organization (ELSO) reported an overall incidence of 8.78% distributed as follows: respiratory: 6.5% (neonatal), 20.8% (pediatric); cardiac: 8.2% (neonatal) and 12.6% (pediatric). METHOD: At BC Children's Hospital (BCCH) daily surveillance blood cultures (BC) are performed and antibiotic prophylaxis is not routinely recommended. Positive BC (BC+) were reviewed, including resistance profiles, collection time of BC+, time to positivity and mortality. White blood cell count, absolute neutrophile count, immature/total ratio, platelet count, fibrinogen and lactate were analyzed 48, 24 and 0 h prior to BSI. A univariate linear regression analysis was performed. RESULTS: From 1999 to 2005, 89 patients underwent ECLS. After exclusion, 84 patients were reviewed. The attack rate was 22.6% (19 BSI) and 13.1% after exclusion of coagulase-negative staphylococci (n = 8). BSI patients were significantly longer on ECLS (157 h) compared to the no-BSI group (127 h, 95% CI: 106-148). Six BSI patients died on ECLS (35%; 4 congenital diaphragmatic hernias, 1 hypoplastic left heart syndrome and 1 after a tetralogy repair). BCCH survival on ECLS was 71 and 58% at discharge, which is comparable to previous reports. No patient died primarily because of BSI. No BSI predictor was identified, although lactate may show a decreasing trend before BSI (P = 0.102). CONCLUSION: Compared with ELSO, the studied BSI incidence was higher with a comparable mortality. We speculate that our BSI rate is explained by underreporting of "contaminants" in the literature, the use of broad-spectrum antibiotic prophylaxis and a higher yield with daily monitoring BC. We support daily surveillance blood cultures as an alternative to antibiotic prophylaxis in the management of patients on ECLS.

There is a need for increased consensus in the definition of fever and neutropenia, the approach to risk stratification (including outpatient therapy and early discharge) and choices of empiric antimicrobial therapy in children. There has been an increased incidence of Gram positive infection in FN patients, in particular with VGS in patient with AML. However, Gram negative bacteria are still responsible for most of the mortality associated with FN. Piperacillin/tazobactam, cefipime, or meropenem are all effective first-choice antimicrobial monotherapy in FN. There is no good evidence for adding an aminoglycoside compound to the initial empiric therapy regimen. Following local microbiological data is of utmost importance in choosing the right empiric antimicrobial regimen for a particular institution. Outpatient management of a well-defined subset of low-risk patient for bacterial invasive infection with intravenous ceftriaxone or oral ciprofloxacin and daily re-evaluation is possible. Early CT of the chest (after 5-7 days of FN) in high-risk patients is essential to make a prompt diagnosis of pulmonary aspergillosis and improve outcome.