Bloodstream infections (BSI) are a severe complication of antineoplastic chemotherapy or hematopoietic stem cell transplantation (HSCT), especially in the presence of antibiotic resistance (AR). A multinational, multicenter retrospective study in patients aged ≤ 18 years, treated with chemotherapy or HSCT from 2015 to 2017 was implemented to analyze AR among non-common skin commensals BSI. Risk factors associated with AR, intensive care unit (ICU) admission and mortality were analyzed by multilevel mixed effects or standard logistic regressions. A total of 1291 BSIs with 1379 strains were reported in 1031 patients. Among Gram-negatives more than 20% were resistant to ceftazidime, cefepime, piperacillin-tazobactam and ciprofloxacin while 9% was resistant to meropenem. Methicillin-resistance was observed in 17% of S. aureus and vancomycin resistance in 40% of E. faecium. Previous exposure to antibiotics, especially to carbapenems, was significantly associated with resistant Gram-negative BSI while previous colonization with methicillin-resistant S. aureus was associated with BSI due to this pathogen. Hematological malignancies, neutropenia and Gram-negatives resistant to >3 antibiotics were significantly associated with higher risk of ICU admission. Underlying disease in relapse/progression, previous exposure to antibiotics, and need of ICU admission were significantly associated with mortality. Center-level variation showed a greater impact on AR, while patient-level variation had more effect on ICU admission and mortality. Previous exposure to antibiotics or colonization by resistant pathogens can be the cause of AR BSI. Resistant Gram-negatives are significantly associated with ICU admission and mortality, with a significant role for the treating center too. The significant evidence of center-level variations on AR, ICU admission and mortality, stress the need for careful local antibiotic stewardship and infection control programs.

Human enterovirus (EV) and parechovirus (HPeV) are significant causes of encephalitis and meningitis in children. The aim of this study was to determine the prevalence, type and viral RNA concentration of EV and HPeV in cerebrospinal fluid (CSF) samples in an unselected cohort of patients <18 years admitted to Bonn university hospital from 1998 to 2008. A total of 327 CSF samples from 327 patients were retrospectively tested by real-time reverse-transcriptase PCR (RT-PCR) for EV and HPeV, and by real-time PCR for cytomegalovirus (CMV), herpes simplex virus 1/2 (HSV), and varizella zoster-virus (VZV). Samples had been submitted for routine virological work-up due to suspected meningitis or encephalitis and had been stored at −20 °C hereafter. Positive samples for EV and HPeV were sequenced within the gene encoding the VP1 region (EV), the VP2 and the VP3/VP1 junction region (HPeV). The overall prevalence was 4.3 % (14/327) for EV, 0.6 % (2/327) for HPeV, and 0.3 % (1/327) for HSV and VZV, respectively. CMV was not detected in this cohort. In children less than 3 months of age the prevalence was 7.7 % (2/26) for EV and 7.7 % (2/26) for HPeV, respectively. Frequency of EV detection ranged from 0 to 12 % per year and highest rates were observed from June to September. All typed EV belonged to species B. Both HPeV infections were detected in the fall of 2008 and were typed as HPeV genotype 3. Viral RNA concentrations were highest in patients with HPeV infection, followed by echovirus 30 and other EV. In total, 86 % (12/14) of EV infections presented as aseptic meningitis, whereas both HPeV infections presented as severe sepsis-like illness. EV and HPeV were equally prevalent in children <3 months of age. Beyond the detection of EV and HPeV, the determination of viral RNA concentration and typing of EV and HPeV might prove beneficial for patient management and public health.

Background: The standard treatment of fever in chemotherapy‐induced neutropenia (FN) includes emergency hospitalization and empirical intravenous antimicrobial therapy. This study determined if first‐day step‐down to oral outpatient treatment is not inferior to continued standard regarding safety and efficacy in children with low‐risk FN.Procedure: In a randomized controlled non‐blinded multicenter study, pediatric patients with FN after non‐myeloablative chemotherapy were reassessed after 8–22 hours of inpatient intravenous antimicrobial therapy. Low‐risk patients were randomized to first‐day step‐down to experimental (outpatient, oral amoxicillin plus ciprofloxacin) versus continued standard treatment. Exact non‐inferiority tests were used for safety (no serious medical complication; non‐inferiority margin of difference, 3.5%) and efficacy (resolution of infection without recurrence, no modification of antimicrobial therapy, no adverse event; 10%).Results: In 93 (26%) of 355 potentially eligible FN episodes low‐risk criteria were fulfilled, and 62 were randomized, 28 to experimental (1 lost to follow‐up) and 34 to standard treatment. In intention‐to‐treat analyses, non‐inferiority was not proven for safety [27 of 27 (100%) vs. 33 of 34 (97%; 1 death) episodes; 95% upper confidence border, 6.7%; P = 0.11], but non‐inferiority was proven for efficacy [23 of 27 (85%) vs. 26 of 34 (76%) episodes; 95% upper confidence border, 9.4%; P = 0.045]. Per‐protocol analyses confirmed these results.Conclusions: In children with low‐risk FN, the efficacy of first‐day step‐down to oral antimicrobial therapy with amoxicillin and ciprofloxacin in an outpatient setting was non‐inferior to continued hospitalization and intravenous antimicrobial therapy. The safety of this procedure, however, was not assessable with sufficient power. Pediatr Blood Cancer 2012;59:423–430.

The outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019 in Wuhan challenges pediatric oncologists in an unexpected way. We provide a comprehensive overview, which systematically summarizes and grades evidence (QoE) on SARS-CoV-2 infections in pediatric cancer patients at 1.5 years of pandemic. A systematic literature search in PubMed combined with an additional exploratory literature review in other international databases was conducted to identify studies on children (aged < 18 years) with a malignant disease and COVID-19 infections. In total, 45 reports on 1003 pediatric cancer patients with SARS-CoV-2 infections were identified out of 1397 reports analyzed. The clinical course of COVID-19 was reported mild or moderate in 358 patients (41.7%), whereas 11.1% of patients showed severe COVID-19. In 12.7% of patients, chemotherapy was postponed, whereas 19% of patients with different underlying malignancies received chemotherapy during SARS-CoV-2 infection. Twenty-five patients with SARS-CoV-2 infections died, potentially related to COVID-19.Conclusion: Despite a favorable COVID-19 outcome in most pediatric cancer patients, the morbidity is reported higher than in children without comorbidities. However, no severe COVID-19 complications were associated to the continuation of chemotherapy in some cohort studies and reports on two patients. Therefore, the risk of cancer progress or relapse due to interruption of chemotherapy has carefully to be weighed against the risk of severe COVID-19 disease with potentially fatal outcome. What is Known:• Most of pediatric patients with malignant diseases show an asymptomatic, mild or moderate clinical course of SARS-CoV-2 infection. • Current need for a basis for decision-making, whether to stop or interrupt cancer treatment in a patient infected with SARS-CoV-2, and when to continue chemotherapy. What is New:• Review results comprising over 1000 pediatric COVID-19 cancer patients confirm mild courses of SARS-CoV-2 infection in most patients but also show the attributable mortality is at least 10 times higher compared to reports on hospitalized children without comorbidities.• Review identifies that chemotherapy was continued despite SARS-CoV-2 positivity in 18% of patients with individual chemotherapy modification according to the clinical course of SARS-CoV-2 infection and existing comorbidities. On this basis, no severe COVID-19 complications were associated to the continuation of chemotherapy in several cohort studies and two case reports.