{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T01:11:28Z","timestamp":1789521088627,"version":"build-2803163510"},"reference-count":34,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives: Children and adolescents with haematologic malignancies or other causes of immunosuppression are at high risk of severe infections. Determining the probability of Gram-negative bacilli bloodstream infections (GNB-BSI) within 24 h of blood culture (BC) incubation could support early antibiotic de-escalation, compared to the current guidelines recommending de-escalation after 48\u201372 h. Methods: Retrospective, observational single-centre study describing BC time-to-positivity (TTP) in GNB-BSI in a paediatric cohort of immunocompromised children. Results: In 128 episodes (100 patients), TTP was less than 24 h in &gt;95% cases. TTP did not differ based on sex, underlying disease, degree of neutropenia, or PICU admission. Antibiotic initiation prior to BC collection and microbiological aetiology (microbiological aetiology different from Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, or Enterobacter cloacae) were the only identified risk factors associated with BC growth beyond 24 h. No patients with late BC growth died or required PICU admission. Conclusions: If BC remains negative after 24 h of incubation, GNB-BSI is unlikely in immunocompromised children and adolescents with fever. These results support early de-escalation strategies, shortening unnecessary exposure to broader-spectrum antibiotics, and potentially decreasing adverse events and costs.<\/jats:p>","DOI":"10.3390\/antibiotics14080847","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T07:41:45Z","timestamp":1755848505000},"page":"847","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Blood Cultures Time-to-Positivity as an Antibiotic Stewardship Tool in Immunocompromised Children with Gram-Negative Bacteraemia"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4139-5323","authenticated-orcid":false,"given":"Juli\u00e0","family":"Gotzens","sequence":"first","affiliation":[{"name":"Infectious Diseases and Systemic Inflammatory Response in Pediatrics, Pediatric Infectious Diseases Department, Institut de Recerca Sant Joan de D\u00e9u, Hospital Sant Joan de D\u00e9u, 08950 Esplugues de Llobregat, Spain"},{"name":"Department of Surgery and Medical-Surgical Specialties, Faculty of Medicine and Health Sciences, Universitat de Barcelona (UB), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aina","family":"Colom-Bala\u00f1\u00e0","sequence":"additional","affiliation":[{"name":"Pediatrics Department, Hospital Sant Joan de D\u00e9u, 08950 Esplugues de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Monson\u00eds","sequence":"additional","affiliation":[{"name":"Microbiology Department, Hospital Sant Joan de D\u00e9u Barcelona, 08950 Esplugues de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laia","family":"Alsina","sequence":"additional","affiliation":[{"name":"Department of Surgery and Medical-Surgical Specialties, Faculty of Medicine and Health Sciences, Universitat de Barcelona (UB), 08036 Barcelona, Spain"},{"name":"Clinical Immunology and Primary Immunodeficiencies Unit, Pediatric Allergy and Clinical Immunology Department, Hospital Sant Joan de D\u00e9u, 08950 Esplugues de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1287-7561","authenticated-orcid":false,"given":"Mar\u00eda Antonia","family":"Ruiz-Cobo","sequence":"additional","affiliation":[{"name":"Leukemia, Lymphoma and CART Department, Pediatric Cancer Center Barcelona (PCCB), Hospital Sant Joan de D\u00e9u de Barcelona, 08950 Esplugues de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2499-0817","authenticated-orcid":false,"given":"Mar\u00eda","family":"R\u00edos-Barn\u00e9s","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Systemic Inflammatory Response in Pediatrics, Pediatric Infectious Diseases Department, Institut de Recerca Sant Joan de D\u00e9u, Hospital Sant Joan de D\u00e9u, 08950 Esplugues de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9411-8189","authenticated-orcid":false,"given":"Anna","family":"Gamell","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Systemic Inflammatory Response in Pediatrics, Pediatric Infectious Diseases Department, Institut de Recerca Sant Joan de D\u00e9u, Hospital Sant Joan de D\u00e9u, 08950 Esplugues de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2400-3033","authenticated-orcid":false,"given":"Eneritz","family":"Velasco-Arnaiz","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Systemic Inflammatory Response in Pediatrics, Pediatric Infectious Diseases Department, Institut de Recerca Sant Joan de D\u00e9u, Hospital Sant Joan de D\u00e9u, 08950 Esplugues de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Mart\u00ednez-de-Alb\u00e9niz","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Systemic Inflammatory Response in Pediatrics, Pediatric Infectious Diseases Department, Institut de Recerca Sant Joan de D\u00e9u, Hospital Sant Joan de D\u00e9u, 08950 Esplugues de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Fumad\u00f3","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Systemic Inflammatory Response in Pediatrics, Pediatric Infectious Diseases Department, Institut de Recerca Sant Joan de D\u00e9u, Hospital Sant Joan de D\u00e9u, 08950 Esplugues de Llobregat, Spain"},{"name":"Department of Surgery and Medical-Surgical Specialties, Faculty of Medicine and Health Sciences, Universitat de Barcelona (UB), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e0udia","family":"Fortuny","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Systemic Inflammatory Response in Pediatrics, Pediatric Infectious Diseases Department, Institut de Recerca Sant Joan de D\u00e9u, Hospital Sant Joan de D\u00e9u, 08950 Esplugues de Llobregat, Spain"},{"name":"Department of Surgery and Medical-Surgical Specialties, Faculty of Medicine and Health Sciences, Universitat de Barcelona (UB), 08036 Barcelona, Spain"},{"name":"Center for Biomedical Network Research on Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain"},{"name":"Translational Research Network in Pediatric Infectious Diseases (RITIP), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7485-0583","authenticated-orcid":false,"given":"Antoni","family":"Noguera-Julian","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Systemic Inflammatory Response in Pediatrics, Pediatric Infectious Diseases Department, Institut de Recerca Sant Joan de D\u00e9u, Hospital Sant Joan de D\u00e9u, 08950 Esplugues de Llobregat, Spain"},{"name":"Department of Surgery and Medical-Surgical Specialties, Faculty of Medicine and Health Sciences, Universitat de Barcelona (UB), 08036 Barcelona, Spain"},{"name":"Center for Biomedical Network Research on Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain"},{"name":"Translational Research Network in Pediatric Infectious Diseases (RITIP), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00edlvia","family":"Sim\u00f3-Nebot","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Systemic Inflammatory Response in Pediatrics, Pediatric Infectious Diseases Department, Institut de Recerca Sant Joan de D\u00e9u, Hospital Sant Joan de D\u00e9u, 08950 Esplugues de Llobregat, Spain"},{"name":"Center for Biomedical Network Research on Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e160","DOI":"10.1097\/MPH.0000000000002258","article-title":"Bloodstream Infections in Children with Cancer: Pathogen Distribution and Antimicrobial Susceptibility Patterns over a 10-Year Period","volume":"44","author":"Maarbjerg","year":"2022","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1007\/s00431-015-2525-5","article-title":"Bloodstream infection in paediatric cancer centres\u2014leukaemia and relapsed malignancies are independent risk factors","volume":"174","author":"Ammann","year":"2015","journal-title":"Eur. J. Pediatr."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Willis, D.N., McGlynn, M.C., Reich, P.J., and Hayashi, R.J. (2023). Mortality in pediatric oncology and stem cell transplant patients with bloodstream infections. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.1063253"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e270","DOI":"10.1016\/S1470-2045(20)30725-7","article-title":"8th European Conference on Infections in Leukaemia. 2020 guidelines for the use of antibiotics in paediatric patients with cancer or post-haematopoietic cell transplantation","volume":"22","author":"Lehrnbecher","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1016\/j.cmi.2023.10.019","article-title":"Frequency of bloodstream infections caused by six key antibiotic-resistant pathogens for prioritization of research and discovery of new therapies in Europe: A systematic review","volume":"30","author":"Pezzani","year":"2024","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e242","DOI":"10.1016\/S1470-2045(25)00079-8","article-title":"Antimicrobial resistance in patients with haematological malignancies: A scoping review","volume":"26","author":"Sallah","year":"2025","journal-title":"Lancet Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1093\/jac\/dkz571","article-title":"Longitudinal analysis of ESBL and carbapenemase carriage among Enterobacterales and Pseudomonas aeruginosa isolates collected in Europe as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance programme, 2013\u20132017","volume":"75","author":"Kazmierczak","year":"2020","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Stergiotis, M., Ammann, R.A., Droz, S., Koenig, C., and Agyeman, P.K.A. (2021). Pediatric fever in neutropenia with bacteremia-Pathogen distribution and in vitro antibiotic susceptibility patterns over time in a retrospective single-center cohort study. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0246654"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1200\/JCO.22.02224","article-title":"Guideline for the Management of Fever and Neutropenia in Pediatric Patients With Cancer and Hematopoietic Cell Transplantation Recipients: 2023 Update","volume":"41","author":"Lehrnbecher","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Castagnola, E., Bagnasco, F., Mesini, A., Agyeman, P.K.A., Ammann, R.A., Carlesse, F., Santolaya de Pablo, M.E., Groll, A.H., Haeusler, G.M., and Lehrnbecher, T. (2021). Antibiotic Resistant Bloodstream Infections in Pediatric Patients Receiving Chemotherapy or Hematopoietic Stem Cell Transplant: Factors Associated with Development of Resistance, Intensive Care Admission and Mortality. Antibiotics, 10.","DOI":"10.3390\/antibiotics10030266"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e51","DOI":"10.1093\/cid\/ciw118","article-title":"Implementing an Antibiotic Stewardship Program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America","volume":"62","author":"Barlam","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.jpeds.2020.06.008","article-title":"Benefits of a Pediatric Antimicrobial Stewardship Program in Antimicrobial Use and Quality of Prescriptions in a Referral Children\u2019s Hospital","volume":"225","author":"Jordan","year":"2020","journal-title":"J. Pediatr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.jinf.2019.07.002","article-title":"Clinical impact of an educational antimicrobial stewardship program associated with infectious diseases consultation targeting patients with cancer: Results of a 9-year quasi-experimental study with an interrupted time-series analysis","volume":"79","author":"Molina","year":"2019","journal-title":"J. Infect."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1177\/1060028019890886","article-title":"Inpatient Antibiotic Stewardship Interventions in the Adult Oncology and Hematopoietic Stem Cell Transplant Population: A Review of the Literature","volume":"54","author":"Pillinger","year":"2020","journal-title":"Ann. Pharmacother."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Muratore, E., Baccelli, F., Leardini, D., Campoli, C., Belotti, T., Viale, P., Prete, A., Pession, A., Masetti, R., and Zama, D. (2022). Antimicrobial Stewardship Interventions in Pediatric Oncology: A Systematic Review. J. Clin. Med., 11.","DOI":"10.3390\/jcm11154545"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Liberati, C., Barbieri, E., Cavagnero, F., Petris, M.G., Brigadoi, G., Reggiani, G., De Pieri, M., Pierobon, M., Marzollo, A., and Gabelli, M. (2024). Impact of a two step antimicrobial stewardship program in a paediatric haematology and oncology unit. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-80163-1"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.cmi.2024.06.002","article-title":"Infectious complications in the paediatric immunocompromised host: A narrative review","volume":"31","author":"Lehrnbecher","year":"2025","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.ejca.2011.01.021","article-title":"Time for paediatric febrile neutropenia guidelines - children are not little adults","volume":"47","author":"Sung","year":"2011","journal-title":"Eur. J. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e732","DOI":"10.1016\/S2214-109X(24)00511-4","article-title":"Strengthening the paediatric clinical trial ecosystem to better inform policy and programmes","volume":"13","author":"Berkley","year":"2025","journal-title":"Lancet Glob. Health"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"87","DOI":"10.14785\/lymphosign-2016-0007","article-title":"Management of infections in theimmunocompromised child: General principles","volume":"3","author":"Upton","year":"2016","journal-title":"LymphoSign J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.cmi.2018.12.001","article-title":"Blood culture time-to-positivity: Making use of the hidden information","volume":"25","author":"Lamy","year":"2019","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.cll.2020.07.001","article-title":"Modern Blood Culture: Management Decisions and Method Options","volume":"40","author":"Gonzalez","year":"2020","journal-title":"Clin. Lab. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.cmi.2018.07.026","article-title":"Current time-to-positivity of blood cultures in febrile neutropenia: A tool to be used in stewardship de-escalation strategies","volume":"25","author":"Cardozo","year":"2019","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1111\/ejh.13001","article-title":"Distribution and clinical determinants of time-to-positivity of blood cultures in patients with neutropenia","volume":"100","author":"Lambregts","year":"2018","journal-title":"Eur. J. Haematol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1097\/MPH.0b013e3181b1edc6","article-title":"Etiology and clinical course of febrile neutropenia in children with cancer","volume":"31","author":"Hakim","year":"2009","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1542\/hpeds.2021-005873","article-title":"Time to Blood Culture Positivity by Pathogen and Primary Service","volume":"11","author":"MacBrayne","year":"2021","journal-title":"Hosp. Pediatr."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Dierig, A., Berger, C., Agyeman, P.K.A., Bernhard-Stirnemann, S., Giannoni, E., Stocker, M., Posfay-Barbe, K.M., Niederer-Loher, A., Kahlert, C.R., and Donas, A. (2018). Swiss Pediatric Sepsis Study. Time-to-Positivity of Blood Cultures in Children With Sepsis. Front. Pediatr., 6.","DOI":"10.3389\/fped.2018.00222"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.mimet.2013.02.005","article-title":"Time-to-positivity-based discrimination between Enterobacteriaceae, Pseudomonas aeruginosa and strictly anaerobic Gram-negative bacilli in aerobic and anaerobic blood culture vials","volume":"93","author":"Defrance","year":"2013","journal-title":"J. Microbiol. Methods"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"136.e7","DOI":"10.1016\/j.cmi.2021.05.043","article-title":"Time to positivity in bloodstream infection is not a prognostic marker for mortality: Analysis of a prospective multicentre randomized control trial","volume":"28","author":"Hamilton","year":"2022","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_30","unstructured":"WHO (2024). Bacterial Priority Pathogens List. Bacterial Pathogens of Public Health Importance to Guide Research, Development and Strategies to Prevent and Control Antimicrobial Resistance, World Health Organization."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1007\/s10096-013-1833-9","article-title":"Clinical and microbiological implications of time-to-positivity of blood cultures in patients with Gram-negative bacilli bacteremia","volume":"32","author":"Palmer","year":"2013","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Xu, H., Cheng, J., Yu, Q., Li, Q., Yi, Q., Luo, S., Li, Y., Zhang, G., Tian, X., and Cheng, D. (2020). Prognostic role of time to positivity of blood culture in children with Pseudomonas aeruginosa bacteremia. BMC Infect. Dis., 20.","DOI":"10.1186\/s12879-020-05257-3"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1007\/s00431-020-03675-8","article-title":"Time to positivity of Klebsiella pneumoniae in blood culture as prognostic indicator for pediatric bloodstream infections","volume":"179","author":"Cheng","year":"2020","journal-title":"Eur. J. Pediatr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1128\/JCM.40.3.898-901.2002","article-title":"Initial concentration of Staphylococcus epidermidis in simulated pediatric blood cultures correlates with time to positive results with the automated, continuously monitored BACTEC blood culture system","volume":"40","author":"Vellozzi","year":"2002","journal-title":"J. Clin. Microbiol."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/8\/847\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:33:00Z","timestamp":1760034780000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/8\/847"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,21]]},"references-count":34,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["antibiotics14080847"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics14080847","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,21]]}}}