Neutropenic fever is a common complication of therapy for haematological malignancy and in about 40% of episodes, no clinical focus or microbiological cause is identified. 1 Verlinden A Jansens H Goossens H et al. Safety and efficacy of antibiotic de-escalation and discontinuation in high-risk hematological patients with febrile neutropenia: a single-center experience. Open Forum Infect Dis. 2022; 9ofab624 Crossref PubMed Scopus (6) Google Scholar , 2 Averbuch D Orasch C Cordonnier C et al. European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia. Haematologica. 2013; 98: 1826-1835 Crossref PubMed Scopus (343) Google Scholar , 3 Aguilar-Guisado M Espigado I Martín-Peña A et al. Optimisation of empirical antimicrobial therapy in patients with haematological malignancies and febrile neutropenia (How Long study): an open-label, randomised, controlled phase 4 trial. Lancet Haematol. 2017; 4: e573-e583 Summary Full Text Full Text PDF PubMed Scopus (93) Google Scholar The optimal strategy for antibiotic management in the setting of neutropenic fever with no identified source is yet to be defined. Common strategies include early de-escalation from empiric therapy to antibiotic prophylaxis until neutrophil recovery or complete cessation of antibiotic therapy with different cessation thresholds used. 2 Averbuch D Orasch C Cordonnier C et al. European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia. Haematologica. 2013; 98: 1826-1835 Crossref PubMed Scopus (343) Google Scholar , 4 Freifeld AG Bow EJ Sepkowitz KA et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011; 52: e56-e93 Crossref PubMed Scopus (2014) Google Scholar A cellular recovery threshold (neutrophil count ≥0·5×109/L) for cessation has been recommended, 4 Freifeld AG Bow EJ Sepkowitz KA et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011; 52: e56-e93 Crossref PubMed Scopus (2014) Google Scholar but, new data suggest the use of clinically guided cessation using clinical stability and resolution of fever for earlier antibiotic cessation. 1 Verlinden A Jansens H Goossens H et al. Safety and efficacy of antibiotic de-escalation and discontinuation in high-risk hematological patients with febrile neutropenia: a single-center experience. Open Forum Infect Dis. 2022; 9ofab624 Crossref PubMed Scopus (6) Google Scholar , 3 Aguilar-Guisado M Espigado I Martín-Peña A et al. Optimisation of empirical antimicrobial therapy in patients with haematological malignancies and febrile neutropenia (How Long study): an open-label, randomised, controlled phase 4 trial. Lancet Haematol. 2017; 4: e573-e583 Summary Full Text Full Text PDF PubMed Scopus (93) Google Scholar Earlier antibiotic cessation compared with continuation until resolution of neutropenia is associated with lower antibiotic exposure and no significant difference in rates of clinical failure, safety, or mortality. 1 Verlinden A Jansens H Goossens H et al. Safety and efficacy of antibiotic de-escalation and discontinuation in high-risk hematological patients with febrile neutropenia: a single-center experience. Open Forum Infect Dis. 2022; 9ofab624 Crossref PubMed Scopus (6) Google Scholar , 3 Aguilar-Guisado M Espigado I Martín-Peña A et al. Optimisation of empirical antimicrobial therapy in patients with haematological malignancies and febrile neutropenia (How Long study): an open-label, randomised, controlled phase 4 trial. Lancet Haematol. 2017; 4: e573-e583 Summary Full Text Full Text PDF PubMed Scopus (93) Google Scholar Short versus extended treatment with a carbapenem in patients with high-risk fever of unknown origin during neutropenia: a non-inferiority, open-label, multicentre, randomised trialEarly discontinuation of carbapenem treatment in patients with febrile neutropenia of unknown origin does not result in increased treatment failure. Our study supports short treatment if patients are afebrile after 3 days of carbapenem treatment. However, because secondary analyses suggested that serious adverse events and all-cause mortality occurred more often in patients who are persistantly febrile the short treatment group, we recommend vigilance for non-susceptible pathogens and early resumption of empirical therapy in patients who are deteriorating. Full-Text PDF