Aguilar-Guisado M, et al. - In this study, researchers sought to ascertain whether empirical antimicrobial therapy (EAT) discontinuation driven by a clinical approach regardless of neutrophil recovery would optimise the duration of therapy. as per observations, EAT can be discontinued after 72 h of apyrexia and clinical recovery irrespective of their neutrophil count in high-risk patients with haematological malignancies and febrile neutropenia. This clinical approach proved safe and reduced unnecessary exposure to antimicrobials.

Methods

• In six academic hospitals in Spain, an investigator-driven, superiority, open-label, randomised, controlled phase 4 clinical trial was performed.
• Adults with haematological malignancies or haemopoietic stem-cell transplantation recipients, with high-risk febrile neutropenia without aetiological diagnosis were eligible.
• Researchers used an independent, computer-generated randomisation sequence to randomly enroll patients (1:1) to the experimental or control group.
• Only before randomisation, investigators were masked to assignment.
• They started EAT based on an antipseudomonal β-lactam drug as monotherapy (ceftazidime or cefepime, meropenem or imipenem, or piperacillin-tazobactam) or as combination therapy (with an aminoglycoside, fluoroquinolone, or glycopeptide) in accordance to local protocols and following international guidelines and recommendations.
• After 72 h or more of apyrexia, EAT was withdrawn with clinical recovery in the experimental group; treatment was withdrawn when the neutrophil count was also 0·5 × 10⁹ cells per L or higher in the the control group,.
• The number of EAT-free days was assessed as the primary efficacy endpoint.
• They performed primary analyses in the intention-to-treat population.
• The intention-to-treat population and the per-protocol population were analyzed for efficacy and safety.

Results

• This analysis included 157 episodes among 709 patients assessed for eligibility from April 10, 2012, to May 31, 2016.
• They randomly assigned 78 patients to the experimental group and 79 to the control group.
• In the experimental group, the mean number of EAT-free days was markedly higher than in the control group (16·1 [SD 6·3] vs 13·6 [7·2], absolute difference -2·4 [95% CI -4·6 to -0·3]; p=0·026).
• Researchers noticed 636 adverse events (341 in the experimental group vs 295 in the control group; p=0·057); most (580 [91%]; 323 in the experimental group vs 257 in the control group) were considered mild or moderate (grade 1–2).
• In this study, the most common adverse events in the experimental vs the control group were mucositis (28 [36%] of 78 patients vs 20 [25%] of 79 patients), diarrhoea (23 [29%] of 78 vs 24 [30%] of 79), and nausea and vomiting (20 [26%] of 78 vs 22 [28%] of 79).
• They noticed 56 severe adverse events; 18 in the experimental group and 38 in the control group.
• From hepatic veno-occlusive disease after an allogeneic haemopoietic stem-cell transplantation, 1 patient died in the experimental group.
• In the control group, three patients died (one from multiorgan failure, one from invasive pulmonary aspergillosis, and one from a post-chemotherapy intestinal perforation)