This single-arm, open-label clinical study evaluates the efficacy and safety of a standardized empirical anti-infective escalation protocol for patients with hematological malignancies complicated by febrile neutropenia. The treatment algorithm follows a sequential strategy: initial carbapenem monotherapy (2 days) → if ineffective, combination with vancomycin/linezolid (3 days) → if no response, escalation to antifungal therapy (7 days). For patients demonstrating persistent or recurrent fever with uncontrolled infection parameters after 12-14 days of prior empirical anti-infective therapy, switching to ceftazidime-avibactam combined with aztreonam is implemented. Therapeutic efficacy is assessed through comprehensive evaluation of clinical manifestations, inflammatory biomarkers, radiographic imaging, and microbiological findings. Comprehensive safety surveillance includes continuous monitoring of adverse events and all-cause mortality throughout the treatment course.

This study is a single-arm, open-label, observational clinical investigation focusing on patients with hematological malignancies complicated by febrile neutropenia. It aims to evaluate the overall efficacy and safety of a standardized empirical anti-infective treatment algorithm. The protocol employs a unified step-up therapeutic strategy: initial empirical administration of a carbapenem antibiotic (for 2 days); if ineffective, combination with an anti-Gram-positive agent (e.g., vancomycin or linezolid) (for 3 days); if there is still no response, initiation of antifungal therapy (for 7 days); For patients exhibiting persistent or recurrent fever with uncontrolled infection-related parameters after 12-14 days of prior empirical anti-infective therapy, an empirical multidrug-resistant regimen consisting of ceftazidime-avibactam combined with aztreonam is considered. The treatment duration will be adjusted based on neutrophil recovery and febrile status. The study will assess overall efficacy through a comprehensive evaluation of clinical symptoms and signs, inflammatory biomarkers (e.g., C-reactive protein, procalcitonin), radiographic findings, and microbiological results. Safety monitoring will include continuous surveillance of adverse events (AEs) and all-cause mortality throughout the treatment course.

Inclusion Criteria:

• Age 18-75 years.
• Documented haematological malignancy: acute leukaemia, severe aplastic anaemia, lymphoma, or multiple myeloma.
• Neutropenia: absolute neutrophil count (ANC) < 0.5 × 10⁹/L, or ANC anticipated to fall below this threshold within 48 h; severe neutropenia defined as ANC < 0.1 × 10⁹/L.
• Fever: single oral temperature ≥ 38.3 °C (axillary ≥ 38.0 °C), or oral temperature ≥ 38.0 °C (axillary ≥ 37.7 °C) sustained for > 1 h.
• Eastern Cooperative Oncology Group performance status (ECOG-PS) 0-2.
• Planned or current empirical use of ceftazidime-avibactam (CAZ-AVI) for febrile neutropenia.

Exclusion Criteria:

• Drug-related fever or fever attributable to rheumatic/autoimmune disease.
• Concomitant intracranial haemorrhage.
• Pregnancy, lactation, or intention to become pregnant.
• Psychiatric disorder or any condition precluding protocol compliance.
• Life-threatening arrhythmia or QTc > 500 ms on electrocardiography.

This single-arm, open-label, observational study will enrol adult patients with haematological malignancies who develop febrile neutropenia and are scheduled to receive empirical ceftazidime-avibactam. Eligible participants are aged 18-75 years with acute leukaemia, severe aplastic anaemia, lymphoma or multiple myeloma, an absolute neutrophil count < 0.5 × 10⁹/L (or expected to fall below this within 48 h), fever ≥ 38.3 °C, ECOG performance status 0-2, and no contraindications such as drug fever, intracranial haemorrhage, pregnancy, or QTc > 500 ms. The cohort will reflect the real-world haematology ward population at high risk for multidrug-resistant Gram-negative infections.