Efficacy of Empirical Anti-Infective Therapy in Neutropenic Febrile Patients.

Condition(s) studied

Investigational drug(s) / intervention(s)

Carbapenems: First-line empirical agent for febrile neutropenia complicating hematologic malignancies: carbapenem.

Anti-Gram-positive agent: Escalation to a carbapenem plus an anti-Gram-positive agent (vancomycin or linezolid) is instituted if no defervescence occurs after 48h of first-line therapy; this combination is maintained for 3 days before further escalation in febrile-neutropenia patients with underlying hematologic malignancies.

Antifungal agent: If combination therapy with a carbapenem plus an anti-Gram-positive agent (vancomycin or linezolid) remains ineffective after 72 h, empirical antifungal coverage is added while continuing antibacterial therapy for an additional 7 days; failure to defervesce thereafter mandates further therapeutic escalation in febrile-neutropenic patients with hematologic malignancies.

Ceftazidime-avibactam + Aztreonam: If the combination of a carbapenem and an anti-Gram-positive agent (vancomycin or linezolid) fails to achieve defervescence after 3 days of treatment, an antifungal agent is added while continuing the original antibacterial regimen for an additional 7 days. Should fever persist or recur with uncontrolled infection-related parameters after 12-14 days of empirical anti-infective therapy, the carbapenem/anti-Gram-positive combination is discontinued. Therapy is then switched to ceftazidime-avibactam plus aztreonam to cover multidrug-resistant pathogens, while concurrently maintaining antifungal treatment. This escalation strategy is indicated for febrile neutropenic patients with underlying hematologic malignancies.

Study summary

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.

Eligibility

Primary outcome measure(s)

• Symptom Resolution Rate by Patient-Reported Temperature Diary — two days
  Proportion of patients achieving defervescence (oral temperature \< 38 °C sustained for ≥ 8 h) AND absence of infection-related symptoms recorded in a validated patient diary within 48 h after starting empirical therapy.
• C-Reactive Protein Serum Concentration Change (mg/L) — two days
  Absolute decrease from baseline in high-sensitivity CRP measured by immunoturbidimetric assay at 48 h.
• Procalcitonin Plasma Concentration Change (ng/mL) — Two days
  Absolute decrease from baseline in PCT measured by electrochemiluminescence immunoassay at 48 h.
• Pulmonary Infiltrate Resolution on CT or Chest X-ray — Two weeks
  Proportion of patients with ≥ 50 % reduction in the longest diameter of any lung infiltrate compared with baseline scan.
• Pathogen Positivity Rate in Blood or Sterile-Site Cultures — one week
  Cumulative proportion of patients with clinically relevant bacteria or fungi isolated from blood or other normally sterile sites processed by automated BACTEC™ culture system.
• Physical Sign Resolution Score by Clinician Examination — two days
  Proportion of patients in whom predefined signs (erythema, tenderness, exudate, etc.) disappear or improve by ≥ 50 % on a 4-point clinician-graded scale.

Trial sites (1)

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