Hematologic malignancy Neutropenia Neutropenic fever Unexplained fever Stem-cell transplantation Chemotherapy
Conditions
Interventions
TREATMENT:
Patients will be included in the first 3x24hours hours after the start of antibiotic treatment and will receive standard diagnostic investigations and empirical treatment with imipenem-ci
Sponsors
VU university medical center
Eligibility
Inclusion criteria
Inclusion criteria: 1. Patients with malignant hematological diseases being treated with cytotoxic chemotherapy or stem cell transplantation; 2. High-risk neutropenia; 3. Fever; 4. Age 18 years or older; 5. Written informed consent.
Exclusion criteria
Exclusion criteria: 1. Contraindications to use of imipenem-cilastatin or meropenem such as allergy, previous severe side-effects or previous microbiological cultures with carbapenem-resistant microorganism(s). 2. Corticosteroid use ≥10 mg per day prednisolone or equivalent during the previous 7 days. 3. Clinically or microbiologically documented infection. 4. Symptoms of septic shock (systolic blood pressure <90 mm Hg unresponsive to fluid resuscitation and/or oliguria (urine production <5mL/kg/hour)). 5. Previous enrollment in this study during the same episode of neutropenia. 6. Any critical illness for which Intensive Care Unit treatment is required. 7. Legal incompetency
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is the percentage of patients with failed treatment. Treatment failure is defined as the occurrence of one of the following events after 3x24hours of treatment with a carbapenem. The patient: 1. Has fever at the first day of the end of the neutropenic episode (defined as the first day with neutrophil count >0.5*109/L). 2. Has experienced recurrence of fever after more than 24 hours of defervescence. 3. Is diagnosed with a clinically or microbiologically documented infection. 4. Shows signs or symptoms of septic shock (systolic blood pressure <90mmHg unresponsive to fluid resuscitation and/or oliguria <5mL/kg/hour). 5. Dies between the start of the investigational treatment protocol and recovery of neutropenia. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. All-cause mortality from 3x24hours of treatment until the end of neutropenia. 2. Infection related mortality from 3x24hours of treatment until the end of neutropenia. 3. All-cause mortality within 30 days after recovery of neutropenia. 4. Infection related mortality within 30 days after recovery of neutropenia. 5. The length of hospitalization in days. 6. Unexpected re-admission within 30 days after discharge other than for planned chemotherapy or other elective treatment. 7. The recurrence of fever within 24 hours after discontinuation of intravenous antibiotic therapy. 8. The total number of febrile episodes during neutropenia. 9. Time to defervescence. 10. Antibiotic or antifungal treatment within 30days after discharge other than standard antibiotic prophylaxis. 11. Bacterial resistance in blood cultures and surveillance cultures (including minimal inhibitory concentrations (MIC)). 12. Incidence and prevalence of Clostridium difficile infection. 13. Incidence and prevalence of liver and kidney dysfunction during intravenous antibiotic treatment. 14. Candida spp. colonization in (surveillance) cultures; 15. Cost of antimicrobial therapy per admission 16. MASCC-score (appendix C) 17. The percentage of patients with mucositis and positive blood cultures or antibiotic treatment failure. | — |
Contacts
Public ContactN.A. Jonge, de
VU Medisch Centrum
Outcome results
None listed