This is a prospective, single-arm, observational, exploratory clinical study to evaluate whether the standard fixed dose of ceftazidime-avibactam (CAZ-AVI) achieves sufficient drug exposure (pharmacokinetic/pharmacodynamic, or PK/PD targets) in patients with blood cancers (or those undergoing stem cell transplantation).
Patients with hematological malignancies are at high risk for severe, drug-resistant Gram-negative bacterial infections due to weakened immune systems. CAZ-AVI is a critical antibiotic used to treat these infections. However, there is limited evidence on whether the standard recommended dose achieves adequate drug concentrations for both ceftazidime and avibactam simultaneously in this specific patient group, and whether low drug exposure drives the development of antibiotic resistance during treatment.
This study will enroll 60 participants who are already prescribed CAZ-AVI by their treating physicians based on routine clinical needs. The study will not change or interfere with any clinical treatment decisions. To measure drug levels, 5 small blood samples (about 2-3 mL each) will be collected within one dosing interval after the drug reaches a steady level in the body (typically 48 to 72 hours after starting treatment). Microbiological samples (such as blood cultures or swabs) will also be collected at multiple time points to monitor bacterial clearance and detect any newly developed resistance. Participants will be followed up for clinical outcomes and survival status up to 30 days after the completion of treatment.
The primary goal of this study is to determine the percentage of patients who achieve the target drug exposure for both ceftazidime and avibactam simultaneously. The secondary goals are to observe clinical cure rates, bacterial clearance rates, 30-day survival, and the rate of newly induced antibiotic resistance during therapy.
Age 16 years or older.
Diagnosed with hematological malignancies (including but not limited to acute leukemia, lymphoma, multiple myeloma, or myelodysplastic syndrome [MDS]) or having received/undergoing autologous or allogeneic hematopoietic stem cell transplantation (HSCT).
Prescribed ceftazidime-avibactam (CAZ-AVI) therapy for suspected or confirmed Gram-negative bacterial infections based solely on routine clinical decisions.
Expected duration of CAZ-AVI therapy is no less than 72 hours.
Known severe allergy or hypersensitivity to ceftazidime, avibactam, cephalosporins, or other beta-lactam antibiotics.
Confirmed infection caused by metallo-beta-lactamase (MBL)-producing pathogens, without receiving appropriate combination therapy.
Expected survival time of less than 72 hours.
Inability to complete critical pharmacokinetic (TDM) or microbiological sampling.
The study population consists of hospitalized patients with hematological malignancies (such as acute leukemia, lymphoma, multiple myeloma, or myelodysplastic syndrome) or those who have underwent/are undergoing autologous or allogeneic hematopoietic stem cell transplantation (HSCT) at the Institute of Hematology \& Blood Diseases Hospital, Chinese Academy of Medical Sciences, who are prescribed standard-dose ceftazidime-avibactam for suspected or confirmed Gram-negative bacterial infections based on routine clinical decisions.
Cohort
Prospective
Ceftazidime-avibactam
DrugPatients receive standard-dose ceftazidime-avibactam (CAZ-AVI) intravenously. The standard recommended dosage for adults is 2.5 g (ceftazidime 2.0 g and avibactam 0.5 g) administered every 8 hours via a 2-hour intravenous infusion, with adjustments made for renal impairment according to the drug's official product label. This study is purely observational; the initiation, dosing regimen, combination with other antibiotics, and duration of therapy are determined entirely by the treating physicians based on clinical routine, without any study-active interference.
Therapeutic Drug Monitoring (TDM) and Microbiological Surveillance
Procedure/SurgeryAuxiliary non-interventional procedures added to routine care: 1) Standardized TDM sampling: 5 blood samples (2-3 mL each, total \~15 mL) collected within a single dosing interval at steady state (48-72 hours after treatment initiation, typically after the 4th or 5th dose) to measure ceftazidime and avibactam plasma concentrations via LC-MS/MS. 2) Microbiological surveillance: longitudinal collection of blood cultures, clinical infection site specimens, and oropharyngeal/perianal colonization swabs at Baseline, Day 3±1, Day 7±1, end of therapy, and 7 days post-therapy to monitor bacterial clearance and screen for newly induced resistance.
Joint Pharmacokinetic/Pharmacodynamic (PK/PD) Target Attainment Rate of Ceftazidime-Avibactam
The percentage of patients who simultaneously achieve the target drug exposure for both ceftazidime and avibactam in plasma during the early phase of therapy. The joint PK/PD target attainment is defined as meeting both of the following criteria concurrently within a single dosing interval: 1. Ceftazidime free drug concentration remains above the Minimum Inhibitory Concentration (MIC) of the pathogen for at least 50% of the dosing interval (50% fT \> MIC). 2. Avibactam free drug concentration remains above 1 mg/L for at least 50% of the dosing interval (50% fT \> 1 mg/L). The pathogen's MIC is determined under a fixed concentration of 4 mg/L avibactam using the broth microdilution (BMD) method.
Incidence of Induced Resistance to Ceftazidime-Avibactam During Therapy
The percentage of patients who experience a transition of their baseline pathogen from ceftazidime-avibactam susceptible/non-resistant to non-susceptible/resistant. This is defined as isolating the same pathogen species during the therapy period or within 7 days post-therapy that exhibits ceftazidime-avibactam non-susceptibility/resistance, whereas the baseline isolate was susceptible/non-resistant.
7-Day Clinical Response Rate
The percentage of patients achieving clinical response within 7 days of starting therapy. Clinical response is defined as meeting at least two of the following criteria: 1. Temperature normalization (body temperature \< 38.0°C) or significant decrease; 2. Improvement of infection-related clinical symptoms; 3. Decrease in inflammatory markers; 4. Hemodynamic stability.
Microbiological Clearance Rate
The percentage of patients achieving microbiological clearance. This is defined as the target Gram-negative pathogen culture turning negative in follow-up clinical specimens, or when follow-up specimens are no longer obtainable due to clinical resolution of the infection site.
7-Day Re-fever Rate
The percentage of patients who experience a recurrence of infection-related fever (body temperature ≥ 38.0°C) within 7 days after initial defervescence (fever resolution) during the treatment period.
Click on the lead sponsor to view all of their trials.
Sizhou Feng
Lead sponsor
Institute of Hematology & Blood Diseases Hospital, China
Sponsor institution
This trial is not recruiting at the moment. You can still explore other options:
