Ceftazidime-Avibactam PK/PD and Resistance in Hematology Patients

NCT07703644 | Not Yet Recruiting

• 2 other identifiers: CZA-TDM-012025-I2M-XHCL-061
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hematologic Neoplasms; Gram-Negative Bacterial Infections; Pseudomonas Aeruginosa Infection; Klebsiella Pneumoniae Infections; Drug Resistance, Bacterial

Keywords

Ceftazidime-avibactam; CAZ-AVI; Therapeutic Drug Monitoring; TDM; PK/PD Target Attainment; Hematopoietic Stem Cell Transplantation; Induced Resistance

Outcome Measures

Primary Outcomes (1)

• 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.

  48 to 72 hours after starting ceftazidime-avibactam therapy (assessed over a single dosing interval at steady state, typically after the 4th or 5th dose).

Secondary Outcomes (5)

• Incidence of Induced Resistance to Ceftazidime-Avibactam During Therapy

  From baseline up to 7 days after completion of ceftazidime-avibactam therapy.

• 7-Day Clinical Response Rate

  7 days after starting ceftazidime-avibactam therapy.

• Microbiological Clearance Rate

  Up to 7 days after completion of ceftazidime-avibactam therapy.

• 7-Day Re-fever Rate

  Up to 7 days after initial defervescence during the therapy period.

• 30-Day All-Cause Mortality Rate

  30 days after the initiation of ceftazidime-avibactam therapy.

Study Arms (1)

CAZ-AVI Single-Arm Observation Group

Patients with hematological malignancies or those undergoing hematopoietic stem cell transplantation (HSCT) who are prescribed standard-dose ceftazidime-avibactam (CAZ-AVI) for suspected or confirmed Gram-negative bacterial infections based solely on routine clinical decisions \[4, 6.1, 17\]. This group will undergo standard-of-care antibiotic therapy combined with protocol-specified therapeutic drug monitoring (TDM) and microbiological surveillance.

Drug: Ceftazidime-avibactam; Procedure: Therapeutic Drug Monitoring (TDM) and Microbiological Surveillance

Interventions

Ceftazidime-avibactam DRUG

Patients 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.

Also known as: CAZ-AVI, Zavicefta, 思福妥

CAZ-AVI Single-Arm Observation Group

Therapeutic Drug Monitoring (TDM) and Microbiological Surveillance PROCEDURE

Auxiliary 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.

CAZ-AVI Single-Arm Observation Group

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• 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.
• Willing and able to comply with the study-specified therapeutic drug monitoring (TDM) and microbiological surveillance.

You may not qualify if:

• 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.
• Pregnancy or lactation.

Sponsors & Collaborators

• Sizhou Feng: lead

Study Sites (1)

Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, 300020, China

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Two types of biospecimens will be retained in this study: 1. Plasma Samples: K2-EDTA anticoagulated plasma samples (approx. 2-3 mL per sample, 5 samples per participant, total \~15 mL) collected within a single dosing interval at steady state (48-72 hours after starting therapy). Samples are stored at -80°C for therapeutic drug monitoring (TDM) to quantify ceftazidime and avibactam concentrations. No host human genomic DNA or RNA will be extracted from these samples. 2. Bacterial Isolates: Key Gram-negative pathogen strains (specifically focusing on Pseudomonas aeruginosa and Klebsiella pneumoniae complex) isolated from microbiological specimens (blood, infection sites, or oropharyngeal/perianal swabs) collected at specified time points (baseline, Days 3, 7, end of therapy, and 7 days post-therapy). These bacterial isolates are preserved and stored at -80°C for research-use BMD susceptibility testing, resistance mechanism screening, and whole-genome sequencing (WGS).

MeSH Terms

Conditions

Hematologic Neoplasms; Gram-Negative Bacterial Infections; Pseudomonas Infections

Interventions

avibactam, ceftazidime drug combination

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Sizhou Feng, MD

  Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiaomeng Feng, MD, PhD

CONTACT

+86-22-23608592; fengxiaomeng@ihcams.ac.cn

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Chief Physician, Professor

Study Record Dates

• First Submitted: July 8, 2026
• First Posted: July 14, 2026
• Study Start: July 9, 2026
• Primary Completion (Estimated): July 9, 2027
• Study Completion (Estimated): July 9, 2027
• Last Updated: July 14, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)