Bacterial Infections
Conditions
Brief summary
Ceftazidime-avibactam is used for treatment of invasive Gram-negative bacterial infections among critically ill patients, including those on continuous venovenous hemodiafiltration . However, dosing of ceftazidime-avibactam for these patients remains undefined. The purpose of this study was to evaluate the pharmacokinetics of ceftazidime and avibactam among critically-ill patients, including those receiving CVVHD. This is a registration of Dr. Shields' exempt project under IRB approved research study STUDY19040363
Detailed description
Patients who received ceftazidime-avibactam as part of their clinical care were consented. EMR data was collected as well as PK sampling around their dosing to include the following samples immediately pre-dose, then at the following times thereafter: 1, 2, 4, 6, and 8 hours. Blood samples were collected in lithium-heparin tubes from a central venous catheter that is not being used for the continuous venovenous hemodiafiltration. The tubes were centrifuged at 2500 rpm for 10 minutes within 1 hour from collection and the samples will be frozen at 80°C. The total concentrations of ceftazidime and avibactam were determined simultaneously from plasma by using a validated HPLC-tandem MS assay. Noncompartmental pharmacokinetics were calculated using the linear-up and logarithmic-down trapezoidal method, based on the assumption of first-order elimination.
Interventions
collection of blood samples around clinical dosing immediately pre-dose, then at the following times thereafter: 1, 2, 4, 6, 8, and 12 hours and EMR review.
Sponsors
Allergan
University of Pittsburgh
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients receiving ceftazidime-avibactam as standard care
Exclusion criteria
* Less than 18 years-old
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Levels of Ceftazidime and Avibactam Among Critically-ill Patients | 8 hours | PK samples obtained around standard of care dosing regimens immediately before and at 1, 2, 4, 6, and 8 hours after administration |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Subjects Included 20 patients meeting inclusion criteria were enrolled into the trial | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Subjects Included |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 20 |
| other Total, other adverse events | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
Serum Levels of Ceftazidime and Avibactam Among Critically-ill Patients
PK samples obtained around standard of care dosing regimens immediately before and at 1, 2, 4, 6, and 8 hours after administration
Time frame: 8 hours
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Subjects Included | Serum Levels of Ceftazidime and Avibactam Among Critically-ill Patients | Ceftazidime Cmax | 80.6 mcg/mL |
| Subjects Included | Serum Levels of Ceftazidime and Avibactam Among Critically-ill Patients | Avibactam Cmax | 15.9 mcg/mL |