Pneumonia, Bacterial, Community-acquired
Conditions
Keywords
pneumonia, ceftaroline, community-aquired
Brief summary
This study will further analyze the use of ceftaroline for CABP and compare its potential to eradicate bacterial pathogens to standard fluoroquinolone therapy. The enhanced spectrum of ceftaroline compared to levofloxacin may be further highlighted from this investigation.
Interventions
DRUGCeftaroline
600 mg Q12h
DRUGLevofloxacin
750 mg QD
Sponsors
Forest Laboratories
Gary E. Stein, Pharm.D.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* non-pregnant adults (≥ 18 years old) with suspected CABP admitted to the hospital for parenteral antibiotic therapy. * All patients will have a creatinine clearance (CrCl) \>50 ml/min.
Exclusion criteria
* pregnant or nursing patients, * allergy to penicillin/cephalosporin antibiotics, * allergy to fluoroquinolones, * renal or hepatic failure, or have received an antimicrobial in past 96h. * Patients who require antibiotics other than the study drugs will also be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Cidal Activity as Tested Against Staphylococcus Aureus Isolates and Reported as Ex-vivo Effect (Log Inhibition of Growth) | 2 hour (levofloxacin) and 12 hour (ceftaroline) after receiving the drug | Serum cidal activity of serum collected at 2 hour (levofloxacin) and 12 hour (ceftaroline) time points from the patients was tested against methyicillin-sensitive staphylococcus aureus isolates and the ex-vivo effect reported as log inhibition (logrithmic measurement of the decrease in microbiological growth). These staphylococcus aureus isolates had a range of minimum inhibitory concentrations (MIC) to Levofloxacin, 0.5, 1.0, 2.0, and 4.0 and the MIC's to Ceftaroline were 0.125, 0.19, 0.094, 0.094, respectively. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean (SD) Ceftaroline and Levofloxacin Pharmacokinetic Volume of Distribution Parameter in Community-Acquired Bacterial Pneumonia Patients | 2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion | To determine the serum pharmacokinetic volume of distribution of ceftaroline and levofloxacin in community-acquired bacterial pneumonia patients. We obtained blood at 2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion and measured these levels (mg/L)by LC/MS/MS assay. |
| Mean (SD) Doripenem Pharmacokinetic (PK) Clearance of Drug Parameter in Community-Acquired Bacterial Pneumonia Patients | 2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion | To determine the serum pharmacokinetic clearance of drug parameter of ceftaroline and levofloxacin in community-acquired bacterial pneumonia patients. We obtained blood at 2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion and measured these levels (mg/L)by LC/MS/MS assay. |
| Mean (SD) Ceftaroline and Levofloxacin Pharmacokinetic (PK) Half Life Parameter in Community-Acquired Bacterial Pneumonia Patients | 2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion | To determine the serum pharmacokinetic half life parameter of ceftaroline and levofloxacin in community-acquired bacterial pneumonia patients. We obtained blood at 2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion and measured these levels (mg/L)by LC/MS/MS assay. |
| Mean (SD) Doripenem Pharmacokinetic (PK) Area Under Serum Curve (mg*h/L) Parameter in Community-Acquired Bacterial Pneumonia Patients. | 2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion | To determine the serum pharmacokinetic Area Under Serum Curve parameter of ceftaroline and levofloxacin in community-acquired bacterial pneumonia patients. We obtained blood at 2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion and measured these levels (mg/L)by LC/MS/MS assay. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Levofloxacin Pharmacodynamics
Levofloxacin: 750 mg QD | 6 |
| Ceftaroline Pharmacodynamics
Ceftaroline: 600 mg Q12h | 6 |
| Total | 12 |
Baseline characteristics
| Characteristic | Ceftaroline | Levofloxacin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 3 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 3 Participants | 9 Participants |
| Age, Continuous | 52 years | 56 years | 54 years |
| Region of Enrollment United States | 6 participants | 6 participants | 12 participants |
| Sex: Female, Male Female | 5 Participants | 4 Participants | 9 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 6 | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 |
Outcome results
Primary
Serum Cidal Activity as Tested Against Staphylococcus Aureus Isolates and Reported as Ex-vivo Effect (Log Inhibition of Growth)
Serum cidal activity of serum collected at 2 hour (levofloxacin) and 12 hour (ceftaroline) time points from the patients was tested against methyicillin-sensitive staphylococcus aureus isolates and the ex-vivo effect reported as log inhibition (logrithmic measurement of the decrease in microbiological growth). These staphylococcus aureus isolates had a range of minimum inhibitory concentrations (MIC) to Levofloxacin, 0.5, 1.0, 2.0, and 4.0 and the MIC's to Ceftaroline were 0.125, 0.19, 0.094, 0.094, respectively.
Time frame: 2 hour (levofloxacin) and 12 hour (ceftaroline) after receiving the drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Levofloxacin | Serum Cidal Activity as Tested Against Staphylococcus Aureus Isolates and Reported as Ex-vivo Effect (Log Inhibition of Growth) | Levofloxacin | 2 Log inhibition |
| Levofloxacin | Serum Cidal Activity as Tested Against Staphylococcus Aureus Isolates and Reported as Ex-vivo Effect (Log Inhibition of Growth) | Ceftaroline | 3 Log inhibition |
| Ceftaroline | Serum Cidal Activity as Tested Against Staphylococcus Aureus Isolates and Reported as Ex-vivo Effect (Log Inhibition of Growth) | Ceftaroline | 5 Log inhibition |
| Ceftaroline | Serum Cidal Activity as Tested Against Staphylococcus Aureus Isolates and Reported as Ex-vivo Effect (Log Inhibition of Growth) | Levofloxacin | 4 Log inhibition |
| Log Inhibition of 2.0mg/L MIC Levofloxacin | Serum Cidal Activity as Tested Against Staphylococcus Aureus Isolates and Reported as Ex-vivo Effect (Log Inhibition of Growth) | Levofloxacin | 1 Log inhibition |
| Log Inhibition of 2.0mg/L MIC Levofloxacin | Serum Cidal Activity as Tested Against Staphylococcus Aureus Isolates and Reported as Ex-vivo Effect (Log Inhibition of Growth) | Ceftaroline | 3 Log inhibition |
| Log Inhibition of 4.0mg/L MIC Levofloxacin | Serum Cidal Activity as Tested Against Staphylococcus Aureus Isolates and Reported as Ex-vivo Effect (Log Inhibition of Growth) | Levofloxacin | 1 Log inhibition |
| Log Inhibition of 4.0mg/L MIC Levofloxacin | Serum Cidal Activity as Tested Against Staphylococcus Aureus Isolates and Reported as Ex-vivo Effect (Log Inhibition of Growth) | Ceftaroline | 3 Log inhibition |
Secondary
Mean (SD) Ceftaroline and Levofloxacin Pharmacokinetic (PK) Half Life Parameter in Community-Acquired Bacterial Pneumonia Patients
To determine the serum pharmacokinetic half life parameter of ceftaroline and levofloxacin in community-acquired bacterial pneumonia patients. We obtained blood at 2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion and measured these levels (mg/L)by LC/MS/MS assay.
Time frame: 2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Levofloxacin | Mean (SD) Ceftaroline and Levofloxacin Pharmacokinetic (PK) Half Life Parameter in Community-Acquired Bacterial Pneumonia Patients | 7.2 hours | Standard Deviation 1.4 |
| Ceftaroline | Mean (SD) Ceftaroline and Levofloxacin Pharmacokinetic (PK) Half Life Parameter in Community-Acquired Bacterial Pneumonia Patients | 1.9 hours | Standard Deviation 0.2 |
Secondary
Mean (SD) Ceftaroline and Levofloxacin Pharmacokinetic Volume of Distribution Parameter in Community-Acquired Bacterial Pneumonia Patients
To determine the serum pharmacokinetic volume of distribution of ceftaroline and levofloxacin in community-acquired bacterial pneumonia patients. We obtained blood at 2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion and measured these levels (mg/L)by LC/MS/MS assay.
Time frame: 2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Levofloxacin | Mean (SD) Ceftaroline and Levofloxacin Pharmacokinetic Volume of Distribution Parameter in Community-Acquired Bacterial Pneumonia Patients | 92 Liters | Standard Deviation 15 |
| Ceftaroline | Mean (SD) Ceftaroline and Levofloxacin Pharmacokinetic Volume of Distribution Parameter in Community-Acquired Bacterial Pneumonia Patients | 20.6 Liters | Standard Deviation 5.2 |
Secondary
Mean (SD) Doripenem Pharmacokinetic (PK) Area Under Serum Curve (mg*h/L) Parameter in Community-Acquired Bacterial Pneumonia Patients.
To determine the serum pharmacokinetic Area Under Serum Curve parameter of ceftaroline and levofloxacin in community-acquired bacterial pneumonia patients. We obtained blood at 2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion and measured these levels (mg/L)by LC/MS/MS assay.
Time frame: 2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Levofloxacin | Mean (SD) Doripenem Pharmacokinetic (PK) Area Under Serum Curve (mg*h/L) Parameter in Community-Acquired Bacterial Pneumonia Patients. | 87 mg*hr/L | Standard Deviation 23 |
| Ceftaroline | Mean (SD) Doripenem Pharmacokinetic (PK) Area Under Serum Curve (mg*h/L) Parameter in Community-Acquired Bacterial Pneumonia Patients. | 90 mg*hr/L | Standard Deviation 15 |
Secondary
Mean (SD) Doripenem Pharmacokinetic (PK) Clearance of Drug Parameter in Community-Acquired Bacterial Pneumonia Patients
To determine the serum pharmacokinetic clearance of drug parameter of ceftaroline and levofloxacin in community-acquired bacterial pneumonia patients. We obtained blood at 2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion and measured these levels (mg/L)by LC/MS/MS assay.
Time frame: 2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Levofloxacin | Mean (SD) Doripenem Pharmacokinetic (PK) Clearance of Drug Parameter in Community-Acquired Bacterial Pneumonia Patients | 9.4 liters per hour | Standard Deviation 3.1 |
| Ceftaroline | Mean (SD) Doripenem Pharmacokinetic (PK) Clearance of Drug Parameter in Community-Acquired Bacterial Pneumonia Patients | 7.3 liters per hour | Standard Deviation 1.5 |