Pharmacodynamic of Ceftaroline and Levofloxacin Against Pathogens Associated With Community Acquired Bacterial Pneumonia

Study Overview
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Brief Summary
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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.

Official Title
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Pharmacodynamic of Ceftaroline and Levofloxacin Against Pathogens Associated With Community Acquired Bacterial Pneumonia (CABP)

Conditions
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Pneumonia, Bacterial, Community-acquired

Intervention / Treatment
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* Drug: Ceftaroline
* Drug: Levofloxacin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Levofloxacin<br>Pharmacodynamics | Drug: Levofloxacin<br>* 750 mg QD<br>* Other names: Levaquin;|
| Active Comparator: Ceftaroline<br>Pharmacodynamics | Drug: Ceftaroline<br>* 600 mg Q12h<br>* Other names: Teflaro;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 2 hour (levofloxacin) and 12 hour (ceftaroline) after receiving the drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion | 
| 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. | 2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion | 
| 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. | 2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion | 
| 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. | 2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pneumonia, ceftaroline, community-aquired