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

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

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.

Study Overview

• Status: Completed
• Conditions: Pneumonia, Bacterial; Community-acquired
• Intervention / Treatment: Drug: Levofloxacin; Drug: Ceftaroline

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Lansing, Michigan, United States
      • Sparrow Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Levofloxacin; Pharmacodynamics	Drug: Levofloxacin; 750 mg QD; Other Names: Levaquin
Active Comparator: Ceftaroline; Pharmacodynamics	Drug: Ceftaroline; 600 mg Q12h; Other Names: Teflaro

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Gary E. Stein, Pharm.D.
• Collaborators: Forest Laboratories

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: January 30, 2012
• First Submitted That Met QC Criteria: January 31, 2012
• First Posted (Estimate): February 1, 2012

Study Record Updates

• Last Update Posted (Estimate): April 12, 2016
• Last Update Submitted That Met QC Criteria: March 14, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: pneumonia; ceftaroline; community-aquired
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Pneumonia; Pneumonia, Bacterial; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Anti-Infective Agents, Urinary; Renal Agents; Levofloxacin; Ofloxacin; Ceftaroline fosamil
• Other Study ID Numbers: TEF-MD-02