Table 2.
Summary of Animal Studies Evaluating the Efficacy of Ceftaroline
| Study Reference | Study Type/Methods | Infection | Sample Size | Antibiotics | Results |
|---|---|---|---|---|---|
| Iizawa 2004 [60] | Murine Antibiotic administered at 2, 20, and 26 hours after infection Thigh muscle infected removed day 7 and homogenized in trypticase soy broth and bacterial counts estimated |
Pyomyositis | 10 mice per group | Ceftaroline Linezolid Vancomycin *All dosed at 20mg/kg |
All three drugs reduced bacterial counts compared to placebo Ceftaroline and linezolid reduced counts to ≤0.1% and were superior to vancomycin |
| Jacqueline 2010 [61] | Rabbit Knee injected with bacteria (MRSA) Antibiotic administered 3-days later following I&D for duration 4 days Comparison of bacterial load prior to antibiotics and at day 7 in the synovial fluid |
Septic Arthritis | Controls (8), ceftaroline (10), linezolid (8), and vancomycin (10) | Ceftaroline *dosed to mimic 10 mg/kg or 600 mg bid Vancomycin continuous infusion to achieve 20x the MIC Linezolid *mimic 10mg/kg or 600 mg bid |
Bacterial load in joint fluid: Mean +/− SD log10 CFU/g (D7–D3) Ceftaroline*: −1.98 +/− 1.00 Vancomcyin −0.19+/− 1.19 Linezolid −0.77 +/−1.39 Control 0.09+/−0.59 *P<0.05 vs. all comparisons |
| Izawa 2004 [60] | Murine Antibiotic administered one day after neutropenic pneumonia Bacterial counts detection at day 3 |
Pneumonia | 10 mice per group | Ceftaroline Vancomycin Linezolid *All dosed at 20mg/kg tid subcutaneously |
Ceftaroline decreased counts 99.9% from control (p<0.01) and was superior to both comparators (p<0.01) |
| Jacqueline 2007 [52] | Rabbit Antibiotic administered 24 hours after infection of aortic valve with MRSA and continued 4 days Valves then excised and homogenized for culture |
Endocarditis | Control (6), ceftaroline (10), linezolid (7), and vancomycin (6) | Ceftaroline 58 mg/kg over 12 hours to mimic human dose of 600 mg bid Vancomycin continuous infusion to achieve 20x the MIC Linezolid 10mg/kg to mimic human dose of 600 mg bid |
Bacterial CFU/g Mean log10 +/− SD (number with sterile vegetation) a,bCeftaroline: 2.5 +/− 0.3 (9/10) a,bVancomycin 2.7+/− 0.8 (4/6) aLinezolid 7.1 +/− 0.6 (0/7) Control 8.9+/−0.5 (0/6) aP<0.001 vs. controls bP<0.001 vs. linezolid |
| Jacqueline 2007 [52] | Rabbit Antibiotic administered 24 hours after infection of aortic valve with VISA and continued 4 days Valves then excised and homogenized for culture |
Endocarditis | Control (6), ceftaroline (10), linezolid (8), and vancomycin (5) | Ceftaroline 58 mg/kg over 12 hours to mimic human dose of 600 mg bid Vancomycin continuous infusion to achieve 20x the MIC Linezolid at 10 mg/kg to mimic human dose of 600 mg bid |
a,bCeftaroline: 3.0 +/− 0.9 (6/10) bVancomycin 6.7+/− 0.4 (0/5) bLinezolid 6.9 +/− 0.4 (0/8) Control 9.4+/−0.3 (0/6) aP<0.001 vs. control bP<0.001 vs. linezolid and vancomycin |
| Jacqueline 2009 [48] | Rabbit Vancomycin-sensitive E. faecalis Antibiotic administered 24 hours after infection of aortic valve and continued 4 days Valves then excised and homogenized for culture |
Endocarditis | Control (8), ceftaroline (7), linezolid (7), and vancomycin (8) | Ceftaroline to mimic human dose of 10 mg/kg/12 hr Vancomycin continuous infusion to achieve 20x the MIC Linezolid to mimic dose of 10 mg/kg/12hr |
Bacterial CFU/g Mean log10 +/− SD a,bCeftaroline: 5.68 +/− 0.49 Vancomcyin 6.70 +/− 0.25 Linezolid 6.88 +/− 0.7 Control 8.56+/−0.74 aP<0.001 vs. control bP<0.05 vs. linezolid and vancomycin |
| Jacqueline 2009 [48] | Rabbit Vancomycin-resistant E. faecalis Antibiotic administered 24 hours after infection of aortic valve and continued 4 days Valves then excised and homogenized for culture |
Endocarditis | Control (9), ceftaroline (9), linezolid (9), and Vancomycin (8) | Ceftaroline to mimic human dose of 10 mg/kg/12 hour Vancomycin continuous infusion to achieve 20x the MIC Linezolid to mimic dose of 10 mg/kg/12hour |
a,Ceftaroline: 3.98 +/− 0.85 Vancomycin 8.01 +/− 0.76 Linezolid 6.88 +/− 0.77 Control 8.60 +/− 0.54 aP<0.001 vs. all comparators |