Abstract
This study was conducted to develop a rapid, simple and reproducible method for the quantification of ceftaroline in plasma samples by high-performance liquid chromatography with ultraviolet detection (HPLC-UV). Sample processing consisted of methanol precipitation and then, after centrifugation, the supernatant was injected into the HPLC system, working in isocratic mode. Ceftaroline was detected at 238 nm at a short acquisition time (less than 5 min). The calibration curve was linear over the concentration range from 0.25 to 40 µg/mL, and the method appeared to be selective, precise and accurate. Ceftaroline in plasma samples was stable at −80 °C for at least 3 months. The method was successfully applied to characterize the pharmacokinetic profile of ceftaroline in two critically ill patients and to evaluate whether the pharmacokinetic/pharmacodynamic (PK/PD) target was reached or not with the dose regimen administered.
Highlights
Ceftaroline is a broad-spectrum fifth generation cephalosporin with bactericidal activity against Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and drug-resistant Streptococcus pneumoniae, as well as non-beta-lactamaseproducing Gram-negative organisms [1,2,3]
We evaluated the applicability of the method for PK studies by analyzing plasma samples collected from two critically ill patients diagnosed with pneumonia and treated with ceftaroline fosamil (600 mg every 8 h) after positive cultures of methicillin-resistant
No interfering peaks were observed either in the samples obtained from healthy subjects or in the samples from critically ill patients not treated with ceftaroline
Summary
Ceftaroline is a broad-spectrum fifth generation cephalosporin with bactericidal activity against Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and drug-resistant Streptococcus pneumoniae, as well as non-beta-lactamaseproducing Gram-negative organisms [1,2,3]. Ceftaroline acts to inhibit the growth of bacterial cells by interfering in the synthesis of the cell wall. It has a high affinity for modified penicillin-binding proteins (PBPs), such as PBP2a in S. aureus and PBP2x in S. pneumoniae, leading to high activity against resistant Gram-positive cocci [4,5,6]. This new antibiotic was approved in 2010 by the Food and Drug Administration (FDA). Ceftaroline fosamil was approved for pediatric populations (≥2 months to
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