Pharmacokinetic and pharmacodynamic evaluation of ceftaroline fosamil

Abstract

Ceftaroline provides in vitro bactericidal activity against methicillin-, vancomycin-, daptomycin-, and linezolid-resistant Gram-positive organisms and select Gram-negative pathogens. The pharmacodynamics of ceftaroline is similar to other β-lactam agents. Ceftaroline exhibits a favorable adverse effect profile and is generally well tolerated. There is little data on clinical success of ceftaroline in patients with bacteremia or endocarditis other than what has been published in a small series of case reports. Randomized-control studies are needed to establish clinical outcomes and safety in these patient populations.

Pharmacokinetics of Ceftaroline in Normal Body Weight and Obese (Classes I, II, and III) Healthy Adult Subjects

“…eftaroline fosamil is a novel intravenously administered antimicrobial agent approved for use in the United States as a treatment of acute bacterial skin and skin structure infections (ABSSSIs) and community-acquired bacterial pneumonia (1,2). Unlike other regulatory approved cephalosporins, ceftaroline is uniquely active in vitro against methicillin-resistant Staphylococcus aureus (MRSA) (1)(2)(3).…”

“…Unlike other regulatory approved cephalosporins, ceftaroline is uniquely active in vitro against methicillin-resistant Staphylococcus aureus (MRSA) (1)(2)(3). The current dosage regimen of ceftaroline fosamil is a fixed-dose of 600 mg every 12 h irrespective of body size in adult patients.…”

“…Some evidence suggests obese patients may be at risk of worse clinical outcomes attributed in part to inadequate antimicrobial exposure with standard dosage regimens (7,8). A dedicated pharmacokinetic study comparing the concentration-time profile of ceftaroline with a standard dosage regimen across the spectrum of adult body size has not been previously investigated (2). Pharmacokinetic studies of antimicrobials in obese subjects have often compared drug disposition between two groups of subjects: normal weight and obese class III (BMI Ն 40 kg/m 2 ) (9)(10)(11).…”

The use of extrapolation based on modeling and simulation to support high‐dose regimens of ceftaroline fosamil in pediatric patients with complicated skin and soft‐tissue infections

“…3 Ceftaroline fosamil is rapidly converted to active ceftaroline by plasma phosphatases, with concentrations of the prodrug generally not measureable beyond the completion of an intravenous (IV) infusion; ceftaroline has linear pharmacokinetics (PK) with plasma clearance in healthy subjects of 10 L/h, renal clearance of 4-7 L/h, volume of distribution of 30-40 L, and half-life of approximately 2.6 hours. [4][5][6] Elimination is predominantly renal, necessitating dose adjustments for patients with moderate or severe renal impairment. [7][8][9] Renal function, age and presence of acute infection (cSSTI or community-acquired pneumonia [CAP]) have been shown to affect clearance, and presence of infection also affects distribution.…”

Pharmacokinetic and Pharmacodynamic Target Attainment in Adult and Pediatric Patients Following Administration of Ceftaroline Fosamil as a 5‐Minute Infusion

“…Ceftaroline, the active metabolite of the prodrug ceftaroline fosamil, is a β‐lactam antibiotic with in vitro activity against Gram‐positive bacteria, including Staphylococcus aureus (methicillin‐susceptible and ‐resistant strains) and Streptococcus pneumoniae , and common Gram‐negative pathogens that do not express extended‐spectrum β‐lactamase enzymes 1–3 . Ceftaroline fosamil is rapidly converted to active ceftaroline by plasma phosphatases upon intravenous (IV) administration.…”