Dataset Information

Pharmacokinetic-pharmacodynamic analyses for efficacy of ceftaroline fosamil in patients with community-acquired bacterial pneumonia.

ABSTRACT: Pharmacokinetic-pharmacodynamic (PK-PD) analyses for efficacy using phase III trial data from patients treated with a ceftaroline fosamil dosing regimen of 600 mg intravenously (i.v.) every 12 h (q12h) for 5 to 7 days for community-acquired bacterial pneumonia (CABP) were conducted. High clinical and microbiological success rates (84.7 and 86.3%, respectively) and percentages of time during the dosing interval that free-drug steady-state concentrations remained above the MIC (f%T>MIC) (98.4% had f%T>MIC values of ?63.3) were observed among 124 microbiologically evaluable patients. As a result, significant PK-PD relationships could not be identified. These data provide support for the use of a ceftaroline fosamil dosing regimen of 600 mg i.v. q12h to treat patients with CABP.

SUBMITTER: Bhavnani SM

PROVIDER: S-EPMC3837912 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Pharmacokinetic-pharmacodynamic analyses for efficacy of ceftaroline fosamil in patients with community-acquired bacterial pneumonia.

Bhavnani Sujata M SM Hammel Jeffrey P JP Van Wart Scott A SA Rubino Christopher M CM Reynolds Daniel K DK Forrest Alan A Khariton Tatiana T Friedland H David HD Riccobene Todd A TA Ambrose Paul G PG

Antimicrobial agents and chemotherapy 20130916 12

Pharmacokinetic-pharmacodynamic (PK-PD) analyses for efficacy using phase III trial data from patients treated with a ceftaroline fosamil dosing regimen of 600 mg intravenously (i.v.) every 12 h (q12h) for 5 to 7 days for community-acquired bacterial pneumonia (CABP) were conducted. High clinical and microbiological success rates (84.7 and 86.3%, respectively) and percentages of time during the dosing interval that free-drug steady-state concentrations remained above the MIC (f%T>MIC) (98.4% had ...[more]

PMID: 24041902

Similar Datasets

Project description:Ceftaroline fosamil (ceftaroline hereafter) is the latest addition to the armamentarium for the treatment of patients with community-acquired pneumonia (CAP). It is currently approved by the Food and Drug Administration (FDA) for community-acquired bacterial pneumonia (CABP), which is a recent FDA indication that centers on individuals with documented bacterial pneumonias that arise in the community setting. The purpose of this review is to summarize and discuss the major findings from the Phase III CAP clinical trials as well as the clinical experience with ceftaroline among patients with CAP in the "Ceftaroline Assessment Program and Teflaro(®) Utilization Registry" (CAPTURE). In its two Phase III CAP trials, ceftaroline was compared to ceftriaxone among adults with radiographically confirmed CAP requiring hospitalization who were classified as Pneumonia Outcomes Research Team (PORT) risk class III or IV. Among patients with CAP, clinical success at test of cure was 84.3% vs 77.7% (difference 6.6%, 95% confidence interval [CI]: 1.6-11.8%) in those treated with ceftaroline and ceftriaxone, respectively, across the two Phase III clinical trials. Among patients with a culture-confirmed CABP, day 4 response rates were numerically higher, albeit non-significant, among patients that received ceftaroline vs. ceftriaxone (69.5% for ceftaroline vs. 59.4% for ceftriaxone, difference 10.1%, 95% CI, -0.6% to 20.6%). The efficacy of ceftaroline is supported by real-world observational data from CAPTURE for patients with both CAP and CABP. In addition, the CAPTURE program afforded an opportunity to assess the outcomes of patients who were excluded or limited in the original Phase III trials in a non-comparative fashion. These underrepresented patient populations with CAP included: patients that received prior antibiotics, patients in the ICU, patients with severe renal dysfunction, and those with methicillin-resistant Staphylococcus aureus (MRSA) isolated from respiratory or blood culture. As CAPTURE is a retrospective, non-comparator convenience sample registry, all the findings need to be interpreted with caution.

Project description:IntroductionThis retrospective analysis compares the probability of target attainment (PTA) for ceftriaxone, levofloxacin and ceftaroline fosamil against Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae in a representative patient population with moderate-to-severe community-acquired pneumonia (CAP).MethodsPublished pharmacokinetic (PK) models for levofloxacin and ceftriaxone, and an existing model for ceftaroline, were used with standard dosage regimens for simulating individual PK data with covariates representative of patients with CAP (5000 patients/drug regimen). PTA for clinically relevant pharmacokinetic/pharmacodynamic (PK/PD) targets was calculated from steady state PK profiles for a range of minimum inhibitory concentrations (MICs). Cumulative fractions of response (CFRs) were also calculated using MIC distributions from 2012 to 2017 global surveillance data.ResultsCeftaroline fosamil (600 mg q12 h) achieved > 90% PTA at all exposure targets for each pathogen at European Committee on Antimicrobial Susceptibility Testing (EUCAST)/Clinical and Laboratory Standards Institute (CLSI) susceptibility breakpoints, and CFRs were > 99%. Ceftriaxone, but not levofloxacin, achieved 100% PTA and > 90% CFR against S. pneumoniae. Both levofloxacin and ceftriaxone achieved high PTA and CFR against H. influenzae. Levofloxacin achieved PTAs < 90% at EUCAST/CLSI breakpoints and ceftriaxone achieved PTAs < 90% at MICs up to 2 mg/L against S. aureus; both agents produced generally low CFRs against S. aureus (except levofloxacin against methicillin-sensitive S. aureus), reflecting the lack of activity of these agents against methicillin-resistant S. aureus.ConclusionCeftaroline fosamil demonstrated higher overall PTA rates than levofloxacin and ceftriaxone, in particular against S. aureus. These results provide insight regarding the potential comparative efficacy of the described antibiotics for moderate-to-severe CAP.FundingPfizer.

Project description:Ertapenem provides activity against many pathogens commonly associated with hospital-acquired and ventilator-associated bacterial pneumoniae (HABP and VABP, respectively), including methicillin-susceptible Staphylococcus aureus and numerous Gram-negative pathogens with one major gap in coverage, Pseudomonas aeruginosa Pharmacokinetic-pharmacodynamic (PK-PD) target attainment analyses were conducted to evaluate ertapenem against the most prevalent Enterobacteriaceae causing HABP/VABP. The objective of these analyses was to provide dose selection support for and demonstrate the appropriateness of ertapenem to empirically treat patients with HABP/VABP when administered with murepavadin, a novel targeted antimicrobial exhibiting a highly specific spectrum of activity against P. aeruginosa A previously developed population pharmacokinetic model, a total-drug epithelial lining fluid (ELF) to free-drug serum penetration ratio, contemporary in vitro surveillance data for ertapenem against Enterobacteriaceae, and percentage of the dosing interval for which drug concentrations exceed the MIC value (%T>MIC) targets associated with efficacy were used to conduct Monte Carlo simulations for five ertapenem regimens administered over short or prolonged durations of infusion. Overall total-drug ELF percent probabilities of PK-PD target attainment based on a %T>MIC target of 35% among simulated patients with HABP/VABP arising from Enterobacteriaceae based on pathogen prevalence data for nosocomial pneumonia ranged from 89.1 to 92.7% for all five ertapenem regimens evaluated. Total-drug ELF percent probabilities of PK-PD target attainment ranged from 99.8 to 100%, 97.9 to 100%, 10.6 to 74.1%, and 0 to 1.50% at MIC values of 0.06, 0.12, 1, and 4 μg/ml, respectively (MIC90 values for Escherichia coli, Serratia marcescens, Enterobacter species, and Klebsiella pneumoniae, respectively). Results of these analyses provide support for the evaluation of ertapenem in combination with murepavadin for the treatment of patients with HABP/VABP.

Dataset Information

Pharmacokinetic-pharmacodynamic analyses for efficacy of ceftaroline fosamil in patients with community-acquired bacterial pneumonia.

Publications

Pharmacokinetic-pharmacodynamic analyses for efficacy of ceftaroline fosamil in patients with community-acquired bacterial pneumonia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets