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

2021 ◽  
Author(s):  
Todd A. Riccobene ◽  
Timothy J. Carrothers ◽  
William Knebel ◽  
Susan Raber ◽  
Phylinda L.S. Chan
Keyword(s):  
Pediatric Patients ◽  
Target Attainment ◽  
Ceftaroline Fosamil

scholarly journals 1567. Pharmacokinetic/Pharmacodynamic Target Attainment in Adult and Pediatric Patients following Administration of Ceftaroline Fosamil as a 5-Minute Infusion

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S572-S573
Author(s):  
Todd Riccobene ◽  
T J Carrothers, ScD ◽  
William Knebel ◽  
Susan Raber ◽  
Phylinda L S Chan
Keyword(s):  
Renal Function ◽  
Normal Renal Function ◽  
Dose Regimen ◽  
Pediatric Patients ◽  
Systemic Exposure ◽  
The United States ◽  
Simulated Patients ◽  
Population Pharmacokinetic ◽  
Target Attainment ◽  
Ceftaroline Fosamil

Abstract Background Ceftaroline fosamil is approved in the United States for treating patients ≥2 months old with acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia, and for similar indications in Europe. The active metabolite, ceftaroline, has in vitro activity against common Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus and Streptococcus pneumoniae. Population pharmacokinetic (popPK) modeling and simulation were used to assess systemic exposure and PK/pharmacodynamic (PK/PD) target attainment for S. aureus and S pneumoniae for 5- and 60-minute infusions. Methods A simultaneous popPK model, including 2 compartments each, for ceftaroline fosamil and ceftaroline was previously developed using an extensive database of adult and pediatric data. An effect of renal function maturation as a function of postmenstrual age was included on ceftaroline clearance for children <2 years. This model was used to conduct simulations for-approved ceftaroline doses administered as 5- and 60-min infusions to adult and pediatric patients with normal renal function and mild renal impairment. For adults, 100 simulations of 300 patients each were performed for each dose regimen, and covariates were generated from a multivariate normal distribution using covariate correlations from observed data. For pediatric patients, 100 simulations were performed for each dose regimen with 600 patients in each 1-month age group. Weights for pediatric age groups were based on CDC growth charts. Results The median proportion of simulated patients with normal renal function achieving %fT>MIC targets of 35% and 44% (associated with 1-log kill of S. aureus and S pneumoniae, respectively), are shown for 5- and 60-min infusions (figure). PK/PD target attainment was similar for both infusion times and was >99% at an MIC of 1 mg/L for S. aureus and an MIC of 0.5 mg/L for S pneumoniae. Ceftaroline AUC was similar for both infusion times, and Cmax was approximately 30%–40% higher for the 5-min infusion. Conclusion Ceftaroline fosamil gave as a 5-min infusion to adult and pediatric patients ≥2 months of age achieved similar PK/PD target attainment as a 60-min infusion for S. aureus and S pneumoniae for MICs up to 1 mg/L and 0.5 mg/L, respectively. Disclosures All authors: No reported disclosures.

scholarly journals A Retrospective Analysis of Probability of Target Attainment in Community-Acquired Pneumonia: Ceftaroline Fosamil Versus Comparators

2019 ◽  
Vol 8 (2) ◽  
pp. 185-198 ◽  
Author(s):  
Andrew Cristinacce ◽  
James G. Wright ◽  
Gregory G. Stone ◽  
Jennifer Hammond ◽  
Lynn McFadyen ◽  
...  
Keyword(s):  
Retrospective Analysis ◽  
Community Acquired Pneumonia ◽  
Target Attainment ◽  
Ceftaroline Fosamil

scholarly journals Ceftaroline Fosamil Use in 2 Pediatric Patients With Invasive Methicillin-Resistant Staphylococcus aureus Infections

2015 ◽  
Vol 20 (6) ◽  
pp. 476-480 ◽  
Author(s):  
Amanda W. Williams ◽  
Patrick M. Newman ◽  
Sara Ocheltree ◽  
Rachel Beaty ◽  
Ali Hassoun
Keyword(s):  
Staphylococcus Aureus ◽  
Septic Shock ◽  
Pediatric Patients ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Pediatric Intensive Care ◽  
Positive Outcome ◽  
Invasive Infection ◽  
Vancomycin Therapy ◽  
Ceftaroline Fosamil ◽  
Methicillin Resistant

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is one of the most common pathogens causing pediatric infections including skin and soft tissue infections, pyogenic arthritis, osteomyelitis, and septic shock. For decades, patients were treated with antibiotics such as vancomycin and clindamycin, but there is an increasing incidence of resistance to these traditional therapies. We describe 2 cases of patients with CA-MRSA invasive infections with bacteremia who experienced vancomycin therapy failure but who were successfully treated with ceftaroline fosamil. Case 1 involves an 8-year-old Hispanic male who was diagnosed with CA-MRSA bacteremia, thigh abscess, and osteomyelitis. The patient was admitted to the pediatric intensive care unit in septic shock. Case 2 involves an 8-year-old Caucasian male who was diagnosed with CA-MRSA sepsis, right arm abscess, and osteomyelitis. We were able to successfully treat both patients with CA-MRSA sepsis and invasive infection—who failed vancomycin therapy—with ceftaroline fosamil with no adverse efiects. Despite the positive outcome in both pediatric patients, clinical trials with ceftaroline fosamil are needed to further support its use in pediatric patients.

scholarly journals 1507. Pharmacodynamic Target Attainment of Daptomycin Against Staphylococcus aureus for Treatment of Pediatric Osteomyelitis

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S548-S549
Author(s):  
Grant Stimes ◽  
Jennifer E Girotto ◽  
Joshua D Courter
Keyword(s):  
Staphylococcus Aureus ◽  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Pediatric Patients ◽  
Age Groups ◽  
Pharmacokinetic Studies ◽  
Pharmacokinetic Models ◽  
Limited Data ◽  
Target Attainment ◽  
Starting Point

Abstract Background Daptomycin (DAP) is lipopeptide that frequently is used to treat infections caused by Staphylococcus aureus in adult patients. There are limited data using daptomycin in pediatric patients for the treatment of osteomyelitis caused by S. aureus. This study’s objective is to describe pharmacodynamic (PD) target attainment of daptomycin in pediatric patients with osteomyelitis. Methods Medline was queried to obtain PD targets, pediatric pharmacokinetic models, and bone penetration information to build a model for DAP. A 10,000 subject Monte Carlo simulation was performed to estimate steady-state concentrations in the bone. Simulations modeled 30-minute infusions with using 12 mg/kg/dose IV q24h for patients less than 7 years and 10 mg/kg/dose IV q24h for patients 7 years and older. Goal PD targets were: AUC24: MIC of 666 μg hours/mL for log1 killing and AUC24: MIC of 1,061 for log2 killing. The CLSI breakpoint of 1 mg/L was used as a starting point and MIC’s were analyzed below that level. Results PD target attainment in percentages is listed for DAP below in Tables 1 and 2 and are separated by age groups of patients. Conclusion The studied DAP doses did not reach any PD target attainment at the CLSI breakpoint of 1 mg/L. Based on these data, DAP should not be empirically used to treat SA osteomyelitis unless the exact MIC is known. Furthermore, modern pediatric pharmacokinetic studies of DAP for pediatric osteomyelitis are warranted. Disclosures All authors: No reported disclosures.

Evaluation of Intravenous Posaconazole Dosing and Pharmacokinetic Target Attainment in Pediatric Patients

2018 ◽  
Vol 8 (4) ◽  
pp. 365-367 ◽  
Author(s):  
Jenna R Nickless ◽  
Kathryn E Bridger ◽  
Surabhi B Vora ◽  
Adam W Brothers
Keyword(s):  
Body Weight ◽  
Pediatric Patients ◽  
Trough Level ◽  
Transaminase Level ◽  
Alanine Transaminase ◽  
Limited Data ◽  
Minimum Effective Dose ◽  
Therapeutic Level ◽  
Target Attainment ◽  
Trough Levels

Abstract Limited data exist on intravenous (IV) posaconazole dosing and the risk for hepatotoxicity it confers to children. In this study, we evaluated dosing and resulting trough levels in 10 pediatric patients on IV posaconazole. A therapeutic level in these patients was achieved 95% of the time. We found a median minimum effective dose of 6.55 mg/kg of body weight. No correlation was found between the duration or posaconazole trough level and an increased alanine transaminase level.

scholarly journals Pharmacokinetic-Pharmacodynamic Target Attainment Analyses To EvaluateIn VitroSusceptibility Test Interpretive Criteria for Ceftaroline against Staphylococcus aureus and Streptococcus pneumoniae

2013 ◽  
Vol 58 (2) ◽  
pp. 885-891 ◽  
Author(s):  
Scott A. Van Wart ◽  
Paul G. Ambrose ◽  
Christopher M. Rubino ◽  
Tatiana Khariton ◽  
Todd A. Riccobene ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Renal Function ◽  
Streptococcus Pneumoniae ◽  
Renal Impairment ◽  
Severe Renal Impairment ◽  
Simulated Patients ◽  
Target Attainment ◽  
Ceftaroline Fosamil ◽  
Content Type

ABSTRACTTo provide support forin vitrosusceptibility test interpretive criteria decisions for ceftaroline againstStaphylococcus aureusandStreptococcus pneumoniae, as well as dose adjustment recommendations for renal impairment, pharmacokinetic-pharmacodynamic (PK-PD) target attainment was evaluated for simulated patients administered intravenous (i.v.) ceftaroline fosamil at 600 mg twice daily (q12h) and simulated patients with renal impairment administered various dosing regimens. Using a previously developed population PK model, Monte Carlo simulation was used to generate ceftaroline plasma concentration profiles for simulated patients with normal renal function or mild, moderate, or severe renal impairment. Using these profiles, the percentage of time during the dosing interval that free-drug concentrations remained above the MIC (f%T>MIC) for ceftaroline at steady state was calculated. Percentages of simulated patients achievingf%T>MIC targets forS. aureusandS. pneumoniaebased on murine infection models were calculated by MIC. At MICs of 2 mg/liter forS. aureusand 1 mg/liter forS. pneumoniae, the percentages of simulated patients with normal renal function and mild renal impairment following administration of ceftaroline fosamil at 600 mg q12h, moderate renal impairment following administration of ceftaroline fosamil at 400 mg q12h, and severe renal impairment following administration of ceftaroline fosamil at 300 mg q12h achievingf%T>MIC targets (≥26 forS. aureusand ≥44 forS. pneumoniae) exceeded 90%. The results of these analyses, which suggested thatin vitrosusceptibility test interpretive criteria defining susceptible could be as high as MICs of ≤2 and ≤1 mg/liter for ceftaroline againstS. aureusandS. pneumoniae, respectively, provide support for current FDA and CLSI criteria, which define susceptible as MICs of 1 and 0.5 mg/liter, respectively. Recommendations for dose adjustments for patients with renal impairment were also supported by the results of these analyses.

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