To provide support for in vitro susceptibility test interpretive criteria decisions for ceftaroline against Staphylococcus aureus and Streptococcus 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 achieving f %T>MIC targets for S. aureus and S. pneumoniae based on murine infection models were calculated by MIC. At MICs of 2 mg/liter for S. aureus and 1 mg/liter for S. 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 achieving f %T>MIC targets (≥26 for S. aureus and ≥44 for S. pneumoniae) exceeded 90%. The results of these analyses, which suggested that in vitro susceptibility test interpretive criteria defining susceptible could be as high as MICs of ≤2 and ≤1 mg/liter for ceftaroline against S. aureus and S. 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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3910868PMC
http://dx.doi.org/10.1128/AAC.01680-13DOI Listing

Publication Analysis

Top Keywords

renal impairment
28
simulated patients
20
ceftaroline fosamil
16
vitro susceptibility
12
susceptibility test
12
test interpretive
12
interpretive criteria
12
impairment administration
12
administration ceftaroline
12
ceftaroline
9

Similar Publications

Introduction: Arteriovenous (AV) fistula creation is the most common surgical procedure for providing vascular access for haemodialysis in patients with chronic kidney disease (CKD). The functioning of fistula dictates the quality of dialysis and the longevity of patients. The most common circumstances that require surgical takedown of AV fistula are thrombosis and rupture.

View Article and Find Full Text PDF

Introduction: Acute kidney injury involves inflammation and intrinsic renal damage, and is a common complication of severe coronavirus disease 2019 (COVID-19). Baseline chronic kidney disease (CKD) confers an increased mortality risk. We determined the renal long-term outcomes of COVID-19 in patients with baseline CKD, and the risk factors prompting renal replacement therapy (RRT) initiation and mortality.

View Article and Find Full Text PDF

Pseudogenization of the Slc23a4 gene is necessary for the survival of Xdh-deficient mice.

Sci Rep

January 2025

Laboratory of Human Physiology and Pathology, Faculty of Pharmaceutical Sciences, Teikyo University, Tokyo, Japan.

In most patients with type 1 xanthinuria caused by mutations in the xanthine dehydrogenase gene (XDH), no clinical complications, except for urinary stones, are observed. In contrast, all Xdh(- / -) mice die due to renal failure before reaching adulthood at 8 weeks of age. Hypoxanthine or xanthine levels become excessive and thus toxic in Xdh(- / -) mice because enhancing the activity of hypoxanthine phosphoribosyl transferase (HPRT), which is an enzyme that uses hypoxanthine as a substrate, slightly increases the life span of these mice.

View Article and Find Full Text PDF

This study is designed to assess the effect of root extract of P. ginseng on kidney tissue injury attributed to cisplatin and its molecular mechanism involved in this process in the AKI rat model. Twenty-four male Wistar rats were randomly allocated into 4 experimental groups including: the control group, the cisplatin group, the extract 100 mg/kg group, and the extract 200 mg/kg group.

View Article and Find Full Text PDF

Association between intraoperative fluid management and postoperative outcomes in living kidney donors: a retrospective cohort study.

Sci Rep

January 2025

Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.

Optimal fluid strategy for laparoscopic donor nephrectomy (LDN) remains unclear. LDN has been a domain for liberal fluid management to ensure graft perfusion, but this can result in adverse outcomes due to fluid overload. We compared postoperative outcome of living kidney donors according to the intraoperative fluid management.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!