Ceftolozane/tazobactam dose regimens in severely/morbidly obese patients with complicated intra-abdominal infection or complicated urinary tract infection
Autor: | Jennifer A. Huntington, Jianmin Long, Alan J. Xiao, Luzelena Caro |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Microbiology (medical) Male medicine.medical_specialty Tazobactam Urinary system 030106 microbiology Population Renal function Microbial Sensitivity Tests 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Internal medicine Escherichia coli Medicine Humans Pharmacology (medical) Computer Simulation Pseudomonas Infections 030212 general & internal medicine Dosing education Escherichia coli Infections education.field_of_study business.industry General Medicine Middle Aged Anti-Bacterial Agents Cephalosporins Klebsiella Infections Obesity Morbid Klebsiella pneumoniae Infectious Diseases Pharmacodynamics Pseudomonas aeruginosa Urinary Tract Infections Intraabdominal Infections Ceftolozane Female business Monte Carlo Method medicine.drug |
Zdroj: | International journal of antimicrobial agents. 52(3) |
ISSN: | 1872-7913 |
Popis: | Ceftolozane/tazobactam is approved for treatment of complicated intra-abdominal infection (cIAI) and complicated urinary tract infection (cUTI) with renal function-based dose adjustment. Given that creatinine clearance, body weight and sex are highly correlated in severely/morbidly obese patients, this study investigated whether approved dosing regimens for ceftolozane/tazobactam are appropriate in severely/morbidly obese patients based on simulated pharmacokinetic/pharmacodynamic target attainment, with confirmation from observed clinical outcomes data from the phase 3 clinical development programme. Using a previously published population pharmacokinetic model, 1000 patients were randomly sampled from an internal pooled database of 201 severely/morbidly obese patients (BMI ≥ 35 kg/m2) and were used for Monte Carlo simulation to test whether the labelled dose regimens can achieve ≥90% probability of a target of 32.2% (1-log kill) time above free ceftolozane concentration against pathogens at an MIC up to 8 mg/L. Clinical outcomes data for severely/morbidly obese patients with cIAI or cUTI from pivotal phase 3 studies were summarised to calculate clinical and composite cure rates as a complimentary support. With the approved renal function-based dosing regimens, >90% target attainment of bactericidal activity was achieved at MICs up to 8 mg/L in the simulated severely/morbidly obese patients with cIAI or cUTI, similar to target attainment in non-obese patients and further confirmed by phase 3 outcomes where cure rates in severely/morbidly obese patients and non-obese patients are similar. Approved dosing regimens of ceftolozane/tazobactam, adjusted according to renal function, can achieve adequate target attainment and high clinical cure rates in severely/morbidly obese patients with cIAI or cUTI. |
Databáze: | OpenAIRE |
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