School of Medicine and Health Sciences Poster Presentations

Title

Application of Pharmacokinetics and Pharmacodynamics to Determine Dose Optimization using Beta Lactams in Pediatric Cystic Fibrosis Population

Document Type

Poster

Keywords

Cystic Fibrosis; Beta Lactam Antibiotics; Pediatric population; Dosing Strategies; PK modeling

Publication Date

4-2017

Abstract

Rationale:

Cystic Fibrosis (CF) leads to tremendous morbidity and mortality from chronic bacterial infections and acute pulmonary exacerbations (APE). Antibiotic treatment of APEs requires higher dosing and revised dosing strategies in CF patients given the variable absorption, distribution, metabolism, and excretion of the antibiotics in CF patients. Through identification of individual pharmacokinetic (PK) parameters using population PK modeling, the microbiologic efficacy of the drug (pharmacodynamics, PD) can be predicted. For optimal PD of beta lactams, the time above the minimum inhibitory concentration (MIC) must be greater than 40% of the dosing interval for carbapenems, 50% of the dosing interval for penicillins, and 60-70% of the dosing interval for cephalosporins. We sought to determine how many CF patients received an optimal antibiotic dosing with a beta lactam antibiotic regimen for pathogens grown on culture using a population PK modeling with Bayesian feedback approach.

Methods:

Children between the ages of 1-21 years with a known diagnosis of CF at Children’s National Health System and hospitalized for intravenous (IV) antibiotics in the three years prior were recruited to participate. Subjects who experienced one or more APEs requiring IV antibiotics during the study were asked to participate for each treatment course. Information collected for each antibiotic included total daily dose, timing of administration, and duration of therapy. MICs for antibiotics were determined by conventional culture techniques. Plasma drug concentrations of IV beta lactam antibiotics during the treatment course were used to model the subjects’ antimicrobial exposure.

Results:

Twenty patients experienced at least one APE for which they were treated with 31 courses of IV antibiotics. The most common antibiotics used were ceftazidime (65%), tobramycin (61%), meropenem (35%), piperacillin-tazobactam (19%), and vancomycin (16%). The most common combinations of antibiotics were ceftazidime and tobramycin (42%), and meropenem and tobramycin (16%). The patient’s dosage of beta lactam antibiotics was deemed optimal or non-optimal based on the time spent above the MIC. 55% of the beta lactam drug regimens achieved optimal dosing, while 45% were suboptimal. Patients receiving ceftazidime were significantly more likely to achieve optimal PD indices (p=0.0122).

Conclusions:

Patients receiving ceftazidime were significantly more likely to achieve optimal PD indices, while meropenem and piperacillin/tazobactam were equally likely to be suboptimal. This suggests that CF patients could benefit from therapeutic drug monitoring to improve their beta lactam antibiotic exposure, especially when trying to treat antibiotic resistant organisms.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Open Access

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Comments

Poster to be presented at GW Annual Research Day 2017.

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Application of Pharmacokinetics and Pharmacodynamics to Determine Dose Optimization using Beta Lactams in Pediatric Cystic Fibrosis Population

Rationale:

Cystic Fibrosis (CF) leads to tremendous morbidity and mortality from chronic bacterial infections and acute pulmonary exacerbations (APE). Antibiotic treatment of APEs requires higher dosing and revised dosing strategies in CF patients given the variable absorption, distribution, metabolism, and excretion of the antibiotics in CF patients. Through identification of individual pharmacokinetic (PK) parameters using population PK modeling, the microbiologic efficacy of the drug (pharmacodynamics, PD) can be predicted. For optimal PD of beta lactams, the time above the minimum inhibitory concentration (MIC) must be greater than 40% of the dosing interval for carbapenems, 50% of the dosing interval for penicillins, and 60-70% of the dosing interval for cephalosporins. We sought to determine how many CF patients received an optimal antibiotic dosing with a beta lactam antibiotic regimen for pathogens grown on culture using a population PK modeling with Bayesian feedback approach.

Methods:

Children between the ages of 1-21 years with a known diagnosis of CF at Children’s National Health System and hospitalized for intravenous (IV) antibiotics in the three years prior were recruited to participate. Subjects who experienced one or more APEs requiring IV antibiotics during the study were asked to participate for each treatment course. Information collected for each antibiotic included total daily dose, timing of administration, and duration of therapy. MICs for antibiotics were determined by conventional culture techniques. Plasma drug concentrations of IV beta lactam antibiotics during the treatment course were used to model the subjects’ antimicrobial exposure.

Results:

Twenty patients experienced at least one APE for which they were treated with 31 courses of IV antibiotics. The most common antibiotics used were ceftazidime (65%), tobramycin (61%), meropenem (35%), piperacillin-tazobactam (19%), and vancomycin (16%). The most common combinations of antibiotics were ceftazidime and tobramycin (42%), and meropenem and tobramycin (16%). The patient’s dosage of beta lactam antibiotics was deemed optimal or non-optimal based on the time spent above the MIC. 55% of the beta lactam drug regimens achieved optimal dosing, while 45% were suboptimal. Patients receiving ceftazidime were significantly more likely to achieve optimal PD indices (p=0.0122).

Conclusions:

Patients receiving ceftazidime were significantly more likely to achieve optimal PD indices, while meropenem and piperacillin/tazobactam were equally likely to be suboptimal. This suggests that CF patients could benefit from therapeutic drug monitoring to improve their beta lactam antibiotic exposure, especially when trying to treat antibiotic resistant organisms.