Session Type: ePosters
Session Title: ePosters
Authors(s): N. Bashir (1), S. Gastine (2), S. Das (1), R. Mccartney (1), C. Hamilton-Davies (1), A. Shipolini (1), A. Younis (3), J. Standing (2), S. Antoniou (1)
Authors Affiliations(s): (1) Barts Health NHS Trust, United Kingdom, (2) UCL Great Ormond Street Institute of Child Health, United Kingdom, (3) St George's University of London, United Kingdom
Background:
Cardiopulmonary bypass (CPB) is associated with profound physiological changes affecting antimicrobial pharmacokinetics (Pea et al, 2008). Gentamicin provides cover against Gram-negative organisms and is commonly used as prophylaxis for cardiothoracic surgical site infections (SSIs). Systematic reviews and meta-analyses concluded that prolonging prophylaxis for 24–48 hours can reduce SSIs. To establish if this practice is safe and to define an optimal dose, gentamicin therapeutic drug monitoring was evaluated using population pharmacokinetics (PPK).
Methods:An observational cohort study was undertaken in patients receiving single-dose gentamicin for antibiotic prophylaxis in cardiac surgery.
Data were collected from 101 participants, with gentamicin concentrations collected at four sample points over 24-hours, totaling 404 samples. Modeling was undertaken using a parametric non-linear mixed effect model (NONMEM®). Ethical approval and patient consent were obtained.
One- two- and three-compartment models were tested, along with the influence of CPB, age and renal function. Model fit was assessed using visual predictive checks (VPCs), change in objective function value (OFV) and goodness of fit (GOF) plots. The final model was used to simulate a range of doses for this population. Model predictions were made to target a concentration of at least 10mg/L immediately post CPB, as the standard for Cmax:MIC ratio assuming an MIC of 1mg/L.
Results:Single-dose regimen of 5mg/kg maintained Cmax at 10mg/L after CPB in 58% with 24-hour trough levels <1mg/L in 65% of this cohort. A two-compartment model with creatinine on clearance (CL), CBP on CL and volume of distribution (VD), and age on V2 (peripheral volume) provided the best fit. Doses above 7mg/kg achieved the probability of target attainment (PTA) of 10mg/L above 95%. The percentage of probability of trough levels at 24-hours maintaining a concentration greater than MIC of 1mg/L ranges from 55.87% with 6mg/kg up to 70.85% with a 10mg/Kg dose. Please refer to figure 1 demonstrating PTA after CPB using simulated doses and clearance.
Conclusions:
Simulations demonstrated a dose of 7mg/kg produced serum gentamicin concentrations at 10mg/L after CPB with more than 95% PTA. However, 24-hour trough was above 1mg/L in over 60% of cases, suggesting the need for personalisation of dosing based on pre-operative covariates.
Keyword(s): Genatamicin, Population Pharmacokinetics, Cardiac SurgeryCOI Other: Nadhia Bashir (first author) - Researcher funded by the National Institute for Health Research (NIHR) - Master of Research in Clinical Practice (MResClin) qualification undertaken at St George's University of London
Session Type: ePosters
Session Title: ePosters
Authors(s): N. Bashir (1), S. Gastine (2), S. Das (1), R. Mccartney (1), C. Hamilton-Davies (1), A. Shipolini (1), A. Younis (3), J. Standing (2), S. Antoniou (1)
Authors Affiliations(s): (1) Barts Health NHS Trust, United Kingdom, (2) UCL Great Ormond Street Institute of Child Health, United Kingdom, (3) St George's University of London, United Kingdom
Background:
Cardiopulmonary bypass (CPB) is associated with profound physiological changes affecting antimicrobial pharmacokinetics (Pea et al, 2008). Gentamicin provides cover against Gram-negative organisms and is commonly used as prophylaxis for cardiothoracic surgical site infections (SSIs). Systematic reviews and meta-analyses concluded that prolonging prophylaxis for 24–48 hours can reduce SSIs. To establish if this practice is safe and to define an optimal dose, gentamicin therapeutic drug monitoring was evaluated using population pharmacokinetics (PPK).
Methods:An observational cohort study was undertaken in patients receiving single-dose gentamicin for antibiotic prophylaxis in cardiac surgery.
Data were collected from 101 participants, with gentamicin concentrations collected at four sample points over 24-hours, totaling 404 samples. Modeling was undertaken using a parametric non-linear mixed effect model (NONMEM®). Ethical approval and patient consent were obtained.
One- two- and three-compartment models were tested, along with the influence of CPB, age and renal function. Model fit was assessed using visual predictive checks (VPCs), change in objective function value (OFV) and goodness of fit (GOF) plots. The final model was used to simulate a range of doses for this population. Model predictions were made to target a concentration of at least 10mg/L immediately post CPB, as the standard for Cmax:MIC ratio assuming an MIC of 1mg/L.
Results:Single-dose regimen of 5mg/kg maintained Cmax at 10mg/L after CPB in 58% with 24-hour trough levels <1mg/L in 65% of this cohort. A two-compartment model with creatinine on clearance (CL), CBP on CL and volume of distribution (VD), and age on V2 (peripheral volume) provided the best fit. Doses above 7mg/kg achieved the probability of target attainment (PTA) of 10mg/L above 95%. The percentage of probability of trough levels at 24-hours maintaining a concentration greater than MIC of 1mg/L ranges from 55.87% with 6mg/kg up to 70.85% with a 10mg/Kg dose. Please refer to figure 1 demonstrating PTA after CPB using simulated doses and clearance.
Conclusions:
Simulations demonstrated a dose of 7mg/kg produced serum gentamicin concentrations at 10mg/L after CPB with more than 95% PTA. However, 24-hour trough was above 1mg/L in over 60% of cases, suggesting the need for personalisation of dosing based on pre-operative covariates.
Keyword(s): Genatamicin, Population Pharmacokinetics, Cardiac SurgeryCOI Other: Nadhia Bashir (first author) - Researcher funded by the National Institute for Health Research (NIHR) - Master of Research in Clinical Practice (MResClin) qualification undertaken at St George's University of London
Session Type: ePosters
Session Title: ePosters
Authors(s): N. Bashir (1), S. Gastine (2), S. Das (1), R. Mccartney (1), C. Hamilton-Davies (1), A. Shipolini (1), A. Younis (3), J. Standing (2), S. Antoniou (1)
Authors Affiliations(s): (1) Barts Health NHS Trust, United Kingdom, (2) UCL Great Ormond Street Institute of Child Health, United Kingdom, (3) St George's University of London, United Kingdom
Background:
Cardiopulmonary bypass (CPB) is associated with profound physiological changes affecting antimicrobial pharmacokinetics (Pea et al, 2008). Gentamicin provides cover against Gram-negative organisms and is commonly used as prophylaxis for cardiothoracic surgical site infections (SSIs). Systematic reviews and meta-analyses concluded that prolonging prophylaxis for 24–48 hours can reduce SSIs. To establish if this practice is safe and to define an optimal dose, gentamicin therapeutic drug monitoring was evaluated using population pharmacokinetics (PPK).
Methods:An observational cohort study was undertaken in patients receiving single-dose gentamicin for antibiotic prophylaxis in cardiac surgery.
Data were collected from 101 participants, with gentamicin concentrations collected at four sample points over 24-hours, totaling 404 samples. Modeling was undertaken using a parametric non-linear mixed effect model (NONMEM®). Ethical approval and patient consent were obtained.
One- two- and three-compartment models were tested, along with the influence of CPB, age and renal function. Model fit was assessed using visual predictive checks (VPCs), change in objective function value (OFV) and goodness of fit (GOF) plots. The final model was used to simulate a range of doses for this population. Model predictions were made to target a concentration of at least 10mg/L immediately post CPB, as the standard for Cmax:MIC ratio assuming an MIC of 1mg/L.
Results:Single-dose regimen of 5mg/kg maintained Cmax at 10mg/L after CPB in 58% with 24-hour trough levels <1mg/L in 65% of this cohort. A two-compartment model with creatinine on clearance (CL), CBP on CL and volume of distribution (VD), and age on V2 (peripheral volume) provided the best fit. Doses above 7mg/kg achieved the probability of target attainment (PTA) of 10mg/L above 95%. The percentage of probability of trough levels at 24-hours maintaining a concentration greater than MIC of 1mg/L ranges from 55.87% with 6mg/kg up to 70.85% with a 10mg/Kg dose. Please refer to figure 1 demonstrating PTA after CPB using simulated doses and clearance.
Conclusions:
Simulations demonstrated a dose of 7mg/kg produced serum gentamicin concentrations at 10mg/L after CPB with more than 95% PTA. However, 24-hour trough was above 1mg/L in over 60% of cases, suggesting the need for personalisation of dosing based on pre-operative covariates.
Keyword(s): Genatamicin, Population Pharmacokinetics, Cardiac SurgeryCOI Other: Nadhia Bashir (first author) - Researcher funded by the National Institute for Health Research (NIHR) - Master of Research in Clinical Practice (MResClin) qualification undertaken at St George's University of London
Session Type: ePosters
Session Title: ePosters
Authors(s): N. Bashir (1), S. Gastine (2), S. Das (1), R. Mccartney (1), C. Hamilton-Davies (1), A. Shipolini (1), A. Younis (3), J. Standing (2), S. Antoniou (1)
Authors Affiliations(s): (1) Barts Health NHS Trust, United Kingdom, (2) UCL Great Ormond Street Institute of Child Health, United Kingdom, (3) St George's University of London, United Kingdom
Background:
Cardiopulmonary bypass (CPB) is associated with profound physiological changes affecting antimicrobial pharmacokinetics (Pea et al, 2008). Gentamicin provides cover against Gram-negative organisms and is commonly used as prophylaxis for cardiothoracic surgical site infections (SSIs). Systematic reviews and meta-analyses concluded that prolonging prophylaxis for 24–48 hours can reduce SSIs. To establish if this practice is safe and to define an optimal dose, gentamicin therapeutic drug monitoring was evaluated using population pharmacokinetics (PPK).
Methods:An observational cohort study was undertaken in patients receiving single-dose gentamicin for antibiotic prophylaxis in cardiac surgery.
Data were collected from 101 participants, with gentamicin concentrations collected at four sample points over 24-hours, totaling 404 samples. Modeling was undertaken using a parametric non-linear mixed effect model (NONMEM®). Ethical approval and patient consent were obtained.
One- two- and three-compartment models were tested, along with the influence of CPB, age and renal function. Model fit was assessed using visual predictive checks (VPCs), change in objective function value (OFV) and goodness of fit (GOF) plots. The final model was used to simulate a range of doses for this population. Model predictions were made to target a concentration of at least 10mg/L immediately post CPB, as the standard for Cmax:MIC ratio assuming an MIC of 1mg/L.
Results:Single-dose regimen of 5mg/kg maintained Cmax at 10mg/L after CPB in 58% with 24-hour trough levels <1mg/L in 65% of this cohort. A two-compartment model with creatinine on clearance (CL), CBP on CL and volume of distribution (VD), and age on V2 (peripheral volume) provided the best fit. Doses above 7mg/kg achieved the probability of target attainment (PTA) of 10mg/L above 95%. The percentage of probability of trough levels at 24-hours maintaining a concentration greater than MIC of 1mg/L ranges from 55.87% with 6mg/kg up to 70.85% with a 10mg/Kg dose. Please refer to figure 1 demonstrating PTA after CPB using simulated doses and clearance.
Conclusions:
Simulations demonstrated a dose of 7mg/kg produced serum gentamicin concentrations at 10mg/L after CPB with more than 95% PTA. However, 24-hour trough was above 1mg/L in over 60% of cases, suggesting the need for personalisation of dosing based on pre-operative covariates.
Keyword(s): Genatamicin, Population Pharmacokinetics, Cardiac SurgeryCOI Other: Nadhia Bashir (first author) - Researcher funded by the National Institute for Health Research (NIHR) - Master of Research in Clinical Practice (MResClin) qualification undertaken at St George's University of London