Meropenem in a Community Hospital: Clinical Outcomes and Cost Minimization
Meropenem in a Community Hospital: Clinical Outcomes and Cost Minimization
Study Objective. To compare outcomes and cost for the traditional United States Food and Drug Administration–approved dosing regimen for meropenem versus an alternative dosing regimen providing similar pharmacodynamic exposure with a lower total daily dose.
Design. Retrospective cohort study with a cost-minimization analysis.
Setting. A 417-bed, privately owned community hospital.
Patients. One hundred patients who received meropenem 1 g every 8 or 12 hours (traditional dosing regimen) between January 1 and September 30, 2004 (historical controls), and 192 patients who received meropenem 500 mg every 6 or 8 hours (alternative dosing regimen) between October 1, 2004, and September 30, 2005.
Measurements and Main Results. Demographic and clinical data were collected for all patients. Cost-minimization analysis was performed by using the drug acquisition cost for meropenem. Demographics, sources of infection, distributions of organisms, and Charlson Comorbidity Index scores were similar between patients in the traditionally and alternatively dosed groups. Concomitant therapy, duration of therapy, success rates, lengths of stay, and in-hospital mortality rates were also similar between groups. Median time to the resolution of symptoms was 3 days for traditional dosing and 1.5 days for alternative dosing (p<0.0001). A logistic regression model including the dosing strategy showed that only polymicrobial infections and sepsis were associated with increased failure rates. The median cost for antibiotics was $439.05/patient for traditional dosing and $234.08/patient for alternative dosing (p<0.0001).
Conclusion. An alternative dosing regimen for meropenem with a lower total daily dose yielded patient outcomes, including success rates and duration of therapy, equivalent to those of the traditional dosing regimen. Alternative dosing decreased total drug exposure, costs for antibiotics, and time to the resolution of infections.
The treatment of infectious processes is riddled with obstacles. In an era of cost constraints and resistance development, it has become imperative to maximize effectiveness while minimizing drug exposure and reducing adverse events. The study of pharmacodynamics and how it pertains to antimicrobial therapy has revolutionized the approach practitioners take in dosing antibiotics. The term pharmacodynamics is used to describe the uptake, movement, binding, and interactions of agents at their target site of action. In relation to antibiotics, the study of pharmacodynamics has allowed practitioners to optimize dosing to maximize killing, minimize resistance, and potentially limit the cost-prohibitive nature of some agents.
Pharmacodynamic parameters to optimize killing activity for various antibiotics have been established. As these pertain to carbapenems, meropenem and imipenem-cilastatin have demonstrated time-dependent killing activity; the primary parameter predicting effectiveness was the time above the minimum inhibitory concentration (MIC). Substantially increasing drug concentrations above the MIC did not increase the rate of bactericidal activity. Animal models have shown that concentrations of meropenem should remain above the MIC for approximately 20% or 40% of the dosing interval for the drug to have a bacteriostatic or bactericidal effect, respectively.
Mathematic modeling has been applied to predict the attainment of pharmacodynamic targets by using various dosing regimens. Monte Carlo simulations have proven to be particularly useful. Such simulations can be designed to mimic interpatient variability and to assess multiple antibiotic dosing regimens to predict drug exposures and time above the MIC. Investigators used estimates of pharmacokinetic parameters from 5000 healthy volunteers to simulate exposure at the susceptibility breakpoint of meropenem (4 µg/ml) for gram-negative organisms and Staphylococcus aureus. Regimens compared included 500 mg infused over 30 minutes every 6 hours and 1 g over 30 minutes every 8 hours. The mean percentage time above the MIC was 45.77% (95% confidence interval 40.06–50.69%) for 1 g every 8 hours and 43.91% (95% confidence interval 36.77–51.46%) for 500 mg every 6 hours. In addition, cost-minimization analysis showed a predicted decrease in daily costs of $38.64 when 500 mg every 6 hours was used instead of 1 g every 8 hours. Results of this simulation provided the foundation for adopting alternative dosing of meropenem into clinical practice.
On the basis of these mathematic models, researchers evaluated the clinical and economic implications of using meropenem 500 mg over 30 minutes every 6 or 8 hours versus 1 g over 30 minutes every 8 or 12 hours. In a small observational study, they demonstrated that the smaller dose given more frequently achieved microbiologic and clinical success rates equivalent to those of the higher dose given less frequently. Of 60 patients included in the analysis, 78% of those taking 500 mg every 6 hours and 82% of those taking 1 g every 8 hours had clinical success (p=0.862). Thirty-eight patients were included in the microbiologic analysis. Microbiologic success was achieved in 63% of patients given 500 mg every 6 hours and in 79% of patients given 1 g every 8 hours (p=0.334). Equivalent outcomes were attained, and drug acquisition costs for the course of treatment were 41% lower for the 500-mg regimen compared with the 1-g regimen ($576 vs $982, p=0.009). The small sample size may have been a study limitation, but the results suggested that clinical outcomes were similar between the two dosing regimens and that the daily acquisition costs associated with antibiotic therapy were reduced with the 500-mg regimen.
At the Medical Center of Plano, Texas, meropenem has been on formulary since 2002 and traditionally dosed at 1 g every 8 or 12 hours. Given the published outcomes and cost data, we implemented a pharmacist-initiated autosubstitution protocol to convert dosages of meropenem to 500 mg every 6 or 8 hours. The staff at our institution believed that a decreased total daily dose of meropenem could provide equivalent drug exposure. If true, the reduction in dose would allow us to realize clinical success while decreasing drug acquisition cost.
The goal of this study was to describe drug use and outcomes for patients treated with alternative dosing of meropenem compared with a historical control group treated with the United States Food and Drug Administration–approved regimen. Our primary objective was to determine if an alternative dosing strategy provides clinical outcomes similar to those of the traditional regimen while allowing our institution to reduce drug acquisition costs.
Study Objective. To compare outcomes and cost for the traditional United States Food and Drug Administration–approved dosing regimen for meropenem versus an alternative dosing regimen providing similar pharmacodynamic exposure with a lower total daily dose.
Design. Retrospective cohort study with a cost-minimization analysis.
Setting. A 417-bed, privately owned community hospital.
Patients. One hundred patients who received meropenem 1 g every 8 or 12 hours (traditional dosing regimen) between January 1 and September 30, 2004 (historical controls), and 192 patients who received meropenem 500 mg every 6 or 8 hours (alternative dosing regimen) between October 1, 2004, and September 30, 2005.
Measurements and Main Results. Demographic and clinical data were collected for all patients. Cost-minimization analysis was performed by using the drug acquisition cost for meropenem. Demographics, sources of infection, distributions of organisms, and Charlson Comorbidity Index scores were similar between patients in the traditionally and alternatively dosed groups. Concomitant therapy, duration of therapy, success rates, lengths of stay, and in-hospital mortality rates were also similar between groups. Median time to the resolution of symptoms was 3 days for traditional dosing and 1.5 days for alternative dosing (p<0.0001). A logistic regression model including the dosing strategy showed that only polymicrobial infections and sepsis were associated with increased failure rates. The median cost for antibiotics was $439.05/patient for traditional dosing and $234.08/patient for alternative dosing (p<0.0001).
Conclusion. An alternative dosing regimen for meropenem with a lower total daily dose yielded patient outcomes, including success rates and duration of therapy, equivalent to those of the traditional dosing regimen. Alternative dosing decreased total drug exposure, costs for antibiotics, and time to the resolution of infections.
The treatment of infectious processes is riddled with obstacles. In an era of cost constraints and resistance development, it has become imperative to maximize effectiveness while minimizing drug exposure and reducing adverse events. The study of pharmacodynamics and how it pertains to antimicrobial therapy has revolutionized the approach practitioners take in dosing antibiotics. The term pharmacodynamics is used to describe the uptake, movement, binding, and interactions of agents at their target site of action. In relation to antibiotics, the study of pharmacodynamics has allowed practitioners to optimize dosing to maximize killing, minimize resistance, and potentially limit the cost-prohibitive nature of some agents.
Pharmacodynamic parameters to optimize killing activity for various antibiotics have been established. As these pertain to carbapenems, meropenem and imipenem-cilastatin have demonstrated time-dependent killing activity; the primary parameter predicting effectiveness was the time above the minimum inhibitory concentration (MIC). Substantially increasing drug concentrations above the MIC did not increase the rate of bactericidal activity. Animal models have shown that concentrations of meropenem should remain above the MIC for approximately 20% or 40% of the dosing interval for the drug to have a bacteriostatic or bactericidal effect, respectively.
Mathematic modeling has been applied to predict the attainment of pharmacodynamic targets by using various dosing regimens. Monte Carlo simulations have proven to be particularly useful. Such simulations can be designed to mimic interpatient variability and to assess multiple antibiotic dosing regimens to predict drug exposures and time above the MIC. Investigators used estimates of pharmacokinetic parameters from 5000 healthy volunteers to simulate exposure at the susceptibility breakpoint of meropenem (4 µg/ml) for gram-negative organisms and Staphylococcus aureus. Regimens compared included 500 mg infused over 30 minutes every 6 hours and 1 g over 30 minutes every 8 hours. The mean percentage time above the MIC was 45.77% (95% confidence interval 40.06–50.69%) for 1 g every 8 hours and 43.91% (95% confidence interval 36.77–51.46%) for 500 mg every 6 hours. In addition, cost-minimization analysis showed a predicted decrease in daily costs of $38.64 when 500 mg every 6 hours was used instead of 1 g every 8 hours. Results of this simulation provided the foundation for adopting alternative dosing of meropenem into clinical practice.
On the basis of these mathematic models, researchers evaluated the clinical and economic implications of using meropenem 500 mg over 30 minutes every 6 or 8 hours versus 1 g over 30 minutes every 8 or 12 hours. In a small observational study, they demonstrated that the smaller dose given more frequently achieved microbiologic and clinical success rates equivalent to those of the higher dose given less frequently. Of 60 patients included in the analysis, 78% of those taking 500 mg every 6 hours and 82% of those taking 1 g every 8 hours had clinical success (p=0.862). Thirty-eight patients were included in the microbiologic analysis. Microbiologic success was achieved in 63% of patients given 500 mg every 6 hours and in 79% of patients given 1 g every 8 hours (p=0.334). Equivalent outcomes were attained, and drug acquisition costs for the course of treatment were 41% lower for the 500-mg regimen compared with the 1-g regimen ($576 vs $982, p=0.009). The small sample size may have been a study limitation, but the results suggested that clinical outcomes were similar between the two dosing regimens and that the daily acquisition costs associated with antibiotic therapy were reduced with the 500-mg regimen.
At the Medical Center of Plano, Texas, meropenem has been on formulary since 2002 and traditionally dosed at 1 g every 8 or 12 hours. Given the published outcomes and cost data, we implemented a pharmacist-initiated autosubstitution protocol to convert dosages of meropenem to 500 mg every 6 or 8 hours. The staff at our institution believed that a decreased total daily dose of meropenem could provide equivalent drug exposure. If true, the reduction in dose would allow us to realize clinical success while decreasing drug acquisition cost.
The goal of this study was to describe drug use and outcomes for patients treated with alternative dosing of meropenem compared with a historical control group treated with the United States Food and Drug Administration–approved regimen. Our primary objective was to determine if an alternative dosing strategy provides clinical outcomes similar to those of the traditional regimen while allowing our institution to reduce drug acquisition costs.
