TY - JOUR
T1 - Pharmacodynamics of intermittent and continuous infusion piperacillin/tazobactam and cefepime against extended-spectrum β-lactamase-producing organisms
AU - Reese, Alicia M.
AU - Frei, Christopher R.
AU - Burgess, David S.
N1 - Funding Information:
This research was supported by a grant from Wyeth Pharmaceuticals.
PY - 2005/8
Y1 - 2005/8
N2 - The pharmacodynamics of piperacillin/tazobactam and cefepime were evaluated against extended-spectrum β-lactamase (ESBL)-producing organisms. Ten thousand patients were simulated based on ESBL minimum inhibitory concentrations (MICs) from our laboratory (N = 39) and on pharmacokinetic data from peer-reviewed literature. The desired proportion of the dosing interval that the concentration remains above the MIC (%T > MIC) for the intermittent bolus regimens was ≥40% for piperacillin/tazobactam and ≥60% for cefepime. The desired Css/MIC ratio (where Css is the concentration at steady state) was ≥2 for all continuous infusion (CI) regimens. MIC 50, MIC90 and %S were, respectively, 64/4 μg/mL, 1024/4 μg/mL and 33% for piperacillin/tazobactam and 8 μg/mL, 16 μg/mL and 0% for cefepime. For piperacillin/tazobactam, 3.375 g every 4 h (q4h) achieved the highest probability of target attainment (43%), followed by 13.5 g CI (31%), 3.375 g q6h (27%), 4.5 g q8h (17%) and 6.75 g CI (10%). However, for cefepime, 4 g CI had the highest probability of target attainment (77%), followed by 1 g q8h (65%), 2 g q12h (58%), 3 g CI (46%) and 1 g q12h (27%). Although the probabilities of target attainment for cefepime were higher than for piperacillin/tazobactam, neither agent achieved a high probability of target attainment and should not be used routinely for the treatment of ESBL infections.
AB - The pharmacodynamics of piperacillin/tazobactam and cefepime were evaluated against extended-spectrum β-lactamase (ESBL)-producing organisms. Ten thousand patients were simulated based on ESBL minimum inhibitory concentrations (MICs) from our laboratory (N = 39) and on pharmacokinetic data from peer-reviewed literature. The desired proportion of the dosing interval that the concentration remains above the MIC (%T > MIC) for the intermittent bolus regimens was ≥40% for piperacillin/tazobactam and ≥60% for cefepime. The desired Css/MIC ratio (where Css is the concentration at steady state) was ≥2 for all continuous infusion (CI) regimens. MIC 50, MIC90 and %S were, respectively, 64/4 μg/mL, 1024/4 μg/mL and 33% for piperacillin/tazobactam and 8 μg/mL, 16 μg/mL and 0% for cefepime. For piperacillin/tazobactam, 3.375 g every 4 h (q4h) achieved the highest probability of target attainment (43%), followed by 13.5 g CI (31%), 3.375 g q6h (27%), 4.5 g q8h (17%) and 6.75 g CI (10%). However, for cefepime, 4 g CI had the highest probability of target attainment (77%), followed by 1 g q8h (65%), 2 g q12h (58%), 3 g CI (46%) and 1 g q12h (27%). Although the probabilities of target attainment for cefepime were higher than for piperacillin/tazobactam, neither agent achieved a high probability of target attainment and should not be used routinely for the treatment of ESBL infections.
KW - Cefepime
KW - Extended-spectrum β-lactamase
KW - Pharmacodynamics
KW - Piperacillin/tazobactam
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U2 - 10.1016/j.ijantimicag.2005.06.004
DO - 10.1016/j.ijantimicag.2005.06.004
M3 - Article
C2 - 16029947
AN - SCOPUS:22544446755
VL - 26
SP - 114
EP - 119
JO - International Journal of Antimicrobial Agents
JF - International Journal of Antimicrobial Agents
SN - 0924-8579
IS - 2
ER -