Percent Time Above MIC ( T MIC)

Transcription

1 Percent Time Above MIC ( T MIC) MIC 1 1 T MIC mg, 1 2 (500 mg 2) T MIC: 30 (TA30 ) T MIC: 50 (TA50 ) 21.5, 0.1 1,000 mg 2 TA , 68.7 TA , mg 3 TA , 73.7, TA , mg 1 3 Key words: T MIC, Pseudomonas aeruginosa, Monte Carlo simulation, meropenem, imipenem compromised host (MIC) (pharmacokinetics: PK) (parmacodynamics: PD) 1 5) PK (C max ) (AUC) (T 1/2 ) PD MIC, time-kill ( ) TEL: FAX: ken.kaito@jikei.ac.jp C max /MIC AUC/MIC MIC Time above MIC: T MIC T MIC T MIC ) PK/PD 8 Vol. 17 No

2 T MIC 9 10, 11) MIC 1,000 5,000 10,000 PK/PD T MIC 12 14) (IPM) (MEPM) MIC 1 1 T MIC MIC Neg Neg Combo 6K DADE BEHRING, MIC: mg/ ml MicroScan WalkAway 96SI (DADE BEH- RING, CA, USA) (V d ) MEPM L, IPM (T 1/2 ) , MIC V d T 1/2 1,000 T MIC Crystal Ball mg 12 (500 mg 2) mg 8 (500 mg 3) 1 1,000 mg T MIC 10, 20, 30, 40, 50, 60, 70, 80, 90, 100 Target Attainment (TA ) T MIC 30 T MIC 50 TA30 TA50 1. MIC MIC 1 2 MIC 0.5 mg/ml mg/ml MIC 0.5 mg/ml MIC Vol. 17 No

3 10 2. MIC mg 12 T MIC TA ,000 mg 12 T MIC TA 10 Vol. 17 No

4 T MIC mg 8 T MIC TA MIC 1 mg/ml 42 (67.2 ) MIC 16 mg/ml 2 (3.3 ) 3 (4.9 ) 16 mg/ml 2. T MIC (TA ) 500 mg 2, 1,000 mg 2,500 mg 3 T MIC TA 3, 4, mg 2 TA , 59.3 TA , 0.1 1,000 mg 2 TA , 68.7 TA mg 3 TA TA , MIC PK/PD 15) 6, 7, 16) T MIC T MIC ) T MIC 50 17) Kuti PK/ PD TA30 TA50 1,000 mg 3, 2,000 mg 3 18) 5,00 2 1,000 mg mg 3 1,000 mg 3 TA30, TA50 19) TA T MIC50 TA mg ,000 mg , IPM500 mg ,000 mg 0.5, 1, 2, 3 8 T MIC 40 TA 1 TA 6, 20) Vol. 17 No

5 12 1) Craig, W. A Choosing an antibiotic on the basis of pharmacodynamics. Ear Nose Throat J. 77(Suppl. 6): ) Craig, W. A Does the dose matter? Clin. Infect. Dis. 15(Suppl. 3): ) Jacobs, M. R Optimisation of antimicrobial therapy using pharmacokinetic and pharmacodynamic parameters. Clin. Microbiol. Infect. 7: ) Toutain, P. L., J. R. del Castillo, A. Bousquet- Melou The pharmacokinetic pharmacodynamic approach to a rational dosage regimen for antibiotics. Res. Vet. Sci. 73: ) Mattoes, H. M., J. L. Kuti, G. L. Drusano, et al Optimizing antimicrobial pharmacodynamics: dosage strategies for meropenem. Clin. Ther. 26: ) Drusano, G. L., W. A. Craig Relevance of pharmacokinetics and pharmacodynamics in the selection of antibiotics for respiratory tract infections. J. Chemother. 9(Suppl. 3): ) Craig, W. A Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin. Infect. Dis. 26: ) Walker, M. R., W. A. Craig Pharmacodynamic activities of meropenem in animal infection model. ICAAC abstract: A 91. 9) Craig, W. A., D. Andes Pharmacokinetics and pharmacodynamics of antibiotics in otitis media. Pediatr Infect. Dis. J. 15: ) Kuti, J. L., C. H. Nightingale, D. P. Nicolau Optimizing pharmacodynamic target attainment using the MYSTIC antibiogram: data collected in North America in Antimicrob. Agents. Chemother. 48: ) Kuti, J. L., C. Ong, M. Lo, et al Comparison of probability of target attainment calculated by Monte Carlo simulation with meropenem clinical and microbiological response for the treatment of complicated skin and skin structure infections. Int. J. Antimicrob. Agents. 28: ) el-tahtawy, A. A., A. J. Jackson, T. M. Ludden Comparison of single and multiple dose pharmacokinetics using clinical bioequivalence data and Monte Carlo simulations. Pharm. Res. 11: ) Ambrose, P. G., D. M. Grasela The use of Monte Carlo simulation to examine pharmacodynamic variance of drugs: fluoroquinolone pharmacodynamics against Streptococcus pneumoniae. Diagn. Microbiol. Infect. Dis. 38: ) Chabaud, S., P. Girard, P. Nony, et al Therapeutic Modeling and Simulation Group. Clinical trial simulation using therapeutic e#ect modeling: application to ivabradine e$cacy in patients with angina pectoris. J. Pharmacokinet. Pharmacodyn. 29: ) PK/PD 92: ) Smith, P. F., C. H. Ballow, B. M. Booker, et al Pharmacokinetics and pharmacodynamics of aztreonam and tobramycin in hospitalized patients. Clin. Ther. 23: ) Turnidge, J. D The pharmacodynamics of b-lactams. Clin. Infect. Dis. 27: ) Kuti, J. L., P. K. Dandekar, C. H. Nightingale, et al Use of Monte Carlo simulation to design an optimized pharmacodynamic dosing strategy for meropenem. J. Clin. Pharmacol. 43: ) Jap. J. Antibiotics 58: ) Jaruratanasirikul, S., S. Sriwiriyan Comparison of the pharmacodynamics of meropenem in healthy volunteers following administration by intermittent infusions or bolus infection. J. Antimicrob. Chemother. 52: Vol. 17 No

6 T MIC 13 Comparison of the Percent Time above MIC ( T MIC) of Meropenem and Imipenem for Pseudomonas aeruginosa by Monte Carlo Simulation Mariko Wakabayashi, Kenji Tominaga, Kazumi Sakamoto, Harumi Tsurukawa, Saori Maeda, Taku Tamura, Ikurou Abe, Ken Kaito Central Clinical Laboratory, Jikei University Hospital It is very important to pay attention to the pharmacokinetic and pharmacodynamic of antibiotics in the management of infection. We measured the MIC for Pseudomonas aeruginosa of meropenem and imipenem, and analyzed the optimal dose and optimal mode of administration of these drugs by Monte Carlo simulation. Percent time above the MIC ( T MIC) exposures for 500 mg q12h, 500 mg q8h, and 1,000 mg q12h were simulated for 1,000 subjects, and the target attaining rates of bacteriostatic exposure ( T MIC: 30 ) and bacteriocidal exposure ( T MIC: 50 ) were calculated. The probability of attaining T MIC: 30 (TA30 ) oftwo drugs by the 500 mg q12h dosage regimen was high enough (71.9 for meropenem and 59.3 for imipenem), while the probability of attaining T MIC: 50 (TA50 ) waslow (21.5 and 0.1, respectively). The 1,000 mg q12h dosage regimen provided the better TA30 (80.5 and 68.7, respectively) and better TA50 (53.2 and 2.7, respectively). The 500mg q8h dosage regimen provided the highest TA30 (83.7 and 73.7, respectively) and highest TA50 (68.1 and 41.8, respectively), indicating that the 500 mg q8h dosage regimen would provide the most satisfactory bacterial e#ect. Monte Carlo simulation is thought to be very beneficial in choosing the antibiotics and its style of administration. Vol. 17 No