(TDM) (VCM) MRSA VCM mg/ml. (Ccr) Ccr TDM MIC. Key words: VCM, TDM, MRSA, PK/PD TDM TDM. (TDM; Therapeutic Drug Monitoring)

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1 (TDM) 1) 1) 2) 1) 2) (MRSA) (VCM) MRSA VCM 34 VCM 1) 5 15 mg/ml mg/ml 21 (TDM) (Ccr) Ccr TDM MIC Key words: VCM, TDM, MRSA, PK/PD (TDM; Therapeutic Drug Monitoring) (VCM) ( ) 575 TEL: FAX: s-shouichi icntv.ne.jp (MRSA) VCM TDM TDM I. 1) VCM TDM MRSA VCM 34 TDM VCM-TDM on EXCEL VCM-TDM VCM 5

2 112 2) VCM VCM VCM- VCM- (Ccr) 2) Ccr (Scr) Ccr Scr Ccr Ccr Ccr Ccr Ccr Cockcroft Gault C G 3) 4) 5) 3 C G Ccr 140/(72 Scr) (ml/min/kg) Ccr Ccr 0.85 Ccr 176 (kg) / 100 Scr (mg/dl) Ccr 158 (kg) / 100 Scr (mg/dl) Ccr BMI (kg)/scr (mg/ dl)/14.4 Ccr BMI (kg)/scr (mg/ dl)/14.4 3) VCM-TDM VCM 3 VCM TDX; 4) MRSA VCM MIC MRSA28 E MIC E 2 (AST-P525) 1 mg/ml E mg/ml II. 1) TDM VCM VCM 34 VCM 1 VCM 5 15 mg/ml VCM mg/ml 1) mg/ml 3 9 2) Ccr Ccr Ccr Ccr 1 Ccr Ccr STSS/EXCEL 6) (r) C G r 0.765y 1.11x 2.16 r 0.773y 1.12x 1.89 r 0.787y 1.01x Ccr ( p 0.05) 95 Ccr 70 ml/min 95 30ml/min, ml/min 1 VCM 5 mg/ml 5 15 mg/ml 15 mg/ml 25 g/ml 13 (38) 6 (18) 19 (56) mg/ml 7 (21) 2 (6) 9 (27) 40 mg/ml 1 (3) 5 (15) 6 (18) 13 (38) 14 (41) 7 (21) 34 (100) 6

1 mg/dl 2 22 MRSA VCM 0.5 g 2/day 0.5 g/30 min 3 2 24 MRSA 2 25 CT VCM Scr 0.44 mg/dl VCM 1.0 g 2/day 1.

3 (TDM) 113 VCM 2 Ccr 70 ml/min (0.75 g 2/day) 30 ml/ min VCM ml/min 3) VCM-TDM VCM 1: g 2/day /ml, CRP 16.1 mg/dl 2 22 MRSA VCM 0.5 g 2/day 0.5 g/30 min MRSA 2 25 CT VCM Scr 0.44 mg/dl VCM 1.0 g 2/day 1.0 g/60 min 6.1 mg/ ml 25.7 mg/ml VCM 1 Ccr Ccr Ccr Ccr 95 3 Ccr ( p 0.05) 2 Ccr VCM 95 Ccr 70 ml/min 95 Ccr 30 ml/min Ccr 116 ml/min VCM Ccr 70 ml/min (750 mg 2/day) ml/min VCM ml/min VCM VCM 1 7

114 3 1 VCM VCM VCM (5 15 mg/ml) (25 40 mg/ml) 3 3 MRSA 1.0 g 3/day 1.0 g/60 min MRSA 3 23 VCM 3 31 2: 63 DIC 4 27 (CHDF) CK 9890 U/ml, 28950 U/ml, Cre 3.66 mg/dl, CRP 39.

4 VCM VCM VCM (5 15 mg/ml) (25 40 mg/ml) 3 3 MRSA 1.0 g 3/day 1.0 g/60 min MRSA 3 23 VCM : 63 DIC 4 27 (CHDF) CK 9890 U/ml, U/ml, Cre 3.66 mg/dl, CRP 39.9 mg/dl, 42000/ml 5 5 MRSA 5 7 CVP MRSA VCM 0.5 g 1/day 0.5 g/30 min 3 VCM 13.4 mg/ml 18.4 mg/ml CHDF 0.5 g 1/day VCM mg/ml 1.0 g 1.0 g/60 min 36 MRSA 1.5 g 1/ g/90 min 4 MRSA : 60 B X MRSA MRSA VCM MRSA VCM MRSA MIC 1 mg/ml Scr 1.7 mg/dl VCM 1.0 g 1/day 1.0 g/60 min Scr 0.9 mg/dl MRSA MIC 2 mg/ml VCM 1.5 g 2/ 8

5 (TDM) VCM 5 3 VCM 9

116 6 MRSA28 VCM MIC E day 1.5 g/90 min 12 24 25.8 mg/ml 1.0 g 2/day 1.0 g/60 min 12 28 24.5 mg/ ml 1.5 g 1/day 1.5 g/90 min 1 3 VCM 4) MRSA VCM MIC E MRSA 28 VCM MIC 6 MIC 0.5 2.0 mg/ml 40 1.

6 116 6 MRSA28 VCM MIC E day 1.5 g/90 min mg/ml 1.0 g 2/day 1.0 g/60 min mg/ ml 1.5 g 1/day 1.5 g/90 min 1 3 VCM 4) MRSA VCM MIC E MRSA 28 VCM MIC 6 MIC mg/ml mg/ml MIC MIC 1.0 mg/ml MIC mg/ml, MIC mg/ml III. MRSA MRSA MRSA MRSA VCM (TEIC) (ABK) TDM 1) b- VCM 5 15 mg/ml 1) 30 mg/ml MRSA mg/ml VCM TDM 21 1 Ccr Ccr VCM 1 2g ) 9) TDM VCM Ccr Ccr VCM Ccr C G C G Ccr C G r 0.765, r 0.773, r r 0.95 Ccr 2), 10) Ccr 2 Ccr VCM VCM Ccr Scr Ccr 10

7 (TDM) VCM Ccr VCM r ) Ccr VCM Ccr ICU CHDF VCM CHDF VCM VCM 11, 12) VCM Scr VCM Moellering Scr Scr VCM red neck VCM VCM CLSI (Clinical and Laboratory Standards Institute) (Pharmacokinetics; PK) (Pharmacodynamics; PD) 15, 16) PK/PD MIC VCM 24 MIC AUC 24 /MIC Area Under the blood concentration Curve/MIC: /MIC 15, 16) VCM 125 AUC 24 /MIC ratio Moise VCM AUC 24 /MIC ratio ) MRSA MIC 1 mg/ml 5 mg/ml 25 mg/ml AUC 24 /MIC ratio 270 MIC MRSA VCM MIC MRSA mg/ml MIC PK/PD VCM MRSA MIC MIC TDM 14) AUC 24 /MIC MIC MRSA VCM 3 1 MRSA Ccr 1.0 g 3/day 1.0 g/60 min PK/PD AUC 24 / MIC 1.0 g 1.5 g 2/day 1.5 g/90 min 2 CHDF 3 MRSA MRSA MIC 2.0 mg/ml TDM VCM VCM VCM Ccr VCM TDM TDM VCM 11

8 118 IV. TDM TDM 79 TDM TDM Ccr Ccr VCM Ccr TDM MIC PK/PD TDM MRSA 1) 2003 p. 2 5 TDM 2) (1): ) Cockcroft, D. W., M. H. Gault, Prediction of creatinine clearance form serum creatinine. Nephron 16: ) (2): 83. 5) Ccr Scr ) 2002 STSS/EXCEL Ver4.5 87(3): ) (12): ) 1999 JJSHP 35: ) 1999 [I] MRSA TDM (ABK VCM) JJSHP 36: ) (1): ) 1999 ICU CCU 23: ) : ) 2001 N- p ) TDM MRSA VRE PK/PD 20: ) PK/PD DRG/PPS p ) Pharmacokinetics/ pharmacodynamics parameter MIC The Japanese Journal of Antibiotics 56: ) Moise, P. A, A. Forrest, S. M. Bhavnani, et al Area under the inhibitory curve and pneumonia scoring system for predicting outcomes of vancomycin therapy for respiratory infections by Staphylococcus aureus. Am. J. Health-Syst. Pharm. 57(Suppl. 2): S4 S9. 12

9 (TDM) 119 The Need for Therapeutic Drug Monitoring (TDM) When Treating Patients with Vancomycin Hydrochloride: Points to Consider Shouichi Sato, 1) Yoshiko Saito, 1) Hiroko Sato 2) 1) Department of Clinical Laboratory, Chiba Cardiovascular Center 2) Department of Clinical Laboratory, Chiba Children s Hospital To maximize the e$cacy of antimicrobial agents, it is necessary to select the most suitable antimicrobial agent for the patient, establish the most suitable dosage regimen, and monitor the patient for adverse e#ect of drug. We have performed the therapeutic drug monitoring (TDM) of vancomycin (VCM), which is frequently used to treat methicillin resistant Staphylococcus aureus (MRSA) infections. TDM has been performed on 34 patients with MRSA, together with methicillin resistant Staphylococcus epidermidis (MRSE) infection. They were treated with VCM between November 2003 and October The computer-simulation analysis showed that the rate of achieving the therapeutic range of VCM (trough values of 5 to 15 mg/ml and peak values of 25 to 40 mg/ml), was only 21. Most cases of VCM blood concentration levels were found to be below the therapeutic range. When TDM was performed by measuring the blood concentration levels of VCM, it was possible to change the dose and interval of the drug for the most suitable blood concentrations that are within the drug s therapeutic range, thus TDM was considered to be useful. We also evaluated the formula used to calculate creatinine clearance (Ccr), an important element of simulation analysis. The correlation coe$cient with observed values was approximately r 0.76, which is unacceptable for practical application. Therefore, it is necessary to measure the actual Ccr, followed by establishing dose regimen. The performance of TDM of VCM in a microbiology laboratory is suggested to contribute to the feedback of the clinically useful information, as it informs the detection of causative bacteria, the MIC of the bacteria, etc. 13

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