2005 111 (TDM) 1) 1) 2) 1) 2) 16 12 1 17 7 29 (MRSA) (VCM) 2003 11 2004 10 MRSA VCM 34 VCM 1) 5 15 mg/ml 25 40 mg/ml 21 (TDM) (Ccr) Ccr TDM MIC Key words: VCM, TDM, MRSA, PK/PD (TDM; Therapeutic Drug Monitoring) (VCM) ( 290 0512) 575 TEL: 0436 88 3111 FAX: 0436 88 3032 E-mail: s-shouichi icntv.ne.jp (MRSA) VCM TDM TDM I. 1) VCM TDM 2003 11 2004 10 MRSA VCM 34 TDM VCM-TDM on EXCEL VCM-TDM VCM 5
112 2) VCM VCM VCM- VCM- (Ccr) 2) Ccr (Scr) Ccr Scr Ccr Ccr 2 886 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 33 0.065 0.493 BMI (kg)/scr (mg/ dl)/14.4 Ccr 21 0.030 0.216 BMI (kg)/scr (mg/ dl)/14.4 3) VCM-TDM VCM 3 VCM TDX; 4) MRSA VCM MIC 2004 4 2004 10 MRSA28 E MIC E 2 (AST-P525) 1 mg/ml E 0.013 mg/ml II. 1) TDM VCM VCM 34 VCM 1 VCM 5 15 mg/ml VCM 1 25 40 mg/ml 1) 7 21 14 41 9 27 13 38 5 15 30 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 13.49 3 Ccr ( p 0.05) 95 Ccr 70 ml/min 95 30ml/min, 95 116 ml/min 1 VCM 5 mg/ml 5 15 mg/ml 15 mg/ml 25 g/ml 13 (38) 6 (18) 19 (56) 25 40 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
(TDM) 113 VCM 2 Ccr 70 ml/min (0.75 g 2/day) 30 ml/ min VCM 4 116 ml/min 3) VCM-TDM VCM 1: 28 2004 2 16 1g 2/day 2 21 38 18000/ml, CRP 16.1 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 1.0 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) 95 30 ml/min VCM 4 95 116 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 39.9 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 25 40 mg/ml 1.0 g 1.0 g/60 min 36 MRSA 1.5 g 1/ 36 1.5 g/90 min 4 MRSA 7 29 3: 60 B 16 12 1 X 12 7 12 12 MRSA MRSA VCM 12 15 MRSA VCM MRSA MIC 1 mg/ml Scr 1.7 mg/dl VCM 1.0 g 1/day 1.0 g/60 min 12 20 Scr 0.9 mg/dl MRSA MIC 2 mg/ml VCM 1.5 g 2/ 8
(TDM) 115 4 2 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 1.0 mg/ml MIC MIC 1.0 mg/ml MIC 50 1.0 mg/ml, MIC 90 1.5 mg/ml III. MRSA 40 80 2003 38 MRSA MRSA MRSA VCM (TEIC) (ABK) TDM 1) b- VCM 5 15 mg/ml 1) 30 mg/ml MRSA 25 40 mg/ml VCM TDM 21 1 Ccr Ccr VCM 1 2g 2 4 31 7) 9) TDM VCM Ccr Ccr VCM Ccr C G C G Ccr C G r 0.765, r 0.773, r 0.787 r 0.95 Ccr 2), 10) Ccr 2 Ccr VCM VCM Ccr Scr Ccr 10
(TDM) 117 3 VCM Ccr VCM r 0.97 11) 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 345 78 17) MRSA MIC 1 mg/ml 5 mg/ml 25 mg/ml AUC 24 /MIC ratio 270 MIC MRSA VCM MIC MRSA 40 1.0 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
118 IV. TDM TDM 79 TDM TDM Ccr Ccr VCM Ccr TDM MIC PK/PD TDM MRSA 1) 2003 p. 2 5 TDM 2) 2004 32(1): 59 63. 3) Cockcroft, D. W., M. H. Gault, 1976. Prediction of creatinine clearance form serum creatinine. Nephron 16: 31 41. 4) 1980 101(2): 83. 5) 1996. Ccr Scr 7 54 57. 6) 2002 STSS/EXCEL Ver4.5 87(3): 34 62. 7) 2003 31(12): 1279 1283. 8) 1999 JJSHP 35: 955 958. 9) 1999 [I] MRSA TDM (ABK VCM) JJSHP 36: 311 315. 10) 2002 33(1): 191 192. 11) 1999 ICU CCU 23: 371 375. 12) 2001 2169: 718 722. 13) 2001 N- p. 269 272 14) 2004. TDM MRSA VRE PK/PD 20: 1158 1163. 15) 2004. PK/PD DRG/PPS p. 27 40 16) 2003. Pharmacokinetics/ pharmacodynamics parameter MIC The Japanese Journal of Antibiotics 56: 697 704. 17) Moise, P. A, A. Forrest, S. M. Bhavnani, et al. 2000. 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
(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$cacy of antimicrobial agents, it is necessary to select the most suitable antimicrobial agent for the patient, establish the most suitable dosage regimen, and monitor the patient for adverse e#ect of drug. We have performed the therapeutic drug monitoring (TDM) of vancomycin (VCM), which is frequently used to treat methicillin resistant Staphylococcus aureus (MRSA) infections. TDM has been performed on 34 patients with MRSA, together with methicillin resistant Staphylococcus epidermidis (MRSE) infection. They were treated with VCM between November 2003 and October 2004. The computer-simulation analysis showed that the rate of achieving the therapeutic range of VCM (trough values of 5 to 15 mg/ml and peak values of 25 to 40 mg/ml), was only 21. Most cases of VCM blood concentration levels were found to be below the therapeutic range. When TDM was performed by measuring the blood concentration levels of VCM, it was possible to change the dose and interval of the drug for the most suitable blood concentrations that are within the drug s therapeutic range, thus TDM was considered to be useful. We also evaluated the formula used to calculate creatinine clearance (Ccr), an important element of simulation analysis. The correlation coe$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