Case 1: Q#2 Case 1: Q#3

• 於7/13 接受vancomycin 3500 mg stat ，7/14 開始1250 • Vancomycin 調整劑量為1000 mg IV q8h (18 mg/kg/day)
mg IV q8h (23 mg/kg/day)，並於7/15監測血中濃度peak ，其間經過TDM (頻率？)，病人持續使用至7/29 ，接著
& trough。劑量應如何調整？ 改使用口服linezolid 600 mg BID並出院。
Date 7/12 7/15 7/17 7/20 7/24 Date 7/12 7/15 7/17 7/20 7/24
CRP (mg/dL) 1.43 - - CRP (mg/dl) 1.43 - - - 3.88

WBC(k/μL) 6.7 8.11 - WBC(k/μL) 6.7 8.11 - 5.71 4.9

Seg (%) 48.7 61.5 - Seg (%) 48.7 61.5 - 54.5 54.1

SCr (mg/dL) 0.8 0.7 - SCr (mg/dL) 0.8 0.7 - 0.7 0.8

Peak(mg/L) - 23.68 - Peak(mg/L) - 23.68 - - -

Trough(mg/L) - 17.86 Trough(mg/L) - 17.86 14.55 14.67 -

Monitoring Frequency Best Predictor for Activity

- Human Studies
• Treatment course < 3 days or target trough
concentrations 10~15 mcg/mL  Findings not conclusive in determining which
– 1 trough is enough parameter has the most value in predicting
• Treatment course  3~5 days: patient outcome
– At least 1 steady state trough concentration  Peak/MIC, or AUC/MIC , time > MIC
– Repeated as clinically appropriate  organism eradication or overall patient
outcome
• Target trough concentrations 15~20 mcg/mL
 AUC24/MIC ≥ 400: independent factor
– Limited data supporting the safety of sustained
associated with clinical success in the
trough concentrations of 15–20 mg/L
treatment of MRSA pneumonia
– Hemodynamically stable patients: qweek
 Free drug AUC24/MIC ≥ 160
– Hemodynamically unstable: more frequent or daily
trough Rybak MJ. CID 2006;42:S35-9. Moise-Broder PA et al. Clin Pharmacokinet 2004;43:
Rybak M, et al. Am J Health-Syst Pharm 2009;66:82-98. 925-42. Mohr JF et al. CID 2007;44:1536-42. Jeffres MN et al. Chest 2006;130:947-55.

Case 1: Q#4 Calculation of AUC/MIC (1)

 Did the vancomycin regimen achieve the
PK-PD target in this patients?

Moise-Broder PA, Clin

Pharmacokinet 2004; 43
(13): 925-942

1
Calculation of AUC/MIC (2) Case 1: Q#5
 Is there any differences in terms of PK-PD
parameters between vancomycin 1.5 g IV
q12h vs. 1 g IV q8h in the treatment of
Gram-positive infection?
 Strength:
 Simple
 Results  method #1
 Limitation:
 Not reflect differences between 1.5 g q12h vs. 1
g q8h  different troughs
 If Clvanco is estimated  accuracy?

Vancomycin Dosage Regimen in Obese Pts

Trough vs. Mortality: no Different
較低劑量組 傳統劑量組
病人數 74 64
平均維持劑量 (mg/kg/day) 19 ± 2 34 ±7
平均體重 (kg) 129 ± 29 117 ± 19
BMI (kg/m2) 44 ± 10 39 ± 6
CLCr (mL/min) 125 ± 52 128 ± 48
Trough level < 10mg/L (%)* 23 9
Trough level: 10-20 mg/L (%)* 59 36

Trough level > 20mg/L (%)* 18 55

Performance of a vancomycin dosage regimen developed for obese patients.
American journal of health-system pharmacy : AJHP : official journal of the
American Society of Health-System Pharmacists 2012;69:944-50

Trough vs. Mortality: no Different Trough vs. Mortality: no Different

Clin Microbiol Infect 2015; 21: 665–673

2
 Higher Trough  Tx Success Higher Trough  Microbiologic Success

Clin Microbiol Infect 2015; 21: 665–673 Clin Microbiol Infect 2015; 21: 665–673

Monitoring of Adverse Effects Continuous vs. Intermittent Infusion

 Infusion-related
 Phlebitis
 Red-man syndrome
 Nephrotoxicity
 Min 2 or 3 consecutive documented Scr  ( 0.5
mg/dL or a ≥50% increase from baseline,
whichever is greater) after several days of
vancomycin therapy
 Ototoxicity
 No routine monitoring unless receiving additional
ototoxic agents
 CBC Overall mortality rates
 Neutropenia Nephrotoxicity
 Thrombocytopenia
Cataldo MA, et al. J
 Others: e.g., C.difficile colitis, fever, chills, and rash
Antimicrob Chemother 2011

Question 2 – Dosing after Intermittent

Increased Risk of Nephrotoxicity
Hemodialysis
 Studies have shown an increased
nephrotoxicity of  Y.T. is a 68-year-old male with a serum creatinine
 patients >101kg of 5.2 mg/dL, height of 165 cm, and weight of 55.4
kg. He had amikacin-related nephrotoxicity so now
 receiving doses of >4g in 24 hours
on regular intermittent hemodialysis 3 times a week
 Clcr<86 ml/min
with high-flux membrane.
 ICU residence
 He was recently diagnosed MRSA bacteremia and
 use of vancomycin doses > 2000mg
started vancomycin 1500 mg IV x1 and then 500
 Concomitant meds: pip/tazo, aminoglycosides, mg IV infusion over 60 minutes after IHD.
amphotericin B, cyclosporine, etc. Determine if the dosage regimen of vancomycin is
1.Larger vancomycin doses (at least four grams per day) are associated with an increased incidence of nephrotoxicity.
Antimicrob Agents Chemother 2008;4:1330–6.
2. Impact of vancomycin treatment duration and dose on kidney injury. Int J Antimicrob Agents.2014;3:297–8.
appropriate. What is your plan for monitoring?

3
 Dialysis of Drugs
Vancomycin Pre-HD Level
Dialysis filter
 High-flux
 FX-80
12  Low-flux
Concentration

10
8
6
4
Post-dialysis replacement dose
2
0 12 24 36 48 60 72 84 96 108 120 132
Time
19 PLoS ONE. 2018;13 (3): e0193585

研究流程
• Loading dose (4劑)  Maintenance dose:

0 hr 12th 24th hr 48th 72th Usual Dose Renal Dose

hr hr hr
CLcr = 31~80
6-12 mg/kg QOD
QD CLcr =  30
Q3D

• 抽血: 3 mL (CBC管) ECMO/CRRT換新或每7天

0 hr 12 24 48 72 96

Trough level：5th T T
dose輸注前抽血 P P
Peak level：5th dose輸 換新或 換新與輸注
注完畢後等2 hrs抽血 給藥前 後2 hrs