akinohanayuki ブログ

学位を持っても、センスのない、感染制御専門薬剤師のブログ.  I have Ph.D. but less sense ID pharmacist.

vancomycin 肥満

最近、肥満の高齢者に対して、vancomycin 投与法を、悩む事が多いです。

 
なお、当院の抗MRSA薬はvancomycin のみ採用です。
 
それでは、基本を振り返りましょう。
 
UpToDate 

 

Appropriate vancomycin dosing requires consideration of the infection site, patient weight, renal function, and pathogen susceptibility.
 
Vancomycin is restricted to parenteral administration for the treatment of systemic infections. It is distributed widely to various tissues and body fluids, with a volume of distribution ranging from 0.4 to 1.0 L/kg. Penetration of vancomycin may vary by site and concomitant disease states.
 
In vitro and animal model studies describing vancomycin pharmacodynamics indicate the rate of killing depends primarily upon time of concentration exceeding the organism's minimum inhibitory concentration (MIC). The area under the time concentration curve (AUC; AUC:MIC ratio) is the best predictor of efficacy. 
 
Adverse effects of vancomycin potentially related to dosing and/or rate of administration include infusion-related reactions, nephrotoxicity, and ototoxicity. Risks of nephrotoxicity may be increased with the concomitant use of nephrotoxins (such as aminoglycosides) and/or piperacillin-tazobactam
 
Initial maintenance vancomycin dosing of 15 to 20 mg/kg should be administered to patients with normal renal function, impaired renal function, and/or obesity. For rapid achievement of target concentrations in seriously ill patients, a loading dose of 25 to 30 mg/kg may be administered. Maintenance dosing and dosing frequency should be determined based on weight and creatinine clearance. 
 
Vancomycin trough concentrations of at least 10 mcg/mL should be achieved. In the setting of invasive infections (such as endocarditis, osteomyelitis, prosthetic joint infections, and infections involving the central nervous system), many favor vancomycin trough concentrations of 15 to 20 mcg/mL.
 
Serum trough concentration monitoring should be performed in patients receiving vancomycin therapy longer than three days. Once target concentrations are achieved, the trough vancomycin concentration should be monitored at least weekly for patients in the circumstances outlined above.
 
For patients on hemodialysis, a single initial dose of 15 to 20 mg/kg should be administered following hemodialysis. For patients undergoing hemodialysis via the newer, more permeable high-flux membranes, repeat vancomycin dosing is often required following each session as described above. 
 
Obesity 
 
As with routine administration, initial dosing for obese patients of 15 to 20 mg/kg is appropriate . To avoid individual doses greater than 2 g, the total daily dose (approximately 30 mg/kg/day) can be divided into three administrations (eg, every eight hours) . The rate of infusion can also be adjusted as outlined above. 
 
関連論文
 
Am J Med. 2008;121(6):515.
Multicenter evaluation of vancomycin dosing: emphasis on obesity.
http://www.ncbi.nlm.nih.gov/m/pubmed/18501233/
  • BACKGROUND: There is a paucity of data available regarding the dosing of antimicrobials in obesity. However, data are available demonstrating that vancomycin should be dosed on the basis of actual body weight.
  • METHODS: This study was conducted at 2 tertiary care medical centers that did not have pharmacy-guided vancomycin dosing programs or other institutional vancomycin dosing policies or protocols. Patients who received vancomycin between July 1, 2003, and June 30, 2006, were stratified by body mass index and randomly selected from the computer-generated queries. Patients>or=18 years of age with a creatinine clearance of at least 60 mL/min who received vancomycin for at least 36 hours were included.
  • RESULTS: Data were collected on a random sampling of 421 patients, stratified by body mass index, who met the inclusion criteria. Most patients in each body mass index category received a fixed dose of vancomycin 2 g daily divided into 2 doses (underweight 82%, normal weight 90%, overweight 86%, and obese 91%). Adequate initial dosing (>or=10 mg/kg/dose) was achieved for 100% of underweight, 99% of normal weight, 93.9% of overweight, and 27.7% of obese patients (P<.0001). Ninety-seven percent of underweight, 46% of normal weight, 1% of overweight, and 0.6% of obese patients received>or=15 mg/kg/dose recommended by several Infectious Diseases Society of America guidelines. Pharmacists also failed to correct inadequate dosing because only 3.3% of patients receiving less than 10 mg/kg/dose had their regimen changed in the first 24 hours of therapy.
  • CONCLUSION: In this multicenter pilot study, obese patients routinely received inadequate empiric vancomycin using a lenient assessment of dosing. Greater efforts should be undertaken to ensure patients receive weight-based dosing because inadequate dosing can lead to subtherapeutic concentrations and potentially worse clinical outcomes.
 
Antimicrob Agents Chemother. 1982;21(4):575.
Vancomycin pharmacokinetics in normal and morbidly obese subjects.
http://www.ncbi.nlm.nih.gov/m/pubmed/?term=7081978
  • In an uncontrolled study, vancomycin pharmacokinetics were determined in four normal (total body weight [TBW], 65.9 to 89.1 kg) and six morbidly obese (TBW, 111.4 to 226.4 kg) subjects. The morbidly obese subjects were investigated 3 to 4 h after gastric bypass surgery. Mean terminal half-lives, volumes of distribution, and total body clearances for the normal controls and the morbidly obese (TBW, 111.4 to 226.4 kg) subjects. The morbidly obese subjects were investigated 3 to 4 h after gastric bypass surgery. Mean terminal half-lives, volumes of distribution, and total body clearances for the normal controls and the morbidly obese subjects were 4.8 h, 0.39 liter/kg, and 1.085 ml/min per kg versus 3.2 h, 0.26 liter/kg TBW, and 1.112 ml/min per kg TBW. The mean terminal half-life and volume of distribution values were significantly different between the two groups. Strong correlations were found between TBW and both volume of distribution (correlation coefficient, 0.943) and total body clearance (correlation coefficient, 0.981). There results implied that TBW should be used to calculate vancomycin doses for morbidly obese patients. This was supported by the finding that there was no significant difference in the daily dose (in milligrams per kilogram per day) required to produce an average steady-state concentration of 15 micrograms/ml in the two groups (23.4 +/- 1.5 mg/kg per day for normal weight subjects and 24.0 +/- 3.4 mg/kg per day TBW for the postsurgery morbidly obese subjects). Therefore, the morbidly obese required higher total doses (in milligrams per day) than did normal weight subjects to achieve the same mean steady-state concentrations. In addition, normal weight and morbidly obese subjects had similar volumes of the central compartment (7.7 and 6.4 liters, respectively). To avoid high transient peak concentrations which would occur when obese patients are given larger total doses (in milligrams per day), maintenance doses may be given at more frequent intervals. The shorter mean terminal half-lives observed in morbidly obese patients allows more frequent dosing without excessive accumulation.
Pharmacotherapy 2015 Sep; 35(9):869-75.
Vancomycin Dosing Considerations in a Real-World Cohort of Obese and Extremely Obese Patients.
  • STUDY OBJECTIVE
  • To compare the effects of empiric vancomycin dosing regimens on attainment of optimal target trough concentrations in obese (body mass index [BMI] 30-40 kg/m(2) ) and extremely obese (BMI ≥ 40 kg/m(2) ) patients.
  • DESIGN
  • Retrospective cohort study.
  • DATA SOURCE
  • National Veterans Affairs standardized databases.
  • PATIENTS
  • A total of 263 obese and 71 extremely obese (actual body weight range 72-244 kg in both groups) inpatients from all Veterans Affairs facilities nationally who had suspected methicillin-resistant Staphylococcus aureus pneumonia and were treated with vancomycin between 2002 and 2012.
  • MEASUREMENTS AND MAIN RESULTS
  • Patients with steady-state trough concentrations (measured ≤ 2 hours before the next vancomycin dose) and no evidence of acute kidney injury before vancomycin initiation were included. Logistic regression models were used to measure the effect of various vancomycin dosing regimens on attainment of optimal target trough concentrations (15-20 mg/L). The mean total daily vancomycin dose was lower in obese versus extremely obese patients (2005 ± 736 vs 2306 ± 934 mg, p<0.05). The mean weight-based daily dose was higher in obese patients (20 ± 7 vs 17 ± 7 mg/kg/day, p<0.05). In each group, ~ 20% of patients achieved optimal target trough concentrations. In obese patients, the standard dose of ~ 30 mg/kg/day was appropriate for target trough concentration attainment (odds ratio 5.15, 95% confidence interval 1.69-15.64). In extremely obese patients, a lower dosage of 20 to 25 mg/kg/day was appropriate for target trough concentration attainment (odds ratio 6.07, 95% confidence interval 1.01-36.51).
  • CONCLUSION
  • In this real-world study, we offer additional consideration of vancomycin dosing in obese and extremely obese patients. Extremely obese patients may require a lower weight-based daily dose than obese patients to reach target vancomycin trough concentrations.