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Last approval date 5/27/
SHC Antimicrobial Dosing Guide for Obesity
Definitions and Equations
BMI = weight (kg) height 2 (m 2 )
Body Weight Equation^1
IBW (kg) Ideal body weight
Male: 50. 0 + 2. 3 × (𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛 𝑜𝑜𝑜𝑜 𝑖𝑖𝑛𝑛𝑖𝑖ℎ𝑛𝑛𝑒𝑒 𝑜𝑜𝑜𝑜𝑛𝑛𝑛𝑛 5 𝑜𝑜𝑓𝑓) Female: 45. 5 + 2. 3 × (𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛 𝑜𝑜𝑜𝑜 𝑖𝑖𝑛𝑛𝑖𝑖ℎ𝑛𝑛𝑒𝑒 𝑜𝑜𝑜𝑜𝑛𝑛𝑛𝑛 5 𝑜𝑜𝑓𝑓) ABW (kg) Adjusted body weight
IBW + C × (TBW – IBW)
C = either 0.3 or 0.4 (ABW0.3 or ABW0.4) LBW 2005 (kg) Lean body weight
Male:
9270 × TBW
6680 + 216 × BMI
Female:
9270 × TBW
8780 + 244 × BMI
LBW (for anti- tuberculosis medications):
- Obesity: ATS/CDC Guidelines recommend dosing based on estimated lean body weight.
- Lean Body Weight (men) = (1.10 x Weight(kg)) - 128 x (Weight 2 /(100 x Height(m))^2 )
- Lean Body Weight (women) = (1.07 x Weight(kg)) - 148 x (Weight 2 /(100 x Height(m))^2 ) TBW (kg) Total/actual body weight
Table 1. 1 Recommended Antibiotic Dosing in Obesity (BMI ≥ 30 kg/m^2 )
Drug Maximum Dosea^ Study Typeb^ Comments
Case studies PK/PD studies Clinical outcomes β-lactams
Amoxicillin No Data - Consider upper limit of normal dosing in severe infections, c^ e.g. up to 1g PO TID Ampicillin Insufficient data ● - Consider upper limit of normal dosing in severe infections, c^ e.g. up to 2g q4h
- Single study with 6 patients: higher V (^) d but decreased Vd/kgTBW , CL unchanged^2 Nafcillin Insufficient data ● (^) - Single case report in critically ill, obese patient 3 : consider upper end of normal dosing in severe infections, c^ e.g. up to 2 g q4h Piperacillin- tazobactam 4-
Up to 4.5 g q8h (prolonged infused over 4 hours) or 4.5 g q6h (30 min infusion)
● ● ● - Prolonged infusion preferred for critically ill, FN, CF, obese with CrCl > 100
- infections with less susceptible pathogens (i.e. MIC ≥16) Cefazolin^15 -^21 Insufficient data ● ● - Consider upper limit of normal dosing in severe infections, e.g. up to 2 g q8h (option for continuous infusion)^22 , or 1.5-2 g q6h intermittent dosing
- In post-trauma critically ill patients, data suggests 2g q6h if CrCl > 215 ml/min. 23
WHO BMI Classification Definition Obese Class I and II (obese) BMI 30-40 kg/m 2 Obese Class III (morbidly obese) BMI ≥ 40 kg/m^2
Last approval date 5/27/
Cephalexin No data - Consider upper end of normal dosing in severe infections, c^ e.g. 500-1000 mg q6h Cefepime,
ceftazidime14,24,
Up to 2g q8h prolonged infusion ● Prolonged infusion if critically ill, CF, FN, obese with CrCl > 100 ml/min, infections with less susceptible pathogens (i.e. MIC ≥8) Ceftazidime/ avibactam26,
No change ●
Ceftolozane/ tazobactam 28
No change ●
Doripenem 14,29-31^ No change ● - Consider extended infusion if targeting a higher PD endpoint of 100% fT>MIC or with less susceptible pathogens (i.e. MIC ≥ 2) Ertapenem13,18,32-^35 No change ● ●
Imipenem No data - Use caution in renal impairment and with high doses (1g q6h): increased risk of seizures Meropenem4,9,18,30,36-^42 Same dose: consider prolonged infusion for critically ill patients
● ● - Prolonged infusion if critically ill, FN, CF, obese with CrCl > 100 ml/min, if targeting a higher PD endpoint of 100% fT>MIC, or infections with less susceptible pathogens (i.e. MIC ≥ 2)
Monobactam
Aztreonam Insufficient data ● - Single case report suggests higher dosing needed^43
- Consider upper end of normal dosing in severe infections, c^ e.g. 2g q6-8h Fluoroquinolones
Ciprofloxacin^44 -^47 In critically ill, septic patients on CRRT with organisms with MICs > 0.5mg/L (e.g. P.aeruginosa, A.baumannii ): > 90kg: 400 mg IV q8h
● ● - Insufficient data except as noted in critically ill, septic patients on CRRT.
- Consider upper end of normal dosing in severe infections, c^ e.g. up to 400 mg IV q8h or 750mg PO BID
Levofloxacin^48 -^51 750 mg q24h ● ● - PK reportedly unaltered by obesity, however, serum levels may be sensitive to CrCl: 1,000 mg q24h has been suggested for CrClIBW > 110 ml/min to target gram negative pathogens Moxifloxacin^52 -^54 No change ●
Aminoglycosides
Amikacin^55 -^57 Use adjusted body weight (ABW0.4)
for initial dose
● - Adjust by TDM
Gentamicin^55 -^61 Use adjusted body weight (ABW0.4)
for initial dose
● - Adjust by TDM
Tobramycin^55 - 57,61,62^ Use adjusted body weight (ABW0.4) for initial dose
● - Adjust by TDM
Polymyxins
Colistin methanesulfonate63-
Use IBW ● - Maximum dose of 360 mg daily to limit the risk of nephrotoxicity
Polymyxin B^67 -^70 Limited data. Consider adjusted
body weight (ABW0.4), especially in upper end of dosing range
● - Consider maximum dose 200 mg or 2 million units daily to limit risk of toxicity
Anti-MRSA agents
Last approval date 5/27/
Table 2. Recommended Antifungal Dosing in Obesity (BMI ≥ 30 kg/m^2 )
Drug Maximum Dosea^ Study Typeb^ Comments
Case studies PK/PD studies Clinical outcomes Caspofungin 133 -^135 70 mg x1, then 50-70 mg daily ● ● - Retrospective study from 9 clinical studies found no significant difference in favorable responses in invasive candidiasis between obese and non- obese groups
- PK studies showed no correlation with BMI and PK parameters, but did find negative correlation between caspofungin peak levels and body weight, suggests increased doses needed for higher TBW
- In clinical trial of invasive candidemia, no safety concerns found with caspofungin 150mg daily Fluconazole^135 -^139 Candidiasis: 12mg/kg x1 load, then 6mg/kg q24h (TBW)
● ● ● - Doses up to 1200 mg daily have been reported in the literature for Cryptococcus meningitis
- In critically ill, esp with CrCl > 50, higher doses may be warranted to achieve PK/PD target of fAUC/MIC > 100, esp if MIC > 2 Candida spp
- Consider TDM for severe infections Flucytosine^135 IBW, then adjust by level ● - Single case report.
- Adjusted body weight has been suggested in life-threatening infections Liposomal Amphotericin 135
Total or adjusted body weight in severe infections
Alternative: fixed dose for ≥ 100kg, i.e. 300mg max for 3mg/kg or 500mg max for 5mg/kg. 150
● ● (^) - Limited PK data in obese humans based on 1- 2mg/kg single dose PK; in general pop PK studies, linear increase in Vd and CL with weight
- PK reported to be non-linear at >5mg/kg doses (max Cmax and AUC at 10mg/kg/day)
- Safety data: at doses 7.5-15mg/kg/day, similar discontinuation rates, but high rate (up to 40%) of kidney injury Voriconazole, 135,140- 145
Use adjusted body weight or LBW 2005 ● ● - Adjust dosing based on TDM
- Retrospective TDM studies frequently showed supratherapeutic levels in obese subjects when dosed by TBW
- Steady state plasma PK of voriconazole did not suggest weight-based dose adjustments necessary
Last approval date 5/27/
Table 3. Recommended Antiviral Dosing in Obesity (BMI ≥ 30 kg/m^2 )
Drug Maximum Dosea^ Study Typeb^ Comments
Case studies PK/PD studies Clinical outcomes
Acyclovir^146 -^148 Use ideal or adjusted body weight ● ● (^) - PK study: 5mg/kg IV x1 showed that dosing based on IBW in obese patients led to lower AUC than dosing by TBW in normal-weight patients. Authors suggest using ABW
- Renal function may be a more important consideration than weight-based dosing in obese patients Cidofovir^149 Use adjusted body weight - No data
- Based on similar PK profile and physiochemical properties as acyclovir, long intracellular half-life (except foscarnet, which deposits in bone), dose-limiting toxicity (e.g. myelosuppression)
Foscarnet^149 Use adjusted body weight
Ganciclovir^149 Use adjusted body weight
DOCUMENT INFORMATION
A. Original Author/Date Lina Meng, PharmD, BCIDP, BCCCP: 12/27/
B. Gatekeeper SASS Program
C. Review and Renewal Requirement This document will be reviewed every three years and as required by change of law or practice
D. Revision/Review History Lina Meng, PharmD, BCIDP, BCCCP: 07/24/2017, 5/22/ Emily Mui, PharmD, BCIDP: 03/27/2017, 07/24/2017, 5/22/ Will Alegria PharmD, BCIDP: 5/22/ David Ha, PharmD, BCIDP: 5/22/ Marisa Holubar MD MS: 03/27/2017, 07/24/ Stan Deresinski MD: 03/27/2017, 07/24/
E. Approvals Antimicrobial Subcommittee: 3/30/2017, 8/17/2017, 5/27/ Pharmacy and Therapeutics Committee: 4/21/2017, 9/15/
This document is intended only for the internal use of Stanford Health Care (SHC). It may not be copied or otherwise used, in whole, or in part, without the express written consent of SHC. Any external use of this document is on an AS IS basis, and SHC shall not be responsible for any external use. Direct inquiries to ASP 650-721-
Stanford Health Care Stanford, CA 94305
Last approval date 5/27/
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