Infectious Disease Compendium

Adult Weight-Based Antimicrobial Dosing Protocol

Adult Weight-Based Antimicrobial Dosing Protocol

Legacy Health Modified from original work by Lindsie M. Froehlich, PharmD
  ADULT WEIGHT-BASED ANTIMICROBIAL DOSAGE ADJUSTMENT TABLE

CrCr Formula are at bottom of page

 

WEIGHT (kg)

CrCl > 50

CrCl 30 – 50

CrCl 10 – 30

CrCl <10

PENICILLINS

Ampicillin

<80

1gm q6hb

1gm q8

1gm q12h

1gm q24h

80-139

2gm q6ha

2gm q8h

2gm q12h

2gm q24h

>140

3gm q6ha

3gm q8h

3gm q12h

3gm q24h

Nafcillin

< 100

2gm q4h

No dosage adjustment necessary

>100

3gm q4h

Penicillin G

< 100

3mU q4h

2mU q4h

2mU q8h

1mU q8h

>100

4mU q4h

3mU q4h

3mU q8h

2mU q8h

Ampicillin/sulbactam

< 80

1.5gm q6h

1.5gm q8h

1.5gm q12h

1.5gm q24h

80 – 139

3gm q6h

3gm q8h

3gm q12h

3gm q24h

>140

4.5gm q6h

4.5gm q8h

4.5gm q12h

4.5gm q24h

Piperacillin/tazobactam

 

CrCl >40

CrCl 20 – 40

CrCl <20

 

< 100

PSE

3.375gm q6

2.25gm q6h*

2.25gm q8h*

4.5gm q6h

3.375gm q6h*

2.25gm q6h*

100 - 139

PSE

3.375gm q4h

2.25gm q4h*

2.25gm q6h*

4.5gm q4h

3.375gm q4h*

2.25gm q4h*

>140

PSE

4.5gm q6h

3.375gm q6h*

2.25gm q6h*

6gm q6h

4.5gm q8h*

3.375gm q8h*

CEPHALOSPORINS

Cefazolin

< 80

1gm q8h

500mg q12h*

500mg q24h*

80 – 149

2gm q8h

1gm q12h*

1gm q24h*

>150

3gm q8h

2gm q12h*

2gm q24h*

Ceftazidime

< 80

1gm q8h

1gm q12h

1gm q24h

500mg q24h*

80 – 149

2gm q8h

2gm q12h

2gm q24h

1gm q24h*

>150

3gm q8h

3gm q12h

3gm q24h

1gm q24h*

Ceftriaxone

< 80

1gm q24h

No dosage adjustment necessary

80 - 129

2gm q24h

>130

3gm q24h

Cefotetan

< 80

1gm q12h

Same dose

1gm IV q24h

1gm q48h

81 – 139

2gm q12h

Same dose

2gm q24h

2gm q48h

>140

3gm q12h

Same dose

3gm q24h

3gm q48h

Cefepime

< 100

1gm q8h

1gm q12h

1gm q24h

500mg q24h*

>100

2gm q8h

2gm q12h

2gm q24h

1gm q24h*

CARBAPENEMS

Ertapenem

< 100

1gm q24h

Same dose

500mg q24h*

Same dose*

>100

2gm q24h

Same dose

1gm q24h*

500mg q24h*

Meropenem

< 100

1gm q8h

1gm q12h

500mg q12h*

500mg q24h*

>100

2gm q8h

2gm q12h

1gm q12h*

1gm q24h*

FLUOROQUINOLONES

Ciprofloxacin

< 100

400mg q12h

400mg q24h

200mg q24h*

101 - 139

600mg q12h

600mg q24h

300mg q24h*

>140

800mg q12h

800mg q24h

400mg q24h*

Moxifloxacin

< 100

400mg q24h

No dosage adjustment necessary

101 – 139

600mg q24h

>140

800mg q24h

>150

750mg q24h

 

WEIGHT (kg)

CrCl > 50

CrCl 30 – 50

CrCl 10 – 30

CrCl <10

MISCELLANEOUS

Aztreonam

< 80

1gm q6h

500mg q6h*

250mg q6h*

>80

2gm q6h

1gm q6h*

500mg q6h*

Clindamycin

< 80

600mg q8h

No dosage adjustment necessary

>80

900mg q8h

Daptomycin

Use TBW

4-6 mg/kg q24h

q48h

Fluconazole

<80

400mg q24h

200mg q24h*

80 - 149

800mg q24h

400mg q24h*

>150

1200mg q24h

600mg q24h*

Linezolid

< 150

600mg q12h

No dosage adjustment necessary

>150

600mg q8h

*Give loading dose as if normal renal function x 1, then decrease dose per protocol

a Use same dose q4h for endocarditis and meningitis

b Use 2 gm q4h forendocarditis and meningitis PSE = Pseudomonas infection (excluding urinary tract infection TBW: Total body weight (kg)    

A. Aminoglycosides

1.    Empiric dosing should be based off of an adjusted body weight calculation using a correction factor of 40%

                        ABW = (TBW – IBW) x 0.4 + IBW

            2.  Use normal empiric dosing intervals based on renal function.

            3.  DO NOT use extended interval dosing in the obese population.

            4.  Follow peak and trough levels and adjust dose accordingly.

B. Vancomycin

1.     Patients should receive an initial loading dose of 15 mg/kg based on total body weight.  Maximum single dose = 3gm

2.     Empiric dosing should be continued using total body weight for a total daily dose of 20 – 30 mg/kg/day  with a single dose cap of 3gm.

3.     Vancomycin is a time dependent antibiotic, so shorten administration interval to q6h in patients with normal renal function if necessary to maintain serum trough >10.

4.     Check trough levels regularly and adjust dose accordingly, see LHS protocol for specific trough recommendations

Obesity Dosing Quick Reference Sheet

Drug

IBW

TBW

DW

Comments

Acyclovir

x

   

No need to adjust fixed doses for obese patients

Amikacin

   

x

DW = 0.4 (TBW – IBW) + IBW

Amphotericin B

 

x

 

TBW for both conventional and liposomal

Ampicillin

 

x

   

Azithromycin

x

   

No need to adjust fixed doses for obese patients

Ciprofloxacin

   

x

DW = 0.45 (TBW – IBW) + IBW

Cyclosporine

x

     

Daptomycin

 

x

   

Erythromycin

x

     

Ethambutol

x

     

Fluconazole

 

x

   

Gentamicin

   

x

DW = 0.4 (TBW – IBW) + IBW

Isoniazid

x

   

No need to adjust fixed doses for obese patients

Linezolid

   

x

 

Moxifloxacin

   

x

 

Pyrazinamide

x

     

Rifampin

x

   

No need to adjust fixed doses for obese patients

Tobramycin

   

x

DW = 0.4 (TBW – IBW) + IBW

Trimethoprim/SMZ

   

x

DW = 0.4 (TBW – IBW) + IBW

Vancomycin

 

x

 

Monitor serum trough levels. Max of 3gms, increase frequency

Abbreviations: IBW= ideal body weight, TBW=total body weight, DW=Dosing weight (use correction factor (CF)), MD=maintenance dose, LD=loading dose

BACKGROUND

In general, the volume of distribution (Vd) of hydrophilic drugs relates better to lean body mass because of poor penetration into adipose tissue and the Vd of lipophilic drugs correlates better with total body weight because of good penetration into adipose tissue8-10.

HYDROPHILIC3

LIPOPHILIC

>       B-lactams

-        Penicillins

-        Cephalosporins

-        Monobactams

-        Carbapenems

>       Daptomycin

>       Glycopeptides

                  -      Vancomycin

>       Aminoglycosides

>       Polymyxins

>       Aztreonam

>       Fluoroquinolones

>       Macrolides

>       Lincosamides

>       Linezolid

>       Tetracyclines

>       Tigecycline

>       Sulfamethoxazole/trimethoprim

>       Rifampin

 CREATININE CLEARANCE IN OBESITY19-27

Obese patients tend to have a higher creatinine clearance.   Commonly used equations to estimate creatinine clearance( CrCl) may not be accurate predictors of clearance in the obese.  The Cockcroft-Gault formula is less accurate when total body weight (TBW) is used to estimate CrCl in obese patients21.  

The Salazar-Corcoran formula appears to be the more accurate of all the currently available renal function formulas9.

When a lean body weight (LBW) estimate, based on TBW and body mass index (BMI) was used in the Cockcroft-Gault equation, it provided an accurate, relatively precise estimate of CrCl27.

Salazar-Corcoran on line calculator19

Male: (137 – age) x ([0.285 x TBW] + [12.1 x height in meters]2)

                                            51 x SCr

Female:  (146 – age) x ([0.287 x TBW] + [9.74 x height in meters]2)

                                               60 x SCr

TBW = total body weight (kg)

Cockcroft-Gault using Adjusted Body Weight (Adj. BW) on line calculator 22

Male: (140-age) x Adj. BW                                   IBW male:  [2.3 + (height(in) – 60] + 50

               72 x SCr                                             

Female: (140 – age) x Adj. BW  x 0.85                  IBW female:  [2.3 + (height(in) – 60)] + 50

            72 x SCr

Adj. BW:  (TBW – IBW) x 0.4 + IBW

Cockcroft-Gault using Lean Body Weight (LBW) on line calculator 27

Male: (140-age) x LBW                                        LBW male:        9270 x TBW

                72 x SCr                                                                   6680 +216 x BMI

Female: (140-age) x LBW  x 0.85                          LBW female:     9270 x TBW

                72 x SCr                                                                  8780 +244 x BMI

Body Mass Index (BMI) on line calculator

BMI = Weight (lbs) x 703

               Height2 (in2)

References

1. Overweight and obesity: home. Department of Health and Human Services: centers for Disease Control and Prevention. Accessed at:http://www.cdc.gov/nccdphp/dnpa/obesity/index.htm. Updated 2009 Aug 27. Accessed September 13, 2009.   2. Falagas ME, Karageorgopoulos DE. Adjustment of dosing of antimicrobial agents for bodyweight in adults. Lancet. 2010;  375: 248-251. 3. FalagasME, Athanasoulia AP, Peppas G, Karageorgopoulos DE. Effect of body mass index on the outcome of infections: a systematic review. Obes Rev 2009; 10: 280-89. 4. Falagas ME, Kompoti M. Obesity and infection. Lancet Infect Dis 2006; 6: 438-46. 5. Bosma RJ, Krikken JA, HJoman van der Heide JJ, de Jong PE, Navis GJ. Obesity and renal hemodynamics. Contrib Nephrol 2006.; 151: 184-202. 6. Wurtz R, Itokazu G, Rodvold K. Antimicrobial dosing in obese patients. Clin Infect Dis 1997; 25 (1):112-8. 7. Cheymol G. Effects of obesity on pharmacokinetics implications for drug therapy. Clin Pharmacokinet 2000; 39 (3):215-31. 8. Bearden DT, Rodvold KA. Dosage adjustments for antibacterials in obese patients applying clinical pharmacokinetics. Clin Pharmacokinet 2000; 38 (5):415-26.

9. Pai MP, Bearden DT. Antimicrobial dosing considerations in obese adult patients. Pharmacotherapy 2007;27:1081.. 10. Blouin RA, Kolpek JH, Mann HJ. Influence of obesity on drug disposition. Clin Pharm 1987; 6 (9):706-14. 11. Vachharajani V, Vital S. Obesity and Sepsis. J Intens Care Med 2006; 21(5):288-95. 12. Han PY, Duffull SB, Kirkpatrick CMJ, Green B. Dosing in obesity: a simple solution to a big problem. Clin Pharm Ther 2007; 82(5):505-8. 13. Dellit TH, Owens RC, McGowan JE et al. Infectious diseases society of America and the society for healthcare epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis 2007; 44:159-77. 14. Owens RC. Antimicrobial stewardship: application in the intensive care unit. Infect Dis Clin North Am 2009; 23(3) 683-702. 15. Owens R, Ambrose PG, Nightingale CH. Antibiotic Optimization. Taylor & Francis Group 2005. Boca Raton, FL. Pg 261-326.

16. Bauer LA, Edwards WA, Dellinger EP et al. Influence of weight on aminoglycoside pharmacokinetics in normal weight and morbidly obese patients. Eur J Clin Pharmacol 1983; 24 (5):643-7.

17. Leader WG, Tsubaki T, Chandler MH. Creatinine-clearance estimates for predicting gentamicin pharmacokinetic values in obese patients. Am J Hosp Pharm 1994; 51 (17):2125-30. 18. Traynor AM, Nafziger AN, Bertino JS, Jr. Aminoglycoside dosing weight correction factors for patients of various body sizes. Antimicrob Agents Chemother 1995; 39 (2):545-8. 19. Salazar DE, Corcoran GB. Predicting creatinine clearance and renal drug clearance in obese patients from estimated fat-free body mass. Am J Med 1988; 84 (6):1053-60. 20. Spinler SA, Nawarskas JJ, Boyce EG, Connors JE, Charland SL, Goldfarb S, for the Iohexol Cooperative Study Group. Predictive performance of ten equations for estimating creatinine clearance in cardiac patients. Ann Pharmacother 1998;32:1275–83. 21. Snider RD, Kruse JA, Bander JJ, Dunn GH. Accuracy of estimated creatinine clearance in obese patients with stable renal function in the intensive care unit. Pharmacotherapy 1995;15:747–53. 22. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16 (1):31-41. 23. Dionne RE, Bauer LA, Gibson GA et al. Estimating creatinine clearance in morbidity obese patients. Am J Hosp Pharm 1981; 38 (6):841-4. 24. Erstad BL. Which weight for weight-based dosage regimens in obese patients? Am J Health Syst Pharm 2002; 59 (21):2105-10. 25. Green B, Duffull SB. What is the best size descriptor to use for pharmacokinetic studies in the obese? Br J Clin Pharmacol. 2004; 58:119-133. 26. Spinler SA, Nawarskas JJ, Boyce EG, et al.  Predictive performance of ten equations for estimating creatinine clearance in cardiac patients. Iohexol Cooperative Study Group.  Ann Pharmacother. 1998 Dec;32(12):1275-83. 27. Demirovic JA, Pai AB, Pai MP. Estimation of creatinine clearance in morbidly obese patients. Am J Health-Syst Pharm 2009; 66:642-8. 28. Lodise TP, Lomaestro BM, Drusano GL. Application of antimicrobial pharmcodynamic concepts into clinical practice: focus on B-lactam antibiotics.  Pharmacother 2006; 26(9):1320-32. 29. Kampmann JP, Klein H, Lumholtz B et al. Ampicillin and propylthiouracil pharmacokinetics in intestinal bypass patients followed up to a year after operation. Clin Pharmacokinet 1984; 9 (2):168-76. 30. Yuk J, Nightingale CH, Sweeney K et al. Pharmacokinetics of nafcillin in obesity. J Infect Dis 1988; 157 (5):1088- 31.  Abdullahi M, Annibale B, Capoccia D et al.  The eradication of helicobacter pylori is affected by body mass index (BMI). Obes Surg 2008; 18:1450-1454 32. Newman D, Scheetz MH, Adeyemi OA et al. Serum piperacillin/tazobactam pharmacokinetics in a morbidly obese individual. Ann Pharmacother 2007; 41:1734-9. 33. Kim MK, Capitano B, Mattoes HM. Pharmacokinetic and pharmacodynamic evaluation of two dosing regimens for piperacillin-tazobactam. Pharmacother 2002; 22(5):569-77. 34. Yost RL, Derendorf H. Disposition of cefotaxime and its desacetyl metabolite in morbidly obese male and female subjects. Ther Drug Monit 1986; 8 (2):189-94. 35. Chiba K, Tsuchiya M, Kato J, Ochi K, Kawa Z, Ishizaki T. Cefotiam disposition in markedly obese athlete patients, Japanese sumo wrestlers. Antimicrob Agents Chemother 1989;33:1188–92. 36. Mann HJ, Buchwald H. Cefamandole distribution in serum, adipose tissue, and wound drainage in morbidly obese patients. Drug Intell Clin Pharm 1986;20:869–73. 37. Pories WJ, van Rij AM, Burlingham BT, Fulghum RS, Meelheim D. Prophylactic cefazolin in gastric bypass surgery. Surgery 1981;90:426–32. 38. Mehta U, Malone M, Alger S. Cefazolin use in clinically severe obese patients undergoing gastric restrictive surgery. Ann Pharmacother 1995;29:935–6. 39. Forse RA, Karam B, MacLean LD et al. Antibiotic prophylaxis for surgery in morbidly obese patients. Surgery 1989; 106 (4):750-6; discussion 6-7. 40. Edmiston CE, Krepel C, Kelly H et al. Perioperative antibiotic prophylaxis in the gastric bypass patient: Do we achieve therapeutic levels? Surgery 2004: 136:738-47. 41. Bertino JS, Michalak C, Victory A, et al. Comparative Pharmacokinetics of Ertapenem in Normal Weight Obese and Morbidly Obese Adults. In: 44th Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, D.C.;2004. 42. Bearden DT, Earle SB, McConnell DB et al. Pharmacokinetics of Meropenem in Extreme Obesity. Poster presented at the 45th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2005 Dec; Washington,DC.

43. Caldwell JB, Nilsen AK. Intravenous ciprofloxacin dosing in a morbidly obese patient. Ann Pharmacother 1994; 28 (6):806.

44. Hollenstein UM, Brunner M, Schmid R, et al. Soft tissue concentrations of ciprofloxacin in obese and lean subjects following weight-adjusted dosing. Int J Obes Relat Metab Disord 2001;25:354. 45. Allard S, Kinzig M, Boivin G et al. Intravenous ciprofloxacin disposition in obesity. Clin Pharmacol Ther 1993; 54 (4):368-73.

46. Boccazzi A, Langer M, Mandelli M, Ranzi AM, Urso R.  The pharmacokinetics of aztreonam and penetration into the bronchial secretions of critically ill patients.  J Antimicrob Chemother. 1989 Mar;23(3):401-7.     47. Erstad BL. Dosing of medications in morbidly obese patients in the intensive care unit setting. Intensive Care Med 2004; 30 (1):18-32. 48. Honiden S, McArdle JR. Obesity in the intensive care unit. Clin Chest Med 2009; 30:581-599. 49. Dvorchik BH, Damphousse D. The pharmacokinetics of daptomycin in moderately obese, morbidly obese, and matched nonobese subjects. J Clin Pharmacol 2005; 45 (1):48-56. 50. Pai MP, Mercier RC, Allen SE. Using vancomycin concentrations for dosing daptomycin in a morbidly obese patient with renal insufficiency. Ann Pharmacother 2006; 40:533-8. 51. Pai MP, Norenberg JP, Anderson T et al. Influence of obesity on the single-dose pharmacokinetics of daptomycin. Antimicrob Agent Chemo 2007; 51(8):2741-47. 52. Cohen LG, DiBiasio A, Lisco SJ et al. Fluconazole serum concentrations and pharmacokinetics in an obese patient. Pharmacotherapy 1997; 17 (5):1023-6. 53. Penk PL. Special pharmacokinetics of fluconazole in septic, obese, and burn patients. Mycoses 1999; 42(2):87-90. 54. Stein GE, Schooley SL, Peloquin CA et al. Pharmacokinetics and pharmacodynamics of linezolid in obese patients with cellulitis. Ann Pharmacother 2005; 39 (3):427-32. 55. Mersfelder TL, Smith CL. Linezolid pharmacokinetics in an obese patient. Am J Health-Syst Pharm 2005;62:464, 467. 56. Bauer LA, Black DJ, Lill JS. Vancomycin dosing in morbidly obese patients. Eur J Clin Pharmacol 1998; 54 (8):621-5. 57. Blouin RA, Bauer LA, Miller DD et al. Vancomycin pharmacokinetics in normal and morbidly obese subjects. Antimicrob Agents Chemother 1982; 21 (4):575-80. 58. Vance-Bryan K, Guay DR, Gilliland SS et al. Effect of obesity on vancomycin pharmacokinetic parameters as determined by using a Bayesian forecasting technique. Antimicrob Agents Chemother 1993; 37 (3):436-40. 59. Hall RG, Payne KD, Bain AM. Multicenter evaluation of vancomycin dosing: emphasis on obesity. Am J Med 2008; 121:515-18. 60. Ducharnme MP, Slaughter RL, Edwards DJ. Vancomycin pharmacokinetics in a patient population: effect of age, gender, and body weight. Ther Drug Monit 1994; 16:513-18. 61. Lodise TP, Lomaestro B, Graves J, Drusano GL. Larger vancomycin doses (at least 4 grams per day) are associated with an increased incidence of nephrotoxicity. Antimicro Agent Chemo 2008; 52:1330-36.

62. Nasraway SA Jr, Albert M, Donnelly AM, Ruthazer R, Shikora SA, Saltzman E. Morbid obesity is an independent determinant of death among surgical critically ill patients. Crit Care Med 2006;34:964–70.