Dosing of antibacterial agents in obese adults: Does one size fit all?

Expert Review of Anti-Infective Therapy

Volumn 12, Issue 7, 2014, Pages 829-854

  Payne, Kenna D ^a   Hall, Ronald G ^a,b  

^a TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER   (United States)

^b Dose Optimization and Outcomes Research (DOOR) Program   (United States)

Author keywords

Antibacterial; BMI; Body weight; Dose adjustment; Obesity; Pharmacokinetics

Indexed keywords

AMOXICILLIN; ANTIINFECTIVE AGENT; CARBAPENEM DERIVATIVE; CEFAZOLIN; CEFOTAXIME; CEFOTETAN; CEFOXITIN; CEFUROXIME; CEPHALOSPORIN DERIVATIVE; CILASTATIN PLUS IMIPENEM; CIPROFLOXACIN; CLARITHROMYCIN; CREATINE KINASE; DAPTOMYCIN; DORIPENEM; ERTAPENEM; GLYCYLCYCLINE DERIVATIVE; LINEZOLID; MEROPENEM; MOXIFLOXACIN; NAFCILLIN; OXAZOLIDINONE DERIVATIVE; PANTOPRAZOLE; PENICILLIN DERIVATIVE; PIPERACILLIN PLUS TAZOBACTAM; POLYPEPTIDE ANTIBIOTIC AGENT; QUINOLINE DERIVED ANTIINFECTIVE AGENT; TIGECYCLINE; UNINDEXED DRUG; VANCOMYCIN;

ANTIBIOTIC PROPHYLAXIS; ANTIBIOTIC SENSITIVITY; AREA UNDER THE CURVE; BACTERIAL PNEUMONIA; BACTEROIDES FRAGILIS; BODY MASS; BODY SURFACE; BODY WEIGHT; CREATINE KINASE BLOOD LEVEL; CREATININE CLEARANCE; DOSE CALCULATION; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG DOSE INCREASE; DRUG DOSE REGIMEN; DRUG EXPOSURE; DRUG HALF LIFE; DRUG MEGADOSE; DRUG PENETRATION; DRUG SAFETY; DRUG TISSUE LEVEL; ENDOCARDITIS; ENTEROBACTERIACEAE INFECTION; ENTEROCOCCUS FAECIUM; FAT FREE MASS; FINEGOLDIA MAGNA; GLOMERULUS FILTRATION RATE; HELICOBACTER INFECTION; HUMAN; KIDNEY CLEARANCE; METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS; METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS INFECTION; MINIMUM INHIBITORY CONCENTRATION; NEPHROTOXICITY; OBESITY; REVIEW; SEPSIS; SINGLE DRUG DOSE; STAPHYLOCOCCUS INFECTION; SURGICAL INFECTION; TREATMENT DURATION; TREATMENT OUTCOME; VANCOMYCIN RESISTANT ENTEROCOCCUS; ADULT; CHEMISTRY; COMPLICATION; FEMALE; HALF LIFE TIME; MALE;

ADULT; ANTI-BACTERIAL AGENTS; BODY MASS INDEX; DRUG DOSAGE CALCULATIONS; FEMALE; HALF-LIFE; HUMANS; MALE; OBESITY;

EID: 84902522639     PISSN: 14787210     EISSN: 17448336     Source Type: Journal    
DOI: 10.1586/14787210.2014.912942     Document Type: Review

References (94)

1. Finucane MM, Stevens GA, Cowan MJ, et al. National. regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet 2011;377(9765):557-67
2. Flegal KM, Carroll MD, Ogden CL, Curtin LR. Prevalence and trends in obesity among US adults, 1999-2008. JAMA 2010; 303(3(235):41
3. F as in fat: how obesity threatens America's future. 2013. Available from: http://healthyamericans.org/assets/files/TFAH2013FasInFatReportFinal%209. 9.pdf [Last accessed on 16 January 2014]
4. Pai MP. Estimating the glomerular filtration rate in obese adult patients for drug dosing. Adv Chronic Kidney Dis 2010;17(5):e53-62
5. West GB, Brown JH, Enquist BJ. A general model for the origin of allometric scaling laws in biology. Science 1997;276(5309): 122-6
6. West GB, Brown JH, Enquist BJ. The fourth dimension of life: fractal geometry and allometric scaling of organisms. Science 1999;284(5420):1677-9
7. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16(1):31-41
8. Winter MA, Guhr KN, Berg GM. Impact of various body weights and serum creatinine concentrations on the bias and accuracy of the Cockcroft-Gault equation. Pharmacotherapy 2012;32(7):604-12
9. Kidney Disease: Improving Global Outcomes (KDIGO) CKDWork Group. KDIGO clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 2013;3:1-150
10. National Kidney Disease Education Program. CKD and drug dosing: information for providers. 2012. Available from: http://nkdep.nih.gov/resources/ CKDdrug-dosing.shtml [Last accessed on March 6 [2014]
11. Yuk J, Nightingale CH, Sweeney K, et al. Pharmacokinetics of nafcillin in obesity. J Infect Dis 1988;157(5):1088-9
12. Newman D, Scheetz MH, Adeyemi OA, et al. Serum piperacillin/tazobactam pharmacokinetics in a morbidly obese individual. Ann Pharmacother 2007;41(10): 1734-9
13. Sturm AW, Allen N, Rafferty KD, et al. Pharmacokinetic analysis of piperacillin administered with tazobactam in critically ill, morbidly obese surgical patients. Pharmacotherapy 2014;34(1):28-35
14. Cheatham SC, Fleming MR, Healy DP, et al. Steady-state pharmacokinetics and pharmacodynamics of piperacillin and tazobactam administered by prolonged infusion in obese patients. Int J Antimicrob Agents 2013;41(1):52-6
15. Cheadle WG. Risk factors for surgical site infection. Surg Infect (Larchmt) 2006; 7(Suppl 1):S7-11
16. Forse RA, Karam B, MacLean LD, Christou NV. Antibiotic prophylaxis for surgery in morbidly obese patients. Surgery 1989;106(4):750-6.discussion 756-757
17. Edmiston CE, Krepel C, Kelly H, et al. Perioperative antibiotic prophylaxis in the gastric bypass patient: do we achieve therapeutic levels? Surgery 2004;136(4): 738-47
18. van Kralingen S, Taks M, Diepstraten J, et al. Pharmacokinetics and protein binding of cefazolin in morbidly obese patients. Eur J Clin Pharmacol 2011;67(10):985-92
19. Barbour A, Schmidt S, Rout WR, et al. Soft tissue penetration of cefuroxime determined by clinical microdialysis in morbidly obese patients undergoing abdominal surgery. Int J Antimicrob Agents 2009;34(3):231-5
20. Toma O, Suntrup P, Stefanescu A, et al. Pharmacokinetics and tissue penetration of cefoxitin in obesity: implications for risk of surgical site infection. Anesth Analg 2011; 113(4):730-7
21. Itani KM, Jensen EH, Finn TS, et al. Effect of body mass index and ertapenem versus cefotetan prophylaxis on surgical site infection in elective colorectal surgery. Surg Infect (Larchmt) 2008;9(2):131-7
22. 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
23. Chen M, Nafziger AN, Drusano GL, et al. Comparative pharmacokinetics and pharmacodynamic target attainment of ertapenem in normal-weight, obese, and extremely obese adults. Antimicrob Agents Chemother 2006;50(4):1222-7
24. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing-22nd Information Supplement. CLSI Document M100-S22. CLSI; Wayne, PA: 2012
25. de Werra C, Di Micco R, Pilone V, et al. Serum in vivo and in vitro activity of single dose of ertapenem in surgical obese patients for prevention of SSIs. Obes Surg 2013; 23(7):911-19
26. Bearden DT, Mcconnell DB, Belle DJ, Kohlhepp SJ. Pharmacokinetics of meropenem in extreme obesity. Presented at 45th Interscience Conference on Antimicrobial Agents and Chemotherapy; 16-19 December 2005; Washington, DC, USA
27. Cheatham SC, Fleming MR, Healy DP, et al. Steady-state pharmacokinetics and pharmacodynamics of meropenem in morbidly obese patients hospitalized in an intensive care unit. J Clin Pharmacol 2014; 54(3):324-30
28. Nandy P, Samtani MN, Lin R. Population pharmacokinetics of doripenem based on data from phase 1 studies with healthy volunteers and phase 2 and 3 studies with critically ill patients. Antimicrob Agents Chemother 2010;54(6):2354-9
29. Roberts JA, Lipman J. Optimal doripenem dosing simulations in critically ill nosocomial pneumonia patients with obesity, augmented renal clearance, and decreased bacterial susceptibility. Crit Care Med 2013;41(2):489-95
30. Kays MB, Fleming MR, Cheatham SC, et al. Comparative pharmacokinetics and pharmacodynamics of doripenem and meropenem in obese patients. Ann Pharmacother 2014;48(2):178-86
31. US FDA. FDA Drug Safety Communication: FDA Statement on recently terminated clinical trial with Doribax (doripenem). 2012.Available from: www.fda.gov/Drugs/DrugSafety/ucm285883.htm [Last accessed on 28 March 2014]
32. Blouin RA, Bauer LA, Miller DD, et al. Vancomycin pharmacokinetics in normal and morbidly obese subjects. Antimicrob Agents Chemother 1982;21(4):575-80
33. 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
34. Bauer LA, Black DJ, Lill JS. Vancomycin dosing in morbidly obese patients. Eur J Clin Pharmacol 1998;54(8):621-5
35. Leong JV, Boro MS, Winter M. Determining vancomycin clearance in an overweight and obese population. Am J Health Syst Pharm 2011;68(7):599-603
36. Rybak M, Lomaestro B, Rotschafer JC, et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm 2009;66(1):82-98
37. Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin- resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 2011;52(3):285-92
38. Hall RG 2nd, Payne KD, Bain AM, et al. Multicenter evaluation of vancomycin dosing: emphasis on obesity. Am J Med 2008;121(6):515-18
39. Puzniak LA, Morrow LE, Huang DB, Barreto JN. Impact of weight on treatment efficacy and safety in complicated skin and skin structure infections and nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus. Clin Ther 2013; 35(10):1557-70
40. Hall RG 2nd, Giuliano CA, Haase KK, et al. Empiric guideline-recommended weight-based vancomycin dosing and mortality in methicillin-resistant Staphylococcus aureus bacteremia: a retrospective cohort study. BMC Infect Dis 2012;12:104
41. Hall RG 2nd, Hazlewood KA, Brouse SD, et al. Empiric guideline- recommended weight-based vancomycin dosing and nephrotoxicity rates in patients with methicillin-resistant Staphylococcus aureus bacteremia: a retrospective cohort study. BMC Pharmacol Toxicol 2013;14:12
42. Lodise TP, Patel N, Lomaestro MB, et al. Relationship between initial vancomycin concentration-time profile and nephrotoxicity among hospitalized patients. Clin Infect Dis 2009;49(4):507-14
43. Kullar R, Davis SL, Levine DP, Rybak MJ. Impact of vancomycin exposure on outcomes in patients with methicillin-resistant Staphylococcus aureus bacteremia: support for consensus guidelines suggested targets. Clin Infect Dis 2011; 52(8):975-81
44. 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
45. Pai MP, Norenberg JP, Anderson T, et al. Influence of morbid obesity on the single-dose pharmacokinetics of daptomycin. Antimicrob Agents Chemother 2007;51(8): 2741-7
46. Bhavnani SM, Rubino CM, Ambrose PG, Drusano GL. Daptomycin exposure and the probability of elevations in the creatine phosphokinase level: data from a randomized trial of patients with bacteremia and endocarditis. Clin Infect Dis 2010; 50(12):1568-74
47. Bookstaver PB, Bland CM, Qureshi ZP, et al. Safety and effectiveness of daptomycin across a hospitalized obese population: results of a multicenter investigation in the southeastern United States. Pharmacotherapy 2013;33(12):1322-30
48. Mersfelder TL, Smith CL. Linezolid pharmacokinetics in an obese patient. Am J Health Syst Pharm 2005;62(5):464-7
49. Meagher AK, Forrest A, Rayner CR, et al. Population pharmacokinetics of linezolid in patients treated in a compassionate-use program. Antimicrob Agents Chemother 2003;47(2):548-53
50. Cheatham SC, Kays MB, Fleming MR, Shawa I. Pharmacokinetics of linezolid in obese hospitalized patients utilizing higher doses. Presented at 51st Interscience Conference on Antimicrobial Agents and Chemotherapy; 17-20 September 2011; Chicago, IL, USA
51. 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
52. Rajendran PM, Young D, Maurer T, et al. Randomized, double-blind, placebocontrolled trial of cephalexin for treatment of uncomplicated skin abscesses in a population at risk for community-acquired methicillin-resistant Staphylococcus aureus infection. Antimicrob Agents Chemother 2007;51(11):4044-8
53. Muzevich KM, Lee KB. Subtherapeutic linezolid concentrations in a patient with morbid obesity and methicillin-resistant Staphylococcus aureus pneumonia: case report and review of the literature. Ann Pharmacother 2013;47(6):e25
54. De Pascale G, Fortuna S, Navarra P, Antonelli M. Linezolid use in ventilator-associated pneumonia: look at the body weight of your patient!. Minerva Anestesiol 2012;78(12):1418-19
55. Bhalodi AA, Papasavas PK, Tishler DS, et al. Pharmacokinetics of intravenous linezolid in moderately to morbidly obese adults. Antimicrob Agents Chemother 2013; 57(3):1144-9
56. Hamilton R, Thai XC, Ameri D, Pai MP. Oral bioavailability of linezolid before and after Roux-en-Y gastric bypass surgery: is dose modification necessary in obese subjects? J Antimicrob Chemother 2013; 68(3):666-73
57. Van Wart SA, Owen JS, Ludwig EA, et al. Population pharmacokinetics of tigecycline in patients with complicated intra-abdominal or skin and skin structure infections. Antimicrob Agents Chemother 2006;50(11):3701-7
58. Bhavnani SM, Rubino CM, Ambrose PG, et al. Impact of different factors on the probability of clinical response in tigecycline-treated patients with intra-abdominal infections. Antimicrob Agents Chemother 2010;54(3):1207-12
59. Pai MP. Serum and urine pharmacokinetics of tigecycline in obese class III and normal weight adults. J Antimicrob Chemother 2014;69(1):190-9
60. US FDA. FDA Drug Safety Communication: FDA warns of increased risk of death with IV antibacterial Tygacil (tigecycline) and approves new Boxed Warning. 2013.Available from: www.fda.gov/Drugs/DrugSafety/ucm369580. htm [Last accessed on 16 January 2014]
61. Abdullahi M, Annibale B, Capoccia D, et al. The eradication of Helicobacter pylori is affected by body mass index (BMI). Obes Surg 2008;18(11):1450-4
62. Allard S, Kinzig M, Boivin G, et al. Intravenous ciprofloxacin disposition in obesity. Clin Pharmacol Ther 1993;54(4): 368-73
63. Hollenstein UM, Brunner M, Schmid R, Muller M. Soft tissue concentrations of ciprofloxacin in obese and lean subjects following weight-adjusted dosing. Int J Obes Relat Metab Disord 2001;25(3):354-8
64. Utrup TR, Mueller EW, Healy DP, et al. High-dose ciprofloxacin for serious gram-negative infection in an obese, critically ill patient receiving continuous venovenous hemodiafiltration. Ann Pharmacother 2010;44(10):1660-4
65. Kees MG,Weber S, Kees F, Horbach T. Pharmacokinetics of moxifloxacin in plasma and tissue of morbidly obese patients. J Antimicrob Chemother 2011;66(10):2330-5
66. Cook AM, Martin C, Adams VR, Morehead RS. Pharmacokinetics of intravenous levofloxacin administered at 750 milligrams in obese adults. Antimicrob Agents Chemother 2011;55(7):3240-3
67. Schwartz SN, Pazin GJ, Lyon JA, et al. A controlled investigation of the pharmacokinetics of gentamicin and tobramycin in obese subjects. J Infect Dis 1978;138(4):499-505
68. Blouin RA, Mann HJ, Griffen WO Jr, et al. Tobramycin pharmacokinetics in morbidly obese patients. Clin Pharmacol Ther 1979;26(4):508-12
69. Bauer LA, Blouin RA, Griffen WO Jr, et al. Amikacin pharmacokinetics in morbidly obese patients. Am J Hosp Pharm 1980; 37(4):519-22
70. Korsager S. Administration of gentamicin to obese patients. Int J Clin Pharmacol Ther Toxicol 1980;18(12):549-53
71. Sketris I, Lesar T, Zaske DE,Cipolle RJ. Effect of obesity on gentamicin pharmacokinetics. J Clin Pharmacol 1981;21(7):288-93
72. Bauer LA, Edwards WA, Dellinger EP, Simonowitz DA. Influence of weight on aminoglycoside pharmacokinetics in normal weight and morbidly obese patients. Eur J Clin Pharmacol 1983;24(5):643-7
73. 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
74. 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
75. Pai MP, Nafziger AN, Bertino JS Jr. Simplified estimation of aminoglycoside pharmacokinetics in underweight and obese adult patients. Antimicrob Agents Chemother 2011;55(9):4006-11
76. American Thoracic Society, CDC. Treatment of tuberculosis. MMWR Recomm Rep 2003;52(RR-11):1-77
77. HasenboschRE, Alffenaar JW, Koopmans SA, et al. Ethambutol-induced optical neuropathy: risk of overdosing in obese subjects. Int J Tuberc Lung Dis 2008;12(8):967-71
78. Hall RG 2nd, Swancutt MA, Meek C, et al. Ethambutol pharmacokinetic variability is linked to body mass in overweight, obese, and extremely obese people. Antimicrob Agents Chemother 2012;56(3):1502-7
79. Kinzig-Schippers M, Tomalik-Scharte D, Jetter A, et al. Should we use N-acetyltransferase type 2 genotyping to personalize isoniazid doses? Antimicrob Agents Chemother 2005;49(5):1733-8
80. Wilkins JJ, Langdon G, McIlleron H, et al. Variability in the population pharmacokinetics of pyrazinamide in South African tuberculosis patients. Eur J Clin Pharmacol 2006;62(9):727-35
81. Pasipanodya JG, Gumbo T. Clinical and toxicodynamic evidence that high-dose pyrazinamide is not more hepatotoxic than the low doses currently used. Antimicrob Agents Chemother 2010;54(7):2847-54
82. Gumbo T, Dona CS, Meek C, Leff R. Pharmacokinetics-pharmacodynamics of pyrazinamide in a novel in vitro model of tuberculosis for sterilizing effect: a paradigm for faster assessment of new antituberculosis drugs. Antimicrob Agents Chemother 2009; 53(8):3197-204
83. Ruslami R, Nijland HM, Alisjahbana B, et al. Pharmacokinetics and tolerability of a higher rifampin dose versus the standard dose in pulmonary tuberculosis patients. Antimicrob Agents Chemother 2007;51(7): 2546-51
84. Ruslami R, Nijland HM, Adhiarta IG, et al. Pharmacokinetics of antituberculosis drugs in pulmonary tuberculosis patients with type 2 diabetes. Antimicrob Agents Chemother 2010;54(3):1068-74
85. Nijland HM, Ruslami R, Stalenhoef JE, et al. Exposure to rifampicin is strongly reduced in patients with tuberculosis and type 2 diabetes. Clin Infect Dis 2006;43(7): 848-54
86. Pasipanodya JG, Weis S, Gumbo T. Weight, not diabetes mellitus predicts failure of anti-tuberculosis therapy in treated tuberculosis patients with concurrent diabetes mellitus. Presented at 50th Interscience Conference on Antimicrobial Agents and Chemotherapy; 12-15 September 2010;Boston, MA, USA
87. Pasipanodya J, Hall R, Weis S, Gumbo T. Fats, fractals, and failure of antituberculosis pharmacotherapy. Presented at 50th Interscience Conference on Antimicrobial Agents and Chemotherapy; 12-15 September 2010; Boston, MA, USA
88. Chang KC, Leung CC, Yew WW, et al. Dosing schedules of 6-month regimens and relapse for pulmonary tuberculosis. Am J Respir Crit Care Med 2006;174(10):1153-8
89. Dowsey MM, Choong PF. Obesity is a major risk factor for prosthetic infection after primary hip arthroplasty. Clin Orthop Relat Res 2008;466(1):153-8
90. Dossett LA, Dageforde LA, Swenson BR, et al. Obesity and site-specific nosocomial infection risk in the intensive care unit. Surg Infect (Larchmt) 2009;10(2):137-42
91. Huttunen R, Syrjanen J. Obesity and the outcome of infection. Lancet Infect Dis 2010;10(7):442-3
92. Kiem S, Schentag JJ. Interpretation of antibiotic concentration ratios measured in epithelial lining fluid. Antimicrob Agents Chemother 2008;52(1):24-36
93. Bergan T. Extravascular penetration of ciprofloxacin. A review. Diagn Microb Infect Dis 1990;13(2):103-14
94. Gallagher D, Visser M, Sepulveda D, et al. How useful is body mass index for comparison of body fatness across age, sex, and ethnic groups? Am J Epidemiol 1996; 143(3):228-39