Cefepime Dosing in the Morbidly Obese Patient Population
First Online: 18 January 2012 DOI:
Cite this article as: Rich, B.S., Keel, R., Ho, V.P. et al. OBES SURG (2012) 22: 465. doi:10.1007/s11695-011-0586-8 Abstract
Proper dosing of specific antibiotics in morbidly obese patients has been studied inadequately. However, these data are beneficial as this patient population is at an increased risk to develop postoperative infections. Cefepime is an antibiotic used for the treatment of both gram-positive and especially gram-negative infections; administration of the appropriate dose in the morbidly obese population is crucial. We therefore examined the pharmacokinetics of cefepime in patients with body mass index >40 kg/m
2. Ten morbidly obese patients, with a mean [±SD] estimated glomerular filtration rate of 108.4 ± 34.6 mL/min, undergoing elective weight loss surgical procedures were administered cefepime in addition to standard prophylactic cefazolin and studied. Serial serum cefepime concentrations were analyzed after dosing using a validated high performance liquid chromatography method. Pharmacokinetics and duration above the minimum inhibitory concentration (MIC) were determined using a protein binding value of 15% and a MIC threshold of 8 μg/mL. Mean free cefepime concentrations for t = 30, 120, and 360 min were 69.6, 31.6, and 9.2 μg/mL, respectively. The dosing interval was calculated to maintain the free concentration above the MIC ( fT > MIC) for 60% of the interval. This was determined to be 10.12 h, including time for infusion. There was no toxicity. Based on this analysis, an increased dose of 2 g every 8 h is necessary to maintain an adequate fT > MIC throughout the dosing interval. Further studies are necessary to determine the efficacy of this regimen in the settings of active infections and critical illness. Keywords Antibiotics Cefepime Obesity Pharmacokinetics References
World Health Organization. Obesity and overweight. Fact sheet 311. September 2006.
Choban PS, Heckler R, Burge JC, et al. Increased incidence of nosocomial infections in obese surgical patients. Am Surg. 1995;61:1001–5.
Canturk Z, Canturk NZ, Cetinarslan B, et al. Nosocomial infections and obesity in surgical patients. Obes Res. 2003;11:769–75.
Barie PS, Eachempati SR. Surgical site infections. Surg Clin North Am. 2005;85:1115–35.
Bamgbade OA, Rutter TW, Nafiu OO, et al. Postoperative complications in obese and nonobese patients. World J Surg. 2007;31:556–60.
Nasraway Jr SA, Albert M, Donnelly AM, et al. Morbid obesity is an independent determinant of death among surgical critically ill patients. Crit Care Med. 2005;34:964–70.
Dindo D, Muller MK, Weber M, et al. Obesity in general elective surgery. Lancet. 2003;361:2032–5.
Greenberg JA, Robinson MK. Surgery: how safe is bariatric surgery? Nat Rev Endocrinol. 2009;5:645–6.
Olsen MA, Nepple JJ, Riew KD, et al. Risk factors for surgical site infection following orthopaedic spinal operations. J Bone Joint Surg Am. 2008;90:62–9.
Gillespie EL, Kuti JL, Nicolau DP. Pharmacodynamics of antimicrobials: treatment optimization. Expert Opin Drug Metab Toxicol. 2005;1:351–61.
Edmiston Jr 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.
Salazar DE, Corcoran GB. Predicting creatinine clearance and renal drug clearance in obese patients from estimated fat-free body mass. Am J Med. 1988;84:1053–60.
Pieracci FM, Barie PS, Pomp A. Critical care of the bariatric patient. Crit Care Med. 2006;34:1796–804.
Chiba K, Tsuchiya M, Kato J, et al. Cefotiam disposition in markedly obese athlete patients, Japanese sumo wrestlers. Antimicrob Agents Chemother. 1989;33:1188–92.
Yost RL, Derendorf H. Disposition of cefotaxime and its desacetyl metabolite in morbidly obese male and female subjects. Ther Drug Monit. 1986;8:189–94.
Pai MP, Bearden DT. Antimicrobial dosing considerations in obese adult patients. Pharmacother. 2007;27:1081–91.
Bearden DT, Rodvold KA. Dosage adjustments for antibacterials in obese patients: applying clinical pharmacokinetics. Clin Pharmacokinet. 2000;38:415–26.
Craig WA. Interrelationship between pharmacokinetics and pharmacodynamics in determining dosage regimens for broad-spectrum cephalosporins. Diagn Microbiol Infect Dis. 1995;22:89–96.
Burgess DS, Hastings RW, Hardin TC. Pharmacokinetics and pharmacodynamics of cefepime administered by intermittent and continuous infusion. Clin Ther. 2000;22:66–75.
Hermsen ED, Maiefski M, Florescu MC, et al. Comparison of the modification of diet in renal disease and Cockcroft–Gault equations for dosing antimicrobials. Pharmacotherapy. 2009;29:649–55.
Nguyen NT, Dakin G, Needleman B, et al. Effect of staple height on gastrojejunostomy during laparoscopic gastric bypass: a multicenter prospective randomized trial. Surg Obes Relat Dis. 2010;6:477–82.
Topaloglu S, Avsar FM, Ozel H, et al. Comparison of bariatric and non-bariatric elective operations in morbidly obese patients on the basis of wound infection. Obes Surg. 2005;15:1271–6.
Hospital-Acquired Conditions. [Website]: Centers for Medicare & Medicaid Services, 7500 Security Boulevard Baltimore, MD; 2010 [cited 2010 March 15]; Hospital-Acquired Conditions]. Available from:
Chopra T, Zhao JJ, Alangaden G, et al. Preventing surgical site infections after bariatric surgery: value of perioperative antibiotic regimens. Expert Rev Pharmacoecon Outcomes Res. 2010;10:317–28.
Gonzalez R, Sarr MG, Smith CD, et al. Diagnosis and contemporary management of anastomotic leaks after gastric bypass for obesity. J Am Coll Surg. 2007;204:47–55.
Kermarrec N, Marmuse JP, Faivre J, et al. High mortality rate for patients requiring intensive care after surgical revision following bariatric surgery. Obes Surg. 2008;18:171–8.
Patel S, Szomstein S, Rosenthal RJ. Reasons and outcomes of reoperative bariatric surgery for failed and complicated procedures (excluding adjustable gastric banding). Obes Surg. 2011;21:1209–19.
Angrisani L, Furbetta F, Doldi SB, et al. Lap band adjustable gastric banding system: the Italian experience with 1863 patients operating on 6 years. Surg Endosc. 2003;17:409–12.
Bercault N, Boulain T, Kuteifan K, et al. Obesity-related excess mortality rate in an adult intensive care unit: a risk-adjusted matched cohort study. Crit Care Med. 2004;32:998–1003.
Fry DE. The importance of antibiotic pharmacokinetics in critical illness. Am J Surg. 1996;172:20S–5S.
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.
Barbhaiya RH, Forgue ST, Gleason CR, et al. Pharmacokinetics of cefepime after single and multiple intravenous administrations in healthy subjects. Antimicrob Agents Chemother. 1992;36:552–7.
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;50:1222–7.
Freeman JT, Anderson DJ, Hartwig MG, et al. Surgical site infections following bariatric surgery in community hospitals: a weighty concern? Obes Surg. 2010;21(7):836–40.
Ho VP, Nicolau DP, Dakin GF, et al. Cefazolin dosing for surgical prophylaxis in morbidly obese patients. Surg Infect (Larchmt). 2012 (in press).
Mutnick AH, Rhomberg PR, Sader HS, et al. Antimicrobial usage and resistance trend relationships from the MYSTIC Programme in North America (1999–2001). J Antimicrob Chemother. 2004;53:290–6.
US Food and Drug Administration. Maxipime (cefepime hydrochloride) for injection. NDA 50-679/S021.
Alfandari S, Bonenfant C, Depretere L, et al. Use of 27 parenteral antimicrobial agents in north of France hospitals. Med Mal Infect. 2007;37:103–7.
Sader HS, Fritsche TR, Jones RN. Potency and spectrum trends for cefepime tested against 65746 clinical bacterial isolates collected in North American medical centers: results from the SENTRY Antimicrobial Surveillance Program (1998–2003). Siagn Microbiol Infect Dis. 2005;52:265–73.
Goldstein FW. Cephalosporinase induction and cephalosporin resistance: a longstanding misinterpretation. Clin Microbiol Infect. 2002;8:823–5.
Sanders Jr WE, Tenney JH, Kessler RE. Efficacy of cefepime in the treatment of infections due to multiply resistant
species. Clin Infect Dis. 1996;23:454–61.
Yahav D, Paul M, Fraser A, et al. Efficacy and safety of cefepime: a systematic review and meta-analysis. Lancet Infect Dis. 2007;7:338–48.
Barie PS, Hydo LJ, Larone DH, et al. Influence of antibiotic therapy on mortality of critical surgical illness caused or complicated by infection. Surg Infect (Larchmt). 2005;6:41–54.
Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis. 1998;26:1–10.
Crandon JL, Bulik CC, Kuti JL, et al. Clinical pharmacodynamics of cefepime in patients infected with
. Antimicrob Agents Chemother. 2010;54:1111–6.
Georges B, Conil JM, Cougot P, et al. Cefepime in critically ill patients: continuous infusion vs. an intermittent dosing regimen. Int J Clin Pharmacol Ther. 2005;43:360–9.
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