Vnitr Lek 2024, 70(5):295-302 | DOI: 10.36290/vnl.2024.059

Current recommendations for antibiotic dosing in obese patients

Jan Strojil
Ústav farmakologie, 2. lékařská fakulta, Univerzita Karlova v Praze

Obesity is a growing societal and population health problem the prevalence of which has increased significantly in the recent decades. Pathophysiological changes associated with obesity can alter the pharmacokinetics (PK) of antiinfective drugs and result in subtherapeutic levels and treatment failure. Due to complex changes in distribution volume and elimination functions, a simple correction based on total body weight would often lead to overdosing and risk of toxicity. Thanks to a number of PK studies evaluating antibiotic doses in the critically ill and thanks to dedicated studies in the obese we have gained new insights into adequate dosing in the recent years. Despite this, the information is still lacking for many of the most commonly prescribed antibiotics and where it is available, the recommendations are often based on indirect evidence rather than clinical validation. This paper offers a comprehensive look at the current evidence and recommendations (where available) for dose adjustments in the obese patient.

Keywords: antibiotic, obesity, overweight, dosing, pharmacokinetics, pharmacodynamics.

Accepted: August 28, 2024; Published: September 4, 2024  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Strojil J. Current recommendations for antibiotic dosing in obese patients. Vnitr Lek. 2024;70(5):295-302. doi: 10.36290/vnl.2024.059.
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Open full article

    References

    1. Čechová S. Více než 60 procent Čechů má nadváhu, trpí jí až čtvrtina dětí. Obezita způsobuje závažné zdravotní komplikace, SZÚ | Oficiální web Státního zdravotního ústavu v Praze. Accessed: Jul. 04, 2024. [Internet]. Available from https://szu.cz/aktuality/vice-nez-60-procent-cechu-ma-nadvahu-trpi-ji-az-ctvrtina-deti-obezita-zpusobuje-zavazne-zdravotni-komplikace/.
    2. Nová jednotka intenzivní metabolické péče - Všeobecná fakultní nemocnice v Praze. Accessed: Jul. 04, 2024. [Internet]. Available from: https://www.vfn.cz/aktuality/nova-jednotka-intenzivni-metabolicke-pece-2/.
    3. Pugliese G, Liccardi A, Graziadio C, et a. Obesity and infectious diseases: pathophysiology and epidemiology of a double pandemic condition. Int. J. Obes. 2005;46(3):449-465. Available from doi: 10.1038/s41366-021-01035-6. Go to original source... Go to PubMed...
    4. Grahnén A, Olsson B, Johansson G, et al. Doxycycline carrageenate - an improved formulation providing more reliable absorption and plasma concentrations at high gastric pH than doxycycline monohydrate. Eur. J. Clin. Pharmacol. 1994;46(2):143-146. Available from doi: 10.1007/BF00199878. Go to original source... Go to PubMed...
    5. Ratiopharm GmbH, DOXYBENE 200 mg tablety. May 16, 2024. Accessed: Jul. 04, 2024. (Online). Available from https://prehledy.sukl.cz/prehledy/v1/dokumenty/68699
    6. Gouju J, Legeay S. Pharmacokinetics of obese adults: Not only an increase in weight. Biomed. Pharmacother. 2023;166:115281. Available from doi: 10.1016/j.biopha.2023.115281. Go to original source... Go to PubMed...
    7. Anvari S, Lee Y, Lam M, et al. The Effect of Bariatric Surgery on Oral Antibiotic Absorption: a Systematic Review. Obes. Surg. 2020;30(8):2883-2892. Available from doi: 10.1007/s11695-020-04623-z. Go to original source... Go to PubMed...
    8. McCarron MM, Devine BJ. Clinical Pharmacy: Case Studies: Case Number 25 Gentamicin Therapy. Drug Intell. Clin. Pharm. 1974;8(11):650-655. doi: 10.1177/106002807400801104. Go to original source...
    9. Krogstad V, et al. Correlation of Body Weight and Composition With Hepatic Activities of Cytochrome P450 Enzymes. J. Pharm. Sci. 2021;110(1):432-437. Available from doi: 10.1016/j.xphs.2020. 10. 027. Go to original source...
    10. Lim WH, Lim EM, McDONALD S. Lean body mass-adjusted Cockcroft and Gault formula improves the estimation of glomerular filtration rate in subjects with normal-range serum creatinine. Nephrology. 2006;11(3):250-256. doi: 10.1111/j.1440-1797.2006.00560.x. Go to original source... Go to PubMed...
    11. D'Agati VD, et al. Obesity-related glomerulopathy: clinical and pathologic characteristics and pathogenesis. Nat. Rev. Nephrol. 2016;12(8):453-471. Available from doi: 10.1038/nrneph.2016. 75. Go to original source...
    12. Další literatura u autora a na www.casopisvnitrnilekarstvi.cz
    13. Longo C, et al. The effect of obesity on antibiotic treatment failure: a historical cohort study. Pharmacoepidemiol. Drug Saf. 2013; 22(9): 970-976. Available from doi: 10.1002/pds.3461. Go to original source... Go to PubMed...
    14. Soares A, et al. Pharmacokinetics of amoxicillin in obese and nonobese subjects. Br. J. Clin. Pharmacol. 2021;87(8):3227-3233. Available from doi: 10.1111/bcp.14739. Go to original source... Go to PubMed...
    15. Mellon G, et al.Population pharmacokinetics and dosing simulations of amoxicillin in obese adults receiving co-amoxiclav. J. Antimicrob. Chemother. 2020;75(12): 3611-3618. Available from doi: 10.1093/jac/dkaa368. Go to original source... Go to PubMed...
    16. Garrigue P, Reber M, Perinel-Ragey S, et al. Personalized Amoxicillin Therapy in a Critically Ill Patient Undergoing Renal Replacement Therapy: A Grand Round. Ther. Drug Monit. 2024: 10.1097/FTD.0000000000001242. Available from doi: 10.1097/FTD.0000000000001242. Go to original source... Go to PubMed...
    17. Montanha MC, et al. Reduced bioavailability of oral amoxicillin tablets compared to suspensions in Roux-en-Y gastric bypass bariatric subjects. Br. J. Clin. Pharmacol. 2019; 85(9) 2118-2125. Available from doi: 10.1111/bcp.14023. Go to original source... Go to PubMed...
    18. Kubíčková V, Vojtová V, Urbánek K. Flucloxacillin pharmacokinetic properties. Klin. Farmakol. Farm. 2023;37(1): 34-38. Available from doi: 10.36290/far.2023.006. Go to original source...
    19. Santibañez M, Bunnell K, Harrington A, et al. Association Between Estimated Pharmacokinetic/Pharmacodynamic Predictions of Efficacy and Observed Clinical Outcomes in Obese and Nonobese Patients With Enterobacteriaceae Bloodstream Infections. Open Forum Infect. Dis. 2019;6(10):ofz400. Available from doi: 10.1093/ofid/ofz400. Go to original source... Go to PubMed...
    20. Veillette JJ, Winans SA, Maskiewicz VK, Truong J, et al. Pharmacokinetics and Pharmacodynamics of High-Dose Piperacillin-Tazobactam in Obese Patients. Eur. J. Drug Metab. Pharmacokinet. 2021;46(3):385-394. Available from doi: 10.1007/s13318-021-00677-1. Go to original source... Go to PubMed...
    21. M. Coates, A. Shield, G. M. Peterson, and Z. Hussain, "Prophylactic Cefazolin Dosing in Obesity-a Systematic Review," Obes. Surg., vol. 32, no. 9, pp. 3138-3149, Sep. 2022, doi: 10.1007/s11695-022-06196-5. Go to original source... Go to PubMed...
    22. H. K. Ahmadzia et al., "Obstetric Surgical Site Infections: 2 Grams Compared With 3 Grams of Cefazolin in Morbidly Obese Women," Obstet. Gynecol., vol. 126, no. 4, pp. 708-715, Oct. 2015, doi: 10.1097/AOG.0000000000001064. Go to original source... Go to PubMed...
    23. W. J. Peppard, D. G. Eberle, N. W. Kugler, D. M. Mabrey, and J. A. Weigelt, "Association between Pre-Operative Cefazolin Dose and Surgical Site Infection in Obese Patients," Surg. Infect., vol. 18, no. 4, pp. 485-490, 2017, doi: 10.1089/sur.2016.182. Go to original source... Go to PubMed...
    24. A. J. Morris, S. A. Roberts, N. Grae, and C. M. Frampton, "Surgical site infection rate is higher following hip and knee arthroplasty when cefazolin is underdosed," Am. J. Health-Syst. Pharm. AJHP Off. J. Am. Soc. Health-Syst. Pharm., vol. 77, no. 6, pp. 434-440, Mar. 2020, doi: 10.1093/ajhp/zxz344. Go to original source... Go to PubMed...
    25. H. Ryu et al., "Safety and Effectiveness of High-Dose Cefazolin in Patients With High Body Weight: A Retrospective Cohort Study," Open Forum Infect. Dis., vol. 9, no. 4, p. ofac105, Apr. 2022, doi: 10.1093/ofid/ofac105. Go to original source... Go to PubMed...
    26. S. K. Tøstesen et al., "Weight-based cefuroxime dosing provides comparable orthopedic target tissue concentrations between weight groups - a microdialysis porcine study," APMIS Acta Pathol. Microbiol. Immunol. Scand., vol. 130, no. 2, pp. 111-118, Feb. 2022, doi: 10.1111/apm.13198. Go to original source... Go to PubMed...
    27. H. A et al., "Deep surgical site infections following double-dose perioperative antibiotic prophylaxis in adult obese orthopedic patients," Int. J. Infect. Dis. IJID Off. Publ. Int. Soc. Infect. Dis., vol. 108, Jul. 2021, doi: 10.1016/j.ijid.2021. 06. 008. Go to original source...
    28. A. Barbour, S. Schmidt, W. R. Rout, K. Ben-David, O. Burkhardt, and H. Derendorf, "Soft tissue penetration of cefuroxime determined by clinical microdialysis in morbidly obese patients undergoing abdominal surgery," Int. J. Antimicrob. Agents, vol. 34, no. 3, pp. 231-235, Sep. 2009, doi: 10.1016/j.ijantimicag.2009. 03. 019. Go to original source...
    29. H. H. Alrammaal et al., "Application of a Physiologically Based Pharmacokinetic Model to Predict Cefazolin and Cefuroxime Disposition in Obese Pregnant Women Undergoing Caesarean Section," Pharmaceutics, vol. 14, no. 6, p. 1162, May 2022, doi: 10.3390/pharmaceutics14061162. Go to original source... Go to PubMed...
    30. K. E. Barber, J. T. Loper, A. R. Morrison, K. R. Stover, and J. L. Wagner, "Impact of Obesity on Ceftriaxone Efficacy," Diseases, vol. 8, no. 3, p. 27, Jul. 2020, doi: 10.3390/diseases8030027. Go to original source... Go to PubMed...
    31. K. Arensman Hannan, E. Draper, K. C. Cole, J. Mc Hugh, C. G. Rivera, and O. Abu Saleh, "Impact of hypoalbuminemia on clinical outcomes among patients with obesity treated with ceftriaxone," Antimicrob. Agents Chemother., vol. 68, no. 4, p. e0166323, Apr. 2024, doi: 10.1128/aac.01663-23. Go to original source... Go to PubMed...
    32. M. Hites et al., "Broad-spectrum β-lactams in obese non-critically ill patients," Nutr. Diabetes, vol. 4, no. 6, p. e119, Jun. 2014, doi: 10.1038/nutd.2014. 15. Go to original source...
    33. E. K. Chung, S. C. Cheatham, M. R. Fleming, D. P. Healy, and M. B. Kays, "Population Pharmacokinetics and Pharmacodynamics of Meropenem in Nonobese, Obese, and Morbidly Obese Patients," J. Clin. Pharmacol., vol. 57, no. 3, pp. 356-368, Mar. 2017, doi: 10.1002/jcph.812. Go to original source... Go to PubMed...
    34. A. S. Alobaid et al., "Effect of Obesity on the Population Pharmacokinetics of Meropenem in Critically Ill Patients," Antimicrob. Agents Chemother., vol. 60, no. 8, pp. 4577-4584, Aug. 2016, doi: 10.1128/AAC.00531-16. Go to original source... Go to PubMed...
    35. H. Suchánková and J. Strojil, "Imipenem Dosing in the Obese and in Patients With Augmented Renal Clearance: A PK/PD Analysis," Clin. Ther., vol. 39, no. 8, pp. e96-e97, Aug. 2017, doi: 10.1016/j.clinthera.2017. 05. 303. Go to original source...
    36. Y. Chen, Y. Han, F. Guo, and Z. Yu, "Model-Informed Precision Dosing of Imipenem in an Obese Adolescent Patient with Augmented Renal Clearance and History of Schizophrenia," Infect. Drug Resist., vol. 17, pp. 761-767, 2024, doi: 10.2147/IDR.S450294. Go to original source... Go to PubMed...
    37. "Researcher View | Impact of Obesity on the Pharmacokinetics of Imipenem-Relebactam in ICU Patients | ClinicalTrials.gov." Accessed: Jul. 05, 2024. (Online). Available: https://clinicaltrials.gov/study/NCT05146154?tab=table
    38. J. Q. Del Rosso, J. P. York, and N. Bhatia, "Effective Treatment of Inflammatory Lesions of Rosacea with Subantibiotic Dose Doxycycline Irrespective of Patient Weight or Baseline Lesion Count Severity," J. Clin. Aesthetic Dermatol., vol. 15, no. 11, pp. 69-74, Nov. 2022.
    39. H. Peyriere, A. Makinson, H. Marchandin, and J. Reynes, "Doxycycline in the management of sexually transmitted infections," J. Antimicrob. Chemother., vol. 73, no. 3, pp. 553-563, Mar. 2018, doi: 10.1093/jac/dkx420. Go to original source... Go to PubMed...
    40. M. M. Ibrahim et al., "Best tigecycline dosing for treatment of infections caused by multidrug-resistant pathogens in critically ill patients with different body weights," Drug Des. Devel. Ther., vol. 12, pp. 4171-4179, 2018, doi: 10.2147/DDDT.S181834. Go to original source... Go to PubMed...
    41. C. Dorn et al., "Tigecycline Soft Tissue Penetration in Obese and Non-obese Surgical Patients Determined by Using In Vivo Microdialysis," Eur. J. Drug Metab. Pharmacokinet., vol. 47, no. 5, pp. 749-755, Sep. 2022, doi: 10.1007/s13318-022-00789-2. Go to original source... Go to PubMed...
    42. M. K. Hopkins et al., "Standard-Dose Azithromycin in Class III Obese Patients Undergoing Unscheduled Cesarean Delivery," Am. J. Perinatol., vol. 41, no. S 01, pp. e2645-e2650, May 2024, doi: 10.1055/a-2135-7084. Go to original source... Go to PubMed...
    43. A. K. Polso, J. L. Lassiter, and J. L. Nagel, "Impact of hospital guideline for weight-based antimicrobial dosing in morbidly obese adults and comprehensive literature review," J. Clin. Pharm. Ther., vol. 39, no. 6, pp. 584-608, Dec. 2014, doi: 10.1111/jcpt.12200. Go to original source... Go to PubMed...
    44. M. J. Smith et al., "Pharmacokinetics of Clindamycin in Obese and Nonobese Children," Antimicrob. Agents Chemother., vol. 61, no. 4, pp. e02014-16, Apr. 2017, doi: 10.1128/AAC.02014-16. Go to original source... Go to PubMed...
    45. K. P. van Rhee et al., "Ciprofloxacin Pharmacokinetics After Oral and Intravenous Administration in (Morbidly) Obese and Non-obese Individuals: A Prospective Clinical Study," Clin. Pharmacokinet., vol. 61, no. 8, pp. 1167-1175, Aug. 2022, doi: 10.1007/s40262-022-01130-5. Go to original source... Go to PubMed...
    46. U. M. Hollenstein, M. Brunner, R. Schmid, and M. Müller, "Soft tissue concentrations of ciprofloxacin in obese and lean subjects following weight-adjusted dosing," Int. J. Obes. Relat. Metab. Disord. J. Int. Assoc. Study Obes., vol. 25, no. 3, pp. 354-358, Mar. 2001, doi: 10.1038/sj.ijo.0801555. Go to original source... Go to PubMed...
    47. M. P. Pai, P. Cojutti, and F. Pea, "Levofloxacin Dosing Regimen in Severely Morbidly Obese Patients (BMI ≥40 kg/m2) Should Be Guided by Creatinine Clearance Estimates Based on Ideal Body Weight and Optimized by Therapeutic Drug Monitoring," Clin. Pharmacokinet., vol. 53, no. 8, pp. 753-762, Aug. 2014, doi: 10.1007/s40262-014-0154-1. Go to original source... Go to PubMed...
    48. M. P. Pai, M. Wilcox, S. Chitra, and P. McGovern, "Safety and efficacy of omadacycline by body mass index in patients with community-acquired bacterial pneumonia: Subanalysis from a randomized controlled trial," Respir. Med., vol. 184, Aug. 2021, doi: 10.1016/j.rmed.2021.106442. Go to original source... Go to PubMed...
    49. C. Dorn et al., "Plasma and tissue pharmacokinetics of fosfomycin in morbidly obese and non-obese surgical patients: a controlled clinical trial," J. Antimicrob. Chemother., vol. 74, no. 8, pp. 2335-2340, Aug. 2019, doi: 10.1093/jac/dkz203. Go to original source... Go to PubMed...
    50. M. E. Falagas, E. K. Vouloumanou, G. Samonis, and K. Z. Vardakas, "Fosfomycin," Clin. Microbiol. Rev., vol. 29, no. 2, pp. 321-347, Dec. 2020, doi: 10.1128/cmr.00068-15. Go to original source... Go to PubMed...
    51. A. F. Soule, S. B. Green, and L. M. Blanchette, "Clinical efficacy of 12-h metronidazole dosing regimens in patients with anaerobic or mixed anaerobic infections," Ther. Adv. Infect. Dis., vol. 5, no. 3, pp. 57-62, May 2018, doi: 10.1177/2049936118766462. Go to original source... Go to PubMed...
    52. S. Heidari and H. Khalili, "Linezolid pharmacokinetics: a systematic review for the best clinical practice," Eur. J. Clin. Pharmacol., vol. 79, no. 2, pp. 195-206, Feb. 2023, doi: 10.1007/s00228-022-03446-4. Go to original source... Go to PubMed...
    53. Lek Pharmaceuticals d.d., "Edicin 1 g prášek pro koncentrát pro infuzní roztok." Accessed: Apr. 07, 2024. (Online). Available: https://prehledy.sukl.cz/prehledy/v1/dokumenty/64470
    54. L. Meng, E. Mui, D. R. Ha, C. Stave, S. C. Deresinski, and M. Holubar, "Comprehensive guidance for antibiotic dosing in obese adults: 2022 update," Pharmacotherapy, vol. 43, no. 3, pp. 226-246, Mar. 2023, doi: 10.1002/phar.2769. Go to original source... Go to PubMed...
    55. M. E. Elrggal et al., "Dose optimization of vancomycin in obese patients: A systematic review," Front. Pharmacol., vol. 14, Mar. 2023, doi: 10.3389/fphar.2023.965284. Go to original source... Go to PubMed...
    56. H. Suchánková, K. Lečbychová, J. Strojil, and T. Fürst, "Individualized dosing of vancomycin in geriatric patients," Epidemiol. Mikrobiol. Imunol. Cas. Spolecnosti Epidemiol. Mikrobiol. Ceske Lek. Spolecnosti JE Purkyne, vol. 69, no. 4, pp. 172-180, 2020.
    57. J. Beneš, R. Stebel, V. Musil, M. Krůtová, J. Vejmelka, and P. Kohout, "Aktualizovaný doporučený postup pro léčbu nemocných s kolitidou vyvolanou Clostridioides difficile. Doporučený postup Společnosti infekčního lékařství ČLS JEP." Společnosti infekčního lékařství ČLS JEP, Sep. 20, 2022. Accessed: Apr. 07, 2024. (Online). Available: https://www.infektologie.cz/zprava22-39.htm
    58. "Targocid 400 mg prášek a rozpouštědlo pro injekční/infuzní roztok nebo perorální roztok." Sanofi s.r.o., Mar. 01, 2024. Accessed: Apr. 07, 2024. (Online). Available: https://prehledy.sukl.cz/prehledy/v1/dokumenty/65845
    59. C. J. Hodiamont, A. K. van den Broek, S. L. de Vroom, J. M. Prins, R. A. A. Mathôt, and R. M. van Hest, "Clinical Pharmacokinetics of Gentamicin in Various Patient Populations and Consequences for Optimal Dosing for Gram-Negative Infections: An Updated Review," Clin. Pharmacokinet., vol. 61, no. 8, pp. 1075-1094, 2022, doi: 10.1007/s40262-022-01143-0. Go to original source... Go to PubMed...
    60. C. Smit, A. M. van Schip, E. P. A. van Dongen, R. J. M. Brüggemann, M. L. Becker, and C. A. J. Knibbe, "Dose recommendations for gentamicin in the real-world obese population with varying body weight and renal (dys)function," J. Antimicrob. Chemother., vol. 75, no. 11, pp. 3286-3292, Aug. 2020, doi: 10.1093/jac/dkaa312. Go to original source... Go to PubMed...
    61. L. A. Bauer, R. A. Blouin, W. O. Griffen, K. E. Record, and R. M. Bell, "Amikacin pharmacokinetics in morbidly obese patients," Am. J. Hosp. Pharm., vol. 37, no. 4, pp. 519-522, Apr. 1980. Go to original source...
    62. S. R. Magee, G. Shih, and A. Hume, "Malabsorption of oral antibiotics in pregnancy after gastric bypass surgery," J. Am. Board Fam. Med. JABFM, vol. 20, no. 3, pp. 310-313, 2007, doi: 10.3122/jabfm.2007. 03. 060177. Go to original source...
    63. A. Castro-Balado et al., "Updated antimicrobial dosing recommendations for obese patients," Antimicrob. Agents Chemother., vol. 68, no. 5, p. e0171923, May 2024, doi: 10.1128/aac.01719-23. Go to original source... Go to PubMed...
    64. L. Meng, "SHC Antimicrobial Dosing Guide for Obesity." Stanford Health Care, Jan. 18, 2024. Accessed: Apr. 07, 2024. (Online). Available: https://med.stanford.edu/content/dam/sm/bugsanddrugs/documents/antimicrobial-dosing-protocols/SHC-ABX-Obesity-Dosing-Guide.pdf
    65. Northern Health, "2020 Antimicrobial Stewardship Program Adult Dosing Guidelines." Northern Health, Jun. 2020. Accessed: Apr. 07, 2024. (Online). Available: https://physicians.northernhealth.ca/sites/physicians/files/physician-resources/antimicrobial-stewardship/documents/antimicrobial-stewardship-guidelines.pdf

    Return to the content


    Vnitřní lékařství

    Madam, Sir,
    please be aware that the website on which you intend to enter, not the general public because it contains technical information about medicines, including advertisements relating to medicinal products. This information and communication professionals are solely under §2 of the Act n.40/1995 Coll. Is active persons authorized to prescribe or supply (hereinafter expert).
    Take note that if you are not an expert, you run the risk of danger to their health or the health of other persons, if you the obtained information improperly understood or interpreted, and especially advertising which may be part of this site, or whether you used it for self-diagnosis or medical treatment, whether in relation to each other in person or in relation to others.

    I declare:

    1. that I have met the above instruction
    2. I'm an expert within the meaning of the Act n.40/1995 Coll. the regulation of advertising, as amended, and I am aware of the risks that would be a person other than the expert input to these sites exhibited

    No
    Yes

    If your statement is not true, please be aware
    that brings the risk of danger to their health or the health of others.