Peculiarities of choice of dosing regimen and administration of antibacterial drugs in obese patients
https://doi.org/10.24884/1609-2201-2025-104-1-11-21
Abstract
Obesity poses a particular challenge in the selection of drug therapy, requiring special attention to the dosing of drugs, including antibacterial drugs. Pharmacokinetic and pharmacodynamic parameters in obese patients may differ significantly from those in the general population, which affects the efficacy and safety of antibiotic therapy. The purpose of this review is to analyze current data on antibiotic dosing in obese patients to optimize clinical practice and improve treatment outcomes. The study includes an analysis of current scientific publications, clinical guidelines, and pharmacokinetic data regarding the use of antibiotics in obese patients. Particular attention is paid to changes in distribution volume, clearance, and dose adjustment depending on body mass index and other metabolic changes associated with obesity.
About the Authors
I. R. Svechkareva
Pavlov University
Russian Federation
Russian Federation
Izabella R. Svechkareva, resident of the department of Clinical Pharmacology and Evidence-Based Medicine
6–8, L’va Tolstogo str., Saint Petersburg, 197022
A. H.-M. Valeeva
Pavlov University
Russian Federation
Russian Federation
Altynai H.-M. Valeeva, resident of the department of Clinical Pharmacology and Evidence-Based Medicine
6–8, L’va Tolstogo str., Saint Petersburg, 197022
T. I. Busheva
Pavlov University
Russian Federation
Russian Federation
Tatiana I. Busheva, resident of the department of Clinical Pharmacology and Evidence-Based Medicine
6–8, L’va Tolstogo str., Saint Petersburg, 197022
A. S. Kolbin
Pavlov University; Saint-Petersburg State University
Russian Federation
Russian Federation
Alexey S. Kolbin, associate professor Department of Clinical Pharmacology and Evidence-Based Medicine, Pavlov University, associate professor of the Department of Pharmacology, Saint-Petersburg State University
6–8, L’va Tolstogo str., Saint Petersburg, 197022
References
1. Deng J., Zhu X., Chen Z. et al. A review of food-drug interactions on oral drug absorption. Drugs. 2017;77:1833–1855. https://doi.org/10.1007/s40265-017-0832-z.
2. Martinez M. N., Amidon G. L. A mechanistic approach to understandingthe factors affecting drug absorption: a review of fundamentals. J Clin Pharmacol. 2002;42:620–643. https://doi.org/10.1177/00970002042006005.
3. Maddox A., Horowitz M., Wishart J., Collins P. Gastric and oesophageal emptying in obesity. Scand J Gastroenterol. 1989;24:593–598. https://doi.org/10.3109/00365528909093095.
4. Jackson S. J., Leahy F. E., McGowan A. A. et al. Delayed gastric emptying in the obese: an assessment using the non-invasive (13) C-octanoic acid breath test. Diabetes Obes Metab. 2004;6:264–270. https://doi.org/10.1111/j.1462-8902.2004.0344.x.
5. Janson B., Thursky K. Dosing of antibiotics in obesity. Curr Opin Infect Dis. 2012;25:634–649. https://doi.org/10.1097/QCO.0b013e328359a4c1.
6. Morrish G. A., Pai M. P., Green B. The effects of obesity on drug pharmacokinetics in humans. Expert Opin Drug Metab Toxicol. 2011;7:697–706. https://doi.org/10.1517/17425255.2011.570331.
7. Hanley M. J., Abernethy D. R., Greenblatt D. J. Effect of obesity on the pharmacokinetics of drugs in humans. Clin Pharmacokinet. 2010;49:71–87. https://doi.org/10.2165/11318100-000000000-00000.
8. Alobaid A. S., Hites M., Lipman J. et al. Effect of obesity on the pharmacokinetics of antimicrobials in critically ill patients: a structured review. Int J Antimicrob Agents. 2016;47:259–268. https://doi.org/10.1016/j.ijantimicag.2016.01.009.
9. Poirier P., Giles T. D., Bray G. A. et al. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss. Circulation. 2006;113:898–918. https://doi.org/10.1161/CIRCULATIONAHA.106.171016.
10. Rossi M., Nannipieri M., Anselmino M. et al. Subcutaneous adipose tissue blood flow and vasomotion in morbidly obese patients: long term effect of gastric bypass surgery. Clin Hemorheol Microcirc. 2012;51:159–167. https://doi.org/10.3233/ CH-2011-1517.
11. Suh B., Craig W. A., England A. C., Elliott R. L. Effect of free fatty acids on protein binding of antimicrobial agents. J Infect Dis. 1981;143:609–616. https://doi.org/10.1093/infdis/143.4.609.
12. Polso A. K., Lassiter J. L., Nagel J. L. Impact of hospital guideline for weight-based antimicrobial dosing in morbidly obese adults and comprehensive literature review. J Clin Pharm Ther. 2014;39:584–608. https://doi.org/10.1111/jcpt.12200.
13. Morita K., Yamaji A. Changes in the serum protein binding of vancomycin in patients with methicillin-resistant Staphylococcus aureus infection: the role of serum Α: 1: -acid glycoprotein levels. Ther Drug Monit. 1995;17:107–112. https://doi.org/10.1097/00007691-199504000-00001.
14. Zokufa H. Z., Solem L. D., Rodvold K. A. et al. 1989. The influence
15. of serum albumin and alpha 1-acid glycoprotein on vancomycin protein binding in patients with burn injuries. J Burn Care Rehabil. 1989;10:425–428. https://doi.org/10.1097/00004630-198909000-00010.
16. Smit C., De Hoogd S., Brüggemann R. J. M., Knibbe C. A. J. 2018. Obesity and drug pharmacology: a review of the influence of obesity on pharmacokinetic and pharmacodynamic parameters. Expert Opin Drug Metab Toxicol. 2018;14:275–285. https://doi.org/10.1080/17425255.2018.1440287.
17. Kotlyar M., Carson S. W. Effects of obesity on the cytochrome P450 enzyme system. Int J Clin Pharmacol Ther. 1999;37:8–19.
18. Griffin K. A., Kramer H., Bidani A. K. Adverse renal consequences of obesity. Am J Physiol Renal Physiol. 2008;294:F685–96. https://doi.org/10.1152/ajprenal.00324.2007.
19. Meng L., Mui E., Ha D. R. et al. Comprehensive guidance for antibiotic dosing in obese adults: 2022 update. Pharmacotherapy. 2023;43:226–246. https://doi.org/10.1002/phar.2769.
20. Castro-Balado A., Varela-Rey I., Mejuto B. et al. Updated antimicrobial dosing recommendations for obese patients. Antimicrob Agents Chemother. 2024;68(5):e0171923. https:// doi.org/10.1128/aac.01719-23. PMID: 38526051; PMCID: PMC11064535.
21. Velissaris D., Karamouzos V., Marangos M., et al. Pharmacokinetic changes and dosing modification of aminoglycosides in critically ill obese patients: a literature review. J Clin Med Res. 2014;6:227–233. https://doi.org/10.14740/jocmr1858w.
22. Traynor A. M., Nafziger A. N., Bertino J. S. Aminoglycoside dosing weight correction factors for patients of various body sizes. Antimicrob Agents Chemother. 1995;39:545–548. https:// doi.org/10.1128/AAC.39.2.545.
23. Bergan T. Pharmacokinetics of beta-lactam antibiotics. Scand J Infect Dis Suppl. 1984;42:83–98. PMID: 6597564.
24. Hites M., Taccone F. S., Wolff F. et al. Broad-spectrum β-lactams in obese non-critically ill patients. Nutr Diabetes. 2014;4(6):e119.https://doi.org/10.1038/nutd.2014.15. PMID: 24956136; PMCID: PMC4079925.
25. Kanbay M., Copur S., Bakir C. N. et al. Glomerular hyperfiltration as a therapeutic target for CKD. Nephrol Dial Transplant. 2024;39(8):1228–1238. https://doi.org/10.1093/ndt/gfae027.PMID: 38308513.
26. Roberts J. A., Croom K., Adomakoh N. Continuous infusion of beta lactam antibiotics: narrative review of systematic reviews, and implications for outpatient parenteral antibiotic therapy. Expert Rev Anti Infect Ther. 2023;21:375–385. https://doi.org/10.1080/14787210.2023. 2184347.
27. Clinical Recommendations: Out-of-hospital pneumonia in adults. URL: https://cr.minzdrav.gov.ru/preview-cr/654_2 (accessed: 29.01.2025). (In Russ.).
28. Clinical Recommendations: Sepsis (in adults). URL: https:// cr.minzdrav.gov.ru/preview-cr/898_1 (accessed: 29.01.2025). (In Russ.).
29. Clinical Recommendations: Acute pyelonephritis. URL: https:// cr.minzdrav.gov.ru/preview-cr/9_3 (accessed: 29.01.2025). (In Russ.).
30. Van Rhee K. P., Smit C., Wasmann R. E. et al. Ciprofloxacin Pharmacokinetics After Oral and Intravenous Administration in (Morbidly) Obese and Non-obese Individuals: A Prospective Clinical Study. Clin Pharmacokinet. 2022;61(8):1167–1175. https://doi.org/10.1007/s40262-022-01130-5. PMID: 35641862; PMCID: PMC9349153.
31. Allard S., Kinzig M., Boivin G. et al. Intravenous ciprofloxacin disposition in obesity. Clin Pharmacol Ther. 1993;54(4):368–73. https://doi.org/10.1038/clpt.1993.162. PMID: 8222478.
32. Hollenstein U. M., 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;25:354–8.
33. Hopkins M. K., Tewari S., Yao M. et al. Standard-dose azithromycin in class III obese patients undergoing unscheduled cesarean delivery. Am J Perinatol. 2024;41(S 01):e2645–e2650. https://doi.org/10.1055/a-2135-7084.
34. Peyriere H., Makinson A., Marchandin H., Reynes J. Doxycycline in the management of sexually transmitted infections. J Antimicrob Chemother. 2018;73:553–563. https://doi.org/10.1093/jac/dkx420.
35. Bouazza N., Pestre V., Jullien V. et al. Population pharmacokinetics of clindamycin orally and intravenously administered in patients with osteomyelitis. Br J Clin Pharmacol. 2012;74(6):971–7. https://doi.org/10.1111/j.1365-2125.2012.04292.x. PMID: 22486719; PMCID: PMC3522810.
36. Nicholas P., Meyers B. R., Levy R. N., Hirschman S. Z. Concentration of clindamycin in human bone. Antimicrob Agents Chemother. 1975;8(2):220–1. https://doi.org/10.1128/AAC.8.2.220. PMID: 1180546; PMCID: PMC429291.
37. Nikolos P, Osorio J, Mohrien K, Rose C. Pharmacokinetics of linezolid for methicillin-resistant Staphylococcus aureus pneumonia in an adult receiving extracorporeal membrane oxygenation. Am J Health Syst Pharm. 2020;77(11):877–881. https://doi.org/10.1093/ajhp/zxaa066. PMID: 32426841.
38. Heidari S., Khalili H. Linezolid pharmacokinetics: a systematic review for the best clinical practice. Eur J Clin Pharmacol. 2023;79:195–206. https://doi.org/10.1007/s00228-022-03446-4.
39. Beloborodov V. B., Golovanov O. V., Gusarov V. G. et al. Updated guidelines “Diagnosis and antimicrobial therapy of infections caused by multidrug-resistant strains of microorganisms”. 2022. URL: https://www.antibiotic.ru/files/334/mr-abt.pdf (accessed: 19.03.24). (In Russ.).
40. Polso A. K., Lassiter J. L., Nagel J. L. Impact of hospital guideline for weight-based antimicrobial dosing in morbidly obese adults and comprehensive literature review. J Clin Pharm Ther. 2014;39:584–608. https://doi.org/10.1111/jcpt.12200.
41. Garrett E. R., Süverkrup R. S., Eberst K. et al. Surgically affected sulfisoxazole pharmacokinetics in the morbidly obese. Biopharm Drug Dispos. 1981;2:329–365. https://doi.org/10.1002/bdd.2510020405.
42. Hall R. G., Pasipanodya J. G., Meek C. et al. Fractal geometrybased decrease in trimethoprim-sulfamethoxa zole concentrations in overweight and obese people. CPT Pharmaco metrics Syst Pharmacol. 2016;5:674–681. https://doi.org/10.1002/psp4.12146.
43. Dorn C., Petroff D., Neumann N. et al. Plasma and tissue pharmacokinetics of fosfomycin in morbidly obese and nonobese surgical patients: a controlled clinical trial. J Antimicrob Chemother. 2019;74:2335–2340. https://doi.org/10.1093/jac/dkz203.
44. Busse D., Simon P., Petroff D. et al. 2022. High- dosage fosfomycin results in adequate plasma and target-site exposure in morbidly obese and nonobese nonhyperfiltration patients. Antimicrob Agents Chemother. 2022;66(6):e0230221. https:// doi.org/10.1128/aac.02302-21.
45. Crass R. L., Dunn R., Hong J. et al. Dosing vancomycin in the super obese: less is more. J Antimicrob Chemother. 2018;73:3081–3086. https://doi.org/10.1093/jac/dky310.
46. Monteiro J. F., Hahn S. R., Gonçalves J., Fresco P. Vancomycin therapeutic drug monitoring and population pharmacokinetic models in special patient subpopulations. Pharmacol Res Perspect. 2018;6:e00420. https://doi.org/10.1002/prp2.420.
47. Rybak M. J., Le J., Lodise T. P. et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: a revised consensus guideline and review by the American society of health- system pharmacists, the infectious diseases society of America, the pediatric infectious diseases society, and the society of infectious diseases pharmacists. Am J Health Syst Pharm. 2020;77:835–864. https://doi.org/10.1093/ajhp/zxaa036.
48. Elrggal M. E., Haseeb A., AlGethamy M. et al. Dose optimization of vancomycin in obese patients: a systematic review. Front Pharmacol. 2023;14:965284. https://doi.org/10.3389/fphar.2023.965284.
49. Zhang T., Smit C., Sherwin C. M. T. et al. Vancomycin clearance in obese adults is not predictive of clearance in obese adolescents. Clin Pharmacokinet. 2023;62:749–759. https://doi.org/10. 1007/s40262-023-01227-5.
50. Soule A. F., Green S. B., Blanchette L. M. Clinical efficacy of 12-h metronidazole dosing regimens in patients with anaerobic or mixed anaerobic infections. Ther Adv Infect Dis. 2018;5:57–62. https://doi.org/10. 1177/2049936118766462.
51. Martin C., Auboyer C., Boisson M. et al. Antibiopro phylaxis in surgery and interventional medicine (adult patients). Upd ate 2017. Anaesth Crit Care Pain Med. 2019;38:549–562. https:// doi.org/10.1016/j.accpm.2019.02.017.
52. Nation R. L., Garonzik S. M., Thamlikitkul V. et al. Dosing guidance for intravenous colistin in critically-ill patients. Clin Infect Dis. 2017;64:565–571. https://doi.org/10.1093/cid/ciw839.
53. Tsuji B. T., Pogue J. M., Zavascki A. P. et al. Interna tional consensus guidelines for the optimal use of the polymyxins: endorsed by the American college of clinical pharmacy (ACCP), European society of clinical microbiology and infectious diseases (ESCMID), infectious diseases society of America (IDSA), international society for anti-infective pharmacology (ISAP), society of critical care medicine (SCCM), and society of infectious diseases pharmacists (SIDP). Pharmacotherapy. 2019;39:10–39.
54. WHO (2020), Obesity and overweight. URL: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight (accessed: 29.01.2025).
55. Obesity: etiology, pathogenesis, clinical aspects. Edited by I. I. Dedov, G. A. Melnichenko. Moscow, Medical Information Agency, 2004:16–21. (In Russ.).
56. OECD (2021), Overweight or obese population (indicator). https://doi.org/10.1787/86583552-en (accessed: 28.08.2021).
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For citations:
Svechkareva I.R., Valeeva A.H., Busheva T.I., Kolbin A.S. Peculiarities of choice of dosing regimen and administration of antibacterial drugs in obese patients. New St. Petersburg Medical Records. 2025;(1):11-21. (In Russ.) https://doi.org/10.24884/1609-2201-2025-104-1-11-21
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