Аннотация
В настоящее время в развитых странах ожирением страдают от 15 до 50% населения. Пациенты с ожирением имеют более высокий риск возникновения инфекций, у них чаще развиваются инфекционные осложнения после хирургических вмешательств и выше уровень летальности. Назначение антимикробной терапии пациентам, страдающим ожирением, представляет собой сложную задачу, что связано с изменением фармакокинетики антибактериальных препаратов у такого рода больных. К сожалению, несмотря на значимость проблемы дозирования антибиотиков у пациентов с избыточной массой тела и ожирением, исследований в этой области клинической фармакологии проведено немного. В данном обзоре обобщены имеющиеся на настоящий момент исследования и публикации, посвящённые подходам к дозированию антибиотиков у пациентов с ожирением.
НИИ антимикробной химиотерапии ФГБОУ ВО СГМУ Минздрава России, Смоленск, Россия
НИИ антимикробной химиотерапии ФГБОУ ВО СГМУ Минздрава России, Смоленск, Россия
НИИ антимикробной химиотерапии ФГБОУ ВО СГМУ Минздрава России, Смоленск, Россия
-
1.
Ng M., Fleming T., Robinson M., et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 19802013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384(9945):766-781.
-
2.
Go A.S., Mozaffarian D., Roger V.L., et al; on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics – 2013 update: a report from the American Heart Association. Circulation. 2013;127:e6-e245.
-
3.
Sturm R., Hattori A. Morbid obesity rates continue to rise rapidly in the United States. Int J Obes (Lond). 2013;37(6):889-891.
-
4.
Sturm R. Increases in morbid obesity in the USA: 2000-200
-
5.
Public Health. 2007;121:492-495.
-
6.
Finkelstein E.A., Khavjou O.A., Thompson H., et al. Obesity and severe obesity forecasts through 2030. Am J Prev Med. 2012;42(6):563-570. 6. Falagas M.E., Athanasoulia A.P., Peppas G., et al. Effect of body mass index on the outcome of infections: a systematic review. Obes Rev. 2009;10:280289.
-
7.
Liu Y., Dong Y., Wu X., et al. Influence of high body mass index on mortality and infectious outcomes in patients who underwent open gastrointestinal surgery: A meta-analysis. Am J Infect Control. 2016;44(5):572-578.
-
8.
Hanley M.J., Abernethy D.R., Greenblat D.J. Effect of obesity on the pharmacokinetics of drugs in humans. Clin Pharmacokinet. 2010;49:7187.
-
9.
Tucker C.E., Lockwood A.M., Nguyen N.H. Antibiotic dosing in obesity: the search for optimum dosing strategies. Clin Obes. 2014;4(6):287-295.
-
10.
Arabi Y.M., Dara S.I., Tamim H.M., et al. Clinical characteristics, sepsis interventions and outcomes in the obese patients with septic shock: an international multicenter cohort study. Crit Care. 2013;17:R72.
-
11.
Roe J.L., Fuentes J.M., Mullins M.E. Underdosing of common antibiotics for obese patients in the ED. Am J Emerg Med. 2012;30:1212-1214.
-
12.
Longo C., Bartlett G., Macgibbon B., et al. The effect of obesity on antibiotic treatment failure: a historical cohort study. Pharmacoepidemiol Drug Saf. 2013;22:970-976.
-
13.
WHO. Physical status: the use and interpretation of anthropometry. Report of a WHO Expert Committee. WHO Technical Report Series 854. Geneva: World Health Organization, 1995.
-
14.
WHO. Obesity: preventing and managing the global epidemic. Report of a WHO Consultation. WHO Technical Report Series 894. Geneva: World Health Organization, 2000.
-
15.
Al-Dorzi H.M., Al Harbi S.A., Arabi Y.M. Antibiotic therapy of pneumonia in the obese patient: dosing and delivery. Curr Opin Infect Dis. 2014;27(2):165-173.
-
16.
Pai M.P., Bearden D.T. Antimicrobial dosing considerations in obese adult patients. Pharmacotherapy. 2007;27(8):1081-1091.
-
17.
Janson B., Thursky K. Dosing of antibiotics in obesity. Curr Opin Infect Dis. 2012;25(6):634-649.
-
18.
Udy A.A., Roberts J.A., Lipman J. Clinical implications of antibiotic pharmacokinetic principles in the critically ill. Intensive Care Med. 2013;39:2070-2082.
-
19.
Brill M.J., Diepstraten J., van Rongen A., et al. Impact of obesity on drug metabolism and elimination in adults and children. Clin Pharmacokinet. 2012;51(5):277-304.
-
20.
West G.B., Brown J.H., Enquist B.J. A general model for the origin of allometric scaling laws in biology. Science. 1997;276(5309):122-126.
-
21.
Claus B.O., Hoste E.A., Colpaert K., et al. Augmented renal clearance is a common finding with worse clinical outcome in critically ill patients receiving antimicrobial therapy. J Crit Care. 2013;28:695-700.
-
22.
Payne K.D., Hall R.G. 2nd. Dosing of antibacterial agents in obese adults: does one size fit all? Expert Rev Anti Infect Ther. 2014;12(7):829-854.
-
23.
Cockcroft D.W., Gault M.H. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41.
-
24.
Winter M.A., Guhr K.N., Berg G.M. Impact of various body weights and serum creatinine concentrations on the bias and accuracy of the CockcroftGault equation. Pharmacotherapy. 2012;32(7):604-612.
-
25.
Anderson A.H., Yang W., Hsu C.Y., et al. Estimating GFR among participants in the Chronic Renal Insufficiency Cohort (CRIC) Study. Am J Kidney Dis. 2012;60:250-261.
-
26.
Aggarwal N., Porter A.C., Tang I.Y., et al. Creatinine-based estimations of kidney function are unreliable in obese kidney donors. J Transplant. 2012;2012:872-894.
-
27.
Wurtz R., Itokazu G., Rodvold K. Antimicrobial dosing in obese patients. Clin Infect Dis. 1997;25:112-118.
-
28.
Yuk J., Nightingale C.H., Sweeney K., et al. Pharmacokinetics of nafcillin in obesity. J Infect Dis. 1988;157(5):1088-1089.
-
29.
Cheadle W.G. Risk factors for surgical site infection. Surg Infect (Larchmt). 2006;7(Suppl 1):S7-11.
-
30.
Forse R.A., Karam B., MacLean L.D., Christou N.V. Antibiotic prophylaxis for surgery in morbidly obese patients. Surgery. 1989;106:750-756.
-
31.
Ho V.P., Nicolau D.P., Dakin G.F., et al. Cefazolin dosing for surgical prophylaxis in morbidly obese patients. Surg Infect (Larchmt). 2012;13(1):33-37.
-
32.
van Kralingen S., Taks M., Diepstraten J., et al. Pharmacokinetics and protein binding of cefazolin in morbidly obese patients. Eur J Clin Pharmacol. 2011;67:985-992.
-
33.
Swank M.L., Wing D.A., Nicolau D.P., et al. Increased 3-gram cefazolin dosing for cesarean delivery prophylaxis in obese women. Am J Obstet Gynecol. 2015;213(3):415.e1-8.
-
34.
Barbour A., Schmidt S., Rout W.R., 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):231235.
-
35.
Hites M., Taccone F.S., Wolff F., et al. Broad-spectrum β-lactams in obese non-critically ill patients. Nutr Diabetes. 2014;4:e119.
-
36.
Rich B.S., Keel R., Ho V.P., et al. Cefepime dosing in the morbidly obese patient population. Obes Surg. 2012;22:465-471.
-
37.
Newman D., Scheetz M.H., Adeyemi O.A., et al. Serum piperacillin/ tazobactam pharmacokinetics in a morbidly obese individual. Ann Pharmacother. 2007;41:1734-1739.
-
38.
Deman H., Verhaegen J., Willems L., et al. Dosing of piperacillin/ tazobactam in a morbidly obese patient [letter]. J Antimicrob Chemother. 2012;67:782-783.
-
39.
Sturm A.W., Allen N., Rafferty K.D., et al. Pharmacokinetic analysis of piperacillin administered with tazobactam in critically ill, morbidly obese surgical patients. Pharmacotherapy. 2014;34(1):28-35.
-
40.
Cheatham S.C., Fleming M.R., Healy D.P., 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):52-56.
-
41.
Chen M., Nafziger A.N., Drusano G.L., et al. Comparative pharmacokinetics and pharmacodynamic target attainment of ertapenem in normal-weight, obese, and extremely obese adults. Antimicrob Agents Chemother. 2006;50:1222-1227.
-
42.
Zakrison T.L., Hille D.A., Namias N. Effect of body mass index on treatment of complicated intra-abdominal infections in hospitalized adults: comparison of ertapenem with piperacillin-tazobactam. Surg Infect (Larchmt). 2012;13:38-42.
-
43.
Itani K.M., Jensen E.H., Finn T.S., et al. Effect of body mass index and ertapenem versus cefotetan prophylaxis on surgical site infection in elective colorectal surgery. Surg Infect (Larchmt). 2008;9:131-137.
-
44.
Cheatham S.C., Fleming M.R., Healy D.P., 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):324-330.
-
45.
Hites M., Taccone F.S., Wolff F., et al. Case-control study of drug monitoring of β-lactams in obese critically ill patients. Antimicrob Agents Chemother. 2013;57:708-715.
-
46.
Pai M.P., Cojutti P., Pea F. Pharmacokinetics and pharmacodynamics of continuous infusion meropenem in overweight, obese, and morbidly obese patients with stable and unstable kidney function: a step toward dose optimization for the treatment of severe gram-negative bacterial infections. Clin Pharmacokinet. 2015;54(9):933-941.
-
47.
Kays M.B., Fleming M.R., Cheatham S.C., et al. Comparative pharmacokinetics and pharmacodynamics of doripenem and meropenem in obese patients. Ann Pharmacother. 2014;48(2):178-186.
-
48.
Roberts J.A., 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):489495.
-
49.
Chung E.K., Fleming M.R., Cheatham S.C., et al. Population Pharmacokinetics and Pharmacodynamics of Doripenem in Obese, Hospitalized Patients. Ann Pharmacother. 2017;51(3):209-218.
-
50.
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(4):259-268.
-
51.
Rybak M., Lomaestro B., Rotschafer J.C., 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;66:82-98.
-
52.
Thom H., Thompson J.C., Scott D.A., et al. Comparative efficacy of antibiotics for the treatment of acute bacterial skin and skin structure infections (ABSSSI): a systematic review and network meta-analysis. Curr Med Res Opin. 2015;31(8):1539-1551.
-
53.
Morrill H.J., Caffrey A.R., Noh E., et al. Vancomycin Dosing Considerations in a Real-World Cohort of Obese and Extremely Obese Patients. Pharmacotherapy. 2015;35(9):869-875.
-
54.
Hall R.G., Payne K.D., Bain A.M., et al. Multicenter evaluation of vancomycin dosing: emphasis on obesity. Am J Med. 2008;121:515-518.
-
55.
Bauer L.A., Black D.J., Lill J.S. Vancomycin dosing in morbidly obese patients. Eur J Clin Pharmacol. 1998;54:621-625.
-
56.
Blouin R.A., Bauer L.A., Miller D.D., et al. Vancomycin pharmacokinetics in normal and morbidly obese subjects. Antimicrob Agents Chemother. 1982;21:575-580.
-
57.
Grace E. Altered vancomycin pharmacokinetics in obese and morbidly obese patients: what we have learned over the past 30 years. J Antimicrob Chemother. 2012;67(6):1305-1310.
-
58.
Kullar R., Davis S.L., Levine D.P., et al. 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):975-981.
-
59.
Reynolds D.C., Waite L.H., Alexander D.P., et al. Performance of a vancomycin dosage regimen developed for obese patients. Am J Health Syst Pharm. 2012;69:944-950.
-
60.
Lodise T.P., Lomaestro B., Graves J., et al. Larger vancomycin doses (at least four grams per day) are associated with an increased incidence of nephrotoxicity. Antimicrob Agents Chemother. 2008;52(4):1330-1336.
-
61.
Pai M.P. Anti-infective Dosing for Obese Adult Patients: A Focus on Newer Drugs to Treat Methicillin-resistant Staphylococcus aureus Acute Bacterial Skin and Skin Structure Infections. Clin Ther. 2016;38(9):20322044.
-
62.
Lodise T.P., Patel N., Lomaestro B.M., et al. Relationship between initial vancomycin concentration-time profile and nephrotoxicity among hospitalized patients. Clin Infect Dis. 2009;49(4):507-514.
-
63.
Smith W.J., Drew R.H. Telavancin: a new lipoglycopeptide for gram-positive infections. Drugs Today (Barc). 2009;45(3):159-173.
-
64.
Drug @ FDA Database. US Food and Drug Administration. Vibativ Label 2009. https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022110s000lbl.pdf. Accessed July, 28, 2017.
-
65.
Jauregui L.E., Babazadeh S., Seltzer E., et al. Randomized, double-blind comparison of once-weekly dalbavancin versus twice-daily linezolid therapy for the treatment of complicated skin and skin structure infections. Clin Infect Dis. 2005;41(10):1407-1415.
-
66.
Dunne M.W., Puttagunta S., Giordano P., et al. A Randomized Clinical Trial of Single-Dose Versus Weekly Dalbavancin for Treatment of Acute Bacterial Skin and Skin Structure Infection. Clin Infect Dis. 2016;62(5):545-551.
-
67.
Dowell J.A., Goldstein B.P., Buckwalter M., et al. Pharmacokineticpharmacodynamic modeling of dalbavancin, a novel glycopeptide antibiotic. J Clin Pharmacol. 2008;48(9):1063-1068.
-
68.
Schwartz S.N., Pazin G.J., Lyon J.A., et al. A controlled investigation of the pharmacokinetics of gentamicin and tobramycin in obese subjects. J Infect Dis. 1978;138(4):499-505.
-
69.
Blouin R.A., Mann H.J., Griffen W.O.Jr., et al. Tobramycin pharmacokinetics in morbidly obese patients. Clin Pharmacol Ther. 1979;26(4):508-512.
-
70.
Blouin R.A., Brouwer K.L., Record K.E., et al. Amikacin pharmacokinetics in morbidly obese patients undergoing gastric-bypass surgery. Clin Pharm. 1985;4(1):70-72.
-
71.
Bauer L.A., Edwards W.A., Dellinger E.P., et al. Influence of weight on aminoglycoside pharmacokinetics in normal weight and morbidly obese patients. Eur J Clin Pharmacol. 1983;24(5):643-647.
-
72.
Leader W.G., Tsubaki T., Chandler M.H. Creatinine-clearance estimates for predicting gentamicin pharmacokinetic values in obese patients. Am J Hosp Pharm. 1994;51(17):2125-2130.
-
73.
Pai M.P., Nafziger A.N., Bertino J.S.Jr. Simplified estimation of aminoglycoside pharmacokinetics in underweight and obese adult patients. Antimicrob Agents Chemother. 2011;55:4006-4011.
-
74.
Pai M.P. Drug dosing based on weight and body surface area: mathematical assumptions and limitations in obese adults. Pharmacotherapy. 2012;32:856-868.
-
75.
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.
-
76.
Cerqueira R.M., Manso M.C., Correia M.R., et al. Helicobacter pylori eradication therapy in obese patients undergoing gastric bypass surgery – fourteen days superior to seven days? Obes Surg. 2011;21: 1377-1381.
-
77.
Allard S., Kinzig M., Boivin G., et al. Intravenous ciprofloxacin disposition in obesity. Clin Pharmacol Ther. 1993;54:368-373.
-
78.
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;25:354-358.
-
79.
Caldwell J.B., Nilsen A.K. Intravenous ciprofloxacin dosing in a morbidly obese patient. Ann Pharmacother. 1994;28:806.
-
80.
Kees M.G., Weber S., Kees F., et al. Pharmacokinetics of moxifloxacin in plasma and tissue of morbidly obese patients. J Antimicrob Chemother. 2011;66:2330-2335.
-
81.
Luque S., Grau S., Valle M., et al. Levofloxacin weight-adjusted dosing and pharmacokinetic disposition in a morbidly obese patient [letter]. J Antimicrob Chemother. 2011;66:1653-1654.
-
82.
Cook A.M., Martin C., Adams V.R., et al. Pharmacokinetics of intravenous levofloxacin administered at 750 milligrams in obese adults. Antimicrob Agents Chemother. 2011;55:3240-3243.
-
83.
Muzevich K.M., Lee K.B. 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.
-
84.
Tsuji Y., Hiraki Y., Matsumoto K., et al. Evaluation of the pharmacokinetics of linezolid in an obese Japanese patient. Scand J Infect Dis. 2012;44(8):626629.
-
85.
Stein G.E., Schooley S.L., Peloquin C.A., et al. Pharmacokinetics and pharmacodynamics of linezolid in obese patients with cellulitis. Ann Pharmacother. 2005;39:427-432.
-
86.
Bhalodi A.A., Papasavas P.K., Tishler D.S., et al. Pharmacokinetics of intravenous linezolid in moderately to morbidly obese adults. Antimicrob Agents Chemother. 2013;57:1144-1149.
-
87.
Zhanel G.G., Love R., Adam H., et al. Tedizolid: a novel oxazolidinone with potent activity against multidrug-resistant gram-positive pathogens. Drugs. 2015;75(3):253-270.
-
88.
Flanagan S., Passarell J., Lu Q., et al. Tedizolid population pharmacokinetics, exposure response, and target attainment. Antimicrob Agents Chemother. 2014;58(11):6462-6470.
-
89.
Pai M.P. Pharmacokinetics of Tedizolid in Morbidly Obese and Covariate-Matched Nonobese Adults. Antimicrob Agents Chemother. 2016;60(8):4585-4589.
-
90.
Van Wart S.A., Owen J. S., Ludwig E.A., et al. Population Pharmacokinetics of Tigecycline in Patients with Complicated Intra-Abdominal or Skin and Skin Structure Infections. Antimicrob Agents Chemother. 2006;50(11):37013707.
-
91.
Passarell J., Ludwig E., Liolios K., et al. Exposure-response analyses of tigecycline tolerability in healthy subjects. Diagn Microbiol Infect Dis. 2009;65(2):123-129.
-
92.
Pai M.P. Serum and urine pharmacokinetics of tigecycline in obese class III and normal weight adults. J Antimicrob Chemother. 2014;69(1):190-199.
-
93.
Dvorchik B., Arbeit R.D., Chung J., et al. Population Pharmacokinetics of Daptomycin. Antimicrob Agents Chemother. 2004;48(8):2799-2807.
-
94.
Dvorchik B.H., Damphousse D. The pharmacokinetics of daptomycin in moderately obese, morbidly obese, and matched nonobese subjects. J Clin Pharmacol. 2005;45(1):48-56.
-
95.
Bhavnani S.M., Rubino C.M., Ambrose P.G., et al. 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):1568-1574.
-
96.
Bookstaver P.B., Bland C.M., Qureshi Z.P., et al; SERGE-45 Investigators. Safety and effectiveness of daptomycin across a hospitalized obese population: results of a multicenter investigation in the southeastern United States. Pharmacotherapy. 2013;33(12):1322-1330.
-
97.
Ng J.K., Schulz L.T., Rose W.E., et al. Daptomycin dosing based on ideal body weight versus actual body weight: comparison of clinical outcomes. Antimicrob Agents Chemother. 2014;58(1):88-93.
-
98.
Davido B., Bouchand F., Calin R., et al. High rates of off-label use in antibiotic prescriptions in a context of dramatic resistance increase: a prospective study in a tertiary hospital. Int J Antimicrob Agents. 2016;47:490-494.
-
99.
Somova M.N., Batishheva G.A. Legal aspects of prescribing off-label. Prikladnye informacionnye aspekty mediciny. 2016;19(3):139-143. Russian. (Сомова М.Н., Батищева Г.А. Правовые аспекты назначения лекарственных препаратов off-label. Прикладные информационные аспекты медицины. 2016;19(3):139-143.).
-
100.
Food and Drug Administration Modernization Act of 1997, 21 U.S.C. §360aa, §551 (1997).
-
101.
Pereverzev A.P., Lepahin V.K. Modern view on the problem of the use of medicines in violation of the instructions. Medicinskij sovet. 2013;4:110111. Russian. (Переверзев А.П., Лепахин В.К. Современный взгляд на проблему применения лекарственных средств с нарушением предписаний инструкции. Медицинский совет. 2013;4:110-111.).