The influence of sepsis on antimicrobials tissue penetration: the use of microdialysis technique to access free drug distribution
DOI:
https://doi.org/10.1590/Keywords:
Sepsis, Antimicrobials, Microdialysis, Tissue penetration, Pharmacokinetics, PharmacodynamicsAbstract
Sepsis is described as a life-threatening organ dysfunction caused by a host’s response to infection, leading to an unbalance in body homeostasis. It is one of the leading causes of death in developed countries. Considering that in critically ill patients, such as those with sepsis, plasma concentrations do not necessarily reflect tissue concentrations, one way to assess tissue concentrations is through the microdialysis technique, which allows direct measurements of free drug at the site of action. This review was carried out after searching the Pubmed, Scielo and Web of Science databases, using the following descriptors: (microdialysis AND (sepsis OR septic shock OR severe sepsis OR septicemia)) OR (microdialysis AND (sepsis OR septic shock OR severe sepsis) OR septicemia) AND (antimicrobial OR antibiotic OR antifungal)). The physiological changes generated by sepsis may imply changes in pharmacokinetic parameters, such as in clearance, which may be reduced in these patients and in volume of distribution, which presents an expansion, mainly due to edema. Both events contribute to a high inter- individual variability in tissue penetration of antimicrobials which is generally observed in patients with sepsis.
Downloads
References
Abraham J, Sinollareddy M, Roberts MS, Willians P, Peake SL, Lipman J, et al. Plasma and interstitial ßuid population pharmacokinetics of vancomycin in critically patients with sepsis. Int J Antimicrob Agents. 2018.
Angus DC, Poll TVD. Severe sepsis and septic shock. N Engl J Med. 2013;369(9):840-51.
Baldwin CM, Lyseng-Williamson KA, Keam SJ. Meropenem A Review of its Use in the Treatment of Serious Bacterial Infections. Drugs. 2008;68(6):803-838.
Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992;101(6):1644-1655.
Buerger C, Plock N, Dehghanyar P, Joukhadar C, Kloft C. Pharmacokinetics of unbound linezolid in plasma and tissue interstitium of critically ill patients after multiple dosing usingmicrodialysis. Antimicrob Agents Chemother. 2006;50(7):2455-63.
Chauzy A, Lamarche I, Adiera C, Couet W, Marchand S. Microdialysis Study of Aztreonam-Avibactam Distribution in Peritoneal Fluid and Muscle of Rats with or without Experimental Peritonitis. Antimicrob Agents Chemother . 2018;62(10):e01228-18.
Colombo AL, Guimarães T, Camargo LFA, Ritchtmann R, Queiroz-Telles F, Salles MJC, et al. Brazilian guidelines for the management of candidiasis - a joint meeting report of three medical societies: Sociedade Brasileira de Infectologia, Sociedade Paulista de Infectologia and Sociedade Brasileira de Medicina Tropical. Braz J Infect Dis. 2013;17(3):283-312.
Condon RE, Walker AP, Hanna CB, Greenberg RN, Broom A, Pitkin D. Penetration of meropenem in plasma and abdominal tissues from patients undergoing intraabdominal surgery. Clin Infect Dis. 1997;24 Suppl 2:181-183.
De Gascun C, Rajan L, O’Neill E, Smyth EG. Linezolid use in sepsis due to methicillin-susceptible Staphylococcus aureus. J Antimicrob Chemother. 2006;57(1):150-1.
Dehghanyar P, Buerger C, Zeitlinger M, Isinger F, Kovan F, Muller M, et al. Penetration of linezolid into soft tissues of healthy volunteers after single and multiple doses. Antimicrob Agents Chemother . 2005;49(6):2367-71.
Eggimann P, Garbino J, Pittet D. Epidemiology of Candida species infections in critically ill non-immunosuppressed patients. Lancet Infec Dis. 2003;3(11):685-702.
Eykyn S, Phillips Y. Metronidazole and anaerobic sepsis. Br Med J. 1976;2(6049):1418-1421.
Fly DE. The Importance of Antibiotic Pharmacokinetics in Critical Illness. Excerpta Med. 1996;172(6A):20S-25S.
Ford CW, Zurenko GE, Barbachyn MR. The Discovery of Linezolid, the First Oxazolidinone Antibacterial Agent. Curr Drug Targets Infect Disord. 2001;1(2):181-199.
Gall JR, Lemeshow S, Saulnier F. A New Simplified Acute Physiology Score (SAPS II) Based on a European/North American Multicenter Study. Jama. 1993;270(24):2957-2963.
Grif K, Dierich MP, Pfaller K, Miglioli PA, Allerberger F. In vitro activity of fosfomycin in combination with various antistaphylococcal substances. J Antimicrob Chemother . 2001;48(2):209-17.
Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med . 2003;348(2):138-50.
Ilias L, Apollonatou S, Nikitas N, Theodorakopoulou M, Vassiliou AG, Kotanidou A, et al. Microdialysis-Assessed Adipose Tissue Metabolism, Circulating Cytokines and Outcome in Critical Illness. Metabolites. 2018;8(4):62.
Joukhadar C, Derendorf H, Muller M. Microdialysis a novel tool for clinical studies of anti-infective agents. Eur J Pharmacol. 2001b;57:211-219.
Joukhadar C, Frossard M, Mayer BX, Klein N, Siostrzonek P, Eichler HG, et al. Impaired target site penetration of β-lactam s may account for therapeutic failure in patients with septic shock. Crit Care Med. 2001a;29(2):385-91.
Joukhadar C, Klein N, Dittrich P, Zeitlinger M, Geppert A, Skhirladze K, et al. Target site penetration of fosfomycin in critically ill patients. J Antimicrob Chemother . 2003;51(5):1247-52.
Joukhadar C, Klein N, Mayer BX, Kreischitz N, Delle-Karth G, Palkovits P, et al. Plasma and tissue pharmacokinetics of cefpirome in patients with sepsis. Crit Care Med . 2002;30(7):1478-82.
Karjagin J, Lefeuvre S, Oselin K, Kipper K, Marchand S, Tikkerberi A, et al. Pharmacokinetics of Meropenem Determined by Microdialysis in the Peritoneal Fluid of Patients With Severe Peritonitis Associated With Septic Shock. Clin Pharmacol Ther. 2008;83(3):452-459.
Karjagin J, Pahkla JR, Karki T, Starkopf J. Distribution of metronidazole in muscle tissue of patients with septic shock and its efficacy against Bacteroides fragilis in vitro. J Antimicrob Chemother . 2005;55(3):341-346.
Kaukonen KM, Bailey M, Suzuki S, Pilcher D, Bellomo R. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000- 2012. JAMA. 2014;311(13):1308-16.
Khwannimit B, Bhurayanontachai R, Vattanavanit V. Validation of the sepsis severity score compared with updated severity score in predicting hospital mortality in sepsis patients. Shock. 2017;47(6):720-725.
Knaus AW, Draper EA, Wagner DP, Zimmerman JE. APACHE II: A severity of disease classification system. Crit Care Med . 1985;13(10):818-829.
Lefeuvre S, Marchand S, Lamarche I, Mimoz O, Couet W. Microdialysis Study of Imipenem Distribution in the Intraperitoneal Fluid of Rats with or without Experimental Peritonitis. Antimicrob Agents Chemother . 2006;50(1):34- 37.
Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, et al. Infectious Diseases Society of America. 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):e18-55.
Matzi V, Lindenmann J, Porubsky C, Kugler SA, Maier A, Dittrich P, et al. Extracellular concentrations of fosfomycin in lung tissue of septic patients. J Antimicrob Chemother . 2010;65(5):995-998.
Mauric O, Thallinger C, Kugler SA, Joukhadar SM, Kovar FM, Konz KH, et al. The Ability of Fluconazole to Penetrate into Ventilated, Healthy and Inflamed Lung Tissue in a Model of Severe Sepsis in Rats. Pharmacology. 2011;87(3- 4):130-134.
Micek ST, Hampton N, Kollefc M. Risk Factors and Outcomes for Ineffective Empiric Treatment of Sepsis Caused by Gram- Negative Pathogens: Stratification by Onset of Infection. Antimicrob Agents Chemother . 2018;62(1):e0157 7-17.
Michie HR. Metabolism of Sepsis and Multiple Organ Failure. World J Surg. 1996;20(4):460-4.
Mouton JW, Theuretzbacher U, Craig WA, Tulkens PM, Derendorf H, Cars O. Tissue concentrations: do we ever learn? J Antimicrob Chemother . 2008;61(2):235-237.
Nandi P, Lunte SM. Recent trends in microdialysis sampling integrated with conventional and microanalytical systems for monitoring biological events: A review. Anal Chim Acta. 2009;651(1):1-14
Nedeva C, Menassa J, Puthalakath H. Sepsis: Inflammation Is a Necessary Evil. Front Cell Dev Biol. 2019;7:108.
Nguyen HB, Rivers EP, Havstad S, Knoblich B, Resser JA, Muzzin AM, et al. Critical Care in the Emergency Department: a physiologic assessment and outcome evaluation. Acad Emerg Med. 2000;7(12):1354-61.
Nord CE. The treatment of severe intra-abdominal infections: the role of piperacillin/tazobactam. Intensive Care Med. 1994;20 Suppl 3:S35-38.
Nowak H, Weidemann C, Martini S, Oesterreicher ZA, Dorn C, Adamzik M, et al. Repeated determination of moxifloxacin concentrations in interstitial space fluid of muscle and subcutis in septic patients. J Antimicrob Chemother . 2019;74(9):2681-2689.
Osborn TM, Phillips G, Lemeshow S, Townsend S, Schorr CA, Levy MM, et al. Sepsis Severity Score: an internationally derived scoring system from the surviving sepsis campaign database. Crit Care Med . 2014;42(9):1969-76.
Popovic M, Steinort D, Pillai S, Joukhadar C. Fosfomycin: an old, new friend? Eur J Clin Microbiol Infect Dis. 2009;29(2):127-142.
Power BM, Forbes AM, Van Heerden PV, Llett KF. Pharmacokinetics of Drugs Used in Critically Ill Adults. Clin Pharmacokinet. 1998;34(1):25-56.
Rello J, Ulldemolins M, Lisboa T, Koulenti D, Mãnez R, Martin-Loeches, et al. Determinants of prescription and choice of empirical therapy for hospital-acquired and ventilator-associated pneumonia. Eur Respir J. 2011;37(6):1332-1339.
Roberts JA, Kirkapatrick CM, Roberts MS, Dalley AD, Lipman J. First-dose and steady-state population pharmacokinetics and pharmacodynamics of piperacillin by continuous or intermittent dosing in critically ill patients with sepsis. Int J Antimicrob Agents . 2010;35(2):156-63.
Roberts JA, Kirkpatrick CMJ, Roberts MS, Robertson TA, Dalley AJ, Lipman J. Meropenem dosing in critically ill patients with sepsis and without renal dysfunction: intermittent bolus versus continuous administration? Monte Carlo dosing simulations and subcutaneous tissue distribution. Journal of Antimicrobial Chemotherapy, 2009b;64(1):142-50.
Roberts JA, Roberts MS, Robertson TA, Dalley AJ, Lipman J. Piperacillin penetration into tissue of critically ill patients with sepsis-Bolus versus continuous administration? Crit Care Med . 2009a;37(3):926-933.
Rudd KE, Johnson SC, Agesa KM, Shackelford K, Tsoi D, Kievlan DR, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet. 2020;395(10219):200-11.
São Pedro TC, Morcillo AM, Baracat ECE. Etiology and prognostic factors of sepsis among children and adolescents admitted to the intensive care unit. Rev Bras Ter Intensiva. 2015;27(3):240-246.
Sauermann R, Delle-Karth G, Marsik C, Steiner I, Zeirlinger M, Mayer-Helm BX, et al. Pharmacokinetics and pharmacodynamics of cefpirome in subcutaneous adipose tissue of septic patients. Antimicrob Agents Chemother . 2005;49(2):650-655.
Schouten M, Wiersinga WJ, Levi M, Van Der Pol T. Inflammation, endothelium, and coagulation in sepsis. J Leukoc Biol. 2008;83(3):536-45.
Sekyere JO. Candida auris: A systematic review and meta- analysis of current updates on an emerging multidrug-resistant pathogen. Microbiol Open. 2018;7: 57-8.
Seymour CW, Rosengart MR. Septic Shock Advances in Diagnosis and Treatment. Clinical Review & Education. 2015;314(7):708-17.
Shippenberg TS, Thompson AC. Overview of Microdialysis. Curr Protoc Neurosci. 2001;Chapter 7:Unit7.1.
Silva Júnior GB, Daher EF, Mota RMS, Menezes FA. Risk factors for death among critically ill patients with acute renal failure. Sao Paulo Med J. 2006;124(5):257-63.
Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA . 2016; 315(8):801-810.
Sinnollareddy MG, Roberts MS, Lipman J, Lassing-Smith M, Starr T, Robertson T, et al. Determination of Subcutaneous Interstitial Fluid Penetration and Pharmacokinetics of Fluconazole in Intensive Care Unit Patients with Sepsis Using In Vivo Microdialysis. Antimicrob Agents Chemother . 2015;60(2):827-832.
Sy SKB, Beaudoin ME, Zhuang L, Loblein KI, Lux C, Kissek M, et al. In vitro pharmacokinetics/pharmacodynamics of the combination of avibactam and aztreonam against MDR organisms. J Antimicrob Chemother . 2016;71(7):1866-1880.
Tanriover MD, Guven GS, Sen D, Unal S, Uzun O. Epidemiology and outcome of sepsis in a tertiary-care hospital in a developing country. Epidemiol Infect. 2006;134(2):315-322.
Tenover FC, Biddle JW, Lancaster MV. Increasing Resistance to Vancomycin and Other Glycopeptides in Staphylococcus aureus. Emerg Infec Dis. 2001;7(2):327-332.
Thallinger C, Buerger C, Plock N, Kljucar S, Wuenscher S, Sauermaan R, et al. Effect of severity of sepsis on tissue concentrations of linezolid. J Antimicrob Chemother. 2008;61(1):173-176.
Tjandramaga TB, Mullie A, Verbesselt R, De Schepper PJ, Verbist L. Piperacillin: Human Pharmacokinetics After Intravenous and Intramuscular Administration. Antimicrob Agents Chemother . 1978;14(6):829-837.
Venkatesh B, Morgan TM, Cohen J. Interstitium: The next diagnostic and therapeutic platform in critical illness. Crit Care Med . 2010;38(10 Suppl):S630-6.
Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, et al. The SOFA (Sepsis.related Organ Failure Assessment) score to describe organ dysfunction/failure. Intensive Care Med . 1996;22(7):707-710.
Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, et al. Sepsis in European intensive care units: Results of the SOAP study*.Crit Care Med . 2006;34(2):344- 53.
Wagenlehner FME, Lunz JC, Kees F,Wieland W, Nsber KG. Serum and Prostatic Tissue Concentrations of Moxifloxacin in Patients Undergoing Transurethral Resection of the Prostate. J Chemother. 2006;18(5):485-489.
Wiesholzer M, Pichler P, Reznicek G, Wimmer M, Kussmann M, Balcke P, et al. An Open, Randomized, Single-Center, Crossover Pharmacokinetic Study of Meropenem after Intraperitoneal and Intravenous Administration in Patients Receiving Automated Peritoneal Dialysis. Antimicrob Agents Chemother . 2016;60(5):2790-2797.
World Health Organization, WHO. 2017. https://apps.who.int/iris/bitstream/handle/10665/332081/9789240005587- eng.pdf
» https://apps.who.int/iris/bitstream/handle/10665/332081/9789240005587- eng.pdf
World Health Organization. WHO. 2020. https://apps.who.int/iris/bitstream/handle/10665/334216/9789240010789-eng. pdf?sequence=1&isAllowed=y
» https://apps.who.int/iris/bitstream/handle/10665/334216/9789240010789-eng. pdf?sequence=1&isAllowed=y
Zeitlinger BS, Zeitlinger M, Leitner I, Muller M, Joukhadar C. Clinical Scoring System for the Prediction of Target Site Penetration of Antimicrobials in Patients with Sepsis. Clin Pharmacokinet . 2007;46(1):75-83.
Zeitlinger MA, Dehghanyar P, Mayer BX, Schenk BS, Neckel U, Heinz G, et al. Relevance of Soft-Tissue Penetration by Levofloxacin for Target Site Bacterial Killing in Patients with Sepsis. Antimicrob Agents Chemother . 2003;47(11):3548- 3553.
Zhanel GG, Ennis K, Vercaigne L, Walkty A, Gin AS, Embil J, et al. A Critical Review of the Fluoroquinolones Focus on Respiratory Tract Infection. Drugs . 2002;62(1):13-59.
Downloads
Published
Issue
Section
License
Copyright (c) 2023 Brazilian Journal of Pharmaceutical Sciences
This work is licensed under a Creative Commons Attribution 4.0 International License.
All content of the journal, except where identified, is licensed under a Creative Commons attribution-type BY.
The on line journal has open and free access.