Factors influencing antibiotic treatment cost and outcome in critically ill patients: A “real-life” study

  • Aneta Perić Sector for Pharmacy, Military Medical Academy, Belgrade, Serbia; Faculty of Medicine of the Military Medical Academy, University of Defence, Belgrade, Serbia
  • Maja Šurbatović Faculty of Medicine of the Military Medical Academy, University of Defence, Belgrade, Serbia; Clinic of Anesthesiology and Intensive Therapy, Military Medical Academy, Belgrade, Serbia
  • Sandra Vezmar Kovačević Department of Pharmacokinetics and Clinical Pharmacy, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
  • Mirjana Antunović Sector for Pharmacy, Military Medical Academy, Belgrade, Serbia; Faculty of Medicine of the Military Medical Academy, University of Defence, Belgrade, Serbia
  • Milić Veljović Faculty of Medicine of the Military Medical Academy, University of Defence, Belgrade, Serbia; Clinic of Anesthesiology and Intensive Therapy, Military Medical Academy, Belgrade, Serbia
  • Dragan Djordjević Faculty of Medicine of the Military Medical Academy, University of Defence, Belgrade, Serbia; Clinic of Anesthesiology and Intensive Therapy, Military Medical Academy, Belgrade, Serbia
  • Tamara Andjelić Institute of Medical Biochemistry, Military Medical Academy, Belgrade, Serbia
  • Snježana Zeba Faculty of Medicine of the Military Medical Academy, University of Defence, Belgrade, Serbia; Clinic of Anesthesiology and Intensive Therapy, Military Medical Academy, Belgrade, Serbia
  • Silva Dobrić Faculty of Medicine of the Military Medical Academy, University of Defence, Belgrade, Serbia; Institute for Scientific Information, Military Medical Academy, Belgrade, Serbia
Keywords: critical illness, sepsis, anti-bacterial agents, cost and cost analysis, biological markers,

Abstract


Background/Aim. Critically ill patients are at very high risk of developing severe infections in intensive care units (ICUs). Procalcitonin (PCT) levels are eleveted in the circulation in patients with bacterial sepsis and PCT might be useful in guiding antibiotic treatment. The aim of this study was to estimate factors influencing patients survival and treatment cost in ICU with special emphasis on the impact of PCT serum levels use in guiding antimicrobial therapy. Methods. The study was conducted from August 2010 to May 2012 in the Intensive Therapy Unit, Clinic of Anesthesiology and Intensive Therapy, Military Medical Academy (MMA), Belgrade, Serbia. All adult critically ill patients with sepsis and/or trauma admitted in the ICU were included in the study. This study included only the cost of antimicrobial therapy in the ICU and the cost for PCT analysis. We used prices valid in the MMA for the year 2012. PCT in serum was measured by homogeneous immunoassay on a Brahms Kryptor analyzer. Results. A total of 102 patients were enrolled. The mean patients age was 55 ± 19 years and 61.8% of patients were male. The mean length of stay (LOS) in the ICU was 12 ± 21 days. There was a statistically significant difference (p < 0.001) between the sepsis and trauma group regarding outcome (higher mortality rate was in the sepsis group, particularly in the patients with peritonitis who were mostly women). The patients younger than 70 years had better chance of survival. LOS, the use of carbapenems and PCT-measurement influenced the cost of therapy in the ICU. Conclusions. The obtained results show that age, the diagnosis and gender were the main predictors of survival of critically ill patients in the ICU. The cost of ICU stay was dependent on LOS, use of carbapenems and PCT-measurement although the influence of these three factors on the outcome in the patients did not reach a statistical significance.

References

Wilke MH. Multiresistant bacteria and current therapy: The economical side of the story. Eur J Med Res 2010; 15(12): 571−6.

Pea F, Viale P, Furlanut M. Antimicrobial therapy in critically ill patients: a review of pathophysiological conditions responsible for altered disposition and pharmacokinetic variability. Clin Pharmacokinet 2005; 44(10): 1009−34.

Marik PE. Surviving sepsis: going beyond the guidelines. Ann Intensive Care 2011; 1(1): 17.

Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003; 348(16): 1546−54.

Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001; 29(7): 1303−10.

Vincent J, Sakr Y, Sprung CL, Ranieri MV, 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.

Sharma S, Kumar A. Antimicrobial management of sepsis and septic shock. Clin Chest Med 2008; 29(4): 677−87.

Surbatovic M, Jevdjic J, Veljovic M, Popovic N, Djordjevic D, Radakovic S. Immune Response in Severe Infection: Could Life-Saving Drugs Be Potentially Harmful. ScientificWorldJournal 2013; 2013: 961852.

Cavaillon J, Annane D. Compartmentalization of the inflamma-tory response in sepsis and SIRS. J Endotoxin Res 2006; 12(3): 151−70.

Delinger PR, Levy MM, Rhodes A, Annane D, Gerlach H, Opal S, et al. Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012. Crit Care Med 2013; 41(2): 580−620.

Dellinger PR, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al. Surviving Sepsis Campaign: international guidelines for management for severe sepsis and septic shock: 2008. Crit Care Med 2008; 36(1): 296−327.

Patil VK, Morjaria JB, de Villers F, Babu SK. Associations be-tween procalcitonin and markers of bacterial sepsis. Medicina (Kaunas) 2012; 48(8): 383−7.

Maki DG. Microbiologic diagnosis of blood culture-negative sepsis by hemofiltration. Crit Care Med 2004; 32(4): 1075−7.

Tang BM, Eslick GD, Craig JC, McLean AS. Accuracy of procal-citonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis. Lancet Infect Dis 2007; 7(3): 210−7.

Jensen JU, Hein L, Lundgren B, Bestle MH, Mohr TT, Andersen MH, et al. Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: a randomized trial. Crit Care Med 2011; 39(9): 2048−58.

Schuetz P, Christ-Crain M, Müller B. Procalcitonin and other biomarkers to improve assessment and antibiotic stewardship in infections: hope for hype. Swiss Med Wkly 2009; 139(23−24): 318−26.

Bouadma L, Luyt C, Tubach F, Cracco C, Alvarez A, Schwebel C, et al. Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet 2010; 375(9713): 463−74.

Brun-Buisson C, Roudot-Thoraval F, Girou E, Grenier-Sennelier C, Durand-Zaleski I. The costs of septic syndromes in the inten-sive care unit and influence of hospital-acquired sepsis. Inten-sive Care Med 2003; 29(9): 1464−71.

Edwards SJ, Campbell HE, Plumb JM. Cost-utility analysis com-paring meropenem with imipenem plus cilastatin in the treat-ment of severe infections in intensive care. Eur J Health Econ 2006; 7(1): 72−8.

Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003; 31(4): 1250−6.

Spiegel MR. Theory and problems of probability and statistics. New York: McGraw-Hill; 1992.

Edbrooke DL, Hibbert CL, Kingsley JM, Smith S, Bright NM, Quinn JM. The patient-related costs of care for sepsis patients in a United Kingdom adult general intensive care unit. Crit Care Med 1999; 27(9): 1760−7.

Kumar A, Ellis P, Arabi Y, Roberts D, Light B, Parrillo JE, et al. Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest 2009; 136(5): 1237−48.

Lee H, Doig CJ, Ghali WA, Donaldson C, Johnson D, Manns B. Detailed cost analysis of care for survivors of severe sepsis. Crit Care Med 2004; 32(4): 981−5.

Winters BD, Eberlein M, Leung J, Needham DM, Pronovost PJ, Se-vransky JE. Long-term mortality and quality of life in sepsis: A systematic review. Crit Care Med 2012; 38(5): 1276−83.

Burchardi H, Schneider H. Economic aspects of severe sepsis: a review of intensive care unit costs, cost of illness and cost ef-fectiveness of therapy. Pharmacoeconomics 2004; 22(12): 793−813.

Sogayar AM, Machado FR, Rea-Neto A, Dornas A, Grion CM, Lobo SM, et al. A multicentre, prospective study to evaluate costs of septic patients in Brazilian intensive care units. Pharmacoe-conomics 2008; 26(5): 425−34.

Edwards SJ, Wordsworth S, Clarke MJ. Treating pneumonia in critical care in the United Kingdom following failure of initial antibiotic: a cost-utility analysis comparing meropenem with piperacillin/tazobactam. Eur J Health Econ 2012; 13(2): 181−92.

Hsueh P, Liu C, Shi Z, Lee M, Chang F, Yang M. Cost minimisa-tion analysis of antimicrobial treatment for intra-abdominal in-fections: a multicentre retrospective study from Taiwan. Int J Antimicrob Agents 2010; 35(1): 94−6.

Attanasio E, Russo P, Carunchio G, Basoli A, Caprino L. Cost-Effectiveness Study of Imipenem/Cilastatin versus Merope-nem in Intra-Abdominal Infections. Dig Surg 2000; 17(2): 164−72.

Cheval C, Timsit JF, Garrouste-Orgeas M, Assicot M, de Jonghe B, Misset B, et al. Procalcitonin (PCT) is useful in predicting the bacterial origin of an acute circulatory failure in critically ill pa-tients. Intensive Care Med 2000; 26(Suppl 2): S153−8.

Honh A, Schroeder S, Gehn A, Bernhardt K, Bein B, Wegscheider K. Procalcitonin-guided algorithm to reduce length of antibiotic therapy in patients with severe sepsis and septic shock. BMC Infect Dis 2013; 13: 158.

Heyland DK, Johnson AP, Reynolds SC, Muscedere J. Procalcitonin for reduced antibiotic exposure in the critical care setting: a systematic review and an economic evaluation. Crit Care Med 2011; 397(7): 1792−9.

Adrie C, Alberti C, Chaix-Couturier C, Azoulay E, de Lassence A, Cohen Y, et al. Epidemiology and economic evaluation of se-vere sepsis in France: age, severity, infection site, and place of acquisition (community, hospital, or intensive care unit) as de-terminants of workload and cost. J Crit Care 2005; 20(1): 46−58.

Kollef MH, Golan Y, Micek ST, Shorr AF, Restrego MI. Apprasing contemporary strategies to combat multidrug resistant gram-negative bacterial infections-Proceedings and data from the Gram-Negative Resistance Summit. Clin Infec Dis 2011; 53(Suppl 2): 33−55.

Fraimow HS. Chipping away at unnecessary antibiotic use in the ICU, one day and one study at a time. Crit Care Med 2013; 41(10): 2447−8.

Vandijck DM, Depaemelaere M, Labeau SO, Depuydt PO, Annemans L, Buyle FM, et al. Daily cost of antimicrobial therapy in patients with Intensive Care Unit-acquired, laboratory-confirmed bloodstream infection. Int J Antimicrob Agents 2008; 31(2): 161−5.

Published
2015/04/24
Section
Original Paper