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The Utility of Procalcitonin as a Biomarker to Limit the Duration of Antibiotic Therapy in Adult Sepsis Patients

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DOI: 10.4236/ss.2014.58057    2,714 Downloads   3,803 Views   Citations


Introduction: With rising global antibiotic resistance, stewardship programs aimed at controlling multi-drug resistant (MDR) pathogens have begun to gain acceptance. These programs stress appropriate antibiotic selection, dosage and duration. A growing literature suggests serum procalcitonin (PCT) levels may be useful in guiding antibiotic duration and de-escalation. This report sought to evaluate the evidence-based data available from prospective randomized controlled trials (RCT) on the role of PCT in guiding reductions in antibiotic duration in adult sepsis patients. Methods: A comprehensive search of all published prospective RCT(s) on the use of PCT as a tool for guiding antibiotic therapy in adult sepsis patients was conducted using PubMed, Medline Plus and Google Scholar (2007-2013). Keywords searched included, “procalcitonin”, “sepsis-therapy”, “sepsis biomarker”, “antibiotic duration”, “drug de-escalation”, and “antimicrobial stewardship”. Results: Four RCT(s) involving 826 adult sepsis patients have evaluated the role of serum PCT levels to guide criteria for cessation of antibiotic therapy based either on specific PCT levels or PCT kinetics. Bouadma et al. (N = 621) stopped antibiotics when the PCT concentration was <80% of the peak PCT value, or the absolute PCT concentration was <0.5 μg/L. The PCT arm showed a 2.7-day reduction in antibiotics. Schroeder et al. (N = 27) discontinued antibiotics if clinical signs of infection improved and the PCT value decreased to <1 ng/mL or to <35% of the initial value within three days. The PCT arm had a 1.7-day reduction in antibiotics. Hochreiter et al. (N = 110) ceased antibiotics when the PCT decreased to <1 ng/mL, or to 25% - 35% of the initial value over three days if the value was >1 ng/mL. The PCT arm showed a 2-day reduction in antibiotics. Finally, Nobre et al. (N = 68) stopped antibiotics when PCT levels decreased by 90% or more from the initial value, but not prior to Day 3 (if baseline PCT measured <1 μg/L) or Day 5 (if baseline PCT measured ≥1 μg/L). The PCT arm showed a 4-day reduction in antibiotics. Overall, reduction of PCT levels to 10% - 35% of the initial concentration, to <80% of the peak PCT value, or to an absolute PCT value of <1 μg/L warranted antibiotic discontinuation 1.7 to 4 days earlier. No study reported a significant difference in mortality between the PCT arm and the control arm (p< 0.05). Conclusions: PCT-guided early cessation of antibiotic therapy in adult sepsis patients is associated with a significant decrease in antibiotic days, with no effect on overall mortality. Measurement of serum PCT levels may have a role in antimicrobial stewardship programs aimed at limiting antibiotic therapy duration, decreasing the selective pressure on drug-resistant bacterial strains and reducing hospital costs.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Chamberlain, R. , Shayota, B. , Nyberg, C. and Sridharan, P. (2014) The Utility of Procalcitonin as a Biomarker to Limit the Duration of Antibiotic Therapy in Adult Sepsis Patients. Surgical Science, 5, 342-353. doi: 10.4236/ss.2014.58057.


[1] Gomes Silva, B.N., Andriolo, R.B., Atallah, A.N. and Salomao, R. (2010) De-Escalation of Antimicrobial Treatment for Adults with Sepsis, Severe Sepsis or Septic Shock. Cochrane Database of Systematic Reviews, 12, Article ID: CD007934.
[2] Martin, G.S., Mannino, D.M., Eaton, S. and Moss, M. (2003) The Epidemiology of Sepsis in the United States from 1979 through 2000. The New England Journal of Medicine, 348, 1546-1554.
[3] Hall, M.J., Williams, S.N., De Frances, C.J. and Golosinskiy, A. (2011) Inpatient Care for Septicemia or Sepsis: A Challenge for Patients and Hospitals. NCHS Data Brief, 62, 1-8.
[4] Elixhauser, A., Friedman, B. and Stranges, E. (2006) Septicemia in U.S. Hospitals, 2009: Statistical Brief #122.
[5] (2010) HCUP Facts and Figures: Statistics on Hospital-Based Care in the United States, 2008. Healthcare Cost and Utilization Project (HCUP). Agency for Healthcare Research and Quality, Rockville.
[6] Harbarth, S., Garbino, J., Pugin, J., Romand, J.A., Lew, D. and Pittet, D. (2003) Inappropriate Initial Antimicrobial Therapy and Its Effect on Survival in a Clinical Trial of Immunomodulating Therapy for Severe Sepsis. American Journal of Medicine, 115, 529-535.
[7] (2005) Guidelines for the Management of Adults with Hospital-Acquired, Ventilator-Associated, and Healthcare-Associated Pneumonia. American Journal of Respiratory and Critical Care Medicine, 171, 388-416.
[8] Kumar, A., Roberts, D., Wood, K.E., Light, B., Parrillo, J.E., Sharma, S., Suppes, R., Feinstein, D., Zanotti, S., Taiberg, L., Gurka, D., Kumar, A. and Cheang, M. (2006) Duration of Hypotension before Initiation of Effective Antimicrobial Therapy Is the Critical Determinant of Survival in Human Septic Shock. Critical Care Medicine, 34, 1589-1596.
[9] Micek, S.T., Lloyd, A.E., Ritchie, D.J., Reichley, R.M., Fraser, V.J. and Kollef, M.H. (2005) Pseudomonas Aeruginosa Bloodstream Infection: Importance of Appropriate Initial Antimicrobial Treatment. Antimicrobial Agents and Chemotherapy, 49, 1306-1311.
[10] Proulx, N., Frechette, D., Toye, B., Chan, J. and Kravcik, S. (2005) Delays in the Administration of Antibiotics Are Associated with Mortality from Adult Acute Bacterial Meningitis. QJM, 98, 291-298.
[11] Shehabi, Y. and Seppelt, I. (2008) Pro/Con Debate: Is Procalcitonin Useful for Guiding Antibiotic Decision Making in Critically Ill Patients? Critical Care, 12, 211.
[12] Thursky, K.A., Buising, K.L., Bak, N., Macgregor, L., Street, A.C., Macintyre, C.R., Presneill, J.J., Cade, J.F. and Brown, G.V. (2006) Reduction of Broad-Spectrum Antibiotic Use with Computerized Decision Support in an Intensive Care Unit. International Journal for Quality in Health Care, 18, 224-231.
[13] Scheetz, M.H., Bolon, M.K., Postelnick, M., Noskin, G.A. and Lee, T.A. (2009) Cost-Effectiveness Analysis of an Antimicrobial Stewardship Team on Bloodstream Infections: A Probabilistic Analysis. Journal of Antimicrobial Chemotherapy, 63, 816-825.
[14] Liew, Y.X., Chlebicki, M.P., Lee, W., Hsu, L.Y. and Kwa, A.L. (2011) Use of Procalcitonin (PCT) to Guide Discontinuation of Antibiotic Use in an Unspecified Sepsis Is an Antimicrobial Stewardship Program (ASP). European Journal of Clinical Microbiology & Infectious Diseases, 30, 853-855.
[15] Shah, N.D., Hoffman, J.M., Vermeulen, L.C., Hunkler, R.J. and Hontz, K.M. (2003) Projecting Future Drug Expenditures—2003. American Journal of Health-System Pharmacy, 60, 137-149.
[16] Hoffman, J.M., Shah, N.D., Vermeulen, L.C., Hunkler, R.J. and Hontz, K.M. (2004) Projecting Future Drug Expenditures—2004. American Journal of Health-System Pharmacy, 61, 145-158.
[17] Hoffman, J.M., Shah, N.D., Vermeulen, L.C., Hunkler, R.J. and Hontz, K.M. (2005) Projecting Future Drug Expenditures—2005. American Journal of Health-System Pharmacy, 62, 149-167.
[18] Hoffman, J.M., Shah, N.D., Vermeulen, L.C., Schumock, G.T., Grim, P., Hunkler, R.J. and Hontz, K.M. (2006) Projecting Future Drug Expenditures—2006. American Journal of Health-System Pharmacy, 63, 123-138.
[19] Hoffman, J.M., Shah, N.D., Vermeulen, L.C., Schumock, G.T., Grim, P., Hunkler, R.J. and Hontz, K.M. (2007) Projecting Future Drug Expenditures—2007. American Journal of Health-System Pharmacy, 64, 298-314.
[20] Hoffman, J.M., Shah, N.D., Vermeulen, L.C., Doloresco, F., Grim, P., Hunkler, R.J., Hontz, K.M. and Schumock, G.T. (2008) Projecting Future Drug Expenditures—2008. American Journal of Health-System Pharmacy, 65, 234-253.
[21] Hoffman, J.M., Shah, N.D., Vermeulen, L.C., Doloresco, F., Martin, P.K., Blake, S., Matusiak, L., Hunkler, R.J. and Schumock, G.T. (2009) Projecting Future Drug Expenditures—2009. American Journal of Health-System Pharmacy, 66, 237-257.
[22] Hoffman, J.M., Doloresco, F., Vermeulen, L.C., Shah, N.D., Matusiak, L., Hunkler, R.J. and Schumock, G.T. (2010) Projecting Future Drug Expenditures—2010. American Journal of Health-System Pharmacy, 67, 919-928.
[23] Doloresco, F., Fominaya, C., Schumock, G.T., Vermeulen, L.C., Matusiak, L., Hunkler, R.J., Shah, N.D. and Hoffman, J.M. (2011) Projecting Future Drug Expenditures—2011. American Journal of Health-System Pharmacy, 68, 921-932.
[24] Hoffman, J.M., Li, E., Doloresco, F., Matusiak, L., Hunkler, R.J., Shah, N.D., Vermeulen, L.C. and Schumock, G.T. (2012) Projecting Future Drug Expenditures—2012. American Journal of Health-System Pharmacy, 69, 405-421.
[25] Hoffman, J.M., Li, E., Doloresco, F., Matusiak, L., Hunkler, R.J., Shah, N.D., Vermeulen, L.C., Schumock, G.T. (2013) Projecting Future Drug Expenditures in U.S. Nonfederal Hospitals and Clinics—2013. American Journal of Health-System Pharmacy, 70, 525-539.
[26] Finland, M. (1979) Emergence of Antibiotic Resistance in Hospitals, 1935-1975. Clinical Infectious Diseases, 1, 4-21.
[27] Deege, M.P. and Paterson, D.L. (2011) Reducing the Development of Antibiotic Resistance in Critical Care Units. Current Pharmaceutical Biotechnology, 12, 2062-2069.
[28] Van Duijn, P.J., Dautzenberg, M.J. and Oostdijk, E.A. (2011) Recent Trends in Antibiotic Resistance in European ICUs. Current Opinion in Critical Care, 17, 658-665.
[29] Lawrence, K.L. and Kollef, M.H. (2009) Antimicrobial Stewardship in the Intensive Care Unit: Advances and Obstacles. American Journal of Respiratory and Critical Care Medicine, 179, 434-438.
[30] Masterton, R.G. (2011) Antibiotic De-Escalation. Critical Care Clinics, 27, 149-162.
[31] Schuetz, P., Albrich, W. and Mueller, B. (2011) Procalcitonin for Diagnosis of Infection and Guide to Antibiotic Decisions: Past, Present and Future. BMC Medicine, 9, 107.
[32] Schuetz, P., Christ-Crain, M., Thomann, R., Falconnier, C., Wolbers, M., Widmer, I., Neidert, S., Fricker, T., Blum, C., Schild, U., Regez, K., Schoenenberger, R., Henzen, C., Bregenzer, T., Hoess, C., Krause, M., Bucher, H.C., Zimmerli, W. and Mueller, B. (2009) Effect of Procalcitonin-Based Guidelines vs Standard Guidelines on Antibiotic Use in Lower Respiratory Tract Infections: The ProHOSP Randomized Controlled Trial. The Journal of the American Medical Association, 302, 1059-1066.
[33] Drew, R.H. (2009) Antimicrobial Stewardship Programs: How to Start and Steer a Successful Program. Journal of Managed Care Pharmacy, 15, S18-S23.
[34] Goldmann, D.A., Weinstein, R.A., Wenzel, R.P., Tablan, O.C., Duma, R.J., Gaynes, R.P., Schlosser, J. and Martone, W.J. (1996) Strategies to Prevent and Control the Emergence and Spread of Antimicrobial-Resistant Microorganisms in Hospitals. A challenge to Hospital Leadership. The Journal of the American Medical Association, 275, 234-240.
[35] Apisarnthanarak, A., Buppunharun, W., Tiengrim, S., Sawanpanyalert, P. and Aswapokee, N. (2009) An Overview of Antimicrobial Susceptibility Patterns for Gram-Negative Bacteria from the National Antimicrobial Resistance Surveillance Thailand (NARST) Program from 2000 to 2005. Journal of the Medical Association of Thailand, 92, S91-S94.
[36] Tseng, S.H., Lee, C.M., Lin, T.Y., Chang, S.C., Chuang, Y.C., Yen, M.Y., Hwang, K.P., Leu, H.S., Yen, C.C. and Chang, F.Y. (2012) Combating Antimicrobial Resistance: Antimicrobial Stewardship Program in Taiwan. Journal of Microbiology, Immunology and Infection, 45, 79-89.
[37] Allerberger, F., Lechner, A., Wechsler-Fordos, A. and Gareis, R. (2008) Optimization of Antibiotic Use in Hospitals— Antimicrobial Stewardship and the EU Project ABS International. Chemotherapy, 54, 260-267.
[38] Allerberger, F., Frank, A. and Gareis, R. (2008) Antibiotic Stewardship through the EU Project “ABS International”. Wiener klinische Wochenschrift, 120, 256-263.
[39] George, P. and Morris, A.M. (2010) Pro/Con Debate: Should Antimicrobial Stewardship Programs Be Adopted Universally in the Intensive Care Unit? Critical Care, 14, 205.
[40] Hayashi, Y. and Paterson, D.L. (2011) Strategies for Reduction in Duration of Antibiotic Use in Hospitalized Patients. Clinical Infectious Diseases, 52, 1232-1240.
[41] Sarraf-Yazdi, S., Sharpe, M., Bennett, K.M., Dotson, T.L., Anderson, D.J. and Vaslef, S.N. (2012) A 9-Year Retrospective Review of Antibiotic Cycling in a Surgical Intensive Care Unit. Journal of Surgical Research, 176, e73-e78.
[42] Beardmore, R.E. and Pena-Miller, R. (2010) Antibiotic Cycling Versus Mixing: The Difficulty of Using Mathematical Models to Definitively Quantify Their Relative Merits. Mathematical Biosciences and Engineering, 7, 923-933.
[43] Kollef, M.H. (2006) Is Antibiotic Cycling the Answer to Preventing the Emergence of Bacterial Resistance in the Intensive Care Unit? Clinical Infectious Diseases, 43, S82-S88.
[44] Bal, A.M., Kumar, A. and Gould, I.M. (2010) Antibiotic Heterogeneity: From Concept to Practice. Annals of the New York Academy of Sciences, 1213, 81-91.
[45] Masterton, R.G. (2010) Antibiotic Heterogeneity. International Journal of Antimicrobial Agents, 36, S15-S18.
[46] Singh, N., Rogers, P., Atwood, C.W., Wagener, M.M. and Yu, V.L. (2000) Short-Course Empiric Antibiotic Therapy for Patients with Pulmonary Infiltrates in the Intensive Care Unit. A Proposed Solution for Indiscriminate Antibiotic Prescription. American Journal of Respiratory and Critical Care Medicine, 162, 505-511.
[47] Chastre, J., Wolff, M., Fagon, J.Y., Chevret, S., Thomas, F., Wermert, D., Clementi, E., Gonzalez, J., Jusserand, D., Asfar, P., Perrin, D., Fieux, F. and Aubas, S. (2003) Comparison of 8 vs 15 days of Antibiotic Therapy for Ventilator-Associated Pneumonia in Adults: A Randomized Trial. The Journal of the American Medical Association, 290, 2588-2598.
[48] Micek, S.T., Ward, S., Fraser, V.J. and Kollef, M.H. (2004) A Randomized Controlled Trial of an Antibiotic Discontinuation Policy for Clinically Suspected Ventilator-Associated Pneumonia. Chest, 125, 1791-1799.
[49] Gonsalves, M.D. and Sakr, Y. (2010) Early Identification of Sepsis. Current Infectious Disease Reports, 12, 329-335.
[50] Lavrentieva, A., Papadopoulou, S., Kioumis, J., Kaimakamis, E. and Bitzani, M. (2012) PCT as a Diagnostic and Prognostic Tool in Burn Patients. Whether Time Course Has a Role in Monitoring Sepsis Treatment. Burns, 38, 356-363.
[51] Cosse, C., Regimbeau, J.M., Fuks, D., Mauvais, F. and Scotte, M. (2013) Serum Procalcitonin for Predicting the Failure of Conservative Management and the Need for Bowel Resection in Patients with Small Bowel Obstruction. Journal of The American College of Surgeons, 216, 997-1004.
[52] Markogiannakis, H., Memos, N., Messaris, E., Dardamanis, D., Larentzakis, A., Papanikolaou, D., Zografos, G.C. and Manouras, A. (2011) Predictive Value of Procalcitonin for Bowel Ischemia and Necrosis in Bowel Obstruction. Surgery, 149, 394-403.
[53] Shen, C.J., Wu, M.S., Lin, K.H., Lin, W.L., Chen, H.C., Wu, J.Y., Lee, M.C. and Lee, C.C. (2013) The Use of Procalcitonin in the Diagnosis of Bone and Joint Infection: A Systemic Review and Meta-Analysis. European Journal of Clinical Microbiology & Infectious Diseases, 32, 807-814.
[54] Friederichs, J., Hutter, M., Hierholzer, C., Novotny, A., Friess, H., Buhren, V. and Hungerer, S. (2013) Procalcitonin Ratio as a Predictor of Successful Surgical Treatment of Severe Necrotizing Soft Tissue Infections. The American Journal of Surgery, 206, 368-373.
[55] Nobre, V., Harbarth, S., Graf, J.D., Rohner, P. and Pugin, J. (2008) Use of Procalcitonin to Shorten Antibiotic Treatment Duration in Septic Patients: A Randomized Trial. American Journal of Respiratory and Critical Care Medicine, 177, 498-505.
[56] Hochreiter, M., Kohler, T., Schweiger, A.M., Keck, F.S., Bein, B., von, S.T. and Schroeder, S. (2009) Procalcitonin to Guide Duration of Antibiotic Therapy in Intensive Care Patients: A Randomized Prospective Controlled Trial. Critical Care, 13, R83.
[57] Schroeder, S., Hochreiter, M., Koehler, T., Schweiger, A.M., Bein, B., Keck, F.S. and von, S.T. (2009) Procalcitonin (PCT)-Guided Algorithm Reduces Length of Antibiotic Treatment in Surgical Intensive Care Patients with Severe Sepsis: Results of a Prospective Randomized Study. Langenbeck’s Archives of Surgery, 394, 221-226.
[58] Bouadma, L., Luyt, C.E., Tubach, F., Cracco, C., Alvarez, A., Schwebel, C., Schortgen, F., Lasocki, S., Veber, B., Dehoux, M., Bernard, M., Pasquet, B., Regnier, B., Brun-Buisson, C., Chastre, J. and Wolff, M. (2010) Use of Procalcitonin to Reduce Patients’ Exposure to Antibiotics in Intensive Care Units (PRORATA Trial): A Multicentre Randomised Controlled Trial. The Lancet, 375, 463-474.
[59] Kirby, W.M. and Rantz, L.A. (1942) Sulfonamide Resistance. California and Western Medicine, 57, 174-175.
[60] Hawser, S. (2012) Surveillance Programmes and Antibiotic Resistance: Worldwide and Regional Monitoring of Antibiotic Resistance Trends. Handbook of Experimental Pharmacology, 211, 31-43.
[61] Pendleton, J.N., Gorman, S.P. and Gilmore, B.F. (2013) Clinical Relevance of the ESKAPE Pathogens. Expert Review of Anti-Infective Therapy, 11, 297-308.
[62] Gould, I.M. and Bal, A.M. (2013) New Antibiotic Agents in the Pipeline and How They Can Help Overcome Microbial Resistance. Virulence, 4, 185-191.
[63] Canton, R. and Bryan, J. (2012) Global Antimicrobial Resistance: From Surveillance to Stewardship. Part 1: Surveillance and Risk Factors for Resistance. Expert Review of Anti-Infective Therapy, 10, 1269-1271.
[64] Canton, R. and Bryan, J. (2012) Global Antimicrobial Resistance: From Surveillance to Stewardship. Part 2: Stewardship Initiatives. Expert Review of Anti-Infective Therapy, 10, 1375-1377.
[65] Marr, J.J., Moffet, H.L. and Kunin, C.M. (1988) Guidelines for Improving the Use of Antimicrobial Agents in Hospitals: A Statement by the Infectious Diseases Society of America. The Journal of Infectious Diseases, 157, 869-876.
[66] Wlodaver, C. and May, C.P. (2012) Antibiotic Stewardship: Using Clinical Guidelines to Control Antibiotic Overuse and Deter Microbial Adaptation. Infectious Disease in Clinical Practice, 20, 12-17.
[67] Leophonte, P., Choutet, P., Gaillat, J., Petitpretz, P., Portier, H., Montestruc, F., Pecking, M. and de Bels, F. (2002) Efficacy of a Ten Day Course of Ceftriaxone Compared to a Shortened Five Day Course in the Treatment of Community-Acquired Pneumonia in Hospitalized Adults with Risk Factors. Médecine et Maladies Infectieuses, 32, 369-381.
[68] Dunbar, L.M., Wunderink, R.G., Habib, M.P., Smith, L.G., Tennenberg, A.M., Khashab, M.M., Wiesinger, B.A., Xiang, J.X., Zadeikis, N. and Kahn, J.B. (2003) High-Dose, Short-Course Levofloxacin for Community-Acquired Pneumonia: A New Treatment Paradigm. Clinical Infectious Diseases, 37, 752-760.
[69] Dunbar, L.M., Khashab, M.M., Kahn, J.B., Zadeikis, N., Xiang, J.X. and Tennenberg, A.M. (2004) Efficacy of 750-MG, 5-Day Levofloxacin in the Treatment of Community-Acquired Pneumonia Caused by Atypical Pathogens. Current Medical Research and Opinion, 20, 555-563.
[70] Tellier, G., Niederman, M.S., Nusrat, R., Patel, M. and Lavin, B. (2004) Clinical and Bacteriological Efficacy and Safety of 5 and 7 Day Regimens of Telithromycin Once Daily Compared with a 10 Day Regimen of Clarithromycin Twice Daily in Patients with Mild to Moderate Community-Acquired Pneumonia. Journal of Antimicrobial Chemotherapy, 54, 515-523.
[71] File Jr., T.M., Mandell, L.A., Tillotson, G., Kostov, K. and Georgiev, O. (2007) Gemifloxacin Once Daily for 5 Days versus 7 Days for the Treatment of Community-Acquired Pneumonia: A Randomized, Multicentre, Double-Blind Study. Journal of Antimicrobial Chemotherapy, 60, 112-120.
[72] Li, J.Z., Winston, L.G., Moore, D.H. and Bent, S. (2007) Efficacy of Short-Course Antibiotic Regimens for Community-Acquired Pneumonia: A Meta-Analysis. American Journal of Medicine, 120, 783-790.
[73] Dimopoulos, G., Matthaiou, D.K., Karageorgopoulos, D.E., Grammatikos, A.P., Athanassa, Z. and Falagas, M.E. (2008) Short-Versus Long-Course Antibacterial Therapy for Community-Acquired Pneumonia: A Meta-Analysis. Drugs, 68, 1841-1854.
[74] el Moussaoui, R., de Borgie, C.A., van den Broek, P., Hustinx, W.N., Bresser, P., van den Berk, G.E., Poley, J.W., van den Berg, B., Krouwels, F.H., Bonten, M.J., Weenink, C., Bossuyt, P.M., Speelman, P., Opmeer, B.C. and Prins, J.M. (2006) Effectiveness of Discontinuing Antibiotic Treatment after Three Days versus Eight Days in Mild to Moderate-Severe Community Acquired Pneumonia: Randomised, Double Blind Study. British Medical Journal, 332, 1355.
[75] Sudhir, U., Venkatachalaiah, R.K., Kumar, T.A., Rao, M.Y. and Kempegowda, P. (2011) Significance of Serum Procalcitonin in Sepsis. Indian Journal of Critical Care Medicine, 15, 1-5.
[76] Whang, K.T., Steinwald, P.M., White, J.C., Nylen, E.S., Snider, R.H., Simon, G.L., Goldberg, R.L. and Becker, K.L. (1998) Serum Calcitonin Precursors in Sepsis and Systemic Inflammation. The Journal of Clinical Endocrinology & Metabolism, 83, 3296-3301.
[77] Selberg, O., Hecker, H., Martin, M., Klos, A., Bautsch, W. and Kohl, J. (2000) Discrimination of Sepsis and Systemic Inflammatory Response Syndrome by Determination of Circulating Plasma Concentrations of Procalcitonin, Protein Complement 3a, and Interleukin-6. Critical Care Medicine, 28, 2793-2798.
[78] Castelli, G.P., Pognani, C., Meisner, M., Stuani, A., Bellomi, D. and Sgarbi, L. (2004) Procalcitonin and C-Reactive Protein during Systemic Inflammatory Response Syndrome, Sepsis and Organ Dysfunction. Critical Care, 8, R234-R242.
[79] Dahaba, A.A., Hagara, B., Fall, A., Rehak, P.H., List, W.F. and Metzler, H. (2006) Procalcitonin for Early Prediction of Survival Outcome in Postoperative Critically Ill Patients with Severe Sepsis. British Journal of Anaesthesia, 97, 503-508.
[80] Jensen, J.U., Hein, L., Lundgren, B., Bestle, M.H., Mohr, T.T., Andersen, M.H., Thornberg, K.J., Loken, J., Steensen, M., Fox, Z., Tousi, H., Soe-Jensen, P., Lauritsen, A.O., Strange, D., Petersen, P.L., Reiter, N., Hestad, S., Thormar, K., Fjeldborg, P., Larsen, K.M., Drenck, N.E., Ostergaard, C., Kjaer, J., Grarup, J. and Lundgren, J.D. (2011) Procalcitonin-Guided Interventions against Infections to Increase Early Appropriate Antibiotics and Improve Survival in the Intensive Care Unit: A Randomized Trial. Critical Care Medicine, 39, 2048-2058.
[81] Jensen, J.U., Lundgren, B., Hein, L., Mohr, T., Petersen, P.L., Andersen, L.H., Lauritsen, A.O., Hougaard, S., Mantoni, T., Bomler, B., Thornberg, K.J., Thormar, K., Loken, J., Steensen, M., Carl, P., Petersen, J.A., Tousi, H., Soe-Jensen, P., Bestle, M., Hestad, S., Andersen, M.H., Fjeldborg, P., Larsen, K.M., Rossau, C., Thomsen, C.B., et al. (2008) The Procalcitonin And Survival Study (PASS)-A Randomised Multi-Center Investigator-Initiated Trial to Investigate whether Daily Measurements Biomarker Procalcitonin and Pro-Active Diagnostic and Therapeutic Responses to Abnormal Procalcitonin Levels, Can Improve Survival in Intensive Care unit Patients. Calculated Sample Size (Target Population): 1000 Patients. BMC Infectious Diseases, 8, 91.
[82] Schuetz, P., Albrich, W., Christ-Crain, M., Chastre, J. and Mueller, B. (2010) Procalcitonin for Guidance of Antibiotic Therapy. Expert Review of Anti-Infective Therapy, 8, 575-587.
[83] Stolz, D., Smyrnios, N., Eggimann, P., Pargger, H., Thakkar, N., Siegemund, M., Marsch, S., Azzola, A., Rakic, J., Mueller, B. and Tamm, M. (2009) Procalcitonin for Reduced Antibiotic Exposure in Ventilator-Associated Pneumonia: A Randomised Study. European Respiratory Journal, 34, 1364-1375.
[84] Luyt, C.E., Combes, A., Trouillet, J.L. and Chastre, J. (2011) Value of the Serum Procalcitonin Level to Guide Antimicrobial Therapy for Patients with Ventilator-Associated Pneumonia. Seminars in Respiratory and Critical Care Medicine, 32, 181-187.
[85] Aarts, M.A., Brun-Buisson, C., Cook, D.J., Kumar, A., Opal, S., Rocker, G., Smith, T., Vincent, J.L. and Marshall, J.C. (2007) Antibiotic Management of Suspected Nosocomial ICU-Acquired Infection: Does Prolonged Empiric Therapy Improve Outcome? Intensive Care Medicine, 33, 1369-1378.
[86] Romano, J. (2009) Labs Take New Role in Antibiotic Stewardship, Championing Improved Diagnoses, Guiding Therapy, Saving Lives, and Cutting Costs. Medical Laboratory Observer, 41, 16-18.
[87] Tenover, F.C. (2010) Potential Impact of Rapid Diagnostic Tests on Improving Antimicrobial Use. Annals of the New York Academy of Sciences, 1213, 70-80.
[88] Gould, I.M. (2009) Controversies in Infection: Infection Control or Antibiotic Stewardship to Control Healthcare-Acquired Infection? Journal of Hospital Infection, 73, 386-391. j.jhin.2009.02.023
[89] Wester, C.W., Durairaj, L., Evans, A.T., Schwartz, D.N., Husain, S. and Martinez, E. (2002) Antibiotic Resistance: A Survey of Physician Perceptions. JAMA Internal Medicine, 162, 2210-2216.
[90] Srinivasan, A. and Fishman, N. (2012) Antimicrobial Stewardship 2012: Science Driving Practice. Infection Control and Hospital Epidemiology, 33, 319-321.
[91] Standiford, H.C., Chan, S., Tripoli, M., Weekes, E. and Forrest, G.N. (2012) Antimicrobial Stewardship at a Large Tertiary Care Academic Medical Center: Cost Analysis before, during, and after a 7-Year Program. Infection Control and Hospital Epidemiology, 33, 338-345.
[92] Stevenson, K.B., Balada-Llasat, J.M., Bauer, K., Deutscher, M., Goff, D., Lustberg, M., Pancholi, P., Reed, E., Smeenk, D., Taylor, J. and West, J. (2012) The Economics of Antimicrobial Stewardship: The Current State of the Art and Applying the Business Case Model. Infection Control and Hospital Epidemiology, 33, 389-397.
[93] Beardsley, J.R., Williamson, J.C., Johnson, J.W., Luther, V.P., Wrenn, R.H. and Ohl, C.C. (2012) Show Me the Money: Long-Term Financial Impact of an Antimicrobial Stewardship Program. Infection Control and Hospital Epidemiology, 33, 398-400.

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