Procalcitonin-guided algorithm to reduce length of antibiotic therapy in patients with severe sepsis and septic shock

BMC Infectious Diseases

Marcel Hochreiter⁴  Karl Wegscheider²  Berthold Bein³  Kathrin Bernhardt⁶  Anna Gehrt⁶  Stefan Schroeder⁵  Andreas Hohn¹ 

[1] Department of Anaesthesiology, Intensive Care, Palliative Care and Pain Medicine, BG University Hospital Bergmannsheil, Ruhr-University Bochum, Bürkle-de-la-Camp-Platz 1, Bochum 44789, Germany;Department of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, Hamburg 20246, Germany;Department of Anaesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 21, Kiel 24105, Germany;Department of Anaesthesiology, University Hospital Heidelberg, Im Neuenheimer Feld 110, Heidelberg 69120, Germany;Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, Hospital Düren gem. GmbH, Roonstr. 30, Düren 52351, Germany;Department of Anaesthesiology and Intensive Care Medicine, West Coast Hospital, Esmarchstr. 50, Heide 25746, Germany

关键词: Intensive care;    Economical outcomes;    Sepsis;    Procalcitonin;   

Others  :  1149044
DOI  :  10.1186/1471-2334-13-158

 received in 2012-09-27, accepted in 2013-03-20,  发布年份 2013

【 摘 要 】

Background

Procalcitonin (PCT)-protocols to guide antibiotic treatment in severe infections are known to be effective. But less is known about the long-term effects of such protocols on antibiotic consumption under real life conditions. This retrospective study analyses the effects on antibiotic use in patients with severe sepsis and septic shock after implementation of a PCT-protocol.

Methods

We conducted a retrospective ICU-database search for adult patients between 2005 and 2009 with sepsis and organ dysfunction who where treated accordingly to a PCT-guided algorithm as follows: Daily measurements of PCT (BRAHMS PCT LIA®; BRAHMS Aktiengesellschaft, Hennigsdorf, Germany). Antibiotic therapy was discontinued if 1) clinical signs and symptoms of infection improved and PCT decreased to ≤1 ng/ml, or 2) if the PCT value was >1 ng/ml, but had dropped to 25-35% of the initial value within three days. The primary outcome parameters were: antibiotic days on ICU, ICU re-infection rate, 28-day mortality rate, length of stay (LOS) in ICU, mean antibiotic costs (per patient) and ventilation hours. Data from 141 patients were included in our study. Primary outcome parameters were analysed using covariance analyses (ANCOVA) to control for effects by gender, age, SAPS II, APACHE II and effective cost weight.

Results

From baseline data of 2005, duration of antibiotic therapy was reduced by an average of 1.0 day per year from 14.3 ±1.2 to 9.0 ±1.7 days in 2009 (p=0.02). ICU re-infection rate was decreased by yearly 35.1% (95% CI −53 to −8.5; p=0.014) just as ventilation hours by 42 hours per year (95% CI −72.6 to −11.4; p=0.008). ICU-LOS was reduced by 2.7 days per year (p<0.001). Trends towards an average yearly reduction of 28-day mortality by −22.4% (95% CI −44.3 to 8.1; p=0.133) and mean cost for antibiotic therapy/ patient by −14.3 Euro (95% CI −55.7 to 27.1) did not reach statistical significance.

Conclusions

In a real-life clinical setting, implementation of a PCT-protocol was associated with a reduced duration of antibiotic therapy in septic ICU patients without compromising clinical or economical outcomes.

German clinical trials register

DRKS00003490

【 授权许可】

   
2013 Hohn et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Rice LB: Federal funding for the study of antimicrobial resistance in nosocomial pathogens: no ESKAPE. J Infect Dis 2008, 197(8):1079-1081.
• [2]Spellberg B, Guidos R, Gilbert D, Bradley J, Boucher HW, Scheld WM, Bartlett JG, Edwards J Jr: The epidemic of antibiotic-resistant infections: a call to action for the medical community from the Infectious Diseases Society of America. Clin Infect Dis: an official publication of the Infectious Diseases Society of America 2008, 46(2):155-164.
• [3]Giske CG, Monnet DL, Cars O, Carmeli Y: Clinical and economic impact of common multidrug-resistant gram-negative bacilli. Antimicrob Agents Chemother 2008, 52(3):813-821.
• [4]Slama TG: Gram-negative antibiotic resistance: there is a price to pay. Crit Care 2008, 12(Suppl 4):S4. BioMed Central Full Text
• [5]Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, Suppes R, Feinstein D, Zanotti S, Taiberg L: Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006, 34(6):1589-1596.
• [6]Rice LB: The Maxwell Finland Lecture: for the duration-rational antibiotic administration in an era of antimicrobial resistance and clostridium difficile. Clin Infect Dis: an official publication of the Infectious Diseases Society of America 2008, 46(4):491-496.
• [7]Micek ST, Ward S, Fraser VJ, Kollef MH: A randomized controlled trial of an antibiotic discontinuation policy for clinically suspected ventilator-associated pneumonia. Chest 2004, 125(5):1791-1799.
• [8]Singh N, Rogers P, Atwood CW, Wagener MM, Yu VL: Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. A proposed solution for indiscriminate antibiotic prescription. Am J Respir Crit Care Med 2000, 162(2 Pt 1):505-511.
• [9]Chastre J, Wolff M, Fagon JY, Chevret S, Thomas F, Wermert D, Clementi E, Gonzalez J, Jusserand D, Asfar P: Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA 2003, 290(19):2588-2598.
• [10]Bouadma L, Luyt CE, Tubach F, Cracco C, Alvarez A, Schwebel C, Schortgen F, Lasocki S, Veber B, Dehoux M: Use of procalcitonin to reduce patients’ exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet 2010, 375(9713):463-474.
• [11]Briel M, Schuetz P, Mueller B, Young J, Schild U, Nusbaumer C, Periat P, Bucher HC, Christ-Crain M: Procalcitonin-guided antibiotic use vs a standard approach for acute respiratory tract infections in primary care. Arch Intern Med 2008, 168(18):2000-2007. discussion 2007–2008
• [12]Christ-Crain M, Stolz D, Bingisser R, Muller C, Miedinger D, Huber PR, Zimmerli W, Harbarth S, Tamm M, Muller B: Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. Am J Respir Crit Care Med 2006, 174(1):84-93.
• [13]Schroeder S, Hochreiter M, Koehler T, Schweiger AM, Bein B, Keck FS, von Spiegel T: 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/Deutsche Gesellschaft fur Chirurgie 2009, 394(2):221-226.
• [14]Schuetz P, Christ-Crain M, Thomann R, Falconnier C, Wolbers M, Widmer I, Neidert S, Fricker T, Blum C, Schild U: Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA 2009, 302(10):1059-1066.
• [15]Stolz D, Smyrnios N, Eggimann P, Pargger H, Thakkar N, Siegemund M, Marsch S, Azzola A, Rakic J, Mueller B: Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomised study. Eur Respir J: official journal of the European Society for Clinical Respiratory Physiology 2009, 34(6):1364-1375.
• [16]Hochreiter M, Kohler T, Schweiger AM, Keck FS, Bein B, von Spiegel T, Schroeder S: Procalcitonin to guide duration of antibiotic therapy in intensive care patients: a randomized prospective controlled trial. Crit Care 2009, 13(3):R83. BioMed Central Full Text
• [17]Nobre V, Harbarth S, Graf JD, Rohner P, Pugin J: Use of procalcitonin to shorten antibiotic treatment duration in septic patients: a randomized trial. Am J Respir Crit Care Med 2008, 177(5):498-505.
• [18]Tang H, Huang T, Jing J, Shen H, Cui W: Effect of procalcitonin-guided treatment in patients with infections: a systematic review and meta-analysis. Infection 2009, 37(6):497-507.
• [19]Kopterides P, Siempos II, Tsangaris I, Tsantes A, Armaganidis A: Procalcitonin-guided algorithms of antibiotic therapy in the intensive care unit: a systematic review and meta-analysis of randomized controlled trials. Crit Care Med 2010, 38(11):2229-2241.
• [20]Schuetz P, Briel M, Christ-Crain M, Stolz D, Bouadma L, Wolff M, Luyt CE, Chastre J, Tubach F, Kristoffersen KB: Procalcitonin to guide initiation and duration of antibiotic treatment in acute respiratory infections: an individual patient data meta-analysis. Clin Infect Dis: an official publication of the Infectious Diseases Society of America 2012, 55(5):651-662.
• [21]Schuetz P, Muller B, Christ-Crain M, Stolz D, Tamm M, Bouadma L, Luyt CE, Wolff M, Chastre J, Tubach F: Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane database of systematic reviews (Online) 2012, 9:CD007498.
• [22]Albrich WC, Dusemund F, Bucher B, Meyer S, Thomann R, Kuhn F, Bassetti S, Sprenger M, Bachli E, Sigrist T: Effectiveness and Safety of Procalcitonin-Guided Antibiotic Therapy in Lower Respiratory Tract Infections in “Real Life”: An International, Multicenter Poststudy Survey (ProREAL). Arch Intern Med 2012, 172(9):715-722.
• [23]Schuetz P, Batschwaroff M, Dusemund F, Albrich W, Burgi U, Maurer M, Brutsche M, Huber AR, Muller B: Effectiveness of a procalcitonin algorithm to guide antibiotic therapy in respiratory tract infections outside of study conditions: a post-study survey. Eur J Clin Microbiol Infect Dis: official publication of the European Society of Clinical Microbiology 2010, 29(3):269-277.
• [24]American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992, 20(6):864-874.
• [25]Kuster SP, Ruef C, Bollinger AK, Ledergerber B, Hintermann A, Deplazes C, Neuber L, Weber R: Correlation between case mix index and antibiotic use in hospitals. J Antimicrob Chemother 2008, 62(4):837-842.
• [26]Shiramizo SC, Marra AR, Durao MS, Paes AT, Edmond MB, Pavao dos Santos OF: Decreasing mortality in severe sepsis and septic shock patients by implementing a sepsis bundle in a hospital setting. PLoS One 2011, 6(11):e26790.
• [27]Brunkhorst FM, Engel C, Ragaller M, Welte T, Rossaint R, Gerlach H, Mayer K, John S, Stuber F, Weiler N: Practice and perception–a nationwide survey of therapy habits in sepsis. Crit Care Med 2008, 36(10):2719-2725.
• [28]Jensen JU, Hein L, Lundgren B, Bestle MH, Mohr TT, Andersen MH, Thornberg KJ, Loken J, Steensen M, Fox Z: 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):2048-2058.
• [29]Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM: Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004, 32(3):858-873.
• [30]Brunkhorst FM, Engel C, Bloos F, Meier-Hellmann A, Ragaller M, Weiler N, Moerer O, Gruendling M, Oppert M, Grond S: Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 2008, 358(2):125-139.
• [31]Brunkhorst FM, Oppert M, Marx G, Bloos F, Ludewig K, Putensen C, Nierhaus A, Jaschinski U, Meier-Hellmann A, Weyland A: Effect of empirical treatment with moxifloxacin and meropenem vs meropenem on sepsis-related organ dysfunction in patients with severe sepsis: a randomized trial. JAMA 2012, 307(22):2390-2399.
• [32]Dellit TH, Owens RC, McGowan JE Jr, Gerding DN, Weinstein RA, Burke JP, Huskins WC, Paterson DL, Fishman NO, Carpenter CF: Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis: an official publication of the Infectious Diseases Society of America 2007, 44(2):159-177.
• [33]Hayashi Y, Paterson DL: Strategies for reduction in duration of antibiotic use in hospitalized patients. Clin Infect Dis: an official publication of the Infectious Diseases Society of America 2011, 52(10):1232-1240.
• [34]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, 39(7):1792-1799.
• [35]Wilke MH, Grube RF, Bodmann KF: The use of a standardized PCT-algorithm reduces costs in Intensive Care in septic patients - A DRG-based simulation model. Eur J Med Res 2011, 16(12):543-548. BioMed Central Full Text
• [36]Christ-Crain M, Jaccard-Stolz D, Bingisser R, Gencay MM, Huber PR, Tamm M, Muller B: Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. Lancet 2004, 363(9409):600-607.
• [37]Stolz D, Christ-Crain M, Bingisser R, Leuppi J, Miedinger D, Muller C, Huber P, Muller B, Tamm M: Antibiotic treatment of exacerbations of COPD: a randomized, controlled trial comparing procalcitonin-guidance with standard therapy. Chest 2007, 131(1):9-19.
• [38]Svoboda P, Kantorova I, Scheer P, Radvanova J, Radvan M: Can procalcitonin help us in timing of re-intervention in septic patients after multiple trauma or major surgery? Hepatogastroenterology 2007, 54(74):359-363.
• [39]Kristoffersen KB, Sogaard OS, Wejse C, Black FT, Greve T, Tarp B, Storgaard M, Sodemann M: Antibiotic treatment interruption of suspected lower respiratory tract infections based on a single procalcitonin measurement at hospital admission–a randomized trial. Clin Microbiol Infect 2009, 15(5):481-487.
• [40]Engel C, Brunkhorst FM, Bone HG, Brunkhorst R, Gerlach H, Grond S, Gruendling M, Huhle G, Jaschinski U, John S: Epidemiology of sepsis in Germany: results from a national prospective multicenter study. Intensive Care Med 2007, 33(4):606-618.