Background: In 14 randomized controlled studies to date, a procalcitonin (PCT)-based algorithm has been proven to markedly reduce the use of antibiotics along with an unimpaired high safety and low complication rates in patients with lower respiratory tract infections (LRTIs). However, compliance with the algorithm and safety out of controlled study conditions has not yet been sufficiently investigated. Methods: We performed a prospective international multicenter observational post-study surveillance of consecutive adults with community-acquired LRTI in 14 centers (Switzerland (n = 10), France (n = 3) and the United States (n = 1)). Results: Between September 2009 and November 2010, 1,759 patients were enrolled (median age 71; female sex 44.4%). 1,520 (86.4%) patients had a final diagnosis of LRTI (community-acquired pneumonia (CAP), 53.7%; acute exacerbation of chronic obstructive pulmonary disease (AECOPD), 17.1%; and acute bronchitis, 14.4%). Compliance with the PCT-guided therapy (overall 68.2%) was highest in patients with bronchitis (81.0% vs. AECOPD, 70.1%; CAP, 63.7%; p < 0.001), outpatients (86.1% vs. inpatients, 65.9%; p < 0.001) and algorithm-experienced centers (82.5% vs. algorithm-naive, 60.1%; p < 0.001) and showed significant geographical differences. The initial decision about the antibiotic therapy was based on PCT value in 72.4%. In another 8.6% of patients, antibiotics were administered despite low PCT values but according to predefined criteria. Thus, the algorithm was followed in 81.0% of patients. In a multivariable Cox hazard ratio model, longer antibiotic therapy duration was associated with algorithm-non-compliance, country, hospitalization, CAP vs. bronchitis, renal failure and algorithm-na?vety of the study center. In a multivariable logistic regression complications (death, empyema, ICU treatment, mechanical ventilation, relapse, and antibiotic-associated side effects) were significantly associated with increasing CURB65-Score, CAP vs. bronchitis, multilobar pneumonia, but not with algorithm-compliance. Discussion: Cultural and geographic differences in antibiotic prescribing affected the compliance with our PCT-guided algorithm. Efforts to reinforce compliance are needed. Antibiotic stewardship with PCT is possible, effective and safe without increasing the risk of complications in real-life conditions.
References
[1]
Briel, M.; Schuetz, P.; Mueller, B.; Young, J.; Schild, U.; Nusbaumer, C.; Periat, P.; Bucher, H.C.; Christ-Crain, M. Procalcitonin-guided antibiotic use vs. a standard approach for acute respiratory tract infections in primary care. Arch. Intern. Med. 2008, 168, 2000–2007; discussion 2007–2008, doi:10.1001/archinte.168.18.2000.
[2]
Christ-Crain, M.; Jaccard-Stolz, D.; Bingisser, R.; Gencay, M.M.; Huber, P.R.; 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, 600–607.
[3]
Christ-Crain, M.; Stolz, D.; Bingisser, R.; Muller, C.; Miedinger, D.; Huber, P.R.; 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, 84–93, doi:10.1164/rccm.200512-1922OC.
[4]
Schuetz, P.; Christ-Crain, M.; Thomann, R.; Falconnier, C.; Wolbers, M.; Widmer, I.; Neidert, S.; Fricker, T.; Blum, C.; Schild, U.; et al. Effect of procalcitonin-based guidelines vs. standard guidelines on antibiotic use in lower respiratory tract infections: The prohosp randomized controlled trial. JAMA 2009, 302, 1059–1066, doi:10.1001/jama.2009.1297.
[5]
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, 9–19, doi:10.1378/chest.06-1500.
[6]
Kristoffersen, K.B.; Sogaard, O.S.; Wejse, C.; Black, F.T.; 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, 481–487, doi:10.1111/j.1469-0691.2009.02709.x.
[7]
Burkhardt, O.; Ewig, S.; Haagen, U.; Giersdorf, S.; Hartmann, O.; Wegscheider, K.; Hummers-Pradier, E.; Welte, T. Procalcitonin guidance and reduction of antibiotic use in acute respiratory tract infection. Eur. Respir. J. 2010, 36, 601–607, doi:10.1183/09031936.00163309.
[8]
Schuetz, P.; Batschwaroff, M.; Dusemund, F.; Albrich, W.; Burgi, U.; Maurer, M.; Brutsche, M.; Huber, A.R.; 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. 2010, 29, 269–277, doi:10.1007/s10096-009-0851-0.
[9]
Albrich, W.C.; Dusemund, F.; Bucher, B.; Meyer, S.; Thomann, R.; Kuhn, F.; Bassetti, S.; Sprenger, M.; Bachli, E.; Sigrist, T.; et al. 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, 715–722, doi:10.1001/archinternmed.2012.770.
[10]
Woodhead, M.; Blasi, F.; Ewig, S.; Huchon, G.; Ieven, M.; Ortqvist, A.; Schaberg, T.; Torres, A.; van der Heijden, G.; Verheij, T.J. Guidelines for the management of adult lower respiratory tract infections. Eur. Respir. J. 2005, 26, 1138–1180, doi:10.1183/09031936.05.00055705.
[11]
Schuetz, P.; Albrich, W.; Christ-Crain, M.; Chastre, J.; Mueller, B. Procalcitonin for guidance of antibiotic therapy. Expert Rev. Anti Infect. Ther. 2010, 8, 575–587, doi:10.1586/eri.10.25.
[12]
Yealy, D.M.; Auble, T.E.; Stone, R.A.; Lave, J.R.; Meehan, T.P.; Graff, L.G.; Fine, J.M.; Obrosky, D.S.; Mor, M.K.; Whittle, J.; et al. Effect of increasing the intensity of implementing pneumonia guidelines: A randomized, controlled trial. Ann. Intern. Med. 2005, 143, 881–894.
[13]
Aujesky, D.; McCausland, J.B.; Whittle, J.; Obrosky, D.S.; Yealy, D.M.; Fine, M.J. Reasons why emergency department providers do not rely on the pneumonia severity index to determine the initial site of treatment for patients with pneumonia. Clin. Infect. Dis. 2009, 49, e100–e108, doi:10.1086/644741.
[14]
Harbarth, S.; Albrich, W.; Goldmann, D.A.; Huebner, J. Control of multiply resistant cocci: Do international comparisons help? Lancet Infect. Dis. 2001, 1, 251–261, doi:10.1016/S1473-3099(01)00120-7.
[15]
Filippini, M.; Masiero, G.; Moschetti, K. Socioeconomic determinants of regional differences in outpatient antibiotic consumption: Evidence from switzerland. Health Policy 2006, 78, 77–92, doi:10.1016/j.healthpol.2005.09.009.
[16]
Albrich, W.C.; Monnet, D.L.; Harbarth, S. Antibiotic selection pressure and resistance in streptococcus pneumoniae and streptococcus pyogenes. Emerg. Infect. Dis. 2004, 10, 514–517, doi:10.3201/eid1003.030252.
[17]
Christ-Crain, M.; Muller, B. Procalcitonin in bacterial infections—Hype, hope, more or less? Swiss Me. Wkly. 2005, 135, 451–460.
[18]
Muller, F.; Christ-Crain, M.; Bregenzer, T.; Krause, M.; Zimmerli, W.; Mueller, B.; Schuetz, P.; Pro, H.S.G. Procalcitonin levels predict bacteremia in patients with community-acquired pneumonia: A prospective cohort trial. Chest 2010, 138, 121–129.
[19]
Kruger, S.; Ewig, S.; Papassotiriou, J.; Kunde, J.; Marre, R.; von Baum, H.; Suttor, N.; Welte, T. Inflammatory parameters predict etiologic patterns but do not allow for individual prediction of etiology in patients with cap: Results from the german competence network capnetz. Respir. Res. 2009, 10, doi:10.1186/1465-9921-10-65.
[20]
Kruger, S.; Ewig, S.; Kunde, J.; Hartmann, O.; Marre, R.; Suttorp, N.; Welte, T. Assessment of inflammatory markers in patients with community-acquired pneumonia—Influence of antimicrobial pre-treatment results from the german competence network capnetz. Clin. Chim. Acta 2010, 411, 1929–1934, doi:10.1016/j.cca.2010.08.004.
[21]
Uzzan, B.; Cohen, R.; Nicolas, P.; Cucherat, M.; Perret, G.Y. Procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or trauma: A systematic review and meta-analysis. Crit. Care Med. 2006, 34, 1996–2003, doi:10.1097/01.CCM.0000226413.54364.36.
[22]
Hunziker, S.; Hugle, T.; Schuchardt, K.; Groeschl, I.; Schuetz, P.; Mueller, B.; Dick, W.; Eriksson, U.; Trampuz, A. The value of serum procalcitonin level for differentiation of infectious from noninfectious causes of fever after orthopaedic surgery. J. Bone Joint Surg. Am. 2010, 92, 138–148, doi:10.2106/JBJS.H.01600.
[23]
Sponholz, C.; Sakr, Y.; Reinhart, K.; Brunkhorst, F. Diagnostic value and prognostic implications of serum procalcitonin after cardiac surgery: A systematic review of the literature. Crit. Care 2006, 10, doi:10.1186/cc5067.
[24]
Schuetz, P.; Chiappa, V.; Briel, M.; Greenwald, J.L. Procalcitonin algorithms for antibiotic therapy decisions: A systematic review of randomized controlled trials and recommendations for clinical algorithms. Arch. Intern. Med. 2011, 171, 1322–1331, doi:10.1001/archinternmed.2011.318.
[25]
Schuetz, P.; Muller, B.; Christ-Crain, M.; Stolz, D.; Tamm, M.; Bouadma, L.; Luyt, C.E.; Wolff, M.; Chastre, J.; Tubach, F.; et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst. Rev. 2012, 9, CD007498.
[26]
Simon, L.; Gauvin, F.; Amre, D.K.; Saint-Louis, P.; Lacroix, J. Serum procalcitonin and c-reactive protein levels as markers of bacterial infection: A systematic review and meta-analysis. Clin. Infect. Dis. 2004, 39, 206–217, doi:10.1086/421997.