Abstract
Polymerase chain reaction (PCR)-based techniques allow more rapid and sensitive detection of pathogens compared with conventional blood culture. Nevertheless, the climate of opinion of relevant studies is that currently PCR can supplement but not replace blood culture. In numerous studies, combined detection rate of both methods was significantly higher compared with PCR or blood culture alone. Also, complete determination of antibiotic resistance can currently be performed only by blood culture. Further increase of the panel of multiplex PCR is complicated, because the vast majority of sepsis pathogens are already included, primer interactions leading to primer heteromers limit the amount of targets detectable within one PCR tube, and an array of too many individual PCR reactions for investigation of a single specimen leads to high cost and workload. Except for diagnostics of patients in whom unusual, not culturable, or fastidious pathogens are detected more often, such as immunosuppressed patients with suspected parasitic infection, etc., it might even not be necessary to further increase the spectrum of detectable species. If the primary aim of PCR diagnostics is to decrease inappropriate empirical treatment and improve patient outcome, detection should focus on those pathogens or resistance determinants that are not covered by guideline-recommended treatment regimens and that have been identified as the major cause of inappropriate treatment according to current studies. In our opinion, such a narrower assay is more cost effective, may achieve higher accuracy due to reduced intratest interference, and would better address current and emerging clinical needs.
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Valles J, Rello J, Ochagavia A, Garnacho J, Alcala MA (2003) Community-acquired bloodstream infection in critically ill adult patients: impact of shock and inappropriate antibiotic therapy on survival. Chest 123:1615–1624
Kumar A, Ellis P, Arabi Y, Roberts D, Light B, Parrillo JE, Dodek P, Wood G, Simon D, Peters C, Ahsan M, Chateau D (2009) Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest 136:1237–1248
Alberti C, Brun-Buisson C, Chevret S, Antonelli M, Goodman SV, Martin C, Moreno R, Ochagavia AR, Palazzo M, Werdan K, Le Gall JR (2005) Systemic inflammatory response and progression to severe sepsis in critically ill infected patients. Am J Respir Crit Care Med 171:461–468
Pletz MW, Bloos F, Burkhardt O, Brunkhorst FM, Bode-Boger SM, Martens-Lobenhoffer J, Greer MW, Stass H, Welte T (2010) Pharmacokinetics of moxifloxacin in patients with severe sepsis or septic shock. Intensive Care Med 36:979–983
Scaglione F, Esposito S, Leone S, Lucini V, Pannacci M, Ma L, Drusano GL (2009) Feedback dose alteration significantly affects probability of pathogen eradication in nosocomial pneumonia. Eur Respir J 34:394–400
Hoffken G, Lorenz J, Kern W, Welte T, Bauer T, Dalhoff K, Dietrich E, Ewig S, Gastmeier P, Grabein B, Halle E, Kolditz M, Marre R, Sitter H (2009) Epidemiology, diagnosis, antimicrobial therapy and management of community-acquired pneumonia and lower respiratory tract infections in adults. Guidelines of the Paul-Ehrlich-Society for Chemotherapy, the German Respiratory Society, the German Society for Infectiology and the Competence Network CAPNETZ Germany. Pneumologie 63:e1–68
von Baum H, Welte T, Marre R, Suttorp N, Ewig S (2010) Community-acquired pneumonia through Enterobacteriaceae and Pseudomonas aeruginosa: diagnosis, incidence and predictors. Eur Respir J 35:598–605
Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL (2008) Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med 34:17–60
American Thoracic Society and Infectious Diseases Society of America (2005) Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 171:388–416
Goldmann DA, Weinstein RA, Wenzel RP, Tablan OC, Duma RJ, Gaynes RP, Schlosser J, Martone WJ (1996) Strategies to prevent and control the emergence and spread of antimicrobial-resistant microorganisms in hospitals. A challenge to hospital leadership. J Am Med Assoc 275:234–240
Levy MM, Dellinger RP, Townsend SR, Linde-Zwirble WT, Marshall JC, Bion J, Schorr C, Artigas A, Ramsay G, Beale R, Parker MM, Gerlach H, Reinhart K, Silva E, Harvey M, Regan S, Angus DC (2010) The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Intensive Care Med 36:222–231
Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, Suppes R, Feinstein D, Zanotti S, Taiberg L, Gurka D, Cheang M (2006) Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 34:1589–1596
Labelle AJ, Micek ST, Roubinian N, Kollef MH (2008) Treatment-related risk factors for hospital mortality in Candida bloodstream infections. Crit Care Med 36:2967–2972
Morrell M, Fraser VJ, Kollef MH (2005) Delaying the empiric treatment of candida bloodstream infection until positive blood culture results are obtained: a potential risk factor for hospital mortality. Antimicrob Agents Chemother 49:3640–3645
Garey KW, Rege M, Pai MP, Mingo DE, Suda KJ, Turpin RS, Bearden DT (2006) Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study. Clin Infect Dis 43:25–31
Taur Y, Cohen N, Dubnow S, Paskovaty A, Seo SK (2010) Effect of antifungal therapy timing on mortality in cancer patients with candidemia. Antimicrob Agents Chemother 54:184–190
Reinhart K, Brunkhorst FM, Bone HG, Bardutzky J, Dempfle CE, Forst H, Gastmeier P, Gerlach H, Grundling M, John S, Kern W, Kreymann G, Kruger W, Kujath P, Marggraf G, Martin J, Mayer K, Meier-Hellmann A, Oppert M, Putensen C, Quintel M, Ragaller M, Rossaint R, Seifert H, Spies C, Stuber F, Weiler N, Weimann A, Werdan K, Welte T (2010) Prevention, diagnosis, therapy and follow-up care of sepsis: 1st revision of S-2 k guidelines of the German Sepsis Society (Deutsche Sepsis-Gesellschaft e.V. (DSG)) and the German Interdisciplinary Association of Intensive Care and Emergency Medicine (Deutsche Interdisziplinare Vereinigung fur Intensiv- und Notfallmedizin (DIVI)). Ger Med Sci 8:14 doc
Bruns T, Sachse S, Straube E, Assefa S, Herrmann A, Hagel S, Lehmann M, Stallmach A (2009) Identification of bacterial DNA in neutrocytic and non-neutrocytic cirrhotic ascites by means of a multiplex polymerase chain reaction. Liver Int 29:1206–1214
Kriegsmann J, Hopf T, Jacobs D, Arens N, Krenn V, Schmitt-Wiedhoff R, Kriegsmann M, Heisel C, Biehl C, Thabe H, Schmitz RP, Lehmann M, Otto M (2009) Applications of molecular pathology in the diagnosis of joint infections. Orthopade 38:531–538
Avolio M, Diamante P, Zamparo S, Modolo ML, Grosso S, Zigante P, Tosoni N, De Rosa R, Stano P, Camporese A (2010) Molecular identification of bloodstream pathogens in patients presenting to the emergency department with suspected sepsis. Shock 34:27–30
Dierkes C, Ehrenstein B, Siebig S, Linde HJ, Reischl U, Salzberger B (2009) Clinical impact of a commercially available multiplex PCR system for rapid detection of pathogens in patients with presumed sepsis. BMC Infect Dis 9:126
Lamoth F, Jaton K, Prod’hom G, Senn L, Bille J, Calandra T, Marchetti O (2010) Multiplex blood PCR in combination with blood cultures for improvement of microbiological documentation of infection in febrile neutropenia. J Clin Microbiol 48:3510–3516
Maubon D, Hamidfar-Roy R, Courby S, Vesin A, Maurin M, Pavese P, Ravanel N, Bulabois CE, Brion JP, Pelloux H, Timsit JF (2010) Therapeutic impact and diagnostic performance of multiplex PCR in patients with malignancies and suspected sepsis. J Infect 61:335–342
von Lilienfeld-Toal M, Lehmann LE, Raadts AD, Hahn-Ast C, Orlopp KS, Marklein G, Purr I, Cook G, Hoeft A, Glasmacher A, Stuber F (2009) Utility of a commercially available multiplex real-time PCR assay to detect bacterial and fungal pathogens in febrile neutropenia. J Clin Microbiol 47:2405–2410
Wallet F, Nseir S, Baumann L, Herwegh S, Sendid B, Boulo M, Roussel-Delvallez M, Durocher AV, Courcol RJ (2010) Preliminary clinical study using a multiplex real-time PCR test for the detection of bacterial and fungal DNA directly in blood. Clin Microbiol Infect 16:774–779
Bloos F, Hinder F, Becker K, Sachse S, Mekontso Dessap A, Straube E, Cattoir V, Brun-Buisson C, Reinhart K, Peters G, Bauer M (2010) A multicenter trial to compare blood culture with polymerase chain reaction in severe human sepsis. Intensive Care Med 36:241–247
Sachse S, Straube E, Lehmann M, Bauer M, Russwurm S, Schmidt KH (2009) Truncated human cytidylate-phosphate-deoxyguanylate-binding protein for improved nucleic acid amplification technique-based detection of bacterial species in human samples. J Clin Microbiol 47:1050–1057
Hansen WL, Bruggeman CA, Wolffs PF (2009) Evaluation of new pre-analysis sample treatment tools and DNA isolation protocols to improve bacterial pathogen detection in whole blood. J Clin Microbiol 47:2629–2631
Westh H, Lisby G, Breysse F, Boddinghaus B, Chomarat M, Gant V, Goglio A, Raglio A, Schuster H, Stuber F, Wissing H, Hoeft A (2009) Multiplex real-time PCR and blood culture for identification of bloodstream pathogens in patients with suspected sepsis. Clin Microbiol Infect 15:544–551
Vince A, Lepej SZ, Barsic B, Dusek D, Mitrovic Z, Serventi-Seiwerth R, Labar B (2008) LightCycler SeptiFast assay as a tool for the rapid diagnosis of sepsis in patients during antimicrobial therapy. J Med Microbiol 57:1306–1307
Yanagihara K, Kitagawa Y, Tomonaga M, Tsukasaki K, Kohno S, Seki M, Sugimoto H, Shimazu T, Tasaki O, Matsushima A, Ikeda Y, Okamoto S, Aikawa N, Hori S, Obara H, Ishizaka A, Hasegawa N, Takeda J, Kamihira S, Sugahara K, Asari S, Murata M, Kobayashi Y, Ginba H, Sumiyama Y, Kitajima M (2010) Evaluation of pathogen detection from clinical samples by real-time polymerase chain reaction using a sepsis pathogen DNA detection kit. Crit Care 14:R159
Tsalik EL, Jones D, Nicholson B, Waring L, Liesenfeld O, Park LP, Glickman SW, Caram LB, Langley RJ, van Velkinburgh JC, Cairns CB, Rivers EP, Otero RM, Kingsmore SF, Lalani T, Fowler VG, Woods CW (2010) Multiplex PCR to diagnose bloodstream infections in patients admitted from the emergency department with sepsis. J Clin Microbiol 48:26–33
Wellinghausen N, Kochem AJ, Disque C, Muhl H, Gebert S, Winter J, Matten J, Sakka SG (2009) Diagnosis of bacteremia in whole-blood samples by use of a commercial universal 16S rRNA gene-based PCR and sequence analysis. J Clin Microbiol 47:2759–2765
Hebart H, Klingspor L, Klingebiel T, Loeffler J, Tollemar J, Ljungman P, Wandt H, Schaefer-Eckart K, Dornbusch HJ, Meisner C, Engel C, Stenger N, Mayer T, Ringden O, Einsele H (2009) A prospective randomized controlled trial comparing PCR-based and empirical treatment with liposomal amphotericin B in patients after allo-SCT. Bone Marrow Transplant 43:553–561
Bloos F, Kortgen A, Sachse S, Lehmann M, Straube E, Reinhart K, Bauer M (2009) Performance of a PCR based assay for pathogen detection in critically ill patients. Infection 37(Suppl. III):45
Kortgen A, Bloos F, Sachse S, Lehmann M, Straube E, Reinhart K, Bauer M (2009) Clinical relevance of fungal DNAemia detected by multiplex PCR in septic patients. Infection 37(Suppl. III):44
Butler JC, Bosshardt SC, Phelan M, Moroney SM, Tondella ML, Farley MM, Schuchat A, Fields BS (2003) Classical and latent class analysis evaluation of sputum polymerase chain reaction and urine antigen testing for diagnosis of pneumococcal pneumonia in adults. J Infect Dis 187:1416–1423
Rello J, Lisboa T, Lujan M, Gallego M, Kee C, Kay I, Lopez D, Waterer GW (2009) Severity of pneumococcal pneumonia associated with genomic bacterial load. Chest 136:832–840
Hussein K, Sprecher H, Mashiach T, Oren I, Kassis I, Finkelstein R (2009) Carbapenem resistance among Klebsiella pneumoniae isolates: risk factors, molecular characteristics, and susceptibility patterns. Infect Control Hosp Epidemiol 30:666–671
Tsioutis C, Kritsotakis EI, Maraki S, Gikas A (2010) Infections by pandrug-resistant gram-negative bacteria: clinical profile, therapeutic management, and outcome in a series of 21 patients. Eur J Clin Microbiol Infect Dis 29:301–305
Daikos GL, Petrikkos P, Psichogiou M, Kosmidis C, Vryonis E, Skoutelis A, Georgousi K, Tzouvelekis LS, Tassios PT, Bamia C, Petrikkos G (2009) Prospective observational study of the impact of VIM-1 metallo-beta-lactamase on the outcome of patients with Klebsiella pneumoniae bloodstream infections. Antimicrob Agents Chemother 53:1868–1873
Kumarasamy KK, Toleman MA, Walsh TR, Bagaria J, Butt F, Balakrishnan R, Chaudhary U, Doumith M, Giske CG, Irfan S, Krishnan P, Kumar AV, Maharjan S, Mushtaq S, Noorie T, Paterson DL, Pearson A, Perry C, Pike R, Rao B, Ray U, Sarma JB, Sharma M, Sheridan E, Thirunarayan MA, Turton J, Upadhyay S, Warner M, Welfare W, Livermore DM, Woodford N (2010) Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect Dis 10:597–602
Regueiro BJ, Varela-Ledo E, Martinez-Lamas L, Rodriguez-Calvino J, Aguilera A, Santos A, Gomez-Tato A, Alvarez-Escudero J (2010) Automated extraction improves multiplex molecular detection of infection in septic patients. PLoS One 5(10):e13387
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Pletz, M.W., Wellinghausen, N. & Welte, T. Will polymerase chain reaction (PCR)-based diagnostics improve outcome in septic patients? A clinical view. Intensive Care Med 37, 1069–1076 (2011). https://doi.org/10.1007/s00134-011-2245-x
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DOI: https://doi.org/10.1007/s00134-011-2245-x