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Published in: BMC Infectious Diseases 1/2016

Open Access 01-12-2016 | Research article

Prospective evaluation of SeptiFast Multiplex PCR in children with systemic inflammatory response syndrome under antibiotic treatment

Authors: Franziska Gies, Eva Tschiedel, Ursula Felderhoff-Müser, Peter-Michael Rath, Joerg Steinmann, Christian Dohna-Schwake

Published in: BMC Infectious Diseases | Issue 1/2016

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Abstract

Background

Antimicrobially pre-treated children with systemic inflammation often pose a diagnostic challenge to the physician. We aimed to evaluate the additional use of SeptiFast multiplex polymerase chain reaction (PCR) to identify causative pathogens in children with suspected systemic bacterial or fungal infection.

Methods

Prospective observational study in 39 children with systemic inflammatory response syndrome (SIRS) under empiric antibiotic treatment. Primary outcome was the rate of positive blood cultures (BC), compared to the rate of positive SeptiFast (SF) results.

Results

In total, 14 SF-samples yielded positive results, compared to 4 positive BC (p < 0.05). All blood cultures and 13 of 14 positive SF-tests were considered infection. Median time for positive BC was 2 days, and time to definite result was 6 days, compared to 12 h for SF. Antimicrobial therapy was adapted in 7 of the 14 patients with positive SeptiFast, and in 3 of the 4 patients with positive BC.
Best predictive power for positive SF shown by receiver-operating characteristic was demonstrated for procalcitonin PCT (Area under the curve AUC: 0.79), compared to C-reactive protein CRP (AUC: 0.51) and leukocyte count (AUC: 0.46). A procalcitonin threshold of 0.89 ng/ml yielded a sensitivity of 0.82 and a specifity of 0.7. Children with a positive SeptiFast result on day 0 had a significantly higher risk to require treatment on the Pediatric Intensive Care Unit or to be deceased on day 30 (Odds-Ratio 8.62 (CI 1.44-51.72).

Conclusions

The additional testing with SeptiFast in antimicrobially pre-treated children with systemic inflammation enhances the rate of pathogen detection. The influence of multiplex PCR on clinically relevant outcome parameters has to be further evaluated. (Trial registration: DRKS00004694)
Literature
1.
go back to reference Garnacho-Montero J, Garcia-Garmendia JL, Barrero-Almodovar A, Jimenez-Jimenez FJ, Perez-Paredes C, Ortiz-Leyba C. Impact of adequate empirical antibiotic therapy on the outcome of patients admitted to the intensive care unit with sepsis. Crit Care Med. 2003;31(12):2742–51.CrossRefPubMed Garnacho-Montero J, Garcia-Garmendia JL, Barrero-Almodovar A, Jimenez-Jimenez FJ, Perez-Paredes C, Ortiz-Leyba C. Impact of adequate empirical antibiotic therapy on the outcome of patients admitted to the intensive care unit with sepsis. Crit Care Med. 2003;31(12):2742–51.CrossRefPubMed
2.
go back to reference Kollef MH GS, Ward S, Fraser VJ. Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest. 1999;115:462–74.CrossRefPubMed Kollef MH GS, Ward S, Fraser VJ. Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest. 1999;115:462–74.CrossRefPubMed
3.
go back to reference Leone M, Bourgoin A, Cambon S, Dubuc M, Albanese J, Martin C. Empirical antimicrobial therapy of septic shock patients: adequacy and impact on the outcome. Crit Care Med. 2003;31(2):462–7.CrossRefPubMed Leone M, Bourgoin A, Cambon S, Dubuc M, Albanese J, Martin C. Empirical antimicrobial therapy of septic shock patients: adequacy and impact on the outcome. Crit Care Med. 2003;31(2):462–7.CrossRefPubMed
4.
go back to reference Zubert S, Funk D, Kumar A. Antibiotics in sepsis and septic shock: like everything else in life, timing is everything. Crit Care Med. 2010;38(4):1211–2.CrossRefPubMed Zubert S, Funk D, Kumar A. Antibiotics in sepsis and septic shock: like everything else in life, timing is everything. Crit Care Med. 2010;38(4):1211–2.CrossRefPubMed
5.
go back to reference Connell TG, Rele M, Cowley D, Buttery JP, Curtis N. How reliable is a negative blood culture result? Volume of blood admitted for culture in routine prectice in a children's hospital. Pediatrics. 2007;119:891–6.CrossRefPubMed Connell TG, Rele M, Cowley D, Buttery JP, Curtis N. How reliable is a negative blood culture result? Volume of blood admitted for culture in routine prectice in a children's hospital. Pediatrics. 2007;119:891–6.CrossRefPubMed
6.
go back to reference Goldstein B, Giroir B, Randolph A. International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Ped Crit Care Med. 2005;6(1):2–8.CrossRef Goldstein B, Giroir B, Randolph A. International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Ped Crit Care Med. 2005;6(1):2–8.CrossRef
7.
go back to reference Lehmann LE, Hunfeld KP, Emrich T, et al. A multiplex real-time PCR assay for rapid detection and differentiation of 25 bacterial and fungal pathogens from whole blood samples. Med Microbiol Immunol. 2008;197(3):313–24.CrossRefPubMed Lehmann LE, Hunfeld KP, Emrich T, et al. A multiplex real-time PCR assay for rapid detection and differentiation of 25 bacterial and fungal pathogens from whole blood samples. Med Microbiol Immunol. 2008;197(3):313–24.CrossRefPubMed
8.
go back to reference Tschiedel E, Steinmann J, Buer J, et al. Results and relevance of molecular detection of pathogens by SeptiFast--a retrospective analysis in 75 critically ill children. Klin Padiatr. 2012;224(1):12–6.CrossRefPubMed Tschiedel E, Steinmann J, Buer J, et al. Results and relevance of molecular detection of pathogens by SeptiFast--a retrospective analysis in 75 critically ill children. Klin Padiatr. 2012;224(1):12–6.CrossRefPubMed
9.
go back to reference Paolucci M, Stanzani M, Melchionda F, et al. Routine use of a real-time polymerase chain reaction method for detection of bloodstream infections in neutropaenic patients. Diagn Microbiol Infect Dis. 2013;75(2):130–4.CrossRefPubMed Paolucci M, Stanzani M, Melchionda F, et al. Routine use of a real-time polymerase chain reaction method for detection of bloodstream infections in neutropaenic patients. Diagn Microbiol Infect Dis. 2013;75(2):130–4.CrossRefPubMed
10.
go back to reference Schaub N, Boldanova T, Noveanu M, et al. Incremental value of multiplex real-time PCR for the early diagnosis of sepsis in the emergency department. Swiss Med Wkly. 2014;144:w13911.PubMed Schaub N, Boldanova T, Noveanu M, et al. Incremental value of multiplex real-time PCR for the early diagnosis of sepsis in the emergency department. Swiss Med Wkly. 2014;144:w13911.PubMed
11.
go back to reference Lehmann LE, Hunfeld KP, Steinbrucker M, et al. Improved detection of blood stream pathogens by real-time PCR in severe sepsis. Intensive Care Med. 2010;36(1):49–56.CrossRefPubMed Lehmann LE, Hunfeld KP, Steinbrucker M, et al. Improved detection of blood stream pathogens by real-time PCR in severe sepsis. Intensive Care Med. 2010;36(1):49–56.CrossRefPubMed
12.
go back to reference Chang SS, Hsieh WH, Liu TS, et al. Multiplex PCR system for rapid detection of pathogens in patients with presumed sepsis - a systemic review and meta-analysis. PloS one. 2013;8(5):e62323.CrossRefPubMedPubMedCentral Chang SS, Hsieh WH, Liu TS, et al. Multiplex PCR system for rapid detection of pathogens in patients with presumed sepsis - a systemic review and meta-analysis. PloS one. 2013;8(5):e62323.CrossRefPubMedPubMedCentral
13.
go back to reference Mancini N, Clerici D, Diotti R, et al. Molecular diagnosis of sepsis in neutropenic patients with haematological malignancies. J Med Microbiol. 2008;57(Pt 5):601–4.CrossRefPubMed Mancini N, Clerici D, Diotti R, et al. Molecular diagnosis of sepsis in neutropenic patients with haematological malignancies. J Med Microbiol. 2008;57(Pt 5):601–4.CrossRefPubMed
14.
go back to reference Lucignano B, Ranno S, Liesenfeld O, et al. Multiplex PCR allows rapid and accurate diagnosis of bloodstream infections in newborns and children with suspected sepsis. J Clin Microbiol. 2011;49(6):2252–8.CrossRefPubMedPubMedCentral Lucignano B, Ranno S, Liesenfeld O, et al. Multiplex PCR allows rapid and accurate diagnosis of bloodstream infections in newborns and children with suspected sepsis. J Clin Microbiol. 2011;49(6):2252–8.CrossRefPubMedPubMedCentral
15.
go back to reference Calitri C, Denina M, Scolfaro C, Garazzino S, Licciardi F, Burdino E, Allice T, Carraro F, De Intinis G, Ghisetti V, Tovo PA. Etiological diagnosis of bloodstream infections through a multiplex real-time polymerase chain reaction test in pediatric patients: a case series from a tertiary Italian hospital. Infect Dis (Lond). 2015;47:73–9.CrossRef Calitri C, Denina M, Scolfaro C, Garazzino S, Licciardi F, Burdino E, Allice T, Carraro F, De Intinis G, Ghisetti V, Tovo PA. Etiological diagnosis of bloodstream infections through a multiplex real-time polymerase chain reaction test in pediatric patients: a case series from a tertiary Italian hospital. Infect Dis (Lond). 2015;47:73–9.CrossRef
16.
go back to reference Hartman ME, Linde-Zwirble WT, Angus DC, Watson RS. Trends in the epidemiology of pediatric severe sepsis. Ped Crit Care Med. 2013;14(7):686–93.CrossRef Hartman ME, Linde-Zwirble WT, Angus DC, Watson RS. Trends in the epidemiology of pediatric severe sepsis. Ped Crit Care Med. 2013;14(7):686–93.CrossRef
17.
go back to reference Rosenblum J, Lin J, Kim M, Levy AS. Repeating blood cultures in neutropenic children with persistent fevers when the initial blood culture is negative. Pediatr Blood Cancer. 2013;60:923–7.CrossRefPubMed Rosenblum J, Lin J, Kim M, Levy AS. Repeating blood cultures in neutropenic children with persistent fevers when the initial blood culture is negative. Pediatr Blood Cancer. 2013;60:923–7.CrossRefPubMed
18.
go back to reference Tsalik EL, Jones D, Nicholson B, et al. Multiplex PCR to diagnose bloodstream infections in patients admitted from the emergency department with sepsis. J Clin Microbiol. 2010;48(1):26–33.CrossRefPubMed Tsalik EL, Jones D, Nicholson B, et al. Multiplex PCR to diagnose bloodstream infections in patients admitted from the emergency department with sepsis. J Clin Microbiol. 2010;48(1):26–33.CrossRefPubMed
19.
go back to reference Leli C, Cardaccia A, D'Alo F, Ferri C, Bistoni F, Mencacci A. A prediction model for real-time PCR results in blood samples from febrile patients with suspected sepsis. J Med Microbiol. 2014;63(Pt 5):649–58.CrossRefPubMed Leli C, Cardaccia A, D'Alo F, Ferri C, Bistoni F, Mencacci A. A prediction model for real-time PCR results in blood samples from febrile patients with suspected sepsis. J Med Microbiol. 2014;63(Pt 5):649–58.CrossRefPubMed
20.
go back to reference Mencacci A, Leli C, Cardaccia A, et al. Procalcitonin predicts real-time PCR results in blood samples from patients with suspected sepsis. PloS One. 2012;7(12):e53279.CrossRefPubMedPubMedCentral Mencacci A, Leli C, Cardaccia A, et al. Procalcitonin predicts real-time PCR results in blood samples from patients with suspected sepsis. PloS One. 2012;7(12):e53279.CrossRefPubMedPubMedCentral
21.
go back to reference Pierce R, Bigham MT, Giuliano Jr JS. Use of procalcitonin for the prediction and treatment of acute bacterial infection in children. Curr Opin Pediatr. 2014;26:292–8.CrossRefPubMed Pierce R, Bigham MT, Giuliano Jr JS. Use of procalcitonin for the prediction and treatment of acute bacterial infection in children. Curr Opin Pediatr. 2014;26:292–8.CrossRefPubMed
Metadata
Title
Prospective evaluation of SeptiFast Multiplex PCR in children with systemic inflammatory response syndrome under antibiotic treatment
Authors
Franziska Gies
Eva Tschiedel
Ursula Felderhoff-Müser
Peter-Michael Rath
Joerg Steinmann
Christian Dohna-Schwake
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2016
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-016-1722-9

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