Skip to main content
Erschienen in: European Journal of Clinical Microbiology & Infectious Diseases 7/2004

01.07.2004 | Article

Markers of bacteremia in febrile neutropenic patients with hematological malignancies: procalcitonin and IL-6 are more reliable than C-reactive protein

verfasst von: M. von Lilienfeld-Toal, M. P. Dietrich, A. Glasmacher, L. Lehmann, P. Breig, C. Hahn, I. G. H. Schmidt-Wolf, G. Marklein, S. Schroeder, F. Stuber

Erschienen in: European Journal of Clinical Microbiology & Infectious Diseases | Ausgabe 7/2004

Einloggen, um Zugang zu erhalten

Abstract

Since neutropenic patients with hematological malignancies are at high risk of contracting life-threatening infections, specific markers of infection are needed in cases of febrile neutropenia. The study presented here assessed serum concentrations of C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6) in samples obtained from 31 febrile neutropenic patients. A total of 53 episodes were evaluated, and 18 of these were associated with positive blood culture results. Procalcitonin and IL-6 concentrations differed significantly between bacteremic and non-bacteremic episodes. Procalcitonin values were 0.22 ng/ml [interquartile range (IR), 0.15–1.9] for patients with pneumonia without bacteremia, 0.22 ng/ml (IR, 0.16–0.55) for patients with fever of unknown origin, 0.2 ng/ml (IR, 0.13–0.57) for patients with non-microbial fever and 1.8 ng/ml (IR, 0.35–5.3) for patients with bacteremia. The differences between bacteremic and non-bacteremic episodes had a P-value of 0.003 using the Mann–Whitney test. For IL-6 the median values were 301 pg/ml (IR, 152–1,879) for patients with pneumonia without bacteremia, 207 pg/ml (IR, 94–445) for patients with fever of unknown origin, 177 pg/ml (IR, 142–208) for patients with non-microbial fever and 942 pg/ml (IR, 181–2,807) for patients with bacteremia. Using the Mann–Whitney test, the differences between bacteremic and non-bacteremic episodes were P=0.006. No differences were found in CRP concentrations. Cutoff levels to distinguish between bacteremic and non-bacteremic episodes were chosen using receiver operating characteristic curves: 0.62 ng/ml for PCT and 297 pg/ml for IL-6. Negative predictive values were 84% for PCT and 70% for IL-6. The results indicate that PCT and IL-6 are more reliable markers than CRP for predicting bacteremia in patients with febrile neutropenia.
Literatur
1.
Zurück zum Zitat Buchheidt D, Bohme A, Cornely OA, Fatkenheuer G, Fuhr HG, Heussel G, Junghanss C, Karthaus M, Kellner O, Kern WV, Schiel X, Sezer O, Sudhoff T, Szelenyi H (2003) Diagnosis and treatment of documented infections in neutropenic patients—recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Ann Hematol 82(Suppl 2):127–132CrossRefPubMed Buchheidt D, Bohme A, Cornely OA, Fatkenheuer G, Fuhr HG, Heussel G, Junghanss C, Karthaus M, Kellner O, Kern WV, Schiel X, Sezer O, Sudhoff T, Szelenyi H (2003) Diagnosis and treatment of documented infections in neutropenic patients—recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Ann Hematol 82(Suppl 2):127–132CrossRefPubMed
2.
Zurück zum Zitat Link H, Bohme A, Cornely OA, Hoffken K, Kellner O, Kern WV, Mahlberg R, Maschmeyer G, Nowrousian MR, Ostermann H, Ruhnke M, Sezer O, Schiel X, Wilhelm M, Auner HW (2003) Antimicrobial therapy of unexplained fever in neutropenic patients—guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO), Study Group Interventional Therapy of Unexplained Fever, Arbeitsgemeinschaft Supportivmassnahmen in der Onkologie (ASO) of the Deutsche Krebsgesellschaft (DKG-German Cancer Society). Ann Hematol 82(Suppl 2):105–117CrossRef Link H, Bohme A, Cornely OA, Hoffken K, Kellner O, Kern WV, Mahlberg R, Maschmeyer G, Nowrousian MR, Ostermann H, Ruhnke M, Sezer O, Schiel X, Wilhelm M, Auner HW (2003) Antimicrobial therapy of unexplained fever in neutropenic patients—guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO), Study Group Interventional Therapy of Unexplained Fever, Arbeitsgemeinschaft Supportivmassnahmen in der Onkologie (ASO) of the Deutsche Krebsgesellschaft (DKG-German Cancer Society). Ann Hematol 82(Suppl 2):105–117CrossRef
3.
Zurück zum Zitat Sudhoff T, Giagounidis A, Karthaus M (2000) Serum and plasma parameters in clinical evaluation of neutropenic fever. Antibiot Chemother 50:10–19PubMed Sudhoff T, Giagounidis A, Karthaus M (2000) Serum and plasma parameters in clinical evaluation of neutropenic fever. Antibiot Chemother 50:10–19PubMed
4.
Zurück zum Zitat Engervall P, Granstrom M, Andersson B, Bjorkholm M (1995) Monitoring of endotoxin, interleukin-6 and C-reactive protein serum concentrations in neutropenic patients with fever. Eur J Haematol 54:226–234PubMed Engervall P, Granstrom M, Andersson B, Bjorkholm M (1995) Monitoring of endotoxin, interleukin-6 and C-reactive protein serum concentrations in neutropenic patients with fever. Eur J Haematol 54:226–234PubMed
5.
Zurück zum Zitat Abrahamsson J, Pahlman M, Mellander L (1997) Interleukin 6, but not tumour necrosis factor-alpha, is a good predictor of severe infection in febrile neutropenic and non-neutropenic children with malignancy. Acta Paediatr 86:1059–1064PubMed Abrahamsson J, Pahlman M, Mellander L (1997) Interleukin 6, but not tumour necrosis factor-alpha, is a good predictor of severe infection in febrile neutropenic and non-neutropenic children with malignancy. Acta Paediatr 86:1059–1064PubMed
6.
Zurück zum Zitat Engel A, Mack E, Kern P, Kern WV (1998) An analysis of interleukin-8, interleukin-6 and C-reactive protein serum concentrations to predict fever, gram-negative bacteremia and complicated infection in neutropenic cancer patients. Infection 26:213–221PubMed Engel A, Mack E, Kern P, Kern WV (1998) An analysis of interleukin-8, interleukin-6 and C-reactive protein serum concentrations to predict fever, gram-negative bacteremia and complicated infection in neutropenic cancer patients. Infection 26:213–221PubMed
7.
Zurück zum Zitat Heney D, Lewis IJ, Evans SW, Banks R, Bailey CC, Whicher JT (1992) Interleukin-6 and its relationship to C-reactive protein and fever in children with febrile neutropenia. J Infect Dis 165:886–890PubMed Heney D, Lewis IJ, Evans SW, Banks R, Bailey CC, Whicher JT (1992) Interleukin-6 and its relationship to C-reactive protein and fever in children with febrile neutropenia. J Infect Dis 165:886–890PubMed
8.
Zurück zum Zitat Oberhoffer M, Stonans I, Russwurm S, Stonane E, Vogelsang H, Junker U, Jager L, Reinhart K (1999) Procalcitonin expression in human peripheral blood mononuclear cells and its modulation by lipopolysaccharides and sepsis-related cytokines in vitro. J Lab Clin Med 134:49–55PubMed Oberhoffer M, Stonans I, Russwurm S, Stonane E, Vogelsang H, Junker U, Jager L, Reinhart K (1999) Procalcitonin expression in human peripheral blood mononuclear cells and its modulation by lipopolysaccharides and sepsis-related cytokines in vitro. J Lab Clin Med 134:49–55PubMed
9.
Zurück zum Zitat Meisner M, Muller V, Khakpour Z, Toegel E, Redl H (2003) Induction of procalcitonin and proinflammatory cytokines in an anhepatic baboon endotoxin shock model. Shock 19:187–190CrossRefPubMed Meisner M, Muller V, Khakpour Z, Toegel E, Redl H (2003) Induction of procalcitonin and proinflammatory cytokines in an anhepatic baboon endotoxin shock model. Shock 19:187–190CrossRefPubMed
10.
Zurück zum Zitat Assicot M, Gendrel D, Carsin H, Raymond J, Guilbaud J, Bohuon C (1993) High serum procalcitonin concentrations in patients with sepsis and infection. Lancet 341:515–518PubMed Assicot M, Gendrel D, Carsin H, Raymond J, Guilbaud J, Bohuon C (1993) High serum procalcitonin concentrations in patients with sepsis and infection. Lancet 341:515–518PubMed
11.
Zurück zum Zitat Chirouze C, Schuhmacher H, Rabaud C, Gil H, Khayat N, Estavoyer JM, May T, Hoen B (2002) Low serum procalcitonin level accurately predicts the absence of bacteremia in adult patients with acute fever. Clin Infect Dis 35:156–161CrossRefPubMed Chirouze C, Schuhmacher H, Rabaud C, Gil H, Khayat N, Estavoyer JM, May T, Hoen B (2002) Low serum procalcitonin level accurately predicts the absence of bacteremia in adult patients with acute fever. Clin Infect Dis 35:156–161CrossRefPubMed
12.
Zurück zum Zitat Svaldi M, Hirber J, Lanthaler AI, Mayr O, Faes S, Peer E, Mitterer M (2001) Procalcitonin-reduced sensitivity and specificity in heavily leucopenic and immunosuppressed patients. Br J Haematol 115:53–57CrossRefPubMed Svaldi M, Hirber J, Lanthaler AI, Mayr O, Faes S, Peer E, Mitterer M (2001) Procalcitonin-reduced sensitivity and specificity in heavily leucopenic and immunosuppressed patients. Br J Haematol 115:53–57CrossRefPubMed
13.
Zurück zum Zitat Engel A, Steinbach G, Kern P, Kern WV (1999) Diagnostic value of procalcitonin serum levels in neutropenic patients with fever: comparison with interleukin-8. Scand J Infect Dis 31:185–189PubMed Engel A, Steinbach G, Kern P, Kern WV (1999) Diagnostic value of procalcitonin serum levels in neutropenic patients with fever: comparison with interleukin-8. Scand J Infect Dis 31:185–189PubMed
14.
Zurück zum Zitat Fleischhack G, Kambeck I, Cipic D, Hasan C, Bode U (2000) Procalcitonin in paediatric cancer patients: its diagnostic relevance is superior to that of C-reactive protein, interleukin 6, interleukin 8, soluble interleukin 2 receptor and soluble tumour necrosis factor receptor II. Br J Haematol 111:1093–1102CrossRefPubMed Fleischhack G, Kambeck I, Cipic D, Hasan C, Bode U (2000) Procalcitonin in paediatric cancer patients: its diagnostic relevance is superior to that of C-reactive protein, interleukin 6, interleukin 8, soluble interleukin 2 receptor and soluble tumour necrosis factor receptor II. Br J Haematol 111:1093–1102CrossRefPubMed
15.
Zurück zum Zitat Giamarellos-Bourboulis EJ, Grecka P, Poulakou G, Anargyrou K, Katsilambros N, Giamarellou H (2001) Assessment of procalcitonin as a diagnostic marker of underlying infection in patients with febrile neutropenia. Clin Infect Dis 32:1718–1725PubMed Giamarellos-Bourboulis EJ, Grecka P, Poulakou G, Anargyrou K, Katsilambros N, Giamarellou H (2001) Assessment of procalcitonin as a diagnostic marker of underlying infection in patients with febrile neutropenia. Clin Infect Dis 32:1718–1725PubMed
16.
Zurück zum Zitat Bernard L, Ferriere F, Casassus P, Malas F, Leveque S, Guillevin L, Lortholary O (1998) Procalcitonin as an early marker of bacterial infection in severely neutropenic febrile adults. Clin Infect Dis 27:914–915PubMed Bernard L, Ferriere F, Casassus P, Malas F, Leveque S, Guillevin L, Lortholary O (1998) Procalcitonin as an early marker of bacterial infection in severely neutropenic febrile adults. Clin Infect Dis 27:914–915PubMed
17.
Zurück zum Zitat Schuttrumpf S, Binder L, Hagemann T, Berkovic D, Trumper L, Binder C (2003) Procalcitonin: a useful discriminator between febrile conditions of different origin in hemato-oncological patients? Ann Hematol 82:98–103PubMed Schuttrumpf S, Binder L, Hagemann T, Berkovic D, Trumper L, Binder C (2003) Procalcitonin: a useful discriminator between febrile conditions of different origin in hemato-oncological patients? Ann Hematol 82:98–103PubMed
18.
Zurück zum Zitat Maschmeyer G, Beinert T, Buchheidt D, Einsele H, Heussel CP, Kiehl M, Lorenz J (2003) Diagnosis and antimicrobial therapy of pulmonary infiltrates in febrile neutropenic patients—guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Ann Hematol 82(Suppl 2):118–126PubMed Maschmeyer G, Beinert T, Buchheidt D, Einsele H, Heussel CP, Kiehl M, Lorenz J (2003) Diagnosis and antimicrobial therapy of pulmonary infiltrates in febrile neutropenic patients—guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Ann Hematol 82(Suppl 2):118–126PubMed
19.
Zurück zum Zitat Zweig MH, Campbell G (1993) Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem 39:561–577PubMed Zweig MH, Campbell G (1993) Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem 39:561–577PubMed
20.
Zurück zum Zitat Lecharny JB, Khater D, Bronchard R, Philip I, Durand G, Desmonts JM, Dehoux M (2001) Hyperprocalcitonemia in patients with perioperative myocardial infarction after cardiac surgery. Crit Care Med 29:323–325PubMed Lecharny JB, Khater D, Bronchard R, Philip I, Durand G, Desmonts JM, Dehoux M (2001) Hyperprocalcitonemia in patients with perioperative myocardial infarction after cardiac surgery. Crit Care Med 29:323–325PubMed
21.
Zurück zum Zitat Kettelhack C, Hohenberger P, Schulze G, Kilpert B, Schlag PM (2000) Induction of systemic serum procalcitonin and cardiocirculatory reactions after isolated limb perfusion with recombinant human tumor necrosis factor-alpha and melphalan. Crit Care Med 28:1040–1046PubMed Kettelhack C, Hohenberger P, Schulze G, Kilpert B, Schlag PM (2000) Induction of systemic serum procalcitonin and cardiocirculatory reactions after isolated limb perfusion with recombinant human tumor necrosis factor-alpha and melphalan. Crit Care Med 28:1040–1046PubMed
22.
Zurück zum Zitat Kallio R, Surcel HM, Bloigu A, Syrjala H (2000) C-reactive protein, procalcitonin and interleukin-8 in the primary diagnosis of infections in cancer patients. Eur J Cancer 36:889–894CrossRefPubMed Kallio R, Surcel HM, Bloigu A, Syrjala H (2000) C-reactive protein, procalcitonin and interleukin-8 in the primary diagnosis of infections in cancer patients. Eur J Cancer 36:889–894CrossRefPubMed
23.
Zurück zum Zitat Suzaki H, Asano K, Yu M, Hisamitsu T (2003) Influence of roxithromycin on inflammatory cytokine production from nasal polyp fibroblasts in vitro. Acta Otolaryngol 123:637–642CrossRefPubMed Suzaki H, Asano K, Yu M, Hisamitsu T (2003) Influence of roxithromycin on inflammatory cytokine production from nasal polyp fibroblasts in vitro. Acta Otolaryngol 123:637–642CrossRefPubMed
24.
Zurück zum Zitat Hirata N, Hiramatsu K, Kishi K, Yamasaki T, Ichimiya T, Nasu M (2001) Pretreatment of mice with clindamycin improves survival of endotoxic shock by modulating the release of inflammatory cytokines. Antimicrob Agents Chemother 45:2638–2642CrossRefPubMed Hirata N, Hiramatsu K, Kishi K, Yamasaki T, Ichimiya T, Nasu M (2001) Pretreatment of mice with clindamycin improves survival of endotoxic shock by modulating the release of inflammatory cytokines. Antimicrob Agents Chemother 45:2638–2642CrossRefPubMed
25.
Zurück zum Zitat Holzheimer RG (2003) Oral antibiotic prophylaxis can influence the inflammatory response in aortic aneurysm repair: results of a randomized clinical study. J Chemother 15:157–164CrossRefPubMed Holzheimer RG (2003) Oral antibiotic prophylaxis can influence the inflammatory response in aortic aneurysm repair: results of a randomized clinical study. J Chemother 15:157–164CrossRefPubMed
26.
Zurück zum Zitat Wood GC, Boucher BA, Croce MA, Hanes SD, Herring VL, Fabian TC (2002) Aerosolized ceftazidime for prevention of ventilator-associated pneumonia and drug effects on the proinflammatory response in critically ill trauma patients. Pharmacotherapy 22:972–982CrossRefPubMed Wood GC, Boucher BA, Croce MA, Hanes SD, Herring VL, Fabian TC (2002) Aerosolized ceftazidime for prevention of ventilator-associated pneumonia and drug effects on the proinflammatory response in critically ill trauma patients. Pharmacotherapy 22:972–982CrossRefPubMed
27.
Zurück zum Zitat de Bont ES, Vellenga E, Swaanenburg J, Kamps W (2000) Procalcitonin: a diagnostic marker of bacterial infection in neutropenic cancer patients with fever? Infection 28:398–400CrossRefPubMed de Bont ES, Vellenga E, Swaanenburg J, Kamps W (2000) Procalcitonin: a diagnostic marker of bacterial infection in neutropenic cancer patients with fever? Infection 28:398–400CrossRefPubMed
28.
Zurück zum Zitat Ruokonen E, Nousiainen T, Pulkki K, Takala J (1999) Procalcitonin concentrations in patients with neutropenic fever. Eur J Clin Microbiol Infect Dis 18:283–285PubMed Ruokonen E, Nousiainen T, Pulkki K, Takala J (1999) Procalcitonin concentrations in patients with neutropenic fever. Eur J Clin Microbiol Infect Dis 18:283–285PubMed
Metadaten
Titel
Markers of bacteremia in febrile neutropenic patients with hematological malignancies: procalcitonin and IL-6 are more reliable than C-reactive protein
verfasst von
M. von Lilienfeld-Toal
M. P. Dietrich
A. Glasmacher
L. Lehmann
P. Breig
C. Hahn
I. G. H. Schmidt-Wolf
G. Marklein
S. Schroeder
F. Stuber
Publikationsdatum
01.07.2004
Erschienen in
European Journal of Clinical Microbiology & Infectious Diseases / Ausgabe 7/2004
Print ISSN: 0934-9723
Elektronische ISSN: 1435-4373
DOI
https://doi.org/10.1007/s10096-004-1156-y

Weitere Artikel der Ausgabe 7/2004

European Journal of Clinical Microbiology & Infectious Diseases 7/2004 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.