Zusammenfassung.
Hintergrund: Procalcitonin (PCT) findet zunehmend Anwendung als spezifischer Marker im intensivmedizinischen
Bereich für bakterielle, mykotische und parasitäre Infektionen. Für die schwer immunsupprimierten
und damit höchst infektionsgefährdeten Kinder nach Knochenmarktransplantation (KMT)
wäre dieser Marker ein wertvolles diagnostisches Werkzeug für die Primär- und Differentialdiagnose
septischer Krankheitsverläufe. Methode: In einer prospektiv angelegten Beobachtungsstudie wurde bei 48 Kindern und Jugendlichen
(medianes Alter 12,4 Jahre) nach KMT über 35 Tage PCT im Serum bestimmt, mit dem klinischen
Verlauf korreliert und mit den Werten des C-reaktiven Proteins (CrP) verglichen. Ergebnisse: Das PCT wies eine Sensitivität von 56 %, eine Spezifität von 87 %, einen positiven
prädiktiven Wert von 69 % und einen negativen prädiktiven Wert von 80 % bei der Erkennung
eines Sepsis-Syndroms auf. Die entsprechenden Werte für CrP betrugen 100 %, 41 %,
46 % und 100 %. Das relative Risiko, im Rahmen des Sepsis-Syndroms zu versterben,
war bei PCT 26,4 nach Überschreiten eines Schwellenwertes von 10 ng/Mol, bei CrP 4,0
ab einem Schwellenwert von 200 mg/l. Darüber hinaus konnte gezeigt werden, dass es
auch während der hämatologischen Aplasie zu signifikanten Freisetzungen von PCT kommen
kann. Schlussfolgerungen: (1) Mit Hilfe des PCT-Spiegels im Serum lassen sich Infektionsverläufe nach KMT zuverlässig
differenzieren und prognostische Beurteilungen abgeben. (2) Seine Bestimmung ist angezeigt,
wenn bei deutlich erhöhten CrP-Werten differentialdiagnostische und prognostische
Aussagen zu einer manifesten Infektion gemacht werden sollen.
Background: PCT has recently drawn attention as a quite specific marker for bacterial, fungal,
and parasitic origin of severe sepsis-syndrome. These specific properties could make
PCT to an important tool for sepsis monitoring in severely immunocompromised children.
The clinical value of PCT in comparison to CrP was investigated in children after
bone marrow transplantation (BMT). Methods: PCT was measured in the serum of 48 children (median age 12.4 years) after BMT in
a prospective study. Results were correlated with the clinical findings and compared
to the C-reactive protein (CrP). Results: PCT showed a sensitivity for diagnosing a sepsis-syndrome of 56 %, a specifity of
87 %, a positive predictive value of 69 %, and a negative predictive value of 80 %.
Regarding CrP they were 100 %, 41 %, 46 % and 100 % respectively. The relative risk
to die due to sepsis-syndrome was 26.4 for PCT levels over 10 ng/ml and 4.0 for CrP
levels over 200 mg/l. It could be shown furthermore that there can be a significant
liberation of PCT even during hematological aplasia. Conclusion: (1) Measuring PCT levels in the sera of children undergoing BMT improves the possibility
of diagnosing severe infection and gives an important prognostic tool. (2) Measuring
PCT can be recommended if severe sepsis-syndrome is suspected and there is an additional
need for differential diagnosis and prognostic evaluation.
Key words:
Knochenmarktransplantation - Sepsis-Syndrom - Sepsis - Procalcitonin - C-reaktives
Protein - Kinder
Key words:
Bone marrow transplantation - sepsis-syndrome - sepsis - procalcitonin - c-reactive
protein - children
Literatur
01
Al-Nawas B, Krammer I, Sah P M et al.
Procalcitonin in the diagnosis of severe infections.
Eur J Med Res.
1996;
1
331-333
02
Antonelli M, Raponi G M, Martino P.
High IL-6 levels are associated with septic shock and mortality in septic patients
with severe leukopenia due to hematological malignancies.
Scand J Infect Dis.
1995;
27
381-384
03
Assicot M, Gendrel D, Carsin H.
High serum procalcitonon concentrations in patients with sepsis and infection.
Lancet.
1993;
341
515-518
04
Becker K L, O'Neill W, Snider R H.
Hypercalcitonin-emia in inhalation burn injury: A response of the pulmonary endocrine
cell?.
Anatomic Record.
1993;
236
136-138
05
Bone R, Fisher C, Clemmer T.
Sepsis syndrome: a valid clinical entity. Methylprednisolone Severe Sepsis Study Group.
Crit Care Med.
1989;
17
389-393
06
Brunkhorst F M, Forycki Z F, Wagner J.
Release and kinetics of procalcitonin (PCT after gram-negativ bacterial injection
in a healthy subject.
Shock.
1997;
7
124 (Abst)
07
Dandona P, Nix D, Wilson M F.
Procalcironin increase after endotoxin injection in normal subjects.
J Clin Endocrinol Metab.
1994;
79
1605-1608
08
De Werra I, Jaccard C, Corradin S B.
Cytokines, nitrite/nitrate, soluble tumor necrosis factor receptors, and procalcitonin
concentrations: Comparison in patients with septic shock, cardiogenic shock, and bacterial
pneumonia.
Crit Care Med.
1997;
25
607-613
09
Enright H, Coyle M, O'Connel L.
CRP Concentration pre- and post transfusion.
Clin Lab Haematol.
1990;
12
25-29
10
Erikson S, Grantstöm L, Olander B J.
Sensitivity of interleukin-6 and C-reactive protein concentrations in the diagnosis
of acute appendicitis.
Eur J Surg.
1995;
161
41-45
11
Gerard Y, Hober D, Petitjean S, Assicot M.
High serum procalcitonin level in a 4-year-old liver transplant recipient with a disseminated
candidiasis.
Infection.
1995;
23
310-311
12
Gerard Y, Hober D, Assicot M.
Procalcitonin as a marker of bacterial sepsis in patients infected with HIV 1.
J Infect.
1997;
35
41-46
13 Gramm H J, Reinhart K, Goecke J. Early clinical, laboratory, and hemodynamic
indicators of sepsis and septic shock. In: Reinhart K, Eyrich K (eds.)
Sepsis - An interdisiplinary Challenge. Springer Verlag, Berlin; 1989: 45-57
14
Groll A, Müller F M.
Fortschritte in Prävention und Therapie infektiöser Komplikationen bei Kindern und
Jugendlichen mit neoplastischen Erkrankungen.
Klin Pädiatr.
1998;
210
106-114
15
Hammer C, Staehler M.
Procalcitonin (PCT), a new marker for differential diagnosis of acute rejection of
and bacterial infection of heart transplanted patients.
Clinical Intensive Care.
7
1996;
S39 (Abstract)
16
Jackson S R, Tweeddale M G, Barnett M T.
Admission for bone marrow transplant recipients to the intensiv care unit: outcome,
survival and prognostic factors.
Bone marrow Transplantation.
1998;
21(7)
697-704
17
Kragsberbjer P, Holmberg H, Vikefors T.
Serum concentrations of interleukin-6, tumor necrosis factor-alpha and C-reactive
protein in patients undergoing major operations.
Eur J Surg.
1995;
161
17-22
18
Le Moullec J M, Jullienne A, Chenais J.
The complete sequence of preprocalcitonin.
FEBS.
1984;
67
93-97
19
Leser H G, Gross V, Scheibenbogen C.
Elevation of serum interleukin-6 concentrations precedes acute phase response and
reflects severity of acute pancreatitis.
Gastroenterology.
1991;
101
782-785
20
Manian F.
A prospective study of daily measurement of CRP in serum of adults with neutropenia.
Clinical Infect Dis.
1995;
21
114-121
21
Meisner M, Tschaikowsky K, Schmidt J.
Procalcitonin (PCT) - Indications for a new diagnostic parameter of severe bacterial
infection and sepsis in transplantation, immunsuppression and cardiac assist devices.
Cardiovascular Engineering.
1997;
1
67-76
22
Monneret G, Labaune J M, Isaac C.
Procalcitonin and C-reactive protein levels in neonatal infections.
Acta Pediatr.
1997;
86
209-212
23
Oberhoffer M, Bögel D, Meier-Hellmann A.
Procalcitonin vs immunological markers in infection/inflammation.
Br J Anaesth.
1996;
76
A348 (Abstract)
24
Oberhoffer M, Vogelsang H, Meier Hellmann A.
Anti-Katacalcin-antibody-reaction in different types of human leucococytes indicates
procalcitonon content.
Shock.
1997;
7
487 (Abstract)
25
Rintala E, Pulkki K, Mertsola J.
Endotoxin, interleukin-6, and phospholipase-A2 as markers of sepsis in patients with
hematological malignancies.
Scand J Infect Dis.
1995;
27
39-43
26
Ruescher T J, Sodeifi A, Scrivani S J.
The impact of mucositis on alpha-hemolytic streptococcal infection in patients undergoing
autologous bone marrow transplantations for hematolgic malignancies.
Cancer.
1998;
82(11)
2275-2281
27
Shaw A C.
Serum C-reactive protein and neopterin concentrations in patients with viral or bacterial
infection.
J Clin Pathol.
1991;
44
596-599
28
Smith M D, Suputtamongkol Y, Chaowagul W.
Elevated serum procalcitonin levels in patients with melioidosis.
Clin Infect Dis.
1995;
20
641-645
29
Smith R P, Lipworth B J.
C-reactive protein in simple community acquired pneumonia.
Chest.
1995;
107
1028-1031
30
Zintl F, Sauer M, Fuchs D et al..
High Serum Procalcitonin (PCT) Concentrations in children and adults after hematopoietic
stem cell transplantation - an indicator for poor prognosis in severe infections.
Blood.
1996;
88
3791 (Abstract)
Dr. med. Martin Sauer
Department of Pediatric Hematology, Oncology, and Bone Marrow Transplantation University
of Minnesota
420 Delaware Street, S.E.
Minneapolis, MN 55455
USA