© Borgis - Postępy Nauk Medycznych 9/2013, s. 634-639
*Tomasz Ociepa, Emilia Sawka, Paulina Panek, Magdalena Wołczyk, Tomasz Urasiński
Ocena przydatności jednoczasowego oznaczania liczby krwinek białych i stężeń białka c-reaktywnego oraz prokalcytoniny w przewidywaniu przebiegu zakażenia u dzieci z ostrą białaczką limfoblastyczną i implantowanym centralnym cewnikiem naczyniowym
The value of concomitant measurement of white blood count, C-reactive protein and procalcitonin in predicting the course of infection in children with acute lymphoblastic leukemia and central venous catheter
Clinic of Pediatric Hematology and Oncology, Pomeranian Medical University, Szczecin
Head of Clinic: prof. Tomasz Urasiński, PhD, MD
Wstęp. Zakażenia odcewnikowe odpowiadają za aż 44% wszystkich epizodów bakteremii u dzieci z ostrą białaczką limfoblastyczną (obl). Wczesna ich identyfikacja oraz odpowiednio intensywne leczenie mogą wpłynąć na poprawę wyników leczenia dziecięcej obl.
Cel. Ocena przydatności jednoczasowego oznaczania liczby krwinek białych (WBC), stężeń białka c-reaktywnego (CRP) oraz prokalcytoniny (PCT) w przewidywaniu przebiegu zakażeń u dzieci z obl.
Materiał i metody. Analizowano początkową WBC oraz stężenia CRP i PCT w przebiegu 51 epizodów gorączki u 23 dzieci z obl i implantowanym cewnikiem naczyniowym (CVC). U wszystkich pacjentów zastosowano empiryczną antybiotykoterapię.
Wyniki. Podwyższone początkowe stężenia PCT i CRP stwierdzono odpowiednio w 22/51 (43,1%) i 43/51 (84,3%) analizowanych przypadkach. Średni czas trwania gorączki, jak również średnie stężenie CRP były istotnie wyższe w przypadkach z początkową WBC poniżej 500/μl. Nie wykazano korelacji pomiędzy stężeniami CRP i PCT, jednakże średnie stężenia CRP jak również liczba dodatnich wyników posiewów krwi były istotnie wyższe w epizodach z podwyższonym początkowym stężeniem PCT. Liczba dodatnich wyników posiewów krwi była również istotnie wyższa w epizodach z jednoczasowym podwyższeniem stężeń CRP i PCT. Stwierdzono wyższe początkowe stężenia PCT ale nie CRP w epizodach z dodatnim wynikiem posiewu krwi.
Wnioski. Łączna ocena WBC oraz stężeń CRP i PCT jest przydatna w przewidywaniu przebiegu zakażeń u gorączkujących dzieci z obl i implantowanym centralnym cewnikiem naczyniowym. Umożliwia ona również wyselekcjonowanie pacjentów o wysokim ryzyku rozwoju bakteremii.
Introduction. Catheter related infections are responsible for up to 44% of episodes of bacteremia in children with acute lymphoblastic leukemia (ALL). Early prediction and intensive treatment of this complication may improve survival for children with ALL.
Aim. To assess the value of concomitant measurement of white blood count (WBC), C-reactive protein (CRP) and procalcitonin (PCT) in predicting the course of infection in children with ALL.
Material and methods. 51 febrile episodes recorded in 23 children with ALL and implanted central venous catheter (CVC) were analyzed with respect to initial WBC, CRP, PCT and CVC bacterial culture. Patients were treated with empiric antimicrobial therapy.
Results. Elevated values of PCT were found in 22/51 (43.1%) whereas values of CRP were elevated in 43/51 (84.3%) of studied episodes. Mean number of febrile days and mean CRP values were statistically higher in episodes with initial WBC less than 500/μl. There was no correlation between values of CRP and PCT however mean values of CRP and the number of episodes with positive CVC blood culture were statistically higher among those with elevated PCT. The number of positive CVC blood cultures was statistically higher in episodes where both CRP and PCT levels were elevated. There was higher initial concentration of PCT but no CRP in episodes with positive blood cultures.
Conclusion. WBC, CRP and PCT, when used together are useful indicators of the infection’s course in febrile patients with ALL and CVC. They also allow to select patients at high risk of bacteremia.
Acute lymphoblastic leukemia (ALL) is the commonest form of childhood cancer. Now, in the advent of 21st century the majority of children with this diagnosis may enjoy long-lasting remission which in most of these patients can be considered as a cure (1). However up to 20% of children with ALL suffer from treatment failures. Most of them are relapses, but 3-15% of all children with ALL die in remission and the direct cause of their death are infections (2-4).
Central venous catheters (CVC) are routinely inserted in children with ALL allowing permanent access to venous circulation for blood sampling as well as drugs administration, blood products transfusing and parenteral nutrition. From the other site the insertion of CVC in a child with ALL is associated with a high risk of bacteremia. The rate of catheter related bacteremia in children with ALL and CVC can be as high as 44% (5, 6). It is extremely dangerous since in most of patients it occurs during profound neutropenia resulting from intensive chemotherapy. Early prediction and vigorous treatment of this complication from the very beginning may result in better outcome for children with ALL.
Two laboratory parameters: C-reacting protein (CRP) and procalcitonin (PCT) may be useful in predicting severity of infection in children with ALL. CRP is a protein produced by the liver and the adipose tissue, which enhances complement binding. It’s concentration is less than 5 mg/l in healthy individuals and rises to maximum values within 24-72 hours in response to inflammation (7). It is believed that PCT is an earlier and more specific marker of infection (8). PCT is 14-kDa prohormone of calcitonin that is synthetized by parafollicular cells of the thyroid as well as the neuroendocrine cells of the lung and the intestine. It has been shown that serum PCT levels raise in response to the presence of bacterial endotoxins in the blood; that is why PCT is considered as the marker of bacteremia in adults as well as in children (9, 10).
This study was performed in order to assess the value of concomitant measurement of white blood count, C-reactive protein and procalcitonin in predicting the course of infection in children with acute lymphoblastic leukemia and central venous catheter.
Material and methods
This retrospective study, conducted between February 1st 2007 and January 31st 2010 comprised children with ALL and implanted CVC, who developed at least one episode of fever of unknown origin that is body temperature over 38 degrees Celsius measured with the use of infrared forehead thermometer (Microlife), with no other clinical manifestation except of fever and no site of infection seen on physical examination or on imaging (e.g. chest x-ray). There were 51 episodes recorded in 23 children (12 girls and 11 boys) aged 2-14 years (mean 7.06, median 6 years).
In each of these patients blood was sampled routinely for WBC, CRP as well as PCT. PCT was measured with the use of electrochemiluminescence method (ECLIA) for quantitative determination of procalcitonin (Roche), CRP – with the use of immunoturbidimetric method for quantitative determination of C-reactive protein (Roche). Values of CRP below 5 mg/l and PCT below 0.5 ng/ml were considered normal. A sample of peripheral blood was also drawn from the catheter for bacterial cultures. These were followed by introduction of empiric antimicrobial therapy consisting of piperacillin/tazobactam (112.5 mg/kg every 8 hours) alone or in combination with amikacin (15 mg/kg once daily); the decision regarding a form of treatment was made by a physician in charge.
In patients with no clinical response to the first line antimicrobial therapy i.e. with no resolution of fever within 48 h treatment was modified: either according to the result of CVC bacterial culture or – if culture was negative – to combination of meropenem (20 mg/kg 3 times daily) plus vancomycin (20 mg/kg 3 times daily), than after subsequent 48 h – as a third step – an antifungal agent (amphotericin B or voriconazole) was added.
Duration of fever was reflected by number of days with at least one spike of body temperature over 38 degrees Celsius measured as mentioned above.
WBC, CRP and PCT values were analyzed in relation to results of central catheter blood culture (positive vs negative) and to duration of fever. The correlation between CRP and PCT values was also studied.
The normality of data was assessed with the use of Kolmogorov-Smirnov test. Statistical analysis of data was performed with the use of Fisher test, Mann-Whitney test, t-Student test and linear correlation model. Values of p < 0.05 were considered statistically significant.
There were no treatment failures recorded in the group studied; in all fever episodes antimicrobial therapy resulted in resolution of fever. Mean number of febrile days as well as mean CRP values were statistically higher in episodes with initial WBC less than 500/μl (5.20 vs 10.73 days; p < 0.03, and 37.2 mg/l vs 106.8 mg/l; p < 0.005) respectively however PCT values did not differ significantly. These data are presented in table 1.
Table 1. Mean duration of fever, values of CRP and PCT in episodes with WBC ≥ 500/μl and < 500/μl.
|Variable||WBC ≥ 500/μl (n = 36)||WBC < 500/μl (n = 15)||p-value|
|Duration of fever (days; mean ± SD)||5.2 ± 3.8||10.73 ± 12.5||p = 0.02|
|PCT (ng/ml; mean ± SD)||0.64 ± 0.59||0.76 ± 1.04||p = 0.59|
|CRP (mg/l; mean ± SD)||37.2 ± 53.13||106.8 ± 97.75||p = 0.0019|
|CVC positive blood culture||7/36||2/15||p = 0.71|
95% CI: 0.75-1.69
Elevated values of PCT were found in 22/51 (43.1%) whereas values of CRP were elevated in 43/51 (84.3%) of studied episodes.
There was no correlation between values of CRP and PCT (r = 0.4983) however mean values of CRP (34.82 vs 87.78; p < 0.01) and the number of episodes with positive CVC blood culture (8/22 vs 1/29; p < 0.005) were statistically higher among those with elevated PCT. These data are presented in figure 1 and table 2.
Fig. 1. Correlation between CRP and PCT in febrile children with ALL and implanted CVC.
Table 2. Mean duration of fever, values of CRP and number of positive CVC blood culture in episodes with normal and elevated PCT concentration.
|Variable||PCT < 0.5 ng/ml (n = 29)||PCT ≥ 0.5 ng/ml (n = 22)||p-value|
|Duration of fever (days; mean ± SD)||6 ± 4.35||8 ± 10.7||p = 0.37|
|CRP (mg/l; mean ± SD)||34.82 ± 46.76||87 78 ± 95.51||p < 0.05|
|CVC positive blood culture||1/29||8/22||p < 0.005|
95% CI: 1.82-141
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