BACKGROUND. Procalcitonin has been identified as a useful blood marker of serious bacterial infection in febrile infants.

Many infants present with a febrile reaction after receiving immunizations. The effects of immunization on procalcitonin have not been investigated. METHODS.We performed a prospective observational cohort study at a large, urban pediatric emergency department. Infants _90 days of age with fever of _38C were enrolled. Subjects were divided into 3 groups: infants with serious bacterial infection; subjects without serious bacterial infection who received recent (_48 hours) immunizations; and subjects without serious bacterial infection who did not recently receive immunizations. Procalcitonin was measured by using a quantitative immunometric assay. RESULTS. Over 13 months, procalcitonin was measured for 271 infants. There were 44 (16%) patients with serious bacterial infection, 35 in the recent-immunization group, and 192 in the no-recentimmunization group. The median procalcitonin level for serious bacterial infection was 0.53 ng/mL, for recent immunization was 0.29 ng/mL, and for no recent immunizations was 0.17 ng/mL. Procalcitonin values were elevated for patients with serious bacterial infection compared with patients both with and without recent immunizations. Compared with patients who had no recent immunizations, procalcitonin levels were elevated in patients with recent immunization. Using a cut point of 0.12 ng/mL, the sensitivity of procalcitonin for serious bacterial infection was 96%, specificity was 23%, and negative predictive value was 96%. Two patients with recent immunization who had serious bacterial infection were identified with this cut point. CONCLUSIONS. Among febrile infants with recent immunization, procalcitonin levels are increased compared with patients with fever and no identified bacterial infection. Despite this increase, procalcitonin can still reliably discriminate infants with serious bacterial infection. Pediatrics 2008;122:e1119 e1122 FEVER WITHOUT AN identifiable source of infection is a common presenting complaint at primary care offices and emergency departments. For infants _3 months of age, fever may be the only sign of a serious bacterial infection (SBI). In addition, infants routinely receive their first group of vaccinations between 6 and 10 weeks of age. With the advent of the Pediarix (GlaxoSmithKline, Research Triangle Park, NC) vaccine, there have been reported rates of fever after vaccination as high as 27.9%.1 There is no standard evaluation or management of fever in recently vaccinated

infants. Recent studies have identified procalcitonin as a biomarker of bacterial infections.26 We previously reported the procalcitonin values in a prospective cohort of infants _90 days old who presented to a pediatric emergency department with fever without source.7 Procalcitonin was found to be a highly sensitive marker of SBI in this cohort. The effect of immunization on procalcitonin levels has not been well described and theoretically might interfere with the use of procalcitonin as a diagnostic marker for SBI. Herein, we investigate the effect of recent immunization on the diagnostic performance of procalcitonin in young febrile infants. METHODS This study was part of a larger study investigating the performance of procalcitonin as a discriminator of SBI in this age group.7 The complete study methods are detailed in the original publication. We conducted a prospective cohort study of infants _90 days of age who presented to the emergency department with a documented temperature of _38.0C. Infants were excluded if they had an Key Words: fever, infant, immunization, vaccination, procalcitonin Abbreviations: SBI, serious bacterial infection; RI, recent immunization; NRI, no recent immunization; CI, confidence interval; UTI, urinary tract infection; WBC, white blood cell; NPV, negative predictive value www.pediatrics.org/cgi/doi/10.1542/peds.2008-1884 doi:10.1542/peds.2008-1884 Accepted for publication Jul 21, 2008 Address correspondence to Andrew Dauber, MD, Childrens Hospital Boston, Division of Endocrinology, LO-605, 300 Longwood Ave, Boston, MA 02115. E-mail: andrew.dauber@childrens. harvard.edu PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright 2008 by the American Academy of Pediatrics PEDIATRICS Volume 122, Number 5, November 2008 e1119 Downloaded from www.pediatrics.org. Provided by Indonesia:AAP Sponsored on December 12, 2010 underlying chronic illness or antibiotic use within the previous 48 hours. Patients were classified as having an SBI if they had a blood, urine, or cerebrospinal culture that grew a pathogenic organism or had a chest radiograph that was interpreted by an attending radiologist who diagnosed pneumonia. Subjects were divided into 3 groups. The first group included all patients with an SBI regardless of

their recent immunization status (SBI group). The second group included those patients without SBI who had received immunizations within the previous 48 hours (RI group). The third group included those patients without SBI who had not received immunizations in the previous 48 hours (NRI group). At the time of enrollment, the attending physician responsible for the care of the patient completed a questionnaire to assess the appearance of the infant on a 5-point scale. Procalcitonin was measured on stored samples by using an immunometric assay (Brahms [Hennigsdorf, Germany] procalcitonin-sensitive Kryptor kit). Statistical analysis was performed by using SPSS 14.0 (SPSS Inc, Chicago, IL). For continuous variables, independentsamples t tests and the nonparametric Wilcoxon rank-sum test were used; for categorical data, Fishers exact test or _2 analysis was used. Analyses were performed between the SBI and RI groups, the SBI and NRI groups, and RI and NRI groups. The 95% confidence intervals (CIs) for proportions were calculated by using Stata 6 (Stata Corp, College Station, TX). The study was approved by the Childrens Hospital Boston institutional review board and was compliant with the Health Insurance Portability and Accountability Act of 1996. RESULTS During the study period, 874 infants _90 days old with a temperature of _38C were evaluated in the emergency department. Fifty-two patients met the exclusion criteria. Of the remaining 822 patients, consent was obtained for 501 (61%) of them. Of those patients, we were able to measure the procalcitonin level from an available blood specimen in 271 patients (54% of consented eligible patients). Of the 271 patients comprising the study group, there were 44 (16%) patients in the SBI group, 35 (13%) patients in the RI group, and 192 (71%) patients in the NRI group. Of the 44 SBIs, 33 were urinary tract infections (UTIs), 2 were UTIs with bacteremia, 4 were bacteremia, and 5 were pneumonia. Demographics of the infants in these 3 groups are presented in Table 1. As predicted by the timing of immunizations, the mean age of patients in the RI group was significantly higher than in the SBI and NRI groups. The patients were significantly more well-appearing in the RI group in comparison to those in the SBI group but not in comparison to those in the NRI group. The white blood cell (WBC) and procalcitonin data for the 3 groups are presented in Table 1. WBC values were significantly higher in the SBI and RI groups when

compared with the NRI group. There was no difference in the mean WBC count between the RI and SBI groups. Median procalcitonin levels were significantly higher in the SBI group when compared with both the RI and NRI groups. The procalcitonin levels in the RI group were also higher than in the NRI group. Figure 1 depicts the distribution of procalcitonin values in the SBI, RI and NRI groups. Two of 37 patients with recent immunization had an SBI. The first patient was a 77-day-old girl with a temperature of 40.0C who had received immunizations 2 days before presentation. Her urine culture grew _100 000 colony-forming units/mL Escherichia coli. Her procalcitonin level was 0.36 ng/mL. The second patient was a 71-day-old boy who had received immunizations earlier that day and presented with a temperature of 38.4C. His urine culture grew 30 000 colony-forming units/mL E coli. His procalcitonin level was 0.211 ng/mL. Using our previously published cut point of 0.12 ng/ mL, the sensitivity of procalcitonin for SBI in the entire cohort was 96% (95% CI: 83%99%), the specificity was 23% (95% CI: 18%29%), and the negative predictive value (NPV) was 96% (95% CI: 86%99%). Using the same cut point for the 37 patients who had received immunizations in the past 48 hours (35 in the RI group and 2 with recent immunization in the SBI group), the sensitivity of procalcitonin for SBI was 100% (2 of 2), and the specificity for non-SBI was 8.6% (3 of 35). This calculation was limited by the small sample size of 2 patients with SBI and recent immunizations. DISCUSSION Fever is the most frequently reported serious and nonserious adverse event after immunization according to the Vaccine Adverse Event Reporting System.8 This presents a unique problem in those infants _3 months of age who are at higher risk of having an SBI. TABLE 1 Comparison of the Study Subgroups SBI Group (N_44) RI Group (N_35) NRI Group (N_192) P SBI vs RI SBI vs NRI RI vs NRI Age, mean (SD), d 45 (25) 63 (7) 51 (23) _.001 .133 .002 Highest temperature, mean (SD), C 38.9 (0.68) 38.7 (0.53) 38.6 (0.46) .207 .002 .32 Overall appearance, median (IQR)a 4 (45) 5 (45) 4 (45) .019 .118 .112 WBC, mean (SD), 103/_L 14.3 (7.8) 13.8 (4.7) 11.2 (4.2) .781 _.001 .001

Procalcitonin, median (IQR), ng/mL 0.53 (0.182.50) 0.29 (0.180.41) 0.17 (0.12 0.27) .017 _.001 .001 IQR indicates interquartile range. a Appearance scale: 1, moribund, toxic, ill appearing, unresponsive; 5, perfectly healthy, interactive infant. e1120 DAUBER et al Downloaded from www.pediatrics.org. Provided by Indonesia:AAP Sponsored on December 12, 2010 There is no consensus on whether to treat these patients differently than those with fever and no recent history of immunization. The effect of vaccination on procalcitonin levels has not been well studied. A Medline database search revealed only 1 article about procalcitonin levels after vaccination: in a letter to the editor of the Pediatric Infectious Disease Journal,9 Korczowski reported on a cohort of 17 patients who presented to a pediatric emergency department in Poland with vaccination-associated adverse events. Sixteen of these patients had temperatures of _38.5C. The mean age of the infants was 20 weeks (range: 637 weeks). The mean serum procalcitonin level in these patients was 0.8 _ 0.9 ng/mL (range: 0.13.6 ng/mL). There were no SBIs. Korczowski concluded that procalcitonin levels can be modestly elevated after vaccination in the absence of infection. Ours was a prospective cohort study that included 271 infants _90 days old with documented temperatures of _38C in a pediatric emergency department. We previously reported the utility of procalcitonin level for predicting SBI in those patients who had not received immunizations in the previous 48 hours. In that cohort, a cut point of 0.12 ng/mL had a sensitivity of 95% (95% CI: 83%99%), specificity of 26% (95% CI: 20%32%), NPV of 96% (95% CI: 85%99%), and negative likelihood ratio of 0.19 (95% CI: 0.050.74); all cases of bacteremia were identified accurately with the cut-point value. In the current study, we further subcategorized the patients as those with SBI, those without SBI who had recently received immunizations, and those without SBI who had not recently received immunizations. The median procalcitonin level was significantly higher in the group of infants who had received immunizations compared with those who had not, but it was significantly lower than in the SBI group. On the basis of this, it seems that immunization leads to an increase in serum procalcitonin values, but it can still be used to identify a group at low risk for SBI regardless of immunization status. The WBC count was also elevated in the RI group when compared with non-SBI patients without recent immunization

but was similar to those with SBI. Therefore, WBC count, a commonly used marker for SBI, is less useful for patients who have recently received vaccinations. When using our previously published cut point of 0.12 ng/mL, the sensitivity of procalcitonin for SBI in the entire cohort was 96% (95% CI: 83%99%), specificity was 23% (95% CI: 18%29%), and NPV was 96% (95% CI: 86%99%). Overall, the addition of vaccinated infants into the analysis of the entire cohort led to a similar sensitivity and NPV but decreased the specificity of procalcitonin level as a marker of SBI. This change is because of the vast majority of immunized patients having a procalcitonin value that was greater than our cut point of 0.12 ng/mL. However, procalcitonin levels can continue to be used to identify patients at low risk for SBI, and by using the same cut point, both patients in our cohort with SBIs who had recently received immunizations were identified. Our study has several limitations. The study was conducted at an academic pediatric emergency department and, therefore, may not represent the larger population of patients after immunization. In addition, even among those febrile infants who were recently vaccinated and presented with fever, there may be a bias of who had any laboratory evaluation. Furthermore, we did not collect information on the type of vaccinations received and, thus, cannot provide further details on the specific effects of individual vaccines on procalcitonin values. SBI RI NRI Study subgroup 5 4 3 2 1 0 Procalcitonin, ng/mL FIGURE 1 Comparison of the study subgroups. The boxes represent the limits of the 25th and 75th percentiles and are divided with a line at the median. The whiskers represent 1.5 times the IQR. PEDIATRICS Volume 122, Number 5, November 2008 e1121 Downloaded from www.pediatrics.org. Provided by Indonesia:AAP Sponsored on December 12, 2010 Finally, our definitions of SBI were intended to be conservative to include all possible SBIs, because we were hoping to identify a low-risk group for SBI. We acknowledge that some of the patients with low-colony-count UTIs and radiographic pneumonia may not have represented

true bacterial infections. Our initial study provides further analysis on definite and possible SBIs to account for this difficulty in definitions. CONCLUSIONS Among young febrile infants with recent immunization, procalcitonin levels are increased compared with patients with fever and no identified bacterial infection. Despite this increase, procalcitonin levels can still reliably discriminate infants with SBI. ACKNOWLEDGMENTS We thank the physician colleagues in the emergency department who facilitated enrollment for the study, and we gratefully acknowledge the help and expertise of Richard Snider, PhD, and Robyn Neches, BS, for work on the procalcitonin assays. We are thankful for the financial support of the Frederick H. Lovejoy, Jr, MD, Resident Research Fund and the American Academy of Pediatrics Resident Research Grant. In addition, we acknowledge technical support related to specimen processing by the General Clinical Research Center at Childrens Hospital Boston (National Center for Research Resources, General Clinical Research Centers Program, National Institutes of Health grant M01RR02172). The funding organizations had no role in the design, data analysis, or manuscript preparation. The Childrens Hospital Boston General Clinical Research Center was involved in sample processing

terjemahan.
LATAR BELAKANG. Procalcitonin telah diidentifikasi sebagai penanda darah yang berguna infeksi bakteri serius pada bayi demam. Banyak bayi hadir dengan reaksi demam setelah menerima imunisasi. Efek dari imunisasi pada procalcitonin belum diselidiki. METHODS.We melakukan studi kohort prospektif observasional di sebuah departemen, darurat kota besar pediatrik. Bayi usia _90 hari dengan demam _38 C yang terdaftar. Subyek dibagi menjadi 3 kelompok: bayi dengan serius infeksi bakteri; subyek tanpa infeksi bakteri serius yang menerima terakhir (_48 jam) imunisasi, dan subyek tanpa infeksi bakteri serius yang tidak baru-baru menerima imunisasi. Procalcitonin diukur dengan menggunakan uji immunometric kuantitatif. HASIL. Selama 13 bulan, procalcitonin diukur untuk 271 bayi. Ada 44 (16%) pasien dengan serius

infeksi bakteri, 35 dalam kelompok terakhir-imunisasi, dan 192 pada kelompok tidakterakhir-imunisasi. Median tingkat procalcitonin untuk infeksi bakteri yang serius adalah 0,53 ng / mL, untuk imunisasi terakhir adalah 0,29 ng / mL, dan untuk tidak ada imunisasi terakhir adalah 0,17 ng / mL. Nilai Procalcitonin terangkat untuk pasien dengan bakteri yang serius infeksi dibandingkan dengan pasien baik dengan dan tanpa imunisasi terakhir. Dibandingkan dengan pasien yang tidak memiliki imunisasi terakhir, tingkat procalcitonin meningkat pada pasien dengan imunisasi terakhir. Menggunakan titik potong dari 0,12 ng / mL, kepekaan procalcitonin untuk infeksi bakteri yang serius adalah 96%, spesifisitas adalah 23%, dan negatif nilai prediksi adalah 96%. Dua pasien dengan imunisasi terakhir yang mengalami infeksi bakteri serius diidentifikasi dengan titik potong. KESIMPULAN. Di antara bayi demam dengan imunisasi terakhir, tingkat procalcitonin meningkat dibandingkan dengan pasien dengan demam dan tidak ada infeksi bakteri diidentifikasi. Meskipun peningkatan ini, procalcitonin masih bisa dipercaya diskriminasi bayi dengan infeksi bakteri serius. Pediatri 2008; 122: e1119-e1122 TANPA DEMAM AN diidentifikasi sumber infeksi menyajikan keluhan umum di perawatan primer kantor dan departemen darurat. Untuk bayi _3 bulan usia, demam bisa jadi hanya tanda yang serius infeksi bakteri (SBI). Selain itu, bayi secara rutin Kelompok pertama menerima mereka vaksinasi antara 6 dan 10 minggu usia. Dengan munculnya Pediarix yang (GlaxoSmithKline, Research Triangle Park, NC) vaksin, ada telah dilaporkan tingkat demam setelah vaksinasi setinggi 27,9% .1 Tidak ada standar evaluasi atau manajemen demam pada baru-baru divaksinasi bayi. Penelitian terbaru telah mengidentifikasi procalcitonin sebagai biomarker bakteri infections.2-6 Kami sebelumnya dilaporkan nilai-nilai procalcitonin dalam kohort prospektif bayi _90 hari tua yang disajikan kepada anak-anak gawat darurat dengan demam tanpa source.7 Procalcitonin ditemukan untuk menjadi sangat sensitif penanda SBI pada kohort ini. Efek dari imunisasi pada tingkat procalcitonin belum dijelaskan dengan baik dan secara teoritis dapat mengganggu penggunaan dari procalcitonin sebagai penanda diagnostik untuk SBI. Di sini, kami menyelidiki efek dari imunisasi baru pada kinerja diagnostik procalcitonin di muda demam bayi. METODE Penelitian ini merupakan bagian dari penelitian yang lebih besar menyelidiki kinerja procalcitonin sebagai diskriminator SBI di usia ini group.7 Metode studi lengkap yang rinci dalam publikasi asli. Kami melakukan prospektif

kohort studi _90 hari bayi usia yang disampaikan kepada departemen darurat dengan suhu didokumentasikan dari _38.0 C. Bayi dikeluarkan jika mereka memiliki Kata Kunci: demam, bayi, imunisasi, vaksinasi, procalcitonin Singkatan: SBI, infeksi bakteri yang serius; RI, imunisasi terakhir; NRI, tidak barubaru ini imunisasi; CI, interval kepercayaan, ISK, infeksi saluran kemih, WBC, darah putih sel, NPV, nilai prediksi negatif www.pediatrics.org/cgi/doi/10.1542/peds.2008-1884 doi: 10.1542/peds.2008-1884 Diterima untuk publikasi, 21 Juli 2008 Alamat korespondensi untuk Andrew pengoles, MD, Rumah Sakit Anak Boston, Divisi Endokrinologi, LO-605, 300 Longwood Ave, Boston, MA 02115. E-mail: andrew.dauber @ anak-anak. harvard.edu Pediatrics (ISSN Nomor: Cetak, 0031-4005; Online, 1098-4275). Hak Cipta 2008 oleh American Academy of Pediatrics Pediatri Volume 122, Nomor 5, November 2008 e1119 Download dari www.pediatrics.org. Diberikan oleh Indonesia: AAP sponsor pada 12 Desember 2010 kronis yang mendasari penyakit atau penggunaan antibiotik dalam sebelumnya 48 jam. Pasien diklasifikasikan sebagai memiliki SBI jika mereka memiliki darah, urin, atau budaya serebrospinal yang tumbuh patogen yang organisme atau memiliki radiograf dada yang ditafsirkan oleh seorang ahli radiologi menghadiri yang didiagnosis pneumonia. Subyek dibagi menjadi 3 kelompok. Para Kelompok pertama termasuk semua pasien dengan SBI terlepas dari mereka terakhir imunisasi status (SBI kelompok). Yang kedua termasuk kelompok pasien tanpa SBI yang telah menerima imunisasi dalam waktu 48 jam sebelumnya (Kelompok RI). Kelompok ketiga termasuk pasien tanpa SBI yang belum menerima imunisasi di sebelumnya 48 jam (NRI kelompok). Pada saat pendaftaran, dokter yang hadir bertanggung jawab untuk perawatan pasien menyelesaikan kuesioner untuk menilai penampilan bayi pada titik 5skala. Procalcitonin diukur pada sampel yang disimpan oleh menggunakan uji immunometric (Brahms [Hennigsdorf, Jerman] procalcitonin-sensitif kit Kryptor). Analisis statistik dilakukan dengan menggunakan SPSS 14.0 (SPSS Inc, Chicago, IL). Untuk variabel kontinyu, mandirisampel t tes dan Wilcoxon nonparametrik rank-sum test digunakan; untuk data kategori, Uji eksak Fisher atau _2 analisis digunakan. Analisis dilakukan antara SBI dan kelompok RI, SBI dan Kelompok NRI, dan RI dan kelompok NRI. Kepercayaan 95% interval (CI) untuk proporsi dihitung dengan menggunakan

Stata 6 (Stata Corp, College Station, TX). Penelitian ini disetujui oleh Rumah Sakit Anak Boston papan review kelembagaan dan sesuai dengan Asuransi Kesehatan Portabilitas dan Akuntabilitas Act of 1996. HASIL Selama masa penelitian, 874 bayi _90 hari tua dengan suhu _38 C dievaluasi dalam keadaan darurat departemen. Lima puluh dua pasien bertemu pengecualian kriteria. Dari 822 pasien yang tersisa, persetujuan itu diperoleh untuk 501 (61%) dari mereka. Dari pasien, kita mampu mengukur tingkat procalcitonin dari darah yang tersedia spesimen dalam 271 pasien (54% dari persetujuan pasien yang memenuhi kriteria). Dari 271 pasien yang terdiri dari kelompok studi, ada adalah 44 (16%) pasien dalam kelompok SBI, 35 (13%) pasien dalam kelompok RI, dan 192 (71%) pasien dalam NRI kelompok. Dari 44 SBI, 33 adalah infeksi saluran kemih (UTI), 2 adalah UTI dengan bakteremia, 4 adalah bakteremia, dan 5 pneumonia. Demografi dari bayi dalam 3 kelompok disajikan pada Tabel 1. Sebagai diprediksi oleh waktu imunisasi, usia rata-rata dari pasien dalam kelompok RI secara signifikan lebih tinggi dari dalam kelompok SBI dan NRI. Para pasien secara signifikan lebih baik muncul pada kelompok RI dibandingkan kepada mereka dalam kelompok SBI tetapi tidak dibandingkan dengan pada kelompok NRI. Sel darah putih (WBC) dan data procalcitonin untuk 3 kelompok disajikan pada Tabel 1. WBC nilai secara signifikan lebih tinggi di SBI dan kelompok RI saat dibandingkan dengan kelompok NRI. Tidak ada perbedaan dalam hitungan WBC rata-rata antara RI dan kelompok SBI. Tingkat procalcitonin median secara signifikan lebih tinggi pada SBI kelompok bila dibandingkan dengan kedua RI dan NRI kelompok. Tingkat procalcitonin dalam kelompok RI yang juga lebih tinggi dari pada kelompok NRI. Gambar 1 menggambarkan distribusi nilai procalcitonin di SBI, RI dan NRI kelompok. Dua dari 37 pasien dengan imunisasi terakhir memiliki SBI. Pasien pertama adalah seorang gadis 77-hari-tua dengan suhu dari 40,0 C yang telah menerima imunisasi 2 hari sebelum presentasi. Kultur urin nya tumbuh _100 000 unit pembentuk koloni / mL Escherichia coli. Nya tingkat procalcitonin adalah 0,36 ng / mL. Pasien kedua adalah seorang anak 71-hari-tua yang telah menerima imunisasi sebelumnya hari itu dan disajikan dengan suhu 38,4 C. Kultur urin nya tumbuh 30 000 pembentuk koloni unit / mL E coli. Tingkat procalcitonin Nya adalah 0,211 ng / mL. Menggunakan dipotong diterbitkan sebelumnya kami titik 0,12 ng / mL, kepekaan procalcitonin untuk SBI di seluruh

kohort adalah 96% (95% CI: 83% -99%), spesifisitas adalah 23% (95% CI: 18% -29%), dan prediksi negatif nilai (NPV) adalah 96% (95% CI: 86% -99%). Menggunakan titik potong yang sama untuk 37 pasien yang telah menerima imunisasi dalam 48 jam terakhir (35 pada RI kelompok dan 2 dengan imunisasi terakhir di SBI kelompok), kepekaan procalcitonin untuk SBI adalah 100% (2 dari 2), dan spesifisitas untuk non-SBI adalah 8,6% (3 dari 35). Perhitungan ini dibatasi oleh ukuran sampel yang kecil dari 2 pasien dengan SBI dan imunisasi terakhir. PEMBAHASAN Demam adalah yang paling sering dilaporkan "serius" dan "Nonserious" peristiwa buruk setelah imunisasi menurut untuk Event Vaksin Merugikan Pelaporan System.8 Hal ini menimbulkan masalah unik dalam mereka bayi _3 bulan usia yang berisiko lebih tinggi memiliki SBI. Tabel 1 Perbandingan Subkelompok Studi Kelompok SBI (N_44) Kelompok RI (N_35) NRI Kelompok (N_192) P SBI SBI vs vs RI NRI RI vs NRI Umur, rata-rata (SD), d 45 (25) 63 (7) 51 (23) 0,133 0,002 _.001 Suhu tertinggi, rata-rata (SD), C 38,9 (0,68) 38,7 (0,53) 38,6 (0,46) .207 .002 .32 Secara keseluruhan penampilan, median (IQR) dengan 4 (4-5) 5 (4-5) 4 (4-5) .019 . 118 .112 WBC, rata-rata (SD), 103/_L 14,3 (7,8) 13,8 (4,7) 11,2 (4,2) .781 .001 _.001 Procalcitonin, median (IQR), ng / mL 0,53 (0,18-2,50) 0,29 (0,18-0,41) 0,17 (0,120,27) 0,017 0,001 _.001 IQR menunjukkan kisaran interkuartil. skala Penampilan: 1, "sekarat, beracun, sakit muncul, tidak responsif", 5, "yang sehat bayi, interaktif." pengoles E1120 dkk Download dari www.pediatrics.org. Diberikan oleh Indonesia: AAP sponsor pada 12 Desember 2010 Tidak ada konsensus pada apakah untuk mengobati pasien berbeda dibandingkan dengan demam dan tidak ada sejarah baru-baru imunisasi. Pengaruh vaksinasi pada tingkat procalcitonin telah belum diteliti dengan baik. Sebuah pencarian database Medline mengungkapkan hanya 1 artikel tentang tingkat procalcitonin setelah vaksinasi: dalam sebuah surat kepada editor dari Pediatric Infectious Penyakit Journal, 9 Korczowski melaporkan pada kohort 17 pasien yang disajikan untuk keadaan darurat pediatrik departemen di Polandia dengan vaksinasi terkait merugikan peristiwa. Enam belas pasien memiliki suhu dari _38.5 C. Usia rata-rata bayi adalah 20 minggu

(Rentang: 6-37 minggu). Para procalcitonin serum rata-rata tingkat pada pasien ini adalah 0,8 _ 0,9 ng / mL (kisaran: 0,1-3,6 ng / mL). Tidak ada SBI. Korczowski menyimpulkan bahwa tingkat sederhana procalcitonin dapat meningkat setelah vaksinasi dengan tidak adanya infeksi. Kita adalah sebuah studi kohort prospektif yang mencakup _90 271 hari tua dengan suhu didokumentasikan bayi dari _38 C dalam departemen darurat pediatrik. Kami dilaporkan sebelumnya utilitas tingkat procalcitonin untuk memprediksi SBI pada pasien yang tidak menerima imunisasi dalam 48 jam sebelumnya. Dalam kohort itu, titik potong dari 0,12 ng / mL memiliki sensitivitas 95% (95% CI: 83% -99%), spesifisitas 26% (95% CI: 20% -32%), NPV dari 96% (95% CI: 85% -99%), dan kemungkinan negatif rasio 0,19 (95% CI: 0,05-0,74), semua kasus bakteremia diidentifikasi secara akurat dengan titik cutnilai. Dalam studi saat ini, kami lebih lanjut subcategorized yang pasien yang dengan SBI, mereka tanpa SBI yang telah baru-baru menerima imunisasi, dan mereka tanpa SBI yang tidak baru saja menerima imunisasi. Median tingkat procalcitonin secara signifikan lebih tinggi dalam kelompok bayi yang telah menerima imunisasi dibandingkan dengan mereka yang tidak, tetapi secara signifikan lebih rendah dibandingkan pada kelompok SBI. Atas dasar ini, tampaknya bahwa imunisasi menyebabkan peningkatan serum procalcitonin nilai-nilai, tetapi masih dapat digunakan untuk mengidentifikasi kelompok berisiko rendah untuk SBI tanpa memandang status imunisasi. Para WBC count juga meningkat pada kelompok RI saat dibandingkan dengan non-SBI pasien tanpa imunisasi terakhir tetapi mirip dengan mereka dengan SBI. Oleh karena itu, WBC count, penanda umum digunakan untuk SBI, kurang berguna untuk pasien yang baru menerima vaksinasi. Bila menggunakan memotong diterbitkan sebelumnya kami titik 0,12 ng / mL, kepekaan procalcitonin untuk SBI dalam seluruh kelompok adalah 96% (95% CI: 83% -99%), spesifisitas adalah 23% (95% CI: 18% -29%), dan NPV adalah 96% (95% CI: 86% -99%). Secara keseluruhan, penambahan divaksinasi bayi ke dalam analisis kohort seluruh menyebabkan serupa sensitivitas dan NPV tetapi menurun kekhususan dari procalcitonin tingkat sebagai penanda SBI. Perubahan ini karena dari sebagian besar pasien diimunisasi memiliki procalcitonin nilai yang lebih besar dari titik potong kami dari 0,12 ng / mL. Namun, tingkat procalcitonin dapat melanjutkan yang akan digunakan untuk mengidentifikasi pasien yang beresiko rendah untuk SBI, dan dengan menggunakan titik potong yang sama, kedua pasien di kami kohort dengan SBI yang baru menerima imunisasi diidentifikasi. Penelitian kami memiliki beberapa keterbatasan. Penelitian dilakukan pada departemen darurat akademis pediatrik

dan, karenanya, tidak dapat mewakili populasi yang lebih besar pasien setelah imunisasi. Selain itu, bahkan di antara orang demam bayi yang baru-baru divaksinasi dan disajikan dengan demam, mungkin ada bias yang telah setiap evaluasi laboratorium. Selain itu, kami tidak mengumpulkan informasi tentang jenis vaksinasi yang diterima dan, dengan demikian, tidak dapat memberikan rincian lebih lanjut tentang spesifik efek dari vaksin individu pada nilai-nilai procalcitonin. SBI RI NRI Studi subkelompok 5 4 3 2 1 0 Procalcitonin, ng / mL GAMBAR 1 Perbandingan dari subkelompok studi. Kotak mewakili batas dari persentil 25 dan 75 dan dibagi dengan garis di median. Kumis mewakili 1,5 kali IQR tersebut. Pediatri Volume 122, Nomor 5, November 2008 e1121 Download dari www.pediatrics.org. Diberikan oleh Indonesia: AAP sponsor pada 12 Desember 2010 Akhirnya, definisi kami SBI yang dimaksudkan untuk menjadi konservatif untuk mencakup semua SBI mungkin, karena kami berharap untuk mengidentifikasi kelompok berisiko rendah untuk SBI. Kami mengakui bahwa beberapa pasien dengan rendah-koloni-hitungan UTI dan pneumonia radiografi mungkin tidak terwakili benar bakteri infeksi. Studi awal kami menyediakan lanjut analisis terhadap SBI yang pasti dan mungkin untuk account ini kesulitan dalam definisi. KESIMPULAN Di antara bayi demam muda dengan imunisasi terakhir, tingkat procalcitonin meningkat dibandingkan dengan pasien dengan demam dan tidak ada infeksi bakteri diidentifikasi. Meskipun peningkatan ini, tingkat procalcitonin masih bisa dipercaya diskriminasi bayi dengan SBI. UCAPAN TERIMA KASIH Kami berterima kasih kepada rekan-rekan dokter di darurat departemen yang memfasilitasi pendaftaran untuk penelitian, dan kami mengucapkan terima kasih atas bantuan dan keahlian Richard Snider, PhD, dan Robyn Neches, BS, untuk bekerja pada tes procalcitonin. Kami berterima kasih atas dukungan keuangan Frederick H. Lovejoy, Jr, MD, Residen Research Fund dan American Academy of Pediatrics Residen Penelitian Grant. Selain itu, kita mengakui dukungan teknis

terkait dengan pemrosesan spesimen oleh Klinis Umum Research Center di Rumah Sakit Anak Boston (Nasional Pusat Penelitian Sumber Daya, Penelitian Klinis Umum Pusat Program, Institut Kesehatan Nasional hibah M01RR02172). Organisasi pendanaan tidak peran dalam desain, analisis data, atau persiapan naskah. Anak-Anak Rumah Sakit Umum Boston Klinis Pusat Penelitian terlibat dalam pengolahan sampel. PROCALCITONIN Procalcitonin (PCT) is a peptide precursor of the hormone calcitonin, the latter being involved with calcium homeostasis. It is composed of 116 amino acids and is produced by parafollicular cells (C cells) of the thyroid and by the neuroendocrine cells of the lung and the intestine. The level of procalcitonin in the blood stream of healthy individuals is below the limit of detection (10 pg/mL) of clinical assays.[1] The level of procalcitonin raises in a response to a proinflammatory stimulus, especially of bacterial origin. In this case, it is produced mainly by the cells of the lung and the intestine. It does not raise significantly with viral or non-infectious inflammations. With the derangements that a severe infection with an associated systemic response brings, the blood levels of procalcitonin may rise to 100 ng/ml. In serum, procalcitonin has a half-life of 25 to 30 hours. Remarkably the high procalcitonin levels produced during infections are not followed by a parallel increase in calcitonin or serum calcium levels.

Contents
[hide]

1 Uses 1.1 Diagnosis and prognosis of sepsis 1.2 Diagnosis of bacteremia 1.3 Prognosis of pneumonia 2 References
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3 External links

[edit] Uses
[edit] Diagnosis and prognosis of sepsis
Measurement of procalcitonin can be used as a marker of severe sepsis and generally grades well with the degree of sepsis,[2] although levels of procalcitonin in the blood are very low. PCT has the greatest sensitivity (85%) and specificity (91%) for differentiating patients with SIRS from those with sepsis, when compared with IL-2, IL-6, IL-8, CRP and TNF-alpha.[3] Evidence is emerging that procalcitonin levels can

reduce unnecessary antibiotic prescribing to people with lower respiratory tract infections.[4] Currently, procalcitonin assays are widely used in the clinical environment.[5]

[edit] Diagnosis of bacteremia

A meta-analysis reported a sensitivity of 76% and specificity of 70%.[6]

[edit] Prognosis of pneumonia

A cluster randomized trial found that the procalcitonin level can help guide antibiotic therapy. In this trial, "on the basis of serum procalcitonin concentrations, use of antibiotics was more or less discouraged (<0.1 mcg/L or <0.25 mcg/L) or encouraged (> or =0.5 mcg/L or > or =0.25 mcg/L), respectively".[7] However, an earlier nonrandomized, observational study reported "limited, prognostic value" of procalcitonin measurement.[8] Procalcitonin levels may be useful to distinguish bacterial infections from nonbacterial infections. Trials from 2008 and 2009 have shown that they may help guide therapy and reduce antibiotic use, which can help save on cost of antibiotic prescriptions and drug resistance.

Procalcitonin May Help Guide Antibiotic Use in Intensive Care Units

January 27, 2010 A procalcitonin-guided strategy to treat suspected bacterial infections in nonsurgical patients in intensive care units (ICUs) may safely reduce antibiotic exposure and selective pressure, according to the results of a multicenter, prospective, parallel-group, open-label trial reported online January 23 in The Lancet. Procalcitonin is a calcitonin precursor hormone thought to be a fairly specific marker for severe bacterial infection in patients with suspected sepsis. Use of blood procalcitonin concentration to guide antibiotic use has been associated with markedly less antibiotic prescriptions in patients seen in the emergency department or hospitalized for lower respiratory tract infections. "Reduced duration of antibiotic treatment might contain the emergence of multidrugresistant bacteria in intensive care units," write Lila Bouadma, MD, from Universit Paris 7Denis-Diderot, Hpital BichatClaude-Bernard, Assistance PubliqueHpitaux de Paris in Paris, France, and colleagues from the PRORATA trial group. "We aimed to establish the effectiveness of an algorithm based on the biomarker procalcitonin to reduce antibiotic exposure in this setting." Inclusion criteria were expected length of ICU stay of more than 3 days, suspected bacterial infection, and age 18 years or older. Patients were randomly assigned in a 1:1 ratio to receive procalcitonin (n = 311) or to a control group (n = 319) with use of

an independent, computer-generated randomization sequence. The investigators were blinded to assignment before randomization but not subsequently. On the basis of predefined cutoff ranges of procalcitonin concentrations, antibiotics were started or stopped for patients in the procalcitonin group. In the control group, antibiotics were prescribed according to current guidelines. The treating physician controlled drug selection and the final decision to start or stop antibiotics. The main study outcomes were mortality at days 28 and 60 (noninferiority analysis) and number of days without antibiotics by day 28 (superiority analysis). Analyses were by intentto-treat, with use of a 10% margin of noninferiority. After exclusion of 9 patients, analyses included 307 patients in the procalcitonin group and 314 in the control group. Compared with the control group, the procalcitonin group had apparently noninferior mortality at day 28 (21.2% [65/307] vs 20.4% [64/314]; absolute difference, 0.8%; 90% confidence interval [CI], 4.6 to 6.2) and day 60 (30.0% [92/307] vs 26.1% [82/314]; absolute difference, 3.8%, 95% CI 2.1 to 9.7). Compared with the control group, the procalcitonin group also had significantly more days without antibiotics (14.3 9.1 days vs 11.6 8.2 days; absolute difference, 2.7 days; 95% CI, 1.4 - 4.1; P < .0001). "A procalcitonin-guided strategy to treat suspected bacterial infections in non-surgical patients in intensive care units could reduce antibiotic exposure and selective pressure with no apparent adverse outcomes," the study authors write. "The diverse clinical characteristics and reasons for admissions to the intensive care unit for patients enrolled in this study suggest that our conclusions could be applicable to most nonsurgical patients in the intensive care unit, including those who are immunocompromised." Limitations of this study include open design, inability to extrapolate the findings to surgical patients, lack of algorithm-guided treatment in more than half of patients randomly assigned to the procalcitonin group, and definitions of relapse and superinfection based on microbiological criteria. "We stress that infection is the tip of the iceberg compared with digestive colonisation," the study authors conclude. "Rectal, nasal, and axillary swab screening was not routinely done and might more accurately show antibiotic selective pressure. Moreover, a 3-day reduction of antibiotic use for only a small subset of admitted patients might not be sufficient to record a decreased resistance-emergence rate, especially for some intensive care units with high cross-transmission rates." In an accompanying comment, Marin H. Kollef, MD, FACP, from Washington University School of Medicine in St. Louis, Missouri, discusses treatment bias and other potential limitations of this study. "Experience so far suggests that unnecessary antibiotic use can be curtailed in the hospital setting, particularly within intensive care units," Dr. Kollef writes. "Whether the ideal strategy involves the use of a serum marker such as procalcitonin or a locally applied practice protocol remains to be established."

Assistance Publique-Hpitaux de Paris, France, and Brahms, Germany supported this study. Some of the study authors have disclosed various financial relationships with Brahms, Merck Sharp & Dohme-Chibret, AstraZeneca, Lilly, Pfizer, Wyeth, Johnson & Johnson, Nektar-Bayer, Arpida, Janssen-Cilag, Gilead, and/or AstraZeneca. Dr. Kollef has disclosed no relevant financial relationships. Lancet. Published online January 23, 2010. http://www.medscape.com/viewarticle/716014

Sepsis is systemic inflammation due to infection. It is the most common cause of death in intensive care units (1), with a mortality rate up to 50% depending on severity. Sepsis can be considered in individuals with systemic inflammatory response syndrome (SIRS) manifested by alterations in at least two of temperature, heart rate, respiratory rate, and/or white blood cell count. These SIRS criteria are non-specific for sepsis and may be present in alternative pathophysiologic states, both medical and surgical (1). The earlier sepsis is identified and treated the better the prognosis (1). Currently diagnosis involves documentation of infection (by culture) in patients with SIRS. Cultures take at least 24 hours and > 50% may be false negative and 30% false positive. A biomarker that could identify sepsis early in a population of patients with overlapping clinical symptoms, i.e. patients with non-infectious SIRS would improve patient care. Many suggest that Procalcitonin (PCT) is an ideal sepsis biomarker. PCT is the pro-hormone form of calcitonin and is produced by extra-thyroidal immune cells within 2-4 hours of a bacterial insult and/or inflammatory response. Elevated PCT is seen in septic patients and concentrations correlate with severity of disease. Increasing PCT over time is associated with poor prognosis, while decreasing concentrations correlate to good prognosis and/or response to antibiotic therapy. Thus, proponents suggest that the clinical utilities of PCT are: to differentiate patients with sepsis from those with non-infectious SIRS; to guide antibiotic therapy; and to predict prognosis of critically ill patients (2). Procalcitonin: an early predictor of sepsis? Thousands of studies have investigated the clinical utility of almost 200 biomarkers of sepsis (3). Among these, PCT and CRP are most often referenced. In comprehensive reviews comparing their diagnostic accuracies, PCT consistently performs better, but sensitivity and specificities to predict sepsis are <90% for both markers. Two meta-analyses recommend routine use of PCT for diagnosis of sepsis while two others discourage its use (3-6). Why the discrepancy? Lack of a gold standard for sepsis diagnosis. Diverse patient populations--PCT is elevated postsurgery, trauma, or in other instances of systemic inflammation limiting its diagnostic accuracy. Different PCT cut-offs are used. Sepsis is diagnosed retrospectively with knowledge of bacterial cultures and a full clinical picture in most studies. To date, few studies have addressed the utility of PCT to predict sepsis in real time. Until, large real time studies with well defined patient populations are completed, the utility of PCT to predict sepsis will remain controversial. Does PCT have a role in tailoring antibiotic therapy? Overuse of antibiotics in ICU settings has contributed to the increase in antibiotic resistant bacteria. Most randomized control trials demonstrate that using serial PCT based algorithms to guide continuation/cessation of antibiotic therapy reduces the number of days patients are on antibiotics without adverse effects. None has demonstrated a reduction in multidrug

resistant (MDR) bacterial infections (7). In practice, there is limited utility for PCT to guide initiation of antimicrobial therapy because most ICU patients are taking antibiotics at admission. Further, these algorithms are not effective in patients with recent trauma, surgery or other global inflammation. Thus, PCT based algorithms for guiding antibiotic therapy are limited to guiding secession/continuation of therapy in non-surgical/trauma ICU patients. And even in these populations, serial PCT measurements may be cost prohibitive if no reduction in MDR infections is observed. Can procalcitonin be used to predict prognosis? Increasing PCT concentrations correlate with increasing severity of sepsis and poor outcome, while decreasing or low PCT predicts a good prognosis for ICU patients. Most studies exclude patients with a recent trauma, surgery or other inflammatory event (6). Given the complicated pathobiology of sepsis and significant overlap in clinical symptoms with SIRS patients, it may be that no one biomarker works for sepsis. Studies looking at multibiomarker panels have shown promise in the prediction and monitoring of sepsis in ICU and ED patients (3).

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