Procalcitonin (PCT) is a precursor of the hormone calcitonin, and its levels have been found to increase

during bacterial infection [9].

. Becker KL, Nylen ES, White JC, Muller B, Snider RH Jr. Procalcitonin and the calcitonin gene family of
peptides in inflammation, infection, and sepsis: a journey from calcitonin back to its precursors. J Clin
Endocrinol Metab. 2004; 89:1512–25 https://doi.org/10.1210/jc.2002-021444 PMID: 15070906

Current status of procalcitonin in the ICU

M. Meisner Clinic of Anaesthesology and Intensive Care Medicine, Staedtisches Krankenhaus Dresden-
Neustadt, Germany

Neth j crit care – volume 17 – no 2 – may 2013

Use of PCT as a sepsis marker on the ICU

PCT has been recognized as a marker of sepsis since 1993.1 Initially, PCT was mainly used for the
diagnosis of (bacterial) sepsis and for the differential diagnosis of a bacterial versus non-bacterial
aetiology of systemic inflammation. In the meantime, indications have been extended to a more
dynamic use, e.g. to follow up and guide sepsis-related therapy, including antibiotic treatment and focus
control – both in outpatients and ICU patients. The uniform induction during sepsis, the correlation of
concentrations with severity of inflammation (high levels in patients with severe sepsis), the relative
specificity for bacteria-induced systemic inflammation and a short half-life of induction and elimination
fitting the needs of daily routine diagnostics support the clinical use of PCT as a biomarker on the ICU.

Biochemistry and induction

PCT is produced by the organism and therefore an indirect or host-response related biomarker of
systemic inflammation, mainly induced by microbial infection (sepsis, severe sepsis, septic shock). The
114-116 amino acid protein and its shorter calcitonin-N-ProCT fragments are measured by the presently
Current status of procalcitonin in the ICU available diagnostic tests. The protein is induced within several
hours (3-6 hrs, peak 12-24 hours) after the respective stimulus (e.g. endotoxinemia, sepsis, systemic
inflammation and various proinflammatory mediators). Peak levels decline with a 50% plasma
disappearance rate of roughly 1,5 days and somewhat more in patients with severe renal dysfunction.
The normal range of PCT in healthy individuals is quite low (< 0.1 ng/ ml), so that as the reference range
for diagnosis of sepsis, concentrations above 0.25 - 0.5 ng/ml are usually used. When deciding on
antibiotic therapy, the lower threshold with higher sensitivity is usually used. The protein has various
biological functions, e.g. chemotactic effects on monocytic cells and modulation of expression of
inducible nitric oxide synthase (iNOS) in vascular smooth muscle cells. These functions are partially time-
dependent and they are different in native and prestimulated cells. PCT neutralisation affects survival
and organ dysfunction in animal septic shock models. PCT can be produced by adherent (not circulating)
activated monocytes and tissue cells, where induction is augmented by a crosstalk of invading
monocytic cells with adipocytes, as demonstrated by ex vivo experiments.2 Also, the liver obviously
plays a major role in PCT induction.3,4 PCT can be induced by a variety of non-septic conditions as well,
e.g., during cardiogenic shock, in patients with severe renal or hepatic dysfunction, after major surgery,
in patients with severe systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction
syndrome (MODS), as well as in severe pancreatitis or during release of proinflammatory cytokines.4
However, as compared to severe sepsis, induction in these cases is often moderate (usually < 2 ng/ml)
and – if related to a specific event – for a short period of time only (1-2 days). However, conditions
inducing PCT without sepsis are more frequent in ICU patients and hence should be considered (table 1).
In addition, in patients with local infection or those with a weak systemic inflammatory response, PCT
levels may remain low. In patients with neutropenia or those under immunosuppression (e.g.
corticosteroids) suppression of PCT is only moderate.

Procalcitonin in bacterial infections – hype, hope, more or less?

Mirjam Christ-Crain, Beat Müller Department of Internal Medicine, University Hospital, Basel,
Switzerland

SWISS MED WKLY 2005;135:451–460 · www.smw.ch

Procalcitonin (ProCT) is a precursor peptide from the hormone calcitonin (CT) [1] (figure 1). After
translation from CT-messenger RNA (mRNA), ProCT is cleaved enzymatically into smaller peptides, finally
to yield the thirty-two amino acid mature CT [2]. Most CT precursor peptides, including ProCT, are found
in the serum of normal persons. Mature calcitonin (CT), named after its mild and transient
hypocalcaemic effect, was originally thought to be a hormone exclusively of thyroidal C-cell origin and to
play an important role in skeletal homeostasis [3, 4]. However, provided that thyroid hormone is
replaced, thyroidectomy in humans has no important pathologic consequences: calcium homeostasis
remains intact and bone density is not decreased [5, 6]. Possibly, different CT peptides (eg, CT, CT gene
related peptide [CGRP]) had once an evolutionary role in becoming vestigial in the context of
establishing, protecting and regulating the skeletal mass [7]. However, the presence of the parathyroid
gland and other evolutionary changes occurring in tetrapods suggest that the function of the mature CT
hormone in humans is no longer essential [8]. Conversely, in microbial infections and in various forms of
inflammation, circulating levels of several calcitonin precursors, including ProCT but not mature CT,
increase up to several thousand-fold. This increase and especially the course correlates with the severity
of the condition and with mortality [9–12]

How to measure ProCT levels

For the diagnosis of infections, the diagnostic accuracy of ProCT and its optimum cut-offs are completely
dependent on the use of a sensitive assay in a predefined clinical setting (figure 3). Ideally, an ultra-
sensitive assay should reliably measure circulating concentrations of ProCT in all healthy individuals.
Such assays are currently available for research purposes (PCT sensitive® and N-ProCTKLB) and should
be made widely available for the clinician in the near future. A rapid assay assures that results can be
timely incorporated into clinical decision making. We recently evaluated a newly developed ProCT assay
for the guidance of antimicrobial therapy in lower respiratory tract infections [17]. This commercially
available assay takes advantage of a time-resolved amplified cryptate emission (TRACE) technology
(Kryptor® PCT, Brahms, Hennigsdorf, Germany). It is based on a sheep polyclonal anti-calcitonin
antibody and a monoclonal anti-katacalcin antibody, which bind to the calcitonin and katacalcin
sequence of calcitonin precursor molecules. The assay has a functional assay sensitivity of 0.06 mg/L, ie
3- to 10-fold above normal mean values [18]. Assay time is 19 minutes and in clinical routine results can
be obtained within one hour using 20 to 50 mL of plasma or serum [19]. Another commercially available
twosite assay (LUMItest® PCT, Brahms), measures both ProCT and the conjoined CT:CCP I by means of a
luminometer. This assay is useful to detect markedly elevated ProCT levels in severe, systemic bacterial
infections, ie in sepsis. However, this manual assay has the disadvantage of a relative insensitivity, with
an accurate detection limit of ~0.3 to 0.5 mg/L [10,18]. Thus; the LUMItest® assay is not sensitive
enough to detect mildly or moderately elevated ProCT levels, which limits the diagnostic use in
conditions other than overt sepsis. A colorimetric, “quick” bedside test (PCT®-Q, BRAHMS, Hennigsdorf,
Germany) has the advantage of rapid determination of circulating CTpr levels in 30 minutes.
Unfortunately, the assay is only semi-quantitative and is not sensitive enough to detect moderately
elevated ProCT levels [20].

ProCT levels in sepsis

Critically ill patients often manifest a systemic inflammatory response syndrome (SIRS). When SIRS is
present and infection is proven or suspected, the term sepsis is used. The traditional clinical signs of
infection and the routine laboratory tests in sepsis (eg C-reactive protein [CRP] or white blood cell
count) lack diagnostic accuracy and are sometimes misleading. In severe infection, most classical pro-
inflammatory cytokines (eg TNF-a, IL-1b‚ or IL-6) are increased only briefly or intermittently, if at all.
Mortality in sepsis remains high, often due to delayed diagnosis and treatment. In view of this diagnostic
and therapeutic dilemma, a more unequivocal test for the differential diagnosis of infection and sepsis is
of paramount importance. Recently, in an attempt to improve current definitions of SIRS and sepsis, it
was suggested to include ProCT as additional diagnostic tool to improve and expedite the difficult
clinical diagnosis [21]. This was based on evidence from the literature that in sepsis, ProCT levels
increase several fold until several thousand-fold and on admission this increase often correlates with the
severity of the condition and with subsequent mortality [11, 12]. A variety of studies and reviews have
shown the superior diagnostic accuracy of ProCT as compared to other parameters for the diagnosis of
sepsis, independent of the origin of infection (References in [12, 22, 23]). Whereas the increase of other
inflammatory markers such as CRP is attenuated by immunosuppressive medication (namely steroids),
the diagnostic accuracy of ProCT remains unaffected [24]. In addition, ProCT seems to have an
advantage over CRP because of its earlier increase upon infection and a better negative predictive value,
as for example shown in children with fever of unknown origin [25]

ProCT – a marker for other infectious diseases?

The diagnosis of bacterial infections of extrapulmonary sites remains a challenge for clinicians. The
general consensus is not to provide antibiotics for every suspected infection because of emerging issues
with bacterial resistance. Therefore, a specific marker for bacterial infection would be helpful. Usual
markers such as fever, leucocytosis with increased rate of polymorphonuclear cells (or leucopenia), and
elevation of CRP, respectively, are sometimes helpful. A positive culture result has a relatively high
specificity, but even this is not a gold standard, because it lacks sensitivity and the results are only
available after 2 to 3 days. Despite this fact, many researchers use the positive blood culture plus clinical
signs of infection as a positive gold standard, and patients without any clinical evidence plus a negative
blood culture as the negative gold standard. This forces all patients to be omitted who cannot be
classified unambiguously from the analysis [77]. Such an analysis probably circumvents the problem of
misclassification bias, at the price of introducing a new bias. The results of a recent meta-analysis
showed that ProCT is a more accurate marker for systemic bacterial infections independent of the
source as compared to CRP levels, both when differentiating bacterial infections from non-infective
causes of inflammation and when differentiating bacterial infections from viral infections [42]. Thereby,
pooled sensitivity for ProCT was 88% (95%CI 80–93%), compared with 75% (95%CI 62–84%) for CRP
levels. Pooled specificity for ProCT was also significantly higher than for CRP (81%, 95%CI 67–90% vs 67%
(95%CI 56–77%). ProCT was also significantly better as compared to CRP in differentiating bacterial
infections versus viral infections. Pooled sensitivity for ProCT was 92% (95%CI 86–95%) and for CRP 86%
(95%CI 65–95%). Pooled specificities were comparable (73%, 95%CI 42–91%) for ProCT and 70%, 95%CI
19–96%, for CRP. This superior diagnostic performance of ProCT has been shown for a variety of
infections [23, 43], eg for meningitis [11, 44], infectious endocarditis [45, 46], pancreatitis [46–49], and
others [36]. Serum ProCT is more accurate than the currently available markers for differentiating
between viral and bacterial meningitis in both children and adults [50, 51]. Conversely, there is a large
overlap of usually determined parameters like glucose, proteins and cells of the cerebrospinal fluid and,
to a lesser extent, CRP concentrations. The variability in the clinical presentation of infectious
endocarditis makes the diagnosis a clinical challenge. The use of current imaging techniques in the
diagnosis of infectious endocarditis is also suboptimal. For example, echocardiography detected
infective endocarditis in only 43 of 500 consecutive patients [52]. A simple blood test to predict the
presence or absence of infectious endocarditis in suspected cases would be highly desirable. In acute
infectious endocarditis, ProCT levels are significantly higher as compared to patients with other final
diagnoses [53]. In a recent study, ProCT was the only significant independent predictor of acute
infectious endocarditis on admission in a multivariate analysis, in contrast to other parameters like CRP.
The diagnostic accuracy was comparable to that of B-type natriuretic peptide for the emergency
diagnosis of heart failure [45, 54]. Using a cut-off of 2.3 mg/L, ProCT for the diagnosis of acute infectious
endocrditis had a sensitivity of 81%, a specificity of 85%, a positive predictive value of 72% and a
negative predictive value of 92%. A word of caution must be added. In some patients, especially with
sub-acute endocarditis, ProCT levels may remain very low [55, 56]. Thus, beyond doubt, the diagnosis of
infectious endocarditis, as all other infectious diagnoses, will continue to require a critical clinical
awareness, careful patient history, dedicated physical examination and blood cultures in all patients.
The use of ProCT, albeit not being a perfect marker, might still help to significantly improve the resource
utilisation of diagnostic imaging. Patients with oedematous or toxic pancreatitis have low concentrations
of ProCT whereas patients with infectious pancreatitis have very high ProCT concentrations [46]. This is
especially useful for the monitoring of these patients in whom secondary infection of the initial
pancreatic focus might necessitate surgical intervention. ProCT levels in pancreatitis may reflect the
derangement in gut barrier function (rather than the extent of systemic inflammation) and may hence
predict those patients in whom the translocation of bacteria and fungi into dead pancreas with
consecutive infected necrosis is more likely [48, 57]. Data on the clinical use of ProCT in diverticulitis or
other gastro-intestinal infections are lacking. In patients with localised infections, ProCT is usually lower
as compared to patients with generalised infections and positive blood cultures, as expected. In strictly
localised infections there is a pronounced increase in ProCT levels only if the infection involves
surrounding tissues or becomes systemic. In a closed focus, ProCT concentrations are only moderately
high, as in some cases of infectious arthritis in adults [58]. ProCT in urinary tract infections is useful in
the absence of well-identified severity markers [59]. In a paediatric study, ProCT unlike TNF, IL6, IL-8 or
CRP was correlated with the severity of renal scars caused by the infection itself, as assessed by
scintigraphy [60]. Malaria is the main infectious condition, other than bacterial infections, in which
ProCT concentration is high [61]. Even in simple bouts of malaria without neurologic complications, the
levels reached are frequently high. The reason for the increased ProCT levels in malaria patients is
probably the elevated TNFa level [62]. It is known that large quantities of ProCT are produced after
perfusion of TNFa in humans [63].

DIAGNOSIS SEPSIS MENGGUNAKAN PROCALCITONIN (Sepsis Diagnosis by Procalcitonin)

Buchori*, Prihatini

Indonesian Journal of Clinical Pathology and Medical Laboratory, Vol. 12, No. 3, Juli 2006: 131-137

Sejak awal tahun 1990-an procalcitonin (PCT) pertama kali digambarkan sebagai tanda spesifik infeksi
bakteri.2,3 Kepekatan serum procalcitonin meningkat saat inflamasi sistemik, khususnya ketika hal
tersebut disebabkan oleh infeksi bakteri. Procalcitonin ialah prohormon calcitonin, kadarnya meningkat
saat sepsis dan sudah dikenali sebagai petanda penyakit infeksi sebab penyakit berat. Kepekatan PCT
dapat mencapai 1000 ng/ml saat sepsis berat dan syok sepsis. Namun demikian, sumber asal PCT selama
sepsis belum jelas, apakah nilai kadar PCT dapat membedakan antara penyakit infeksi dan non infeksi.3-
7 Pada keadaan fisiologis, kadar procalcitonin rendah bahkan tidak terdapati (dalam ng/ml), tetapi akan
meningkat bila terjadi bakteremia atau fungimia yang timbul sesuai dengan berat infeksi. Tetapi pada
temuan beberapa peneliti peningkatan procalcitonin terdapat juga pada keadaan bukan infeksi, selain
itu juga merupakan pengukuran yang lebih sensitif dibandingkan dengan beberapa uji laboratorik lain.
Misalnya laju endap darah (LED), perhitungan lekosit dan C reactive protein sebagai sarana bantu
diagnosis sepsis bakteri anak-anak.6 Pada telaah pustaka ini akan dibahas manfaat procalcitonin dan
pemeriksaan untuk kepentingan diagnostik penyakit.

Tanggap Inflamasi (inflammatory response)

Bila mikroorganisme masuk ke dalam epidermis atau permukaan epitel mukosa membran, maka akan
dikeluarkan mediator sebagai pertahanan komponen pejamu. Tanda klinik inflamasi (panas, eritema,
nyeri dan pembengkakan) dalam berbagai bentuk luka jaringan disertai produksi sitokin dan protein fase
akut, pengukurannya bisa digunakan untuk menunjukkan adanya inflamasi dan luas keparahannya. Di
beberapa contoh perbedaan tanggap protein fase akut tertentu atau sitokin, dapat memberikan
petunjuk sifat proses inflamasi atau komplikasinya; tetapi pada umumnya penanggapannya sangat
mirip.5,8 Infeksi bakteri lokal dapat menimbulkan sepsis, melalui aliran darah (bakteremia dan kultur
darah positif), di dalam peredaran darah bakteri berkembang biak dan mengeluarkan toksin. Toksin
dikeluarkan dari struktur komponen bakteri (endotoksin antigen teichoic acid, dll.) atau mungkin
eksotoksin. Endotoksin ialah lipopolysaccaride (LPS) yang terdapat di membran luar bakteri negatif
Gram. Komposisi endotoksin terdiri atas rantai polisakarida (rantai O), yang di berbagai spesies
bervariasi dan tidak toksik melapisi luar membran. Pemberian injeksi endotoksin murni atau lipid pada
hewan coba dapat menimbulkan gejala syok sepsis. Beberapa mediator pejamu secara tidak langsung
menyebabkan sepsis, endotoksin bakteri negatif Gram mengikat larutan LPS-binding protein atau
membran luar sel mononuklear, CD14. Pengaruh interaksi antara monosit, makrofag dan netrofil
melepas mediator inflamasi seperti interleukin (IL), interferron (IF), platelet activating factor (PAF) , dan
tumor necrosis factor. 10 Stadia sepsis, Systemic Inflamatory response Syndrome (SIRS) sampai syok
sepsis mewakili stadium tanggap inflamasi terhadap infeksi. SIRS dapat dilihat secara klinis (Tabel 1),
tetapi keparahan dan prognosisnya sulit dinilai.2,10

Sumber Produksi dan Biologi Procalcitonin

Procalcitonin (PCT) pertama kali dikenali dari sel karsinoma medula tiroid. Terdiri atas 116 asam amino
dengan berat molekul 13 kDa protein, yang disandi oleh gen CALC-1 di lengan pendek kromosom 11.
PCT dan dihasilkan dalam sel-sel C kelenjar tiroid sebagai prohormon calcitonin. Secara normal, semua
PCT dipecah di dalam tiroid menjadi calcitonin.1,5,7,9–12 Kepekatan serum PCT sangat rendah pada
orang sehat yaitu < 0,1 ng/mL.1,5 Pelepasan PCT ke dalam sirkulasi dalam kepekatan besar dalam
berbagai keadaan penyakit tidak disertai dengan peningkatan kadar calcitonin secara bermakna. Gen
Calc-1 menghasilkan dua transkrip yang berbeda dengan sambungan pilihan (alternatif) spesifik jaringan
(Gambar 1).5 Pertama, turunan ekson 1 s.d 4 dari keseluruhan 6 ekson, disandi untuk pre PCT,
merupakan 141-asam amino peptida yang mempunyai 25 asam amino hydroprobic signal peptide.3
Pada sel-sel C tiroid ini secara proteolitik diproses guna menghasilkan fragmen N terminal yaitu
aminoprocalcitonin (57 asam amino), calcitonin (32 asam amino) yang terletak di pusat peptida, dan
calcitonin carboxyterminal peptide-1 (CC-1) atau katacalcin (21 asam amino) di ujung terminal karboksil
(Gambar 2). Jalur ini secara kuat aktif dan dihasilkan hanya dalam getah calcitonin. Namun demikian,
munculnya isyarat peptida memungkinkan PCT tersekresi secara utuh, sesudah glikosilasi oleh sel
lainnya. Hal ini meningkatkan bukti bahwa PCT dan calcitonin sangat berbeda fungsi.4,13 Transkrip
kedua adalah yang dihubungkan secara berpilih (alternatif) ke isi ekson 1, 2, 3, 5, 6 dan menyandi gen
calcitonin yang berhubungan dengan peptida, yang secara luas diekspresikan dalam saraf di dalam otak,
pembuluh darah, dan usus. Hal ini bisa berperan dalam imunomodulasi, neurotransmisi dan kendali
vaskularis.3 Waktu paruh PCT adalah 25 sampai 35 jam, secara signifikan tidak berubah pada gagal
ginjal, oleh karena itu kepekatan serum dapat digunakan untuk tujuan diagnostik pada penderita yang
fungsi ginjalnya rusak. Jaringan asal PCT belum jelas, meskipun ada data yang menyatakan bahwa
makrofag aktif dan hepatosit kemungkinan merupakan tempat asalnya.1,4 Peran biologis PCT yang tepat
selama sepsis masih belum jelas. PCT merupakan satuan inflamasi selama sepsis akibat bakteri.14
Menurut 1 mortalitas hamster akibat sepsis peritoneal secara signifikan lebih tinggi dengan pemberian
PCT dan menurun jika pengaruh PCT dinetralkan (imunonetralisasi).1 Studi lebih lanjut oleh Whang et
al10 menunjukkan bahwa PCT mempengaruhi mortalitas ketika dimasukkan ke binatang pada keadaan
sepsis dan tidak berpengaruh di binatang yang sehat, jelasnya bahwa PCT mungkin memainkan peran
mediator sekunder dalam aksi inflamasi.

Induksi Plasma PCT

PCT diimbas (induksi) oleh endotoksin yang dihasilkan bakteri selama infeksi sistemik. Infeksi yang
disebabkan protozoa, infeksi non-bakteri(virus) dan penyakit autoimun tidak menginduksi PCT Kadar
PCT muncul cepat dalam 2 jam setelah rangsangan, puncaknya setelah 12 sampai 48 jam dan secara
perlahan menurun dalam 48 sampai 72 jam, sedangkan CRP tidak terdapat dalam 6 jam (Gambar 4).
Seperti halnya CRP, IL6 juga tidak dapat membedakan secara jelas sumber inflamasi. Pada keadaan
inflamasi akibat bakteri kadar PCT selalu > 2 ng/ml. Pada kasus akibat infeksi virus kadar PCT > 0,05
ng/ml tetapi biasanya < 1 ng/ml. 15 Pada percobaan orang sehat, yang diberi dosis rendah secara
intravenus endotoksin Escherichia coli, setelah 1 jam injeksi ia merasa sakit. Kemudian dalam 1 sampai 2
jam demam dan berkembang menggigil, kaku dan mialgia dalam waktu 1 sampai 3 jam. PCT tidak dapat
ditemukan dalam plasma pada 2 jam pertama, tetapi secara tetap tertemukan setelah 4 jam, meningkat
tajam pada 6 jam dan tetap tinggi selama 8 sampai 24 jam. Kadar plasma TNF-α meningkat secara tajam
setelah 1 jam, puncaknya setelah 2 jam dan menurun ke garis dasar sesudah 6 jam. Kadar plasma IL-6
mencapai puncak pada 3 jam dan kembali ke garis dasar setelah 8 jam. Peningkatan plasma PCT terjadi
secara singkat sesudah kadar sitokin mencapai puncak.15 Penelitian lain pada pemberian rhTNF-α dan
melphalan melalui isolasi perfusi tungkai menunjukkan hasil yang hampir sama, tetapi melphalan
menunjukkan perubahan kecil. Lebih lanjut, kadarIL-6 dan IL-8 meningkat sesudah perfusi rhTNF-α dan
mencapai puncak beberapa jam sesudah PCT. Dapat disimpulkan bahwa peningkatan kadar serum PCT
secara langsung atau tidak langsung dibantu oleh sitokin rhTNF-α dan rhIL-6. C-reactive protein dan
Serum Amiloid A Protein (SAA) tanggap terhadap rangsangan yang sama walaupun lebih lambat.3

Fungsi Imunologi

Pola produksi procalcitonin tampak mirip dengan beberapa komponen tangga sitokin, dan petanda
aktivasi imunitas seluler yang menunjukkan bahwa ini merupakan pereaksi fase akut. Kadar
procalcitonin dalam serum yang ditemukan sangat berhubungan dengan keparahan infeksi bakteri dan
SIRS. Infeksi yang terjadi terbatas di organ tunggal tanpa ada tanggap sistemik reaksi inflamasi, kadar
procalcitonin rendah atau sedang. Tampaknya proses inflammasi selain infeksi mendukung sekresi
procalcitonin, tetapi menempati tangga sitokin yang terjadi pada sepsis dan proses inflamasi lain yang
tidak diketahui.6

Fungsi PCT terhadap Sepsis

PCT menghambat prostaglandin dan sintesis tromboksan pada limfosit in vitro dan mengurangi
hubungan stimulasi LPS terhadap produksi TNF pada kultur whole blood. Menurut Whicher et al
pemberian rekombinan human PCT terhadap sepsis pada tupai menghasilkan peningkatan mortalitas
yang berbanding terbalik dengan pemberian netralisasi antibodi. Kemungkinan PCT peran dalam fisiologi
sepsis yang didukung oleh untaian (sequensing homolog) antara PCT dan sitokin seperti TNF, IL-6 dan
granulocyte colony-stimulating factor.3

PCT sebagai Petanda Infeksi Penyakit Berat

PCT merupakan petanda diagnostik infeksi bakteri populasi anak. Kadar tinggi PCT di anakanak
berinfeksi bakteri berat juga didapat baik pada yang tidak menderita infeksi, infeksi lokal maupun infeksi
virus. Kadar PCT dapat menurun bila ada tanggapan terapi antibiotika. Di neonatus, PCT merupakan
petanda infeksi bakteri yang lebih akurat dibandingkan dengan protein C reaktif (CRP).1,16 Mengikuti
kerja terdahulu kelompok Assicot,3 data lain yang dipublikasikan mendukung catatan bahwa kadar
serum PCT secara dramatis memuncak di penderita yang terinfeksi bakteri dan malaria, sedangkan pada
sepsis akibat jamur hasilnya kurang meyakinkan.3 Namun demikian, ada juga laporan lain yang
menyatakan sedikit atau tidak adanya peningkatan PCT pada penderita dengan penyebaran sepsis
akibat jamur. Berbeda dengan infeksi bakteri dan parasit, peningkatan PCT yang ringan terlihat pada
infeksi virus. Kadar serum PCT dapat dikatakan sebagai suatu tanda untuk membedakan antara sepsis
virus dan sepsis bakteri, khususnya di penderita dengan meningitis.1,17 Didasari data yang telah
dipublikasikan, terbukti bahwa baik infeksi bakteri maupun virus disertai dengan SIRS berkaitan dengan
kadar PCT yang tinggi dibandingkan dengan infeksi virus dan infeksi bakteri yang bersifat lokal. Namun
demikian, penderita yang mengalami infeksi lokal tanpa tanggap sistemik tidak menampakkan kadar
serum PCT yang tinggi. Sebagai pembanding, penderita yang tidak mengalami perkembangan tanda
Systemic Inflammatory Response Syndrome (SIRS) seperti penderita lanjut usia atau penderita malagizi
(malnustrisi) kemungkinan tidak menurunkan tanggap PCT yang bermakna, meskipun hal ini belum diuji.
Ada juga data yang menunjukkan pada pengamatan bahwa puncak PCT lebih tinggi di meningitis bakteri
positif Gram dari pada negatif Gram.10,18 Nilai 5ng/ml di anak-anak, telah dilaporkan untuk mengenali
sepsis bakteri yang bernilai peramalan positif dan negatif adalah 100% dan 82%, dibandingkan dengan
protein C reaktif yang nilainya 90% dan 36%.1

Procalcitonin dibandingkan dengan petanda inflamasi lain

Pada beberapa kajian dinyatakan bahwa PCT lebih sensitif dan spesifik untuk diagnosis infeksi
dibandingkan dengan C reactive protein, IL-6 dan IL-8 pada berbagai situasi klinis.1,2,8,13 O’Connor et
al,1 meneliti penderita dewasa yang dirawat di unit perawatan intensif dengan suatu prediksi lama
perawatan lebih 24 jam dan dibagi menurut diagnosisnya: tanpa infeksi (SIRS dan infeksi), SIRS dan
tanpa infeksi, sepsis, sepsis berat, dan syok sepsis. Pada penghalangan (cut off) 1,0 ng/ml, kadar PCT
secara bermakna meningkat di penderita dengan sepsis, sepsis berat dan syok sepsis dibandingkan
dengan penderita tanpa SIRS atau infeksi. PCT merupakan variabel uji laboratorium yang paling tepat
betul untuk diagnosis infeksi dengan sensitifitas 89%, spesifisitas 94%, nilai peramalan negatif 90% dan
nilai peramalan positif 94%. Penurunan yang lambat atau tidak adanya penurunan kadar PCT selama 48
jam sesudah rawat inap berkaitan dengan hasil pemeriksaan yang buruk. Pada kasus dengan kematian,
kadar serum PCT tidak pernah < 1,1 ng/ml.3,4 Namun demikian, jelas bahwa SIRS oleh sebab apapun,
berhubungan dengan peningkatan kadar PCT yang berkaitan dengan keparahan tanggap sistemik.17

Pemeriksaan serum procalcitonin

PCT diukur pada serum dengan menggunakan pemeriksaan imunoluminometrik. Pemeriksaan

menggunakan dua antibodi monoklonal antigenspesifik, satu diarahkan ke calcitonin (menggunakan
label luminescence) dan lainnya ke katacalcin (Gambar 4). Batas untuk mengetahui pemeriksaan adalah
0,1 ng/ml dan koefisien variasinya 5 sampai 10% dengan rentang 1 sampai 1000 ng/ml. Pemeriksaan
juga tidak dipengaruhi antibiotika, sedatif dan agen vasoaktif yang secara umum digunakan di dalam
unit perawatan intensif.18
PCT sebagai petanda infeksi menampilkan siasat baru dalam mendiagnosis sepsis. PCT secara umum
memberikan sensitivitas dan spesifisitas lebih baik daripada CRP untuk mendiagnosis infeksi dan
merupakan petunjuk prognostik yang lebih baik dibandingkan dengan CRP Setelah rangsangan bakteri,
kadar PCT meningkat lebih cepat dibandingkan dengan CRP. Kegunaan pengukuran serum PCT sebagai
petanda infeksi bisa diringkas sebagai berikut: 1) PCT dapat membedakan antara infeksi dan non infeksi
pada SIRS, 2) PCT dapat membedakan antara sepsis bakteri dan virus, 3) Cut off PCT memberikan
sensitifitas dan spesifisitas optimum untuk mendiagnosis infeksi beragam dengan keadaan yang
berbeda, 4) Pengaruh obat antimikroba,vasoaktif dll. terhadap PCT sangat rendah. Pada infeksi lokal,
tidak ada peningkatan kadar PCT, penurunan yang tajam kadar PCT terhadap terapi antibiotika tidak
secara langsung menyatakan penghilangan infeksi, tetapi semata-mata merupakan tanggap sistemik
yang terkendali. PCT diukur dalam serum menggunakan pemeriksaan imunoluminometrik. Pemeriksaan
menggunakan dua antibodi monoklonal antigenspesifik yang berdaya lacak pemeriksaan 0,1 ng/ml. Pada
orang sehat kadar PCT < 0,1 mg/ ml dan meningkat pada penderita yang terinfeksi bakteri.