Journal of Critical Care (2011) 26, 331.e1–331.e7

Early changes of procalcitonin may advise about prognosisand appropriateness of antimicrobial therapy in sepsis☆

Antonia-Panagiota Georgopoulou MDa, Athina Savva MDb,Evangelos J. Giamarellos-Bourboulis MD, PhDb,⁎, Marianna Georgitsi b,Maria Raftogiannis MD, PhDb, Nicolaos Antonakos MDb, Efterpi Apostolidou MDc,Dionyssia-Pinelopi Carrer MDb, George Dimopoulos MD, PhDd,Aggelos Economou MDb, George Efthymiou MDe, Nearchos Galanakis MD, PhD f,Labrini Galani MDb, Panagiotis Gargalianos MD, PhDg, Ilias Karaiskos MDb,Chrisostomos Katsenos MDh, Dimitra Kavatha MD, PhDb, Evangelos Koratzanis MDb,Panagiotis Labropoulos MDe, Malvina Lada MDa, George Nakos MD, PhD i,Evgenia Paggalou MD j, George Panoutsopoulos MD, PhDk, Michael Paraschos MDh,Ioannis Pavleas MD, PhD j, Konstantinos Pontikis MDd, Garyfallia Poulakou MD, PhDb,Athanassios Prekates MD, PhD l, Styliani Sybardi MDd, Maria Theodorakopoulou MDd,Christina Trakatelli MD, PhDm, Panagiotis Tsiaoussis MDn,Charalambos Gogos MD, PhDo, Helen Giamarellou MD, PhDb,Apostolos Armaganidis MD, PhDd, Michael Meisner MD, PhDp

on behalf of the Hellenic Sepsis Study Groupa2nd Department of Internal Medicine, “Sismanogleion” Athens Hospital, Athens 15126, Greeceb4th Department of Internal Medicine, University of Athens, Medical School, Athens 12462, GreececIntensive Care Unit, Protemaida Hospital, Ptolemaida, Greeced2nd Department of Critical Care, University of Athens, Medical School, Athens 12462, GreeceeDepartment of Surgery, Nafplion General Hospital, Naflpion 21100, Greecef1st Department of Internal Medicine, Nikaia General Hospital, Nikaia, Greeceg1st Department of Internal Medicine, “G. Gennimatas” Athens Hospital, Athens 11527, GreecehIntensive Care Unit, “Korgialeneion-Benakeion” Hospital of Athens, Athens 11526, GreeceiDepartment of Critical Care, University of Ioannina, Medical School, Ioannina, GreecejIntensive Care Unit, “Laikon” Athens General Hospital, Athens 11527, Greecek1st Department of Internal Medicine, “Thriassio” Elefsina General Hospital, Magoula 19600, GreecelIntensive Care Unit, “Tzaneion” Hospital of Piraeus, Piraeus, Greecem3rd Department of Medicine, University of Thessaloniki, Medical School, Thessaloniki, Greece

☆ This study was supported by an unrestricted educational grant by BRAHMS GmbH, Germany. The sponsor had no involvement in study design, analysis,and interpretation of data and writing the manuscript.

⁎ Corresponding author. 4th Department of Internal Medicine, Attikon University General Hospital, 124 62 Athens, Greece. Tel.: +30 210 58 31 994;fax: +30 210 53 26 446.

E-mail address: giamarel@ath.forthnet.gr (E.J. Giamarellos-Bourboulis).

0883-9441/$ – see front matter © 2011 Elsevier Inc. All rights reserved.doi:10.1016/j.jcrc.2010.07.012

331.e2 A.-P. Georgopoulou et al.

n2nd Department of Surgery, University of Thessaloniki, Medical School, Thessaloniki 54635, Greeceo1st Department of Internal Medicine, University of Patras, Medical School, Rio 26504, GreecepDepartment of Anaesthesiology and Intensive Care Medicine, Hospital Dresden Neustadt, Dresden D-1129, Germany

Keywords:Procalcitonin;Sepsis;Prognosis;Guidance ofantimicrobials

AbstractPurpose: The objective of this study is to define if early changes of procalcitonin (PCT) may informabout prognosis and appropriateness of administered therapy in sepsis.Methods: A prospective multicenter observational study was conducted in 289 patients. Blood sampleswere drawn on day 1, that is, within less than 24 hours from advent of signs of sepsis, and on days 3, 7,and 10. Procalcitonin was estimated in serum by the ultrasensitive Kryptor assay (BRAHMS GmbH,Hennigsdorf, Germany). Patients were divided into the following 2 groups according to the type ofchange of PCT: group 1, where PCT on day 3 was decreased by more than 30% or was below 0.25 ng/mL, and group 2, where PCT on day 3 was either increased above 0.25 ng/mL or decreased less than30%.Results: Death occurred in 12.3% of patients of group 1 and in 29.9% of those of group 2 (P b .0001).Odds ratio for death of patients of group 1 was 0.328. Odds ratio for the administration of inappropriateantimicrobials of patients of group 2 was 2.519 (P = .003).Conclusions: Changes of serum PCT within the first 48 hours reflect the benefit or not of theadministered antimicrobial therapy. Serial PCT measurements should be used in clinical practice toguide administration of appropriate antimicrobials.© 2011 Elsevier Inc. All rights reserved.

1. Introduction

The incidence of septic syndrome has been dramaticallyincreased over the last decade. Many factors may explain thatdramatic increase. The increased incidence of type 2 diabetesmellitus, prolonged stay of mechanically ventilated patientsin intensive care units (ICUs), increased incidence of solidmalignancies and of hematologic malignancies leading toimmunosuppression, and worldwide increase of resistance toantimicrobials are the most important [1].

Proper management of the septic patient mandates theearly empirical administration of antimicrobials. Choice ofthe correct antimicrobial is often difficult. Many factorssuch as recent exposure to other antimicrobials, multidrugresistance of pathogens, and underlying diseases imposeconsiderably on physicians' decision. Inappropriateness ofthe administered therapy may have a significant impact onfinal outcome [2]. As a consequence, it is helpful to use asurrogate marker that can advise for the early need tochange administered antimicrobials particularly whenculture of biologic specimens are sterile or there isconsiderable time delay until the antibiogram of theimplicated pathogen is available.

The importance of procalcitonin (PCT) to guide antimicro-bial therapy has been recently recognized. A series ofprospective randomized trials has proven that PCT maysuggest the need to start empirical antimicrobial therapy inpatients with lower respiratory tract infections [3-6]. Moreprecisely, empirical antibiotic coverage is encouraged onlywhen PCT in serum is greater than 0.25 ng/mL. In the same

context, 2 randomized trials of patients with ventilator-associated pneumonia (VAP) and community-acquired pneu-monia (CAP) were performed. A decrease of PCT below 0.25ng/mL or more than 90% from the baseline may suggestwhether to stop antimicrobial treatment [7,8]. However, dataabout how PCT can help define an early need to changeempirically administered antimicrobials are lacking.

In an attempt to study the multidimensional problem ofsepsis in Greece, the Hellenic Sepsis Study Group has beenorganized since May 2006 (www.sepsis.gr) with theparticipation of various ICU facilities, departments ofinternal medicine, and departments of surgery across thecountry. Fifteen of these departments have participated in thepresent study. The aim of the study was to define what typesof change of PCT early after patient's admission may belinked to the final outcome and how these changes may pointto empirical antibiotic treatment.

2. Patients and methods

2.1. Study design

This prospective multicenter study was conducted in 15departments across Greece during the period January 2007 toSeptember 2008. Participating departments were 6 mixed-type ICUs, 7 departments of internal medicine, and 2departments of surgery. Written informed consent wasprovided by the patients or their first-degree relatives forpatients unable to consent. The study protocol was approved

331.e3Procalcitonin in sepsis

by the ethics committees of the hospitals of participatingcenters. Each patient was enrolled once in the study. Patientsadmitted to the emergencies, hospitalized in the general wardor inside the ICU, were eligible.

Inclusion criteria were (a) age above 18 years, (b) septicsyndrome due to VAP or CAP or acute pyelonephritis orintra-abdominal infection or primary bacteremia, and (c)survival for at least 72 hours.

Exclusion criteria were (a) human immunodeficiencyvirus infection and (b) neutropenia defined as an absoluteneutrophil count lower than 1000 neutrophils/μL.

Patients with septic syndrome were classified as havinguncomplicated sepsis, severe sepsis, and septic shock.Uncomplicated sepsis was defined as the presence of amicrobiologically documented or clinically diagnosed infec-tion with at least 2 of the following [9]: (a) core temperaturehigher than 38°C or lower than 36°C, (b) heart rate greaterthan 90 beats per minute, (c) respiratory rate greater than 20breaths per minute or PCO2 less than 32 mm Hg, and (d) whiteblood cell (WBC) count greater than 12 000/μL or lower than4000/μL or greater than 10% bands in peripheral blood.

Severe sepsis was defined as sepsis aggravated by the acutedysfunction of at least 1 organ because of tissue hypoperfusion[9]. Organ dysfunction was defined as follows:

• acute respiratory distress syndrome as any PO2/FIO2 lessthan 200 and diffuse bilateral shadows in chest x-ray;

• acute oliguria as any urine output less than 0.5 mL/kgbody weight per hour for at least 2 hours after adequatevolume resuscitation;

• metabolic acidosis as any pH less than 7.30 or any basedeficit greater than 5 mEq/L and a blood lactate levelhigher than 2 times the upper limit of normal; and

• acute coagulopathy as any platelet count lower than100 000/μL and/or any international normalized ratiogreater than 1.5.

Septic shock was defined as severe sepsis aggravated bysystolic arterial pressure lower than 90 mm Hg requiringadministration of vasopressors despite adequate volumeresuscitation [9].

Ventilator-associated pneumonia was diagnosed in everypatient intubated for more than 2 days presenting with all thefollowing [10,11]: (a) core temperature higher than 38°C orlower than 36°C, (b) purulent tracheobronchial secretions,(c) new chest x-ray infiltrates, and (d) clinical pulmonaryinfection score more than 6.

Community-acquired pneumonia was diagnosed in everypatient presenting with all the following [4]: (a) coretemperature higher than 38°C or lower than 36°C, (b)WBC count greater than 12.000/μL, (c) signs of an acutelower respiratory tract infection such as purulent sputum ordyspnea, and (d) a new infiltrate in chest x-ray.

Acute pyelonephritis was diagnosed in a patient with allthe following signs [12]: (a) core temperature higher than38°C or lower than 36°C, (b) lumbar tenderness or radiologic

evidence consistent with the diagnosis of acute pyelonephri-tis, and (c) 10 or greater WBC/high-power field of spun urineor 2 or greater in dipstick test for WBCs and nitrates.

Acute intra-abdominal infection was diagnosed in apatient presenting with all the following signs [13]: (a)core temperature higher than 38°C or lower than 36°C, (b)WBC count greater than 12.000/μL, and (c) radiologicevidence from abdominal x-ray in upright position orabdominal ultrasound or abdominal computed tomographyconsistent with the diagnosis of intra-abdominal infection.

Primary bacteremia was diagnosed in every patientpresenting with all the following [13]: (a) peripheral bloodculture positive for gram-positive cocci or gram-negativebacteria and (b) absence of any primary site of infectionconsistent with the pathogen cultured in blood.

Patients were followed up for 28 days. For everypatient, a complete diagnostic workout was performedcomprising history, thorough physical examination, WBCcount, blood biochemistry, arterial blood gas, bloodcultures from peripheral veins and central lines, urinecultures, cultures of sputum, chest x-ray, and chest andabdominal computed tomography if considered necessary.If necessary, quantitative cultures of tracheobronchialsecretions or of bronchoalveolar lavage were performedand evaluated as already defined [11]. All clinical anddemographic data comprising the type of administeredantimicrobials, underlying pathogens, and antibiogramswere recorded in a case report form. All case report formswere monitored by an independent monitor blind to thestudy design.

2.2. Blood sampling and laboratory procedure

Three milliliters of blood were sampled, as stated earlier,from every patient on day 1, that is, within less than 24 hoursof presentation of signs of sepsis by venipuncture of 1forearm vein under sterile conditions. Blood sampling wasrepeated on days 3, 7, and 10. The selection of days 3, 7, and10 for repeated blood sampling was based on a former studywith limited number of patients showing the importance ofchanges of PCT over these days [14].

Blood was collected into sterile and pyrogen-free andanticoagulant-free tubes (Vacutainer; Becton Dickinson,Cockeysville, Md). Tubes were transported within 1 dayby a courier service to the Laboratory of Immunology ofInfectious Diseases of the 4th Department of InternalMedicine at Attikon University Hospital of Athens. Tubeswere centrifuged and serum was kept refrigerated at −70°Cuntil assayed. Procalcitonin was estimated in serum induplicate by an immuno–time-resolved amplified cryptatetechnology assay (Kryptor PCT; BRAHMS GmbH,Hennigsdorf, Germany) with a functional assay sensitivityof 0.06 ng/mL. All estimations were performed andreported by 2 technicians who were blind to the studyprotocol. Procalcitonin values were transferred next to the

331.e4 A.-P. Georgopoulou et al.

clinical data sheet by a second monitor who wascompletely blind to the study protocol.

Susceptibility reporting of the isolated pathogens toantimicrobials was performed in the microbiology laborato-ries of each one of the participating hospitals using either E-testing or disk diffusion assays and interpretation accordingto the Clinical and Laboratory Standards Institute criteria.Empirically administered antimicrobial treatment within thefirst 48 hours after admission, that is, from days 1 to 3, wasconsidered appropriate if the isolated pathogen was found tobe susceptible to at least one of the administered anti-microbials; it was considered inappropriate if the isolatedpathogen was found to be resistant to all administeredantimicrobials [15].

2.3. Statistical analysis

Concentrations of PCT over consecutive time points wereexpressed by their medians and 95% confidence intervals(CIs). Comparison over follow-up was done by theWilcoxonsigned rank test.

Analysis focused on the changes of PCT between days1 and 3 because only for these days PCT was available forall enrolled patients according to the inclusion criteria.Procalcitonin concentrations of day 3 were distracted fromPCT concentrations of day 1. Three types of changes couldbe defined as follows: (a) PCT on both days was below0.25 ng/mL, (b) PCT was decreased from days 1 to 3, or(c) PCT was increased from days 1 to 3. For patientswhere PCT was decreased, the percentage of decrease fromdays 1 to 3 was calculated. Receiver operator curveanalysis was done to link final outcome with percentage ofchange. A 30% decrease could predict death with morethan 80% sensitivity.

Then, all enrolled patients were divided into the following2 subgroups describing the type of change of PCT:

• group 1, where PCT on day 3 was decreased by morethan 30% or was below 0.25 ng/mL, and

• group 2, where PCT on day 3 was either increasedabove 0.25 ng/mL or decreased by less than 30%.

Survival curves for both groups were designed by Kaplan-Meier statistics. Comparisons were done by the log-rank test.The odds ratios (ORs) for death and 95% CIs weredetermined by Mantel-Haenszel statistics.

Comparisons between the appropriateness of antimicro-bials for the above groups were done by χ2 test.

To define if changes of PCT are determinants ofoutcome or simple biomarkers of outcome, logisticregression analysis was performed with outcome as adependent variable and Acute Physiology and ChronicHealth Evaluation (APACHE) II score, disease severity,and group of change of PCT as independent variables. Tofurther verify the results, we performed a Cox propor-

tional hazards regression analysis with the same indepen-dent variables. Hazard ratios (HRs) and 95% CI weredetermined.

Any value of P below .05 was considered significant.

3. Results

A total of 330 patients were eligible for the study; 289patients were finally enrolled (Ptolemaida ICU, n = 10; 2ndICU University of Athens, n = 35; ICU Korgialeneion-Benakeion, n = 9; ICU Ioannina, n = 7; ICULaikon, n = 6; ICUTzaneion, n = 5; 2nd Internal Sismanogleion, n = 83; 4thInternalUniversity ofAthens, n = 86; 1st InternalNikaia, n = 6;1st Internal G Gennimatas, n = 4; 1st Internal Thriassio, n = 7;3rd Internal University of Thessaloniki, n = 5; 1st InternalUniversity of Patras, n = 5; Surgery Nafplion, n = 6; and 2ndSurgery University of Thessaloniki, n = 15). Reasons for notenrolling were death before day 3 (37 patients) and denial toconsent (4 patients). Regarding ICU patients, enrolled patientswere 72 of 1170 total admissions.

Demographic and clinical characteristics of patientsenrolled in the study are shown in Table 1. The mostcommon underlying infections were acute pyelonephritis,acute intra-abdominal infections, primary bacteremia, andVAP. The most common causative pathogens were gram-negative bacteria. Two hundred forty patients survived and49 died. Concentrations of PCT over follow-up in relation tofinal outcome are given in Table 2.

Survival curves of groups 1 and 2 for all enrolled patients areshown in Fig. 1. It is evident that survival of group 1 wasprolonged compared with that of group 2 whether analysisinvolved the total of enrolled patients (P b .0001) or onlypatients with sepsis (P = .021) or patients with severe sepsis/shock (P = .037). From the 289 enrolled patients, 212 were ofgroup 1; 26 (12.3%) of them died. Another 77 patients were ofgroup 2; 23 (29.9%) of them died (P = .001). Odds ratio fordeath for patients of group 1 was 0.328 (95% CI, 0.173-0.621;P = .001).

Mean ± SD APACHE II score of group 1 was 12.68 ±7.38; for those of group 2, mean ± SD APACHE II score was15.51 ± 8.11 (P = .007).

Microbiological documentation of the implicated patho-gen was achieved in 118 patients; 97 were initiallyempirically prescribed appropriate antimicrobials and 21,inappropriate antimicrobials. Seventy-five (77.3%) and 9(42.9%) of them, respectively, belonged to group 1 (P =.003). Odds ratio for the administration of inappropriateantimicrobials among patients of group 2 was 2.519 (95%CI, 1.495-4.245; P = .003).

The implicated pathogen was isolated from 61 patientswith sepsis; 50 were initially empirically prescribed appro-priate antimicrobials and 11, inappropriate antimicrobials.Forty-three (86.0%) and 6 (54.5%) of them, respectively,belonged to group 1 (P = .031).

Table 1 Demographic and clinical characteristics of the 289septic patients enrolled in the study

Male/female 143/146

Age, mean ± SD (y) 65.5 ± 19.3Stage of sepsis, n (%)Uncomplicated sepsis 159 (55.0)Severe sepsis 70 (24.2)Septic shock 59 (21.8)Underlying infection, n (%)Acute pyelonephritis 107 (37.0)CAP 18 (6.2)VAP 36 (12.4)Intra-abdominal infections 82 (28.4)Primary bacteremia 46 (15.9)Blood culture isolates, n (%)Escherichia coli 27 (9.3)Pseudomonas aeruginosa 16 (5.5)Klebsiella pneumoniae 16 (5.5)Acinetobacter baumannii 20 (6.9)Other gram negatives 14 (4.8)Staphylococcus aureus 5 (1.7)Enterococcus faecalis 2 (0.7)Quantitative urines culture isolates, a n (%)E coli 38 (13.1)P aeruginosa 11 (3.8)K pneumoniae 9 (3.1)Other gram negatives 6 (1.8)E faecalis 4 (1.4)Quantitative TBS or BAL cultures, b n (%)A baumannii 18 (6.2)P aeruginosa 10 (3.5)Comorbidities, n (%)Diabetes mellitus type 2 69 (23.9)Heart failure 48 (16.6)Chronic obstructive pulmonary disease 21 (7.2)Chronic renal failure 27 (9.3)Solid tumor malignancy 36 (12.4)Non–Hodgkin-type lymphoma 4 (1.4)

For quantitative cultures of BAL, a positive finding was considered asany bacterial growth greater than 104 "CFU/mL. BAL indicatesbronchoalveolar lavage; TBS, tracheobronchial secretions.

a For quantitative cultures of urine, a positive finding was consideredas any bacterial growth greater than 105 CFU/mL.

b For quantitative cultures of TBS, a positive finding was consideredas any bacterial growth greater than 105 CFU/mL.

Table 2 Serum concentrations of PCT over follow-up of 289patients enrolled in the study

Survivors(n = 240)

Nonsurvivors(n = 49)

P

Day 1 (baseline) 0.76 (4.45) 1.42 (4.33) .054Day 3 0.51 (2.82) ⁎ 1.40 (5.45) ⁎⁎ .003Day 7 0.49 (0.83) ⁎ 0.89 (1.47) ⁎⁎ .185Day 10 0.13 (0.42) ⁎ 0.46 (0.78) ⁎⁎ .001

Results are given in nanograms per milliliter as medians and interquartileranges (in parenthesis).

⁎ P b .0001 compared with day 1.⁎⁎ P value not significant compared with day 1.

331.e5Procalcitonin in sepsis

The implicated pathogen was isolated from 56 of patientswith severe sepsis and/or shock; 46 were initially empiricallyprescribed appropriate antimicrobials and 10, inappropriateantimicrobials. Thirty-one (67.3%) and 3 (30%) of them,respectively, belonged to group 1 (P = .034).

Logistic regression analysis revealed that a group 1 typeof change of PCT was an independent factor linked withfavorable outcome (OR, 0.408; 95% CI, 0.202-0.822; P =.012) as opposed to APACHE II score and to the presence ofsevere sepsis/shock that were linked with unfavorableoutcome (OR, 1.063; 95% CI, 1.008-1.255; P = .024 forAPACHE II score) (OR, 3.61; 95% CI, 1.499-8.680; P =.004 for the presence of severe sepsis/shock).

This finding was verified by Cox proportional hazardsregression analysis. Group 1 type of PCT changes betweendays 1 and 3 was linked with favorable outcome (HR, 0.466;95% CI, 0.261-0.831; P = .010), and APACHE II score andpresence of severe sepsis/shock were linked with unfavor-able outcome (HR, 1.050; 95% CI, 1.006-1.096; P = .024 forAPACHE II score; HR, 3.152; 95% CI, 1.393-7.133; P =.006 for the presence of severe sepsis/shock).

4. Discussion

Sepsis has become nowadays a major health problem. It isreported that almost 1.5 million people in northern Americaand another 1.5 people in northern Europe present annuallywith severe sepsis and/or septic shock with an estimatedmortality of 35% to 50% [1]. The early and reliablerecognition of sepsis is the cornerstone of early andsuccessful management. In the same context, managementof sepsis relies on the correct application of sepsis bundlesand does not simply depend on the adequate antimicrobialtherapy [16]. This highlights the need for early prediction ofresponse to given therapy.

It may be postulated that biomarkers could help providean answer to this daily question. Procalcitonin is proposed asa biomarker that can help decision making for the septicpatients. The present study is prospective in design.Although PCT was determined after collection of material,measurements were performed in a double-blind fashion.

A major role of early changes of PCT levels for thefinal outcome of the septic patients was defined. Anydecrease of serum PCT within the first 48 hours by 30% orits persistence at levels lower than 0.25 ng/mL was anindicator of favorable outcome. On the contrary, anyincrease of serum PCT or any decrease lower than 30%should alarm about the need for a change of therapeuticstrategy. This finding applied both for patients with sepsisand for patients with severe sepsis/shock. It was a factorrelated with final outcome independently from diseaseseverity. Moreover, statistical analysis rendered evidentthat decrease of serum PCT was linked to the selection of

Fig. 1 Comparative survival of 289 septic patients according to the type of change of serum PCT from baseline. Patients are divided into 2groups: group 1, decrease of PCT on day 3 by more than 30% or PCT on day 3 below 0.25 ng/mL; group 2, increase of PCT or decrease of PCTon day 3 by less than 30%. Survival curves are also shown separately for patients with sepsis and for patients with severe sepsis/shock.

331.e6 A.-P. Georgopoulou et al.

appropriate antimicrobial treatment. On the contrary,increase of PCT or stable PCT values indicated inappro-priateness of the administered antimicrobial treatment.

Several randomized trials have been conducted informingabout the crucial role of PCT as a guide of antimicrobialtherapy both for the start and for the stop of antimicrobials.These trials have been conducted in patients with lowerrespiratory tract infections. Start of antimicrobials isencouraged when serum PCT levels on admission areabove 0.25 ng/mL [3-6]. Stop of antimicrobial therapy isencouraged when PCT levels during follow-up fall below90% of baseline or below 0.1 ng/mL [7,8,17].

However, the present study suggests specific changes ofPCT within the first 48 hours as an indicator for the need tochange antimicrobial therapy. Our findings are consistentwith those of another recently published study similar in

design enrolling 180 patients. Changes of PCT between days2 and 3 were evaluated, and changes above or below 30%may be early indicators of appropriate antimicrobial therapy[18]. In a previous study, Jensen et al [19] showed that PCTof day 1 greater than 1 ng/mL is an alert signal of badoutcome. In patients with PCT of day 1 lower than 1 ng/mL,a trend toward a steady increase over follow-up was linkedwith bad prognosis, and a trend toward a steady increase,with good prognosis.

It should be underscored that most of the isolatedpathogens were gram-negative bacteria. This is a commonfeature regarding the microbiology of sepsis in Greecealready presented elsewhere [20]. Streptococcus pneumoniaewas not isolated from patients with CAP. However, it shouldalways be remembered that S pneumoniae is the commonestcause of CAP although randomly isolated [21]. The few

331.e7Procalcitonin in sepsis

enrolled patients with CAP may explain the lack of isolationof S pneumoniae.

The presented results clearly show that early changes ofPCT serum levels within the first 48 hours reflect the benefitor not of the administered antimicrobial therapy for the septicpatient. The universal application of findings is underscoredby the enrolment of patients with sepsis caused by differentinfectious processes in the present study. In clinical practice,this may signify that when serial PCT measurements withinthe first 48 hours show an increase of PCT or decrease byless than 30%, the empirically prescribed antimicrobialtherapy should be reviewed. However, this may becomeapparent only after a randomized clinical trial.

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