Procalcitonin levels Predict Bacteremia in

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DOI 10.1378/chest.09-2920; Prepublished online March 18, 2010;Chest

GroupWerner Zimmerli, Beat Mueller, Philipp Schuetz and for the ProHOSP StudyFabian Mller, Mirjam Christ-Crain, Thomas Bregenzer, Martin Krause,

A prospective cohort trial.Patients with community-acquired Pneumonia:Procalcitonin levels Predict Bacteremia in

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Word count: abstract: 246 Main text: 2860

Procalcitonin levels Predict Bacteremia in Patients with community-acquired

Pneumonia: A prospective cohort trial.

1Fabian Mller, MD, 1Mirjam Christ-Crain, MD, 2Thomas Bregenzer, MD, 3Martin

Krause, MD, 4 Werner Zimmerli, MD, 2*Beat Mueller, MD and 1Philipp Schuetz, MD

for the ProHOSP Study Group *

1Department of Internal Medicine, Division of Endocrinology, Diabetes and Clinical

Nutrition, University Hospital Basel, 2 Department of Internal Medicine, Kantonsspital

Aarau, 3 Department of Internal Medicine, Kantonsspital Mnsterlingen 4 Department

of Internal Medicine, Kantonsspital Liestal, Switzerland

*Corresponding author:Beat Mueller, MDDepartment of Internal Medicine,Kantonsspital, Tellstrasse, CH-5001 Aarau, [email protected] +41 62 838 68 40Fax +41 62 838 69 45

Funding sources:This trial is supported in part by a grant from the Swiss National Science Foundation

(SNF 3200BO-116177/1), contributions from santsuisse and the Gottfried and JuliaBangerter-Rhyner-Foundation, the University Hospital Basel, the Medical UniversityClinic Liestal, the Medical Clinic Buergerspital Solothurn, the Cantonal HospitalsMuensterlingen, Aarau and Lucerne, respectively, the Swiss Society for InternalMedicine (SGIM), and from the Department of Endocrinology, Diabetology andClinical Nutrition, University Hospital Basel. BRAHMS, the manufacturer of the PCTassay, provided all assay related material.

ClinicalTrials.gov identifier NCT00350987

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Competing InterestNo commercial sponsor had any involvement in design and conduct of this study,namely collection, management, analysis, and interpretation of the data; andpreparation, decision to submit, review, or approval of the manuscript.PS, MCC and BM received support from BRAHMS to attend meetings and fulfilled

speaking engagements. BM has served as a consultant and received research

support.

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Background: Guidelines recommend blood culture sampling from hospitalized

patients with suspected community-acquired pneumonia (CAP). However, the yield

of true positive results is low. We investigated the benefit of procalcitonin (PCT) on

admission to predict blood culture positivity in CAP.

Methods: This is a prospective cohort study with a derivation and validation set

including a total of 925 CAP patients with blood culture sampling upon hospital

admission.

Results: A total of 73 patients (7.9%) had true bacteremia (43/463 in the derivation

cohort, 30/462 in the validation cohort). The area under the receiver-operating-

characteristics curve of PCT in the derivation and validation cohort were similar

(0.83 (95%CI 0.78-0.89), 0.79 (95%CI 0.72-0.88). Overall, PCT was a significantly

better predictor for blood culture positivity as compared to white blood cell count, C-

reactive protein and other clinical parameters. In multivariate regression analysis,

only antibiotic pretreatment (adjusted OR 0.25, p


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Introduction

Community-acquired pneumonia (CAP) is a common and potentially life-threatening

disease which puts an enormous strain on health-care resources 1. In the diagnostic

work up of CAP patients, identification of the causative organism to target a more

favourable antibiotic therapy and to study local resistance patterns is of great value

1,2 . Current guidelines recommend drawing two sets of pre-treatment blood cultures

routinely in all hospitalized patients with CAP{Mandell, 2007 #6340} 3. Nevertheless

the benefit and cost-effectiveness of routine drawing of blood cultures is

controversial, mainly because of the low yield of positive blood cultures, which is in

the range of 3-10% in non-selected hospital admitted patients with CAP 4-10 . In order

to limit blood culture sampling to high-risk patients for growth of bacteria, previous

studies have evaluated clinical and laboratory predictors for blood culture positivity

6,11-13 . However, single parameters lack sensitivity and/or specificity which prevents

its use in daily routine 6,11 . Some authors have developed clinical decision rules with

increased prognostic accuracy 6,12,13 . However, complexity of decision rules often

restricts a widespread adoption. Hence, there is an unmet need to identify simple

and accurate predictors for blood culture positivity in patients with CAP.

Procalcitonin (PCT) has emerged as a biomarker for bacterial infections because it

correlates with the extent and severity of microbial invasion in different infections 14-

22 . Previous trials have demonstrated that patients with bacteremic CAP have

markedly increased initial PCT concentrations 9,14,17,22 , which makes PCT a

promising candidate biomarker for prediction of blood culture positivity. Herein, we

evaluated the prognostic accuracy of PCT as compared to other commonly used

clinical and laboratory parameters in a large and well defined derivation and

validation cohort of CAP patients .

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Material and Methods

Setting and population studied

The present study is a predefined sub-study of the previously published ProHOSP

trial and evaluated data from 925 patients confirmed with radiological CAP who were

admitted to the Emergency Department (ED) of the University Hospital Basel,

Switzerland, between 12/06 and 03/08. A detailed description of the ProHOSP study

has been published elsewhere 14,23 . In brief, consecutive patients with lower

respiratory tract infection (LRTI) were included in six secondary and tertiary care

hospitals in northern and central Switzerland. The aim of this randomized non-

inferiority trial was to compare two different treatment strategies using either a PCT

algorithm or an algorithm based on current guidelines for conducting antibiotic

therapy. The primary endpoint was the combined medical failure rate of patients. A

study website provided information on the evidence-based management of all

patients based on the most recent guidelines 24-28 and explicitly specified the need

for X-ray confirmation of CAP and for sampling two sets of pre-treatment blood

cultures. A predefined secondary endpoint of this study was the evaluation of

prognostic parameters for outcomes and blood culture positivity.

Full ethical approval for this trial has been obtained from all local ethical committees

and all patients gave written informed consent.

Participants and Definitions

Inclusion criteria for patients were written informed consent, age 18 years and

admittance from the community or a nursing home with the main diagnosis of LRTI.

Exclusion criteria were the inability to give written informed consent, insufficient

German language skills, active illegal intravenous drug use, previous hospitalisation

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for LRTI within 14 days, severe immunosuppression other than corticosteroids,

accompanying chronic infection or endocarditis and most severe medical co-

morbidity where death was imminent.

LRTI was defined by the presence of at least one respiratory symptom (cough, with

and without sputum production, dyspnea, tachypnea, pleuritic pain) plus one

auscultatory finding or one sign of infection (core body temperature > 38.0C,

shivers, white blood count > 10 G/L or < 4 G/L cells) independent of antibiotic pre-

treatment. Diagnosis of CAP was made if additionally to the LRTI criteria an

underlying infiltrate on chest radiograph was present 24 .

In all patients with a provisional diagnosis of CAP, two pairs of blood cultures for

both aerobic and anaerobic conditions were collected before starting antibiotic

therapy. Blood cultures were processed using an automated colorimetric detection

system (BacT/ALERT, bioMerieux, Durham, NC, USA) in three hospitals and an

equivalent blood culture system (BACTEC Becton-Dickinson, Cockeysville, Md.) in

the other three hospitals 29 . If blood culture bottles indicated bacterial growth,

samples were gram stained and subcultured. The correct identification of the

pathogen was achieved according to routine laboratory procedures.

In accordance with a recently published study 6, a bacteremic episode was defined

as growth of a typical organism for CAP in at least one of four collected blood

cultures within the first 36 hours of presentation to the ED. Episodes with growth of

coagulase-negative staphylococci were assumed to be contaminants. Growth of

Streptococcus spp. other than pneumococci (n=4) and Enterobacteriaeceae (n=3)

including Serratia marcescens in the blood cultures of one patient were included in

this analysis, even though a causal relationship with CAP is not clear.

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Clinical examination and Laboratory data

In all patients on admission, a thorough clinical examination was performed and two

prognostic scores (Pneumonia Severity Index (PSI) and the CURB-65) werecalculated 30,31 . For all patients laboratory results were collected from the routine

blood analysis including markers of infection (PCT, CRP and WBC), plasma sodium

concentration and blood urea nitrogen. CRP concentrations were determined by an

enzyme immunoassay having a detection limit of < 5 mg/dl (EMIT, Merck

Diagnostica, Zurich, Switzerland). PCT was measured using a time-resolved

amplified cryptate emission (TRACE) technology assay (Kryptor PCT, Brahms AG,

Hennigsdorf, Germany) with a functional assay sensitivity of 0.06 g/L.

Derivation and Validation Sets

We used the first 50% of CAP patients (n=463) as the derivation set and the second

50% (n=462) as the validation set based on the timely inclusion of patients. The

validation set was not used until the analysis with the derivation set was complete

and served as an independent test of the derived rule.

Statistical Analysis

This report adheres to the STROBE guidelines for reporting observational studies 32 .

Discrete variables are expressed as counts (percentage) and continuous variables

as medians and interquartile ranges (IQR). Frequency comparison was done by chi-

square test. Two-group comparison Mann-Whitney-U test was used. To assess the

prognostic performance of different parameters to predict blood culture positivity,

univariate and multivariate regression analysis adjusted for all significant parameters

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were used. Thereby, logarithmic transformation was performed to obtain normal

distribution for skewed variables (i.e. PCT concentrations) and outcomes were either

positive blood cultures or negative blood cultures. Receiver-operating-characteristics

(ROC) were calculated using STATA 9.2 (Stata Corp, College Station, Tex). All

testing was two-tailed and P values less than 0.05 were considered to indicate

statistical significance.

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Results

Baseline parameters

The median age of the overall cohort of 925 CAP patients was 73 years (IQR 59-82)

and 59% were males. The median PSI score was 91 (IQR 66-115) and 51% of

patients were in high risk PSI classes IV and V. True positive blood cultures were

detected overall in 73 patients (43/463 in the derivation cohort and 30/462 in the

validation cohort); thus the overall rate of true positive blood cultures was 7.9%

(Figure 1 ). The following pathogens were detected: Streptococcus pneumoniae

n=59, Escherichia coli n=3, Haemophilus influenzae n=2, Enterobacter cloacae n=2,

Enterobacter aerogenes n=1, Streptococcus pyogenes n=1, Streptococcus

acidominimus n=1, Streptococcus mitis n=1, Pseudomonas aeruginosa n=1,

Staphylococcus aureus n=1, Serratia marcescens n=1. Three patients had

contamined blood cultures with coagulase-negative staphylococci in a single blood

culture bottle each. Table 1 shows baseline characteristics on admission of all

patients (left column) and separated according to blood culture results. Patients with

positive blood cultures were less frequently admitted from nursing facilities, had less

frequent antibiotic pretreatment and congestive heart failure, while renal dysfunction

was more frequent. Laboratory analysis showed that CRP, blood urea nitrogen and

WBC were significantly higher in patients with positive blood cultures. In addition,

patients with positive blood cultures had almost 15 fold higher PCT levels compared

to patients with negative cultures (5.8 vs 0.4 g/L). There was no significant

difference in PCT levels in patients with Streptococcus pneumoniae as compared to

patients with other pathogens (median PCT 5.8 g/L (IQR 2.1-21.1) vs 6.3 g/L

(IQR 3.3-11.4), p=0.98). While, the majority of patients with positive blood cultures

had increased PCT levels, one patients with a PCT level < 0.1 g/L, and 2 patients

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with a PCT level < 0.25 g/L had growth of Streptococcus pneumoniae in blood

cultures. These three patients had an increase of PCT levels of higher than 0.25

g/L in the follow up PCT measurement. Patients with positive blood cultures were

more frequently transferred to the ICU, but mortality was similar.

PCT compared to other parameters to predict positive blood cultures

In univariate analysis ( Table 2 ), antibiotic pretreatment, congestive heart failure, and

systolic blood pressure were negative predictive factors for positivity of blood

cultures. In contrast, renal dysfunction, heart rate, body temperature, blood urea

nitrogen, white blood count, CRP serum levels, as well as PCT serum levels were

positive predictors for positive blood cultures. Multivariate logistic regression

analysis using all significant parameters from univariate analysis showed that only

antibiotic pretreatment (adjusted OR 0.25 (95%CI 0.08-0.76), p


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Positive and negative blood cultures within different risk categories

Blood culture positivity within different risk categories of PCT, CRP and the two

clinical risk scores (PSI and CURB-65) was assessed. Figure 3 shows percentage

of patients with positive (dark grey) and negative (light grey) blood cultures within

risk categories. In patients with a PCT value < 0.1 g/L and between 0.1-0.25 g/L,

only 0.9% (1/117) and 0.9% (2/224) of patients had positive blood cultures, while

16.8% (61/364) had positive results with PCT levels > 1.0 g/L. Patients with CRP 0.5 g/L and especially > 1 g/L may help to identify high-

risk patients who benefit from early and aggressive diagnostic work up and antibiotic

therapy.

Routine sampling of blood cultures in CAP patients have been a cornerstone for

epidemiological reasons, for monitoring antibiotic resistance patterns and for a

better streamlining of antibiotic therapy in individual patients 1,24,27 . Nevertheless, the

routine implementation of blood culture sampling in CAP has been questioned,

because of the low yield of true positive results 4-9 . Consensus guidelines

encourages a more rational approach to blood culture collection without, however,

giving specific criteria 24 . Thus, there is an unmet need for accurate predictors of

blood culture positivity that would increase the pre-test probability of patients and

thus the yield of blood cultures in CAP. In this context, enormous attempts have

been undertaken to correlate the levels of different biomarkers and mediators with

the presence of bacteremia 19,33 . Herein, PCT is a promising biomarker, because it

correlates with the extent and severity of microbial infection, because of high

specificity for bacterial etiology of LRTI and the superior clinical usefulness as

compared to other commonly used laboratory tests, namely CRP and WBC 15-22,33 .

This study validates a series of previous findings. In accordance with previous

studies we found that antibiotic pre-treatment is an important factor to decrease the

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likelihood of positive blood culture findings 6,34 . In a large retrospective cohort study 6

different predictors for bacteremia in hospitalized CAP patients have been identified.

Antibiotic pre-treatment and 40C < body temperature < 35C were negative

predictors, while liver disease, systolic blood pressure < 90 mm Hg, heart rate

125/min., blood urea nitrogen 11 mmol/L, sodium < 130 mmol/L, WBC 20,000/mm 3 were positive predictors. Using this decision support

tool in their data would result in 38% fewer blood cultures when compared with the

standard practice and still allow identification of 88% to 89% of patients with

bacteremia 6. In our study, we validate these predictors. However, after including

PCT in multivariate analysis, only antibiotic pre-treatment and PCT remained

independent predictors. Using a PCT cut off of 0.25 g/L in our study would allow

reducing the amount of blood culture collection by a similar amount (37%), but still

result in a higher sensitivity of 96%.

Waterer and colleagues 7 reported that the yield of positive blood cultures in CAP

patients increases with increasing PSI. Thus, they concluded that blood cultures

should be limited to high risk patients in the PSI classes IV and V 7. In the present

study we found no significant correlation between PSI classes and the yield of

positive blood cultures, and only a weak association between the CURB-65 score

and likelihood of positive blood cultures. The PSI is a mortality prediction tool and is

mainly influenced by the age of patients 30 . Thus, young patients with bacteremic

CAP usually have a lower PSI but still a high risk of blood culture positivity.

Based on the results of two 2 retrospective studies reporting a reduced mortality in

CAP patients who received antibiotic treatment within 4-8 hours, the time to first

antibiotic dose has recently received significant attention from a quality-of-care

perspective24

. Within the ProHOSP trial, PCT was measured using a rapid sensitive

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assay and an assay time of around 20 minutes 14 . The test was performed on-site at

the central lab of each participating hospital and results were routinely available

around the clock within 1 hour and by the time results from routine chemistry were

available. Thus, if PCT is measured on admission in patients with suspicion of CAP,

PCT can be used for the evaluation of the patients without putting him at risk

because of time delays.

Some limitations merit consideration. First, patients with severe immunosuppression

were excluded limiting generalization. In blood cultures of seven patients we found

some pathogens that are not typically found in CAP, and might thus not be the true

cause for the diagnosed CAP. Although we excluded patients with other sites of

infection than the respiratory tract it is not entirely possible to rule out the influence

of concomitant infections. Exclusion of these patients, however, would not have

altered our results (data not shown).

In conclusion, this study suggests PCT to be an accurate parameter for predicting

bacteremia in patients with CAP. Based on the results of this study, we recommend

to draw blood cultures in CAP patients only when PCT levels are 0.25 g/L or higher

because the likelihood for bacteremic CAP in patients with lower PCT levels is very

low. In addition, blood cultures should be considered at lower PCT level, if

antibiotics are prescribed based on validated overruling criteria especially in areas

with increased prevalence of resistant organisms. Obviously, the clinical picture of

bacteraemic infection is far too heterogeneous and complex to be reduced to a

single cut-off of any surrogate marker. Different microbes might induce distinct

responses resulting in a variable upregulation of circulating PCT levels. Still, as

demonstrated in this and other studies, the likelihood for bacterial CAP increases

gradually with increasing serum levels of PCT, making PCT a putative indicator for

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blood culture positivity. Thus, used in the proper context of CAP it may result in a

substantial reduction in the numbers of cultures obtained and to an optimized

allocation of our limited health care resources and in patient costs.

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Competing Interest

No commercial sponsor had any involvement in design and conduct of this study,

namely collection, management, analysis, and interpretation of the data; and

preparation, decision to submit, review, or approval of the manuscript.

PS, MCC and BM received support from BRAHMS to attend meetings and fulfilled

speaking engagements. BM has served as a consultant and received research

support. All other authors declare that the answer to the questions on the competing

interest form are all No and therefore have nothing to declare.

Contributors

MCC, BM, WZ and PS had the idea and initiated the study, FM, BM and PS

performed the analyses and drafted the manuscript. All authors amended and

commented on the manuscript and approved the final version.

Acknowledgement

We are grateful to all local physicians, the nursing staff and patients who

participated in this study. Especially, we thank the staff of the emergency room,

medical clinics and central laboratories of the University Hospital Basel, the

Kantonsspitaeler Liestal, Aarau, Luzern and Muensterlingen and the

Buergerspital Solothurn for their very helpful assistance, patience and technical

support. We thank other members of the Data Safety and Monitoring Board, namely

A.P.Perruchoud, S.Harbarth and A. Azzola and all members of the ProHOSP Study

Group , namely Robert Thomann, MD, Claudine Falconnier, MD, Marcel Wolbers,

PHD, Isabelle Widmer, MD, Stefanie Neidert, MD, Thomas Fricker, MD, Claudine

Blum, MD, Ursula Schild, RN, Katharina Regez, RN, Rita Bossart, RN, Ronald

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Schoenenberger, MD, Christoph Henzen, MD, Claus Hoess, MD, Heiner C. Bucher,

MD, Ayesha Chaudri, Jeannine Haeuptle, Roya Zarbosky, Rico Fiumefreddo,

Melanie Wieland, RN, Charly Nusbaumer, MD, Andres Christ, MD, Roland

Bingisser, MD, Kristian Schneider, RN, Christine Vincenzi, RN, Michael Kleinknecht,

RN, Brigitte Walz, PhD, Verena Briner, MD, Dieter Conen, MD, Andreas Huber, MD,

Jody Staehelin, MD, Aarau, Chantal Bruehlhardt, RN, Ruth Luginbuehl, RN, Agnes

Muehlemann, PhD, Ineke lambinon and Max Zueger, MD. D.Conen, MD,

M.Wieland, RN, C.Nusbaumer, MD, C.Bruehlhardt, RN, R.Luginbuehl, RN, A.Huber,

MD, B.Walz, RN, and M.Zueger, MD.

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23 Schuetz P, Christ-Crain M, Wolbers M, et al. Procalcitonin guided antibiotictherapy and hospitalization in patients with lower respiratory tract infections: aprospective, multicenter, randomized controlled trial. BMC Health Serv Res2007; 7:102

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27 Niederman MS, Mandell LA, Anzueto A, et al. Guidelines for the managementof adults with community-acquired pneumonia. Diagnosis, assessment ofseverity, antimicrobial therapy, and prevention. Am J Respir Crit Care Med2001; 163:1730-1754

28 Woodhead M, Blasi F, Ewig S, et al. Guidelines for the management of adultlower respiratory tract infections. Eur Respir J 2005; 26:1138-1180

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33 Schuetz P, Christ-Crain M, Muller B. Procalcitonin and other biomarkers toimprove assessment and antibiotic stewardship in infections - hope for hype?Swiss Med Wkly 2009; 139:318-326

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Table 1 Baseline characteristics of the overall 925 patients with CAP separated bypositive blood cultures (n=73) and negative or contaminated blood cultures (n=852).

All

(n=925)

Positiveblood cultures

(n=73)

Negative orcontaminatedblood cultures

(n=852)

p-value

Demographic characteristics no. (%)

Age (years)* 73 (59-82) 72 (56-81) 73 (59-82) 0.34

Male 544 (59) 42 (57) 502 (59) 0.82 Admitted from nursing facility 53 (6) 0 (0) 53 (6) 0.03 Antibiotic pretreatment 236 (26) 5(7) 231 (27)


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Table 2 Predictors for positive blood cultures (n=73) in univariate logistic regression

analysis of CAP patients (n=925).

Predictor Odds ratio (95% CI) P-value

Clinical historyAntibiotic pretreatment 0.20 0.08 0.50 0.001Congestive heart failure 0.41 0.17 0.96


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Table 3

Derivation set (n=463)

Parameters AUC 95%CI Sensitivity Specificity LR+ LR-

Procalcitonin 0.83 0.78-0.89

> 0.1 g/L 98% 16% 1.16 0.15

> 0.25 g/L 98% 42% 1.66 0.06

> 0.5 g/L 95% 55% 2.14 0.08

> 1.0 g/L 88% 66% 2.62 0.17

Validation set (n=462)



> 0.1 g/L 100% 11% 1.12 0.01

> 0.25 g/L 93% 38% 1.5 0.18

> 0.5 g/L 80% 54% 1.74 0.37> 1.0 g/L 76% 63% 2.04 0.37

Overall cohort (n=925)



> 0.1 g/L 99% 13% 1.14 0.1

> 0.25 g/L 96% 40% 1.59 0.11

> 0.5 g/L 88% 55% 1.94 0.23

> 1.0 g/L 84% 64% 2.35 0.26

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Table 4 Estimation of costs according to different PCT cut off values

No PCT measurement,Blood culture in all patients

PCT cut off0.1 g/L

PCT cut off0.25 g/L

PCT0.5

Reduction in blood culture collection (%) - 12.6% 36.9% 51.5%

Total costs for blood culture collection in USD 134125 117225 84633 65051

Total costs for initial PCT measurement in USD - 27`750 27`750 27`750

Total costs per patient in USD 145 157 121 100

Missed pathogens in blood cultures, n (%) - 1 (1.4%) 3 (4.1%) 9 (12.3%)

Number needed to screen to detect 1 pathogen 12.7 11.2 8.3 7.0

NOTE.- CAP community-acquired pneumonia, PCT procalcitonin, USD US-Dollars; for cost calculatio

cultures and 30 USD per PCT measurement was assumed.

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Appendix I Area under the curve (AUC) of receiver operating curve (ROC) characteristic plot analysis and Dia

Parameters AUC 95%CI p Sensitivity SpecifProcalcitonin 0.82 0.77-0.86

> 0.1 g/L 99% 13

> 0.25 g/L 96% 40> 0.5 g/L 88% 55> 1.0 g/L 84% 64

C-Reactive Protein 0.67 0.59-0.74 20 mg/L 96% 9% > 50 mg/L 89% 18%> 100 mg/L 81% 33%> 200 mg/L 61% 64%

Blood urea nitrogen 0.64 0.57-0.71 11 mmol/l 32% 78%

White blood count 0.58 0.50-0.65


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25

Figure Legends:

Figure 1: Patient flow in the derivation and the validation cohort

CAP community-acquired pneumonia, LRTI lower respiratory tract infection, COPD

chronic obstructive pulmonary disease.

Figure 2: Receiver operating Curves analysis

A. Comparing Derivation and validation cohort

B. Comparing PCT and other laboratory and clinical parameters in the overall cohort

Figure 3: Percentage of patients with positive (dark grey) and negative (light grey)

blood cultures within different risk categories.

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Figure 1 Flow chart

Figure 2. Receiver operating curve (ROC) analysis

Figure 3. All CAP patients (n=925) with positive (dark grey) and negative (light grey)

blood cultures within different risk categories.

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Flow chart

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ROC curves

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Figure 3. All CAP patients (n=925) with positive (dark grey) and negative (light grey) blood cultures

within different risk categories.

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DOI 10.1378/chest.09-2920; Prepublished online March 18, 2010;Chest

Zimmerli, Beat Mueller, Philipp Schuetz and for the ProHOSP Study GroupFabian Mller, Mirjam Christ-Crain, Thomas Bregenzer, Martin Krause, Werner

community-acquired Pneumonia: A prospective cohort trial.Procalcitonin levels Predict Bacteremia in Patients with

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