ONLINE SUPPLEMENT
Participating general practices, recruitment performance, study periods
The first part of the study was performed by 45 participating general practices in the area of
Hannover/ Germany. Three practices recruited > 50 patients, 22 recruited 10-50 patients, and 20
recruited < 10 patients. The 15 general practices with the highest patient recruitment were selected
for the second part. Of the 15 offices, five recruited more than 50 patients, seven between 10 and
50, and three less than 10. The first took place in a period from December 26, 2006 to April 24, 2007,
the second from November 19, 2007 to April 30, 2008.
Blood specimen handling and randomization
A venous EDTA blood specimen taken from each patient was sent by courier to a central laboratory
for a determination of PCT. Besides the blood sample, the package contained the provisional decision
of the treating physician regarding the treatment with antibiotic, a patient number and the number
of the center. In the central laboratory, the Web-based randomization of the patient into the PCT
group or the control group took place. After that, the central laboratory determined the PCT value.
PCT determinations were free of charge for all participants.
In the interventional part of the study, baseline adaptive randomization was realized through a webbased randomization data bank (IOMTech GmbH, Berlin, Germany), which had been programmed
specifically for that purpose.
Data recorded
The following patient data were recorded by study nurses: history, comorbidities, smoking and
alcohol consumption, symptoms, results of the physical examination, and the clinical diagnosis. In the
second part of the study, the physician also documented the initial decision regarding antibiotic
prescription, the kind of antibiotic, the dosage, and the laboratory’s recommendation.
Procalcitonin measurement
Procalcitonin was measured in the Wagner Stibbe laboratory at Hanover, Germany. The laboratory is
certified according to DIN EN ISO 9001:2000 and accredited according to DIN EN ISO 17025.
Measurement was done by a time-resolved amplified cryptate emission technology assay (BRAHMS
PCT KRYPTOR sensitive, BRAHMS AG, Hennigsdorf, Germany). The assay is based on a sheep
polyclonal antibody against katacalcin, which binds to the calcitonin and katacalcin sequence of
procalcitonin. The assay has a functional assay sensitivity of 0.06 ng/ml, which guarantees a sufficient
precision at the cut-off (0.25 ng/ml) of this study. The time to result for this assay is 19 min.
Table OS 1.
Clinical characteristics and comorbidities of 550 patients.
Total
n=550
PCT
n=275
Control
n=275
p value
42.4 (15.4)
41.4 (15.3)
43.4 (15.5)
0.127
Gender male - n/total
225/550
111/275
114/275
0.864
BMI m2- mean (SD)
26.2 (5.0)
26.1 (5.0)
26.2 (4.9)
0.713
Temperature / C - mean (SD)
36.6 (0.9)
36.6 (0.8)
36.5 (0.9)
0.054
BP systolic mmHg - mean (SD)
124.5 (16.4)
124.0 (15.6)
125 (17.2)
0.768
BP diastolic mm Hg - mean (SD)
77.8 (10.2)
77.8 (10.3)
77.8 (10.0)
0.925
Heart rate / min - mean (SD)
76.7 (12.0)
77.4 (12.2)
75.9 (11.7)
0.082
Respiratory rate / min - mean (SD)
18.2 (8.0)
17.9 (7.2)
18.5 (8.8)
0.919
Ethnic nonwhite - n/total
43/550
23/275
20/275
0.756
Chronic heart failure - n/total
10/550
5/275
5/275
1.000
COPD - n/total
18/549
9/275
9/274
1.000
Diabetes mellitus - n/total
24/550
15/275
9/275
0.294
Smoker - n/total
139/549
66/275
73/274
0.490
Former Smoker - n/total
43/549
21/275
22/274
0.875
Alcohol - n/total
15/550
7/275
8/275
1.000
Comorbidities - n/total
49/550
26/275
23/275
0.767
Variable
Age, years - mean (SD)
Table OS 2.
Clinical symptoms in 550 patients
Symptom score = number of symptoms
Total
n=550
PCT
n=275
Control
n=275
p value
Headaches - n/total
373/550
186/275
187/275
1.000
Cold - n/total
436/550
212/275
224/275
0.244
Sore throat - n/total
352/550
180/275
172/275
0.532
Gargle - n/total
304/550
155/275
149/275
0.671
Cough - n/total
452/550
224/275
228/275
0.742
Purulent sputum - n/total
189/550
93/275
96/275
0.867
Dyspnea - n/total
123/550
63/275
60/275
0.844
Chest pain - n/total
155/550
75/275
80/275
0.718
Abdominal pain - n/total
43/550
20/275
23/275
0.756
Limb pain - n/total
312/550
149/275
163/275
0.258
Chill - n/total
174/550
82/275
92/275
0.402
Vomitus - n/total
22/550
8/275
14/275
0.275
Diarrhea - n/total
30/550
14/275
16/275
0.848
4/550
3/275
1/275
0.631
5.4 (2.1)
5.3 (2.1)
5.5 (2.1)
0.398
Variable
Confusion - n/total
Symptom Score - mean (SD)
Table OS 3.
Antibiotics prescribed in both groups
Antibiotic class
All
PCT
Control
p
74 / 550
30 / 275
44 / 275
0.080
54 / 550
32 / 275
22 / 275
0.152
11 / 550
4 / 275
7 / 275
0.361
13 / 550
8 / 275
5 / 275
0.400
13 / 550
5 / 275
8 / 275
0.400
5 / 550
3 / 275
2 / 275
0.653
2 / 550
1 / 275
1 / 275
1.000
Macrolides
Aminopenicillins
Doxycyline
Penicillins
Quinolones
Cephalosporins
Others