ORIGINAL ARTICLE 10.1111/j.1469-0691.2009.02856.

Utility of C-reactive protein in assessing the disease severity

and complications of community-acquired pneumonia

U. Hohenthal1, S. Hurme2, H. Helenius2, M. Heiro1, O. Meurman3, J. Nikoskelainen1 and P. Kotilainen1

1) Department of Medicine, Turku University Hospital, 2) Department of Biostatistics, University of Turku and 3) Department of Clinical Microbiology,
Turku University Hospital, Turku, Finland

Abstract

Previous studies on the usefulness of C-reactive protein (CRP) in patients with community-acquired pneumonia (CAP) have yielded
somewhat inconsistent results. Our aim was to assess the value of CRP in estimating the severity and complications of CAP. CRP levels
during the first 5 days of hospitalization were measured in 384 adult patients with CAP, and the data were evaluated using comprehen-
sive statistical analyses. Significantly higher CRP levels on admission were detected in Pneumonia Severity Index (PSI) classes IIIV than
in classes I and II (p <0.001). An increment of 50 mg/L CRP on admission was associated with a 1.22-fold odds for a patient to be in
PSI classes IIIV as compared with classes I and II (OR 1.22, 95% CI 1.111.34; p <0.001). CRP levels were significantly higher in bacte-
raemic pneumonia than in non-bacteraemic pneumonia (p <0.001). An increment of 50 mg/L CRP was associated with a 1.67-fold odds
for a patient to be bacteraemic (OR 1.67, 95% CI 1.461.92; p <0.001). CRP levels >100 mg/L on day 4 after the admission were signif-
icantly associated with complications (p <0.01). There was a trend for an association between the level of CRP on admission and the
time to reach clinical stability (p <0.01). In conclusion, CRP may be valuable for revealing the development of complications in CAP. It
may also be useful to assess the disease severity, thus being complementary to the assessment of the PSI. In our patients, high CRP lev-
els were associated with a failure to reach clinical stability.

Keywords: Aetiology, community-acquired pneumonia, complication, C-reactive protein, disease severity

Original Submission: 14 October 2008; Revised Submission: 17 December 2008; Accepted: 17 December 2008
Editor: M. Paul
Article published online: 22 June 2009
Clin Microbiol Infect 2009; 15: 10261032

CRP levels have been found to be higher in bacteraemic pneu-

Corresponding author and reprint requests: U. Hohenthal,
monia than in non-bacteraemic pneumonia [14,15,17].
Department of Medicine, Turku University Hospital, Kiinamyllynkatu
4-8, 20520 Turku, Finland In the present study, we sought to evaluate whether the
E-mail: ulla.hohenthal@tyks.fi level of CRP on admission could be used to estimate the
severity and potential aetiology of CAP. We also assessed
whether the CRP levels during the first days of hospitaliza-
tion were associated with the clinical stabilization of the
Introduction patient or the development of complications in CAP.

Many studies have shown the clinical utility of C-reactive pro-

tein (CRP) concentration as an acute-phase reactant in
patients with various infections, including septicaemia, meningi-
tis and infective endocarditis [18]. Previous studies have also
shown that the CRP level may contribute to establishing the
diagnosis of community-acquired pneumonia (CAP) [913]. In
addition, the use of CRP as a tool in the aetiological diagnosis
of CAP has been investigated in a number of studies, but the
results have been discordant [11,1418]. Similarly, the results
of the studies evaluating the use of CRP as a prognostic factor
have been somewhat inconsistent [14,1723], although the
Patients and Methods
The patients included in this study are the same as those
included in a prospective clinical study of the aetiology of
CAP in 384 consecutive hospitalized patients treated at the
Department of Infectious Diseases, Turku University Hospi-
tal, Turku, Finland, between December 1999 and 2004 [24].
The diagnostic criteria for CAP included a new infiltrate on
the chest radiograph in a patient with either fever or clinical
signs/symptoms of lower respiratory tract infection, or both

2009 The Authors

Journal Compilation 2009 European Society of Clinical Microbiology and Infectious Diseases
CMI Hohenthal et al. C-reactive protein in community-acquired pneumonia 1027

[24]. Exclusion criteria included immunosuppression of the
patient, an emerging alternative diagnosis during the follow-
up, pneumonia caused by tuberculosis or aspiration, and hos-
pitalization within the previous 10 days.
The microbiological evaluation included blood culture,
sputum culture, urine antigen tests for Streptococcus pneumo-
niae and Legionella pneumophila, detection of a respiratory
virus antigen in a nasopharyngeal sample, PCR tests for Myco-
plasma pneumoniae, Chlamydophila pneumoniae, L. pneumophila,
influenza A virus and influenza B virus from a throat swab
sample, and detection of antibodies against M. pneumoniae,
C. pneumoniae and L. pneumophila in serum samples [24].
The severity of CAP was assessed using the Pneumonia
Severity Index (PSI) [25]. The clinical stability of the patient
was defined on the basis of an approach described by Halm
et al. [26]. Death, transfer to the intensive-care unit (ICU)
and empyema were defined as complications.
CRP levels were determined by an immunoturbidometric
method (Tina-quant) on a Hitachi 917 automated biochem-
istry analyser (Roche Diagnostics GmbH, Mannheim, Ger-
many). The CRP levels were studied on admission, on a daily
basis until the rising trend of CRP level turned into a declin-
ing trend, and subsequently as clinically indicated two to five
times a week during the hospitalization period. In addition,
CRP level was studied at the time of clinical stability. The
CRP level on admission was defined as CRP1, and the CRP
value at the time of clinical stability as CRP2. Patients gave
written informed consent, and the study was approved by
the Ethics Committee of Turku University Central Hospital.
curve in the case of logistic analyses, or by giving hazard
ratios. Statistical confidence of these quantifications was
reported by giving the 95% CIs among the estimates. A sig-
nificance level of 0.05 was used as the limit for significance.
Statistical computing was performed with the SAS System for
Windows, Release 9.1.3/2004.
Results
Patients
Of the 384 patients included, 201 were male and 183 female.
The mean age of the patients was 49.8 years (standard devia-
tion (SD) 19.2 years). Various baseline characteristics of the
patients are presented in Table 1. The distributions of the
patients according to PSI classes and aetiological agents are
presented in tables 2 and 3. S. pneumoniae was the only aeti-
ological agent in 95 (24.7%) patients, M. pneumoniae in 36
(9.4%) patients, C. pneumoniae in 24 (6.3%) patients, another
bacterial agent in seven (1.8%) patients, and a respiratory
virus in 27 (7.0%) patients. Two aetiological agents were
identified in 20 (5.2%) patients, and the aetiology remained
unidentified in 175 (45.6%) patients. Blood culture was
TABLE 1. Mean levels of C-reactive protein on admission
(CRP1) according to baseline patient characteristics,
bacteraemia, admission to intensive-care unit ICU), and
death
CRP1 (mg/L)

Statistical analysis Mean (SD) Range P

The associations of CRP levels with baseline characteristics

Male (n = 201) 199 (125) 4650 0.641
other than age were statistically tested using a two-sample Female (n = 183) 204 (112) 1560
Underlying disease Yes (n = 167) 209 (127) 1560 0.260
t-test. Associations between age and CRP levels were studied No (n = 217) 195 (111) 9650
using Pearsons correlation coefficient. The two-sample t-test COPD Yes (n = 17) 230 (110) 37432 0.309
No (n = 367) 200 (119) 1650
was also applied with other two group comparisons of the Asthma Yes (n = 35) 185 (128) 1494 0.405
No (n = 349) 203 (118) 8650
CRP mean levels. One-way ANOVA with Tukeys adjustment Cardiovascular Yes (n = 70) 180 (126) 8560 0.092
in post hoc comparisons was used when comparing more than disease No (n = 314) 206 (116) 1650
Alcoholism Yes (n = 15) 317 (115) 13539 <0.001
two groups for CRP mean levels. In multivariate analysis, when No (n = 369) 197 (116) 1650
Diabetes Yes (n = 28) 224 (140) 8560 0.300
covariate-adjusted group comparisons were performed, the No (n = 356) 200 (117) 1650
Other Yes (n = 54) 199 (98) 14494 0.885
analysis was carried out using linear model techniques. Predic- No (n = 330) 202 (122) 1650
tive associations of CRP levels and dichotomous clinical classi- Smoking Yes (n = 125) 238 (128) 9650 <0.001
No (n = 259) 184 (110) 1539
fications were analysed using logistic regression models and Preceding antibiotic Yes (n = 110) 178 (91) 1452 0.014
No (n = 274) 211 (127) 4650
receiver operating characteristic (ROC) analysis. Bacteraemia Yes (n = 55) 328 (128) 8650 <0.001
No (n = 329) 181 (103) 1560
Finally, the predictive associations of CRP levels with the Pneumococcal bacteraemia Yes (n = 52) 337 (126) 8650 <0.001
time of stabilization were examined using Coxs proportional No (n = 55) 238 (135) 4528
Admission to ICU Yes (n = 35) 270 (163) 8560 <0.001
hazard regression analysis. The quantifications of the analyses No (n = 349) 194 (111) 1650
Death Yes (n = 13) 217 (131) 14420 0.998
were performed by giving the mean values or differences in No (n = 371) 201 (118) 1650
the mean values in the case of t-test and ANOVA, or by giv- COPD, chronic obstructive pulmonary disease; SD, standard deviation.
ing the ORs, specificity, sensitivity and area under the ROC

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Journal Compilation 2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 15, 10261032
1028 Clinical Microbiology and Infection, Volume 15 Number 11, November 2009 CMI

TABLE 2. Mean levels of C-reactive protein on admission (CRP1) according to Pneumonia Severity Index (PSI) classes

PSI I PSI II PSI III PSI IV PSI V

CRP1 (mg/L) n = 124 n = 113 n = 59 n = 73 n = 15 p

Mean (SD) 163 (88) 200 (104) 232 (139) 220 (140) 320 (126) <0.001
Range 1445 4502 8650 13560 129491
PSI I and II combined PSI IIIV combined

Mean (SD) 180 (97) 236 (139) <0.001

Range 1502 8650

TABLE 3. Comparison of the mean levels of C-reactive protein on admission (CRP1) with respect to the aetiology
of community-acquired pneumonia in 384 patients. Below diagonal, 95% CIs for differences between means; above diagonal,
p-values. Overall ANOVA p-value <0.001 for CRP1 level

Streptococcus Chlamydophila Mycoplasma Respiratory Dual

CRP1, mg/L (SD) pneumoniae pneumoniae pneumoniae virus Other agenta infectionb Unknown
(range) n = 95 n = 24 n = 36 n = 27 n=7 n = 20 n = 175

S. pneumoniae 291 (142) (4650) 0.003 <0.001 <0.001 0.452 0.009 <0.001
C. pneumoniae 200 (110) (25531) 20 to 162 0.200 0.055 1.000 1.000 0.981
M. pneumoniae 133 (53) (28225) 97 to 219 )16 to 149 0.990 0.562 0.259 0.175
Respiratory virus 113 (71) (12248) 109 to 245 )1 to 174 )60 to 99 0.310 0.081 0.034
Other agent 210 (84) (70350) )42 to 202 )145 to 123 )206 to 51 )230 to 35 1.000 0.990
Dual infection 200 (109) (27445) 14 to 168 )95 to 94 )154 to 20 )178 to 6 )126 to 148 0.987
Unknown 181 (92) (1560) 70 to 150 )49 to 87 )105 to 10 )132 to )3 )90 to 150 )54 to 93

SD, standard deviation.

a
Staphylococcus aureus, three cases; Legionella pneumophila, two cases; Streptococcus pyogenes, one case; Fusobacterium sp., one case.
b
S. pneumoniae with a respiratory virus, 11 cases; S. pneumoniae with C. pneumoniae, one case; M. pneumoniae with influenza A virus, three cases; M. pneumoniae with Haemo-
philus influenzae, two cases; C. pneumoniae with Staphylococcus aureus, two cases; C. pneumoniae with adenovirus, one case.

positive in 55 patients (52 S. pneumoniae, two Staphylococcus
aureus, one Streptococcus pyogenes). Of all patients, 35 (9.1%)
were transferred to the ICU and 13 (3.3%) died during the
hospitalization.
CRP1
The mean CRP1 level was 201 mg/L (SD 119 mg/L)
(range 1650 mg/L, n = 384). There were significant differ-
ences in the mean CRP1 levels between the patients with
alcoholism, smoking or preceding antibiotic treatment as
baseline characteristics and those without these characteris-
tics (Table 1). The association between CRP1 level and age
did not reach statistical significance (r = 0.10, p 0.051).
The mean CRP1 level was significantly higher among the
patients who were transferred to the ICU than among the
patients who were not (p <0.001) (Table 1). In prediction of
ICU admission, the area under the ROC curve for CRP1 was
0.639 (95% CI 0.5200.58). Correspondingly, the area under
the ROC curve for PSI was 0.885 (95% CI 0.8470.923).
No significant difference was observed in the mean CRP1
levels between the patients who died and the patients who
survived (p 0.998) (Table 1).
In univariate analysis, significant (p <0.001) differences
were observed in CRP1 levels between the patients belong-
ing to different PSI classes (Table 2). The differences in
CRP1 levels were also significant (p <0.001) when PSI groups I
and II combined were compared with PSI groups IIIV
combined.
In multivariate analysis, the differences between the PSI
groups remained significant after adjustment for age, sex,
cardiovascular disease, bacteraemic pneumonia and aetiologi-
cal agents (p 0.004). In pairwise comparison of the groups,
significant differences in CRP1 levels were observed only
between PSI class V and either PSI class I (p 0.002) or PSI
class II (p 0.022). The difference in CRP1 levels was also sig-
nificant (p 0.023) when PSI groups I and II combined were
compared with PSI groups IIIV combined.
In the logistic regression analysis, an increment of 50 mg/L
of the CRP1 level was associated with a 1.22-fold odds for a
patient to be in PSI classes IIIV as compared with being in
classes I and II (OR 1.22, 95% CI 1.111.34; p <0.001).
The mean CRP1 levels were significantly higher in the
patients with bacteraemic pneumonia than in those with
non-bacteraemic pneumonia (p <0.001). In addition, the dif-
ference was significant between the patients with bacterae-
mic and non-bacteraemic pneumococcal pneumonia
(p <0.001) (Table 1).
An increment of 50 mg/L of the CRP1 level was associ-
ated with a 1.67-fold odds for a patient to be bacteraemic
(OR 1.67, 95% CI 1.461.92; p <0.001).

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CMI Hohenthal et al. C-reactive protein in community-acquired pneumonia 1029

ROC analysis was used to find a cut-off point of CRP1
level that could predict bacteraemia with a sensitivity of at
least 75% combined with the best possible specificity. The
concentration of 230 mg/L was identified as such a cut-off
point. The CRP1 levels were 230 mg/L for 43 of the 55
patients with bacteraemic pneumonia (sensitivity 78%) and
<230 mg/L for 243 of the 324 patients with non-bacteraemic
pneumonia (specificity 75%) (area under the ROC
curve 0.812). In PSI classes I and II, the sensitivity and speci-
ficity of this cut-off point value were 72% and 80%, respec-
tively (area under the ROC curve 0.783).
Significant (p <0.001) differences in mean CRP1 level were
observed between the patients belonging to various aetiolog-
ical groups (Table 3). The CRP1 level was significantly higher
in patients with pneumococcal pneumonia than in those with
any other aetiology, except for a bacterial agent other than
M. pneumoniae or C. pneumoniae.
CRP2 and clinical stabilization
The mean CRP2 level was 80 mg/L (SD 52 mg/L)
(range 1321 mg/L, n = 336). The mean duration between
the admission and the day when the patient was stabilized
was 4.6 days (SD 3.2 days) (range 127 mg/L).
Significant differences in CRP2 level were observed
between the different PSI classes (p 0.022) and the aetiology
of CAP (p 0.029). In pairwise comparisons of the aetiological
agents, the difference was significant only between the
patients with pneumococcal pneumonia and those with
Mycoplasma pneumonia. CRP2 level was not significantly
associated with any of the underlying conditions studied (all
p-values 0.103), or with the age of the patient (r = 0.05,
p 0.398).
There was a trend for an association between CRP1 level
and the time to reach clinical stability. In the Cox regression
analysis, it was found that for an increment of 50 mg/L of
the CRP1 level, the risk for the patient to remain unstabi-
lized increased by 6% (hazard ratio 1.06, 95% CI 1.021.11;
p 0.005).
CRP during the follow-up
The CRP levels during the first 5 days of hospitalization
regarding the different PSI classes, aetiology of CAP, bacte-
raemic and non-bacteraemic disease and the development of
complications are given in Fig. 1.
The median time to reach clinical stability was 4 days. Of
all 384 patients, 23 were discharged, four died, and three
were transferred to another hospital in <4 days after admis-
sion. On day 4 after admission, the CRP level was examined
in 272 (76.8%) of the remaining 354 patients. The risk of
being admitted to the ICU or the need to change the initial
antimicrobial treatment was significantly higher in the
patients with CRP levels >100 mg/L on day 4 after admission,
and a significantly smaller number of these patients than of
those whose CRP levels were 100 mg/L had been stabilized
at that time-point (Table 4). The CRP level was >100 mg/L
in all four patients who developed empyema.
Discussion
In this study, we analysed the utility of CRP in the evaluation
of patients with CAP, focusing particularly on disease sever-
ity. In this respect, the positive correlation between high
CRP levels and severe disease was one of the main findings

(a) (b) S. pneumoniae

PSI 1 350 M. pneumoniae
350 PSI 2
300 C. pneumonie
300 PSI 3 Respiratory virus
250
CRP mg/L

PSI 4
CRP mg/L

250 Others
PSI 5 200
FIG. 1. The mean levels of C-reactive 200
150 150
protein (CRP) in patients with commu-
100 100
nity-acquired pneumonia on admission 50
50
and during the first 5 days of hospital- 0 0
0 1 2 3 4 5 0 1 2 3 4 5
ization with regard to the different Pne- Day Day
umonia Severity Index (PSI) classes (a), (c) (d) Empyema
400 Bacteraemic 400 ICU
the aetiology (b), bacteraemic and non- 350 Nonbacteraemic Death
350
bacteraemic disease (c), and the devel- 300 300 None of these
CRP mg/L

CRP mg/L

250 250
opment of complications (d). Numbers 200 200
of observations: 384 on day 0 (admis- 150 150
100 100
sion), 371 on day 1, 343 on day 2, 323 50 50
on day 3, 272 on day 4, and 233 on da- 0 0
0 1 2 3 4 5 0 1 2 3 4 5
y 5. ICU, intensive-care unit. Day Day

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Journal Compilation 2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 15, 10261032
1030 Clinical Microbiology and Infection, Volume 15 Number 11, November 2009
CRP 100 mg/L
n = 172
Mean duration of hospitalization,days 7.2 (4.0) (436)
(SD) (range)
Patients clinically stabilized 130 (75.6)
Patients admitted to the ICU 12 (7.0)a
Change of antimicrobial treatment 41 (23.8)
Death 4 (2.3)c
Empyema 0 4
Data are number (%) of patients, unless otherwise indicated.
ICU, intensive-care unit.
a
None of the patients was admitted to the ICU later than day 4.
b
Two patients were admitted to the ICU later than day 4.
c
Two patients died on day 4 and two patients later.
d
All patients died later than day 4.
here. This was manifested by the significantly higher CRP1
levels in patients who were transferred to the ICU than in
those who were not, as well as by the significant association
between the CRP1 levels and different PSI classes. Moreover,
the CRP1 levels in PSI classes I and II combined differed sig-
nificantly from those in PSI classes IIIV combined. These are
clinically the two most important groups to be differentiated,
as the mortality risk and the ICU admission rates are known
to be highest in high PSI classes [25,2729].
According to several studies, mortality and admission
rates to the ICU are higher in patients with bacteraemic
pneumonia than in those with non-bacteraemic pneumonia
[2931]. Consequently, it is vitally important that patients
with bacteraemia are rapidly recognized, as they should be
admitted to hospital. In the present study, bacteraemic
patients had significantly higher CRP1 levels than non-
bacteraemic patients. A cut-off point of 230 mg/L CRP1
predicted bacteraemia with a sensitivity of 78% and a speci-
ficity of 75%. The use of this cut-off point may be especially
useful in patients belonging to PSI classes I and II, for
whom outpatient treatment is commonly considered to be
appropriate [25,32]. High CRP levels on admission should
arouse a suspicion of bacteraemia even in this group of
patients. In the present work, the CRP1 level was
>230 mg/L in 13 (72%) of the 18 bacteraemic patients in
PSI classes I and II.
Procalcitonin measurements were not used here. In previ-
ous studies, procalcitonin has not been shown to be superior
to CRP as a diagnostic marker in community-aquired infec-
tions but has seemed to be a better marker of bacteraemia
[4,33].
In addition, CRP proved valuable as a follow-up test: the
CRP levels fell rapidly in accordance with the clinical recov-
ery of the patient. This is in line with the few previous stud-
ies, in which the usefulness of CRP level as a follow-up test
was evaluated [16,20,22,34,35]. An important finding in our
2009 The Authors
Journal Compilation 2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 15, 10261032
CMI
TABLE 4. Comparison between
CRP >100 mg/L CRP missing
n = 100 p n = 82 patients with community-acquired
pneumonia who had C-reactive
13.1 (7.8) (642) <0.001 8.2 (4.4) (429) protein (CRP) levels 100 mg/L and
19 (19.0) <0.001 56 (68.3) >100 mg/L on day 4 after admission
21 (21.0)b <0.001 2 (2.4)
63 (63.0) <0.001 13 (15.8)
4 (4.0)d 0.425 2 (2.4)d
(4.0) 0.008 0
patients was that the CRP level of >100 mg/L on day 4 after
admission was suggestive of a treatment failure or develop-
ment of complications. It is of note that only 19% of the
patients with CRP levels >100 mg/L on day 4 had been stabi-
lized, and 21% of them needed treatment in the ICU.
As far as we know, the present study is the first to evalu-
ate the CRP level at the time of clinical stabilization, and
shows a significant association between CRP2 level and PSI
classes. The significant association observed between CRP1
level and the length of the time to reach clinical stability fur-
ther substantiates the connection between high CRP levels
and severe disease.
Previous studies evaluating the behaviour of CRP with
respect to the aetiology of CAP have yielded somewhat
inconsistent results. A few studies have found no difference
in the CRP levels between different aetiologies [16,17],
whereas others have found significantly higher CRP levels
only in bacteraemic pneumococcal pneumonia [14,15]. In
one study, the CRP levels were significantly higher in L. pneu-
mophila pneumonia than in any other group [18]. In another
study, significantly higher CRP levels were detected in pneu-
mococcal pneumonia or L. pneumophila pneumonia than in
other aetiological groups [11]. Here, CRP1 levels in pneumo-
coccal pneumonia differed significantly from those in all
other aetiologies except for a bacterial agent other than
M. pneumoniae and C. pneumoniae. Although significant differ-
ences in the CRP1 levels between the different causative
agents were observed, the range within each group was
wide, with the lowest values <80 mg/L and the highest values
>200 mg/L. The high variation and large overlap in the values
of the patients with different microbial pathogens indicate
that the CRP concentration is not reliable for guiding deci-
sions regarding the aetiology of CAP in a clinical setting.
In conclusion, our results show that the CRP test may be
valuable as a tool with which to reveal the development of
complications during the treatment of CAP. The positive
CMI Hohenthal et al.
correlation observed between high CRP levels and serious
illness suggests that this biomarker may also be useful for
assessing disease severity in patients with CAP. Towards this
end, the determination of CRP is complementary to, but
cannot substitute for, assessment of the PSI. In our patients,
high CRP levels were associated with a failure to reach clini-
cal stability. The results presented here show that the CRP
test is not reliable for assessing the aetiology of CAP in an
individual patient.
Transparency Declaration
This study was supported by the Maud Kuistila Foundation
and the Turku University Central Hospital Research Fund.
The authors state that there are no dual or conflicting
interests regarding this article.
References
1. Yentis SM, Soni N, Sheldon J. C-reactive protein as an indicator of
resolution of sepsis in the intensive care unit. Intensive Care Med
1995; 21: 602605.
2. Povoa P, Coelho L, Almeida E et al. C-reactive protein as a marker
of infection in critically ill patients. Clin Microbiol Infect 2005; 11: 101
108.
3. Povoa P. C-reactive protein: a valuable marker of sepsis. Intensive
Care Med 2002; 28: 235243.
4. Gani S, Koldkjr OG, Pedersen C, Pedersen SS. Procalcitonin, lipo-
polysaccharide-binding protein, interleukin-6 and C-reactive protein
in community-acquired infections and sepsis: a prospective study. Crit
Care 2006; 10: R53.
5. Hansson LO, Axelsson G, Linne T, Aurelius E, Lindquist L. Serum C-
reactive protein in the differential diagnosis of acute meningitis. Scand
J Infect Dis 1993; 25: 625630.
6. Sormunen P, Kallio MJ, Kilpi T, Peltola H. C-reactive protein is useful
in distinguishing Gram stain-negative bacterial meningitis from viral
meningitis in children. J Pediatr 1999; 134: 725729.
7. Hogevik H, Olaison L, Andersson R, Alestig K. C-reactive protein is
more sensitive than erythrocyte sedimentation rate for diagnosis of
infective endocarditis. Infection 1997; 25: 8285.
8. Heiro M, Helenius H, Sundell J et al. Utility of serum C-reactive pro-
tein in assessing the outcome of infective endocarditis. Eur Heart J
2005; 26: 18731881.
9. Smith RP, Lipworth BJ. C-reactive protein in simple community-
acquired pneumonia. Chest 1995; 107: 10281031.
10. Castro-Guardiola A, Armengou-Arxe A, Viejo-Rodrguez AL,
Penarroja-Matutano G, Garcia-Bragado F. Differential diagnosis
between community-acquired pneumonia and non-pneumonia dis-
eases of the chest in the emergency ward. Eur J Intern Med 2000; 11:
334339.
11. Almirall J, Bolbar I, Toran P et al. Contribution of C-reactive protein
to the diagnosis and assessment of severity of community-acquired
pneumonia. Chest 2004; 125: 13351342.
12. Flanders SA, Stein J, Shochat G et al. Performance of a bedside
C-reactive protein test in the diagnosis of community-acquired pneu-
monia in adults with acute cough. Am J Med 2004; 116: 529535.
Journal Compilation 2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 15, 10261032
C-reactive protein in community-acquired pneumonia 1031
13. Holm A, Pedersen SS, Nexoe J et al. Procalcitonin versus C-reactive
protein for predicting pneumonia in adults with lower respiratory
tract infection in primary care. Br J Gen Pract 2007; 57: 555560.
14. Ortqvist A, Hedlund J, Wretlind B, Carlstrom A, Kalin M. Diagnostic
and prognostic value of interleukin-6 and C-reactive protein in com-
munity-acquired pneumonia. Scand J Infect Dis 1995; 27: 457462.
15. Kragsbjerg P, Jones I, Vikerfors T, Holmberg H. Diagnostic value of
blood cytokine concentrations in acute pneumonia. Thorax 1995; 50:
12531257.
16. Kosmas EN, Baxevanis CN, Papamichail M, Kordossis T. Daily varia-
tion in circulating cytokines and acute-phase proteins correlates with
clinical and laboratory indices in community-acquired pneumonia. Eur
J Clin Invest 1997; 27: 308315.
17. Hedlund J, Hansson LO. Procalcitonin and C-reactive protein levels
in community-acquired pneumonia: correlation with etiology and
prognosis. Infection 2000; 28: 6873.
18. Garcia Vazquez E, Martnez JA, Mensa J et al. C-reactive protein lev-
els in community-acquired pneumonia. Eur Respir J 2003; 21: 702
705.
19. Hedlund J, Hansson LO, Ortqvist A. Short- and long-term prognosis
for middle-aged and elderly patients hospitalized with community-
acquired pneumonia: impact of nutritional and inflammatory factors.
Scand J Infect Dis 1995; 27: 3237.
20. Smith RP, Lipworth BJ, Cree IA, Spiers EM, Winter JH. C-reactive
protein. A clinical marker in community-acquired pneumonia. Chest
1995; 108: 12881291.
21. Igonin AA, Armstrong VW, Shipkova M, Lazareva NB, Kukes VG,
Oellerich M. Circulating cytokines as markers of systemic inflamma-
tory response in severe community-acquired pneumonia. Clin Biochem
2004; 37: 204209.
22. Chalmers JD, Singanayagam A, Hill AT. C-reactive protein is an inde-
pendent predictor of severity in community-acquired pneumonia. Am
J Med 2008; 121: 219225.
23. Brunkhorst FM, Al-Nawas B, Krummenauer F, Forycki ZF, Shah PM.
Procalcitonin, C-reactive protein and APACHE II score for risk evalu-
ation in patients with severe pneumonia. Clin Microbiol Infect 2002; 8:
93100.
24. Hohenthal U, Vainionpaa R, Meurman O et al. Aetiological diagnosis
of community acquired pneumonia: utility of rapid microbiological
methods with respect to disease severity. Scand J Infect Dis 2008; 40:
131138.
25. Fine MJ, Auble TE, Yealy DM et al. A prediction rule to identify low-
risk patients with community-acquired pneumonia. N Engl J Med
1997; 336: 243250.
26. Halm EA, Fine MJ, Marrie TJ et al. Time to clinical stability in patients
hospitalized with community-acquired pneumonia: implications for
practice guidelines. JAMA 1998; 279: 14521457.
27. Renaud B, Coma E, Hayon J et al. Investigation of the ability of the
Pneumonia Severity Index to accurately predict clinically relevant out-
comes: a European study. Clin Microbiol Infect 2007; 13: 923931.
28. Man SY, Lee N, Ip M et al. Prospective comparison of three predic-
tive rules for assessing severity of community-acquired pneumonia in
Hong Kong. Thorax 2007; 62: 348353.
29. Garau J, Baquero F, Perez-Trallero E et al. Factors impacting on
length of stay and mortality of community-acquired pneumonia. Clin
Microbiol Infect 2008; 14: 322329.
30. Fine MJ, Smith MA, Carson CA et al. Prognosis and outcomes of
patients with community-acquired pneumonia. A meta-analysis. JAMA
1996; 275: 134141.
31. Musher DM, Alexandraki I, Graviss EA et al. Bacteremic and nonbac-
teremic pneumococcal pneumonia. A prospective study. Medicine (Bal-
timore) 2000; 79: 210221.
32. Mandell LA, Wunderink RG, Anzueto A et al. Infectious Diseases
Society of America/American Thoracic Society consensus guidelines
2009 The Authors
1032 Clinical Microbiology and Infection, Volume 15 Number 11, November 2009
on the management of community-acquired pneumonia in adults. Clin
Infect Dis 2007; 44 (suppl 2): 2772.
33. Gani S, Koldkjr OG, Mller HJ, Pedersen C, Pedersen SS. A
comparison of high-mobility group-box 1 protein, lipopolysaccharide-
binding protein and procalcitonin in severe community-acquired
infections and bacteraemia: a prospective study. Crit Care 2007; 11:
R76.
2009 The Authors
Journal Compilation 2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 15, 10261032
CMI
34. Menendez R, Cavalcanti M, Reyes S et al. Markers of treatment fail-
ure in hospitalised community acquired pneumonia. Thorax 2008; 63:
447452.
35. Bruns AH, Oosterheert JJ, Hak E, Hoepelman AI. Usefulness of con-
secutive C-reactive protein measurements in follow-up of severe
community-acquired pneumonia. Eur Respir J 2008; 32: 726732.