Usefulness of consecutive C-reactive protein measurements in follow-up of severe community-acquired pneumonia

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Fig. 1—
Patterns of normalisation of C-reactive protein (CRP) levels for the 289 study patients with severe community-acquired pneumonia. Horizontal lines represent the median; boxes, the interquartile range; and whiskers, the highest and lowest non-outlier values.

Table 1—

Characteristics of the study cohort of 289 patients with severe community-acquired pneumonia

Age yrs	69.7±13.8
Females	99 (34.3)
PSI score	112.9±25.7
Class IV	198 (68.5)
Class V	52 (18.0)
APACHE II score	13.8±4.6
Comorbidity	180 (62.3)
Congestive heart failure	36 (12.5)
Neoplasm	65 (22.5)
Liver disease	3.0 (1.0)
Cerebrovascular disease	25 (8.7)
Chronic renal disease	27 (9.3)
COPD	88 (30.4)
Clinical features
Temperature °C	38.5±1.2
Respiratory rate breaths·min⁻¹	26.7±8.7
Laboratory data
CRP mg·L⁻¹	174 (147–390)
White blood cell count 10⁹·L⁻¹	16.5±9.2
Antibiotic therapy
β-lactam	232 (80.3)
Amoxicillin ± clavulanic acid	169 (58.5)
Cephalosporin (2nd or 3rd generation)	60 (20.7)
Cephtriaxone	47 (16.2)
Cephtazidime	12 (4.2)
Cephotaxime	1 (0.3)
Penicillin	3 (1.0)
β-lactam/macrolide combination	47 (16.3)
Amoxicillin ± clavulanic acid and macrolide	32 (11.1)
Cephalosporin (2nd or 3rd generation) and macrolide	14 (4.8)
Cephtriaxone and macrolide	11 (3.8)
Cephtazidime and macrolide	2 (0.7)
Other^#	10 (3.5)
Outcome
ICU admissions during hospitalisation	9 (3.1)
28-day mortality	20 (6.9)

Data are presented as mean±sd, n (%) or median (interquartile range). PSI: Pneunomia Severity Index; APACHE: Acute Physiology and Chronic Health Evaluation; COPD: chronic obstructive pulmonary disease; CRP: C-reactive protein; ICU: intensive care unit. ^#: other antibiotics include: cotrimoxazole (n = 2; 0.7%); β-lactam and ciprofloxacin (n = 2; 0.7%); doxycyclin (n = 2; 0.7%); erytromycin and rifampicin (n = 1; 0.3%); levofloxacin (n = 1; 0.3%); and erythromycin (n = 2; 0.6%).

Table 2—

Median baseline C-reactive protein (CRP) values according to aetiology in patients with severe community-acquired pneumonia

	Subjects	Median CRP level	Size of range	Interquartile range
*Streptococcus pneumoniae^#*	55 (19.0)	278.0	686	147–390
*Haemophilus influenzae*	9 (3.1)	214.0	278	168–313
*Staphylococcus aureus*^¶	8 (2.8)	187.0	299	115–330
*Chlamydia pneumoniae*	10 (3.5)	115.5	328	57–317
*Mycoplasma pneumoniae*	5 (1.7)	49.0	299	27–228
*Legionella pneumophila*⁺	7 (2.4)	247.0	286	176–421
Enterobacteriaciae^§	15 (5.2)	129.0	452	53–272
*Moraxella catarrhalis*	5 (1.7)	64.0	197	49–165
Other pathogens^ƒ	11 (3.8)	185.0	403	117–231
Multiple bacterial pathogens	12 (4.2)	213.0	672	83–404
Unknown aetiology	152 (52.6)	140.5	576	56–293

^#: determined by sputum culture (n = 19), blood culture (n = 24) or urinary antigen test (n = 20), in eight cases S. pneumoniae was determined by multiple tests; ^¶: determined by sputum culture (n = 6) or blood culture (n = 2); ⁺: all determined by both serology and urinary antigen test (n = 7); ^§: Enterobacteriaciae include: Eschericia Coli (n = 6; 2.1%); Klebsiella pneumoniae (n = 4; 1.4%); Proteus mirabilis. (n = 1; 0.3%); Enterobacter spp. (n = 2; 0.7%); Citrobacter spp. (n = 2; 0,7%); ^ƒ:other pathogens include: P. aeruginosa (n = 2; 0.7%); Streptococcus agalactiae (n = 3; 1.0%); H. parainfluenzae (n = 2; 0.7%); Staphylococcus hominis (n = 1; 0.3%); Proprionibacter acnes (n = 1; 0.3%); Gram-positive spp. (n = 2; 0.7%).

Table 3—

Aetiology of the 12 cases with multiple bacterial pathogens specified

^#: determined by blood culture; ^¶: determined by sputum; ⁺: determined by urinary antigen test.

Table 4—

Appropriateness of empirical antibiotic treatment and normalisation patterns of C-reactive protein (CRP)

	Unknown aetiology	Patients with established aetiology
	Unknown aetiology	Received appropriate antibiotic treatment	Received inappropriate antibiotic treatment	Mean difference^# (95% CI)	p-value
Subjects	152 (52.6)	112 (38.8)	25 (8.7)
Median CRP values
Day 0	140.5 (56–293)	233.0 (131–358)	152 (63–243)
Day 3	90.0 (23–153)	98.0 (30–168)	108.5 (55–215)
Day 7	29.0 (12–79)	36.0 (18–75)	29 (15–92)
Mean decline in CRP
Day 0–3	36.3±30.4	44.5±30.5	25.2±24.4	19.3 (6.1–32.5)	<0.001
Day 0–7	63.1±34.6	75.5±24.7	60.4±32.3	15.1 (1.8–28.5)	0.03

Data are presented as n (%), median (interquartile range) or mean±sd, unless otherwise stated. CI: confidence interval. ^#: the mean difference (95% CI) in per cent decline in CRP among patients with appropriate and inappropriate antibiotic treatment (established aetiology) is displayed.

Table 6—

Multivariate analysis of delayed normalisation of C-reactive protein (CRP) and the risk for having an unfavorable outcome

	Mortality (within 28 day)		Early (within 3 days) treatment failure		Late (within 28 days) treatment failure
	OR (95% CI)	p-value	OR (95% CI)	p-value	OR (95% CI)	p-value
Day 0–3 CRP decline <60%	1.09 (0.32–3.73)	0.89	1.57 (0.85–2.92)	0.16	1.29 (0.62–2.68)	0.50
Day 0–7 CRP decline <90%	1.23 (0.45–2.99)	1.00			0.87 (0.39–1.94)	0.74

The displayed odds ratios (ORs) are adjusted for patient characteristics (age, sex and comorbid illnesses), Pneumonia Severity Index score, symptoms and signs of pneumonia (cough, sputum production, sore throat, dyspnoea, chest pain, hemoptoe, confusion, blood pressure, respiratory rate, pulse and oxygen saturation). CI: confidence interval.