The effect of granulocytopenia on experimental tuberculin fever

The febrile responses of hypersensitive, granulocytopenic and hypersensitive, non-granulocytopenic animals to specific antigen have been compared with the following results:

1. Hypersensitive animals, whether granulocytopenic or not, had an equal febrile response when challenged with specific antigen.

2. Hypersensitive animals with agranulocytosis developed fever when challenged with specific antigen.

3. Serum from granulocytopenic, antigen-challenged, hypersensitive donors contained a pyrogenic factor as potent in normal recipients as was serum from non-granulocytopenic, hypersensitive donors.

It is suggested therefore that the granulocyte is not the source of endogenous serum pyrogen in the fever of delayed hypersensitivity and is not necessary for the febrile response of the hypersensitive animal to specific antigen.

     

Value of measurement of C-reactive protein in febrile patients with hematological malignancies

The maximum serum levels of C-reactive protein (CRP) in 126 patients with hematological malignancies who had 554 febrile episodes were analyzed retrospectively with regard to documented infections and fever of unknown origin. The CRP levels were significantly higher when the blood culture was positive than when it was negative (p=0.002). The CRP levels were significantly higher when the infection focus was identified than when it was not (p=0.010). In patients with fever of unknown origin the CRP was significantly lower than in patients with microbiologically documented infections (p<0.001). Cytotoxic treatment neither reduced nor enhanced the CRP reaction. The serial measurement of CRP is a reliable and readily available means for differentiating between bacterial infections and other causes of fever in patients with hematological malignancies, also during neutropenia and after cytotoxic treatment.     

Markers of bacteremia in febrile neutropenic patients with hematological malignancies: procalcitonin and IL-6 are more reliable than C-reactive protein

Since neutropenic patients with hematological malignancies are at high risk of contracting life-threatening infections, specific markers of infection are needed in cases of febrile neutropenia. The study presented here assessed serum concentrations of C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6) in samples obtained from 31 febrile neutropenic patients. A total of 53 episodes were evaluated, and 18 of these were associated with positive blood culture results. Procalcitonin and IL-6 concentrations differed significantly between bacteremic and non-bacteremic episodes. Procalcitonin values were 0.22 ng/ml [interquartile range (IR), 0.15–1.9] for patients with pneumonia without bacteremia, 0.22 ng/ml (IR, 0.16–0.55) for patients with fever of unknown origin, 0.2 ng/ml (IR, 0.13–0.57) for patients with non-microbial fever and 1.8 ng/ml (IR, 0.35–5.3) for patients with bacteremia. The differences between bacteremic and non-bacteremic episodes had a P-value of 0.003 using the Mann–Whitney test. For IL-6 the median values were 301 pg/ml (IR, 152–1,879) for patients with pneumonia without bacteremia, 207 pg/ml (IR, 94–445) for patients with fever of unknown origin, 177 pg/ml (IR, 142–208) for patients with non-microbial fever and 942 pg/ml (IR, 181–2,807) for patients with bacteremia. Using the Mann–Whitney test, the differences between bacteremic and non-bacteremic episodes were P=0.006. No differences were found in CRP concentrations. Cutoff levels to distinguish between bacteremic and non-bacteremic episodes were chosen using receiver operating characteristic curves: 0.62 ng/ml for PCT and 297 pg/ml for IL-6. Negative predictive values were 84% for PCT and 70% for IL-6. The results indicate that PCT and IL-6 are more reliable markers than CRP for predicting bacteremia in patients with febrile neutropenia.     

Easier monitoring of aminoglycoside therapy with once-daily dosing schedules

Little has been reported on serum levels attained using once-daily aminoglycoside regimens and their relation to dosage administered and renal function. Consecutive patients with serious infections were randomized to receive gentamicin 4 mg/kg q 24 h i.v. (n=69), gentamicin 1.33 mg/kg q 8 h i.v. (n=46) or netilmicin 5.5 mg/kg q 24 h i.v. (n=59) (with dose reduction in case of renal dysfunction). In the three groups, median first serum trough levels were 0.4, 1.0 and 0.4 mg/l, respectively, and median first serum peak levels were 9.5, 4.7 and 12.2 mg/l (p<0.01 once-daily vs. thrice-daily regimens). Dose adjustment because of first trough concentrations of > 2 mg/l and/or peak concentrations of < 6 mg/l was required in 6 %, 78 % and 12 % of patients, respectively. Second trough and peak concentrations were significantly higher in the thrice-daily gentamicin group; serum levels remained constant in the other two groups. The six patients in the once-daily groups who developed elevated trough levels later in therapy were characterized in most cases by a decline in renal function.     

Diagnostic value of neopterin during neutropenic fever and determination of disease activity in childhood leukemias

Neopterin, a pteridine group compound that is secreted from macrophages is shown to be increased in adult leukemia; however there are few studies in childhood leukemia. This study aimed to investigate neopterin levels during childhood leukemia treatment and neutropenic fever episodes for the possibility of using as a marker for disease activity and differentiation of infections. A total of 44 children with acute leukemia, 19 children with infection (control group 1) and 21 healthy children (control group 2) were studied. Median serum neopterin level before induction chemotherapy (day 0) in 25 children (patient group 1) was significantly higher (27.7 nmol/L) than those at the beginning of 30 febrile episodes in 19 children in bone marrow remission (2.2 nmol/L) (patient group 2) and in control group 2 (0.4 nmol/L) (p< 0.05). It was (27.7 nmol/L) also significantly higher in control group 1 than in patient group 2 and control group 2 (p< 0.05). Serum neopterin levels at day 15 (2.1 mmol/L) and day 33 (0.4 mmol/L) of induction were significantly lower than day 0 of ALL subgroup at patient group 1. There were no significant difference in neopterin levels between days 0, 3 and 5 of neutropenic fever as well as between patients with microbiologically and/or clinically documented infections and those with fever of unknown origin in patient group 2 (p> 0.05). Serum neopterin did not show significant correlation with absolute neutrophil count and absolute monocyte count (p> 0.05). In conclusion, elevated neopterin at diagnosis of leukemia with decrement during induction therapy suggest that it might be an indicator of leukemic process; however larger studies for its role in identifying infections are warranted.     

Serum procalcitonin for differentiating bacterial infection from disease flares in patients with autoimmune diseases

Early differentiation between bacterial infections and disease flares in autoimmune disease patients is important due to different treatments. Seventy-nine autoimmune disease patients with symptoms suggestive of infections or disease flares were collected by retrospective chart review. The patients were later classified into two groups, disease flare and infection. C-reactive protein (CRP) and serum procalcitonin (PCT) levels were measured. The CRP and PCT levels were higher in the infection group than the disease flare group (CRP,11.96 mg/dL ± 9.60 vs 6.42 mg/dL ± 7.01, P = 0.003; PCT, 2.44 ng/mL ± 6.55 vs 0.09 ng/mL ± 0.09, P < 0.001). The area under the ROC curve (AUC; 95% confidence interval) for CRP and PCT was 0.70 (0.58-0.82) and 0.84 (0.75-0.93), which showed a significant difference (P < 0.05). The predicted AUC for the CRP and PCT levels combined was 0.83, which was not significantly different compared to the PCT level alone (P = 0.80). The best cut-off value for CRP was 7.18 mg/dL, with a sensitivity of 71.9% and a specificity of 68.1%. The best cut-off value for PCT was 0.09 ng/mL, with a sensitivity of 81.3% and a specificity of 78.7%. The PCT level had better sensitivity and specificity compared to the CRP level in distinguishing between bacterial infections and disease flares in autoimmune disease patients. The CRP level has no additive value when combined with the PCT level when differentiating bacterial infections from disease flares.     

Acute hepatitis with or without jaundice: a predominant presentation of acute Q fever in southern Taiwan.

Acute Q fever was previously regarded as an uncommon infectious disease in Taiwan but has been increasingly recognized recently. Acute febrile illness, hepatitis, and pneumonia are the 3 most common manifestations of this condition, whereas jaundice is rarely reported among patients with acute Q fever. We report 2 cases of acute Q fever with jaundice and multi-organ involvement. The first patient presented with fever, severe headache, and acute abdomen necessitating laparotomy and was complicated with acute cholestatic hepatitis, acute non-oliguric renal failure and disseminated intravascular coagulation. The second patient had acute cholestatic hepatitis and thrombocytopenia, and the latter was likely related to the infection of bone marrow by Coxiella burnetii, as evidenced by the presence of C. burnetii DNA detected by nested polymerase chain reaction. The incidence and clinical significance of hyperbilirubinemia was also determined by review of medical records of 35 cases of acute Q fever cases diagnosed serologically at National Cheng Kung University Hospital from 1994 to 2001. All had biochemical hepatitis and 23% had hyperbilirubinemia (serum bilirubin > or =2 mg/dL). The febrile course before admission and the period between the initiation of effective medication to defervescence were longer in patients with hyperbilirubinemia than in patients without hyperbilirubinemia, although this difference was not significant. Our results suggest that the predominant presentation of acute Q fever in southern Taiwan is acute febrile illness with hepatitis and that jaundice is not uncommon. Due to the clinical polymorphism of acute Q fever, the threshold of surveys for C. burnetii infections should be low for febrile patients with elevated transaminases or hyperbilirubinemia of unknown cause.     

Endotoxin fever in granulocytopenic rats: evidence that brain cyclooxygenase-2 is more important than circulating prostaglandin E(2)

PGE(2) is a recognized mediator of many fevers, and cyclooxygenase (COX) is the major therapeutic target for antipyretic therapy. The source, as well as the site of action of PGE(2), as an endogenous pyrogen, is widely accepted as being central, but PGE(2) in the circulation, possibly from leukocytes, may also contribute to the development of fever. However, bacterial infections are important causes of high fever in patients receiving myelosuppressive chemotherapy, and such fevers persist despite the use of COX inhibitors. In the study reported here, the febrile response to bacterial LPS was measured in rats made leukopenic by cyclophosphamide. A striking increase in LPS fever occurred in these granulocytopenic rats when compared with febrile responses in normal animals. Unlike LPS fever in normal rats, fever in granulocytopenic rats was neither accompanied by an increase in blood PGE(2) nor inhibited by ibuprofen. Both leukopenic and normal rats showed LPS-induced COX-2-immunoreactivity in cells associated with brain blood vessels. Furthermore, LPS induced an increase of PGE(2) in cerebrospinal fluid. Induction of COX-2-expression and PGE(2) production was inhibited by ibuprofen in normal but not in leukopenic rats. Although the results presented are, in part, confirmatory, they add new information to this field and open a number of important questions as yet unresolved. Overall, the present results indicate that, in contrast to immunocompetent rats, leukocytes and/or other mechanisms other than PGE(2) are implicated in the mechanisms restricting and reducing the enhanced febrile response to endotoxin in immunosuppressed hosts.     

Dynamics of serum procalcitonin in patients after major neurosurgery

Classical markers of infection cannot differentiate reliably between inflammation and infection after neurosurgery. This study investigated the dynamics of serum procalcitonin (PCT) in patients following major neurosurgery. PCT concentrations remained < 0.2 ng/mL during the post-operative course. In contrast, leukocyte and neutrophil counts, as well as C-reactive protein (CRP) levels, increased significantly post-operatively (leukocytes, range 7.1-23.7 x 10(9)/L, p < 0.001; neutrophils, range 70.8-94.5%, p < 0.001; CRP, median 14 mg/L, range 3-95 mg/L, p < 0.001). Analysis of PCT levels using assays with improved sensitivity may be useful in the diagnosis of neurosurgical patients with post-operative fever of unknown origin.     

C-reactive protein (CRP) response patterns in neonatal septicaemia.

C-reactive protein (CRP) is an unreliable diagnostic tool in the early diagnosis of neonatal septicaemia. However, serial measurements have been shown to be useful in monitoring the effectiveness of treatment. The aim of the present study was to investigate whether a specific CRP response pattern to different groups of pathogens could be identified during treatment of neonatal septicaemia. Serial CRP measurements from day 1 to 4 in monomicrobial blood culture-proven episodes of septicaemia were reviewed. In 4416 admissions, 180 out of 206 positive blood cultures were monomicrobial; 121 monomicrobial septic episodes were eligible for final analysis of the CRP response during treatment. A low median (M) value (day 1 to 4) was identified in coagulase-negative staphylococci (CONS) (M=23 mg/l), contrasting with high median values in Staphylococcus aureus (M=58 mg/l), group B streptococci (M=51 mg/l), Escherichia coli (M=51 mg/l) and Candida species (M=76 mg/l) (p<0.001). Median CRP values in the two groups were different for each of the treatment days 1 to 4 (p<0.001). An increase (p<0.001) in CRP during the 24 h before initiation of treatment was a sign of late-onset CONS septicaemia. In episodes where antimicrobial treatment failed, CRP levels were moderately elevated the day prior to treatment start and increased continuously thereafter, whereas successful treatment was generally accompanied by a decline in CRP in less than 4 days. The CRP response to CONS is significantly less pronounced than to other commonly encountered pathogens in neonatal septicaemia. A rise in CRP beyond the third day of empirical treatment should give rise to a suspicion of fungal infection or ineffective antibacterial treatment.     

The effect of Helicobacter pylori eradication on C-reactive protein: results from a meta-analysis

IntroductionHelicobacter pylori is a bacterium that causes chronic gastroduodenal infection and affects various systemic diseases. An increase in the blood level of C-reactive protein (CRP; a systemic inflammatory marker), at a low-grade chronic inflammation level, is observed in cases of infection. However, the effect of H. pylori eradication on CRP remains undetermined. Therefore, we aimed to evaluate the circulating CRP levels in eradicated patients through a meta-analysis.Material and methodsThe PubMed database was searched from its inception to June 2020. Studies that described the CRP levels following H. pylori eradication were collected. A random-effects meta-analysis was then performed using inverse variance with standardized mean difference.ResultsA total of 10 eligible studies (642 subjects in total) were available. The median age in the studies was 49.9 years. The CRP level was 6.0 (median) mg/l before H. pylori eradication and 5.8 (median) mg/l after eradication. From the results of the overall meta-analysis, there was found to be a significant reduction in the CRP levels with H. pylori eradication (standardized mean difference: –0.64; 95% confidence interval: –1.02 to –0.27). The result was not similarly confirmed in a subanalysis of the available randomized controlled trials.ConclusionsWeak evidence exists regarding the effects of H. pylori eradication on CRP levels. Further research is called for.     

Modulation of the systemic inflammatory response by recombinant human interleukin-11: a prospective randomized placebo controlled clinical study in patients with hematological malignancy

The immunomodulatory activities of recombinant human interleukin-11 (rhIL-11) were investigated in a clinical trial among patients with hematological malignancy, randomized to either rhIL-11 or placebo throughout chemotherapy. Daily serum concentrations of sTNFRI, IL-6, IL-8, TNFalpha, and CRP were measured. Higher sTNFRI levels [mean pg/ml (95% CI)] were detected in patients receiving rhIL-11 compared to placebo [1749.7 (1626-1882.9) versus 1038.5 (953.3-1131.3)] respectively (P = 0.01) for all 898 observations and during febrile days [2327.6 (2142.6-2528.2) versus 1308.9 (1163-1473.2), P = 0.12] and during days without infection [1406.6 (1266.1-1563) versus 871.3 (774.9-979.6), P < 0.001]. A similar pattern in CRP concentrations was observed. Multivariate analysis indicated rhIL-11 was associated with elevated sTNFRI or CRP independent of infectious episodes and other factors. 7 patients (all receiving placebo) of 40 had elevated TNFalpha levels. IL-6 and IL-8 levels were not substantially affected by rhIL-11. Bacteremia, fungal infections, and fever of unknown origin (FUO) were reduced in rhIL-11-treated patients. Given the role of sTNFRI in dampening the deleterious effects of a hyperactive TNFalpha environment, rhIL-11-induced upregulation of sTNFRI shedding is a potentially important mechanism for modulating immune and inflammatory responses in humans.     

The relationship between serum neutrophil gelatinase-associated lipocalin and renal function in patients with vancomycin treatment

Background Vancomycin is used for the treatment of resistant staphylococcal and enterococcal infections but is associated with nephrotoxicity. Neutrophil gelatinase-associated lipocalin (NGAL) was recently identified as a sensitive biomarker for acute kidney injury. Here, we aimed to investigate the usefulness of serum NGAL in monitoring patients undergoing vancomycin therapy. Methods A total of 253 NGAL tests from 59 patients undergoing vancomycin therapy were evaluated. Patients with trough serum concentrations of vancomycin that exceeded 20 ug/mL were included. Serum NGAL was measured using a commercially available ELISA kit, and other biochemical indicators including creatinine, leukocyte count, eGFR and C-reactive protein were assessed. Results At the initiation of vancomycin treatment, serum creatinine level was 0.93 ± 0.40 (mean ± SD) mg/dL, NGAL was 341 ± 354 mg/dL, leukocyte count was 10,750 ± 7190 per uL and CRP level was high (10.8 ± 9.3 mg/dL). About 49% of patients had an elevated leukocyte count, and all patients showed a high CRP level. Basal serum NGAL concentration in the patients with elevated leukocyte level (10,000/uL or higher) was higher compared to that in patients with normal leukocyte levels (mean ± SD, 478 ± 449 mg/dL vs. 176 ± 101 mg/dL, p<0.001). A significant positive relationship was found between NGAL level and creatinine level in patients with normal basal leukocyte levels but not in those with higher leukocytes. Conclusion The clinical usefulness of serum NGAL should be interpreted carefully when evaluating renal impairment in patients undergoing vancomycin treatment.     

Antioxidant potential, paraoxonase 1, ceruloplasmin activity and C-reactive protein concentration in diabetic retinopathy

The aim of this study was to evaluate the ferric-reducing ability of serum (FRAS), paraoxonase 1 (PON1), ceruloplasmin serum oxidase activity and hsCRP level in patients with type1 diabetes mellitus without and with diabetic retinopathy. The study was performed in 76 patients with type 1 diabetes mellitus, 35 without diabetic retinopathy (group 1) and 41 with preproliferative and proliferative retinopathy (group 2). Control group consisted of 35 nondiabetic, age-, gender-, body mass-matched healthy volunteers who came to the outpatient clinic for a routine health check-up. We evaluated FRAS using the method described by Benzie and Strain; PON1 by kinetic spectrophotometric assay with paraoxon as substrate and ceruloplasmin using its oxidative activity with 3-phenylenodiamine as substrate. CRP was measured with a high sensitive enzyme immunoassay. PON1 activity was significantly decreased in patients with diabetic retinopathy (227.66 ± 123.57 U/l) when compared with control (312.04 ± 129.77 U/l). FRAS was significantly decreased in group 2 (439.33 ± 79.87 μmol/l) when compared with group 1 (522.79 ± 167.56 μmol/l) and control (529.80 ± 81.99 μmol/l). Ceruloplasmin activity was significantly elevated in group 1 (58.36 ± 22.56 U/g protein) when compared with control (45.22 ± 14.96 U/g protein). We have found significant increase in hsCRP level in group 2 (3.71 ± 2.47 mg/l) when compared with group 1 (1.75 ± 1.01 mg/l) and control (0.57 ± 0.46 mg/l). The PON1/CRP ratio in control group was significantly increased when compared with diabetic patients and was significantly decreased in group 2 compared with group 1. We have not found gender-dependent difference in studied parameters in both control and in study groups. We have found tendency to decrease the serum activity of FRAS and hsCRP in elder patients but the difference was significant only in group 2. FRAS and PON 1 activity is decreased in patients with type 1 diabetes mellitus with presence of diabetic retinopathy which confirms that oxidative stress could play a role in pathogenesis of diabetic retinopathy. Significantly elevated levels of hsCRP in diabetic patients with the presence of diabetic retinopathy compared with patients without diabetic retinopathy providing a link between inflammation and the development of microvascular complication of diabetes. Because of the significant difference in PON1/CRP ratio between patients without and with the presence of diabetic retinopathy, it seems that PON1:CRP ratio may be used as a biochemical marker for progression of retinopathy. The link between the antioxidant concentration, inflammation and the development of diabetes complications needs further longitudinal studies in order to confirm our findings.     

Antiphospholipid Antibodies are Associated with Low Levels of Complement C3 and C4 in Patients with Systemic Lupus Erythematosus

Complement activation and low complement levels are common in systemic lupus erythematosus (SLE). Antiphospholipid antibodies (aPL) are found in about 30‐40% of patients with SLE. This study aimed to investigate the association between aPL and complement levels in patients with SLE. Serum samples were collected from 269 patients with SLE enrolled in the Norwegian Systemic Connective Tissue and Vasculitis Registry (NOSVAR) during 2003‐2009, and from 353 controls. All samples were analysed for anti‐β2 glycoprotein 1 (anti‐β2GP1) and anticardiolipin antibodies (aCL), C‐reactive protein (CRP) and complement components C3 and C4. Median CRP level was significantly higher in cases than in controls (2.06 versus 0.90 mg/l; P < 0.0001). No significant difference in CRP was found between SLE patients with or without aPL (2.09 versus 1.89; P = 0.665). Median C3 levels were similar in cases (1.03 g/l) and controls (1.00 g/l), whereas median C4 levels were 0.16 g/l in cases versus. 0.19 in controls (P < 0.0001). However, aPL‐positive SLE patients had significantly lower median C3 levels (0.92 versus. 1.07 g/l; P = 0.001) and C4 levels (0.11 versus 0.16 g/l; P < 0.0001) compared to aPL‐negative patients. Lower C3 and C4 values in aPL‐positive SLE patients may reflect a higher consumption of C3 and C4 due to more pronounced complement activation in aPL‐positive SLE patients compared to SLE patients without aPL.     

Radiometric ligand binding assay for C-reactive protein. Complexed C-reactive protein is not detectable in acute phase serum.

A radiometric ligand binding assay for human C-reactive protein (CRP) was established using pneumococcal C polysaccharide (CPS) coupled to magnetizable cellulose particles as the solid phase ligand. Competition for binding to the solid phase between 125I-CRP and unlabelled CRP permitted detection of 30 micrograms/l of CRP and the precise assay of concentrations up to 3000 micrograms/l. Identical results were obtained when the assay was used to quantitate isolated pure CRP and pure CRP added to normal human serum. However in vitro addition of known ligands for CRP to acute phase serum resulted in lowering of the apparent CRP concentration in this assay and addition of as little as 1 microgram/l of free CPS or 1 mg/l of lecithin was demonstrable in this way. A combination of the ligand binding assay and the standard electroimmunoassay for CRP was therefore used to test acute phase sera for the presence of CRP complexed in vitro. No evidence of complexed CRP was detected among sera containing between 1-319 mg/l of CRP from patients with Hodgkin's disease (10), rheumatoid arthritis (10), Crohn's disease (19) and various microbial infections (11), including six with subacute bacterial endocarditis. Since it is likely that CRP does form complexes with its ligands in the plasma these results suggest that complexed CRP is rapidly cleared from the circulation.     

High-sensitivity C-reactive protein, adiposity, and blood pressure in the Yakut of Siberia.

C-reactive protein (CRP), an acute-phase reactant and marker of inflammatory response, is known to be an important predictor of future cardiovascular mortality, independent of other risk factors. The purpose of this research was to investigate the association between CRP, adiposity, and blood pressure in the Yakut, an indigenous Siberian population undergoing rapid cultural change. We conducted a cross-sectional study of 265 healthy Yakut adults in six villages in rural northeastern Siberia. Plasma CRP was measured by high-sensitivity immunoturbidimetric assay. The median CRP value was 0.85 mg/l, with values for the 25th, 50th, and 75th percentiles of 0.30, 0.85, and 2.28 mg/l, respectively. CRP was positively associated with age (r = 0.19; P = 0.002), but not plasma lipids or smoking status. CRP was associated with measures of central adiposity and characteristics of the metabolic syndrome, particularly in women. We found significantly higher CRP across quintiles (Q) of waist circumference for women (difference = 0.7 mg/l; P = 0.035), but not men (difference = 0.36 mg/l; P = 0.515). CRP was significantly associated with systolic blood pressure in men (difference, Q1 vs. Q5 = 1.1 mg/l; P = 0.044) but not women (difference, Q1 vs. Q5 = 0.03 mg/l; P = 0.713) after adjusting for age, waist circumference, and smoking status. CRP in the Yakut was considerably lower than was reported for other populations. The low CRP levels may be explained in part by a low prevalence of abdominal obesity. Among the Yakut, the high physical-activity demands of a traditional herding lifeway likely play a role through high energy expenditure and maintenance of negative energy balance. Our findings underscore the need for further research on the metabolic activity of adipose tissue, blood pressure, and inflammatory activation in non-Western populations.     

Genetic polymorphism of the C-reactive protein (CRP) gene and a deep infection focus determine maximal serum CRP level in Staphylococcus aureus bacteremia

C-reactive protein (CRP) is widely used in early detection of sepsis or organ dysfunction. Several single nucleotide polymorphisms (SNPs) in the CRP gene are shown to be associated with variability of basal CRP. To clarify the effect of these SNPs to CRP response in systemic infections, we compared genetic and clinical data on patients with Staphylococcus aureus bacteremia (SAB). Six SNPs in the CRP gene region (rs2794521, rs30912449, rs1800947, rs1130864, rs1205 and rs3093075) were genotyped in 145 patients and analyzed for associations with CRP and various clinical outcomes. We found that the rare minor A-allele of triallelic SNP rs30912449 (C > T > A) and presence of a deep infection focus were strongly associated to the higher maximal CRP during the first week of SAB. Median of the maximal CRP in patients who had the A-minor allele was 282 mg/L (interquartile range [IQR, defined as the difference between the third quartile and the first quartile], 169 mg/L) but only 179 mg/L (IQR, 148 mg/L) in patients without this allele (P?=?0.004), and CRP in patients who had deep infection focus was higher 208 mg/L (IQR, 147 mg/L) than in other patients 114 mg/L (IQR, 121 mg/l) (P?<?0.0001). Mortality, degree of leucocytosis, time to defervescence or number of deep infections were not affected by CRP gene SNPs. The maximal CRP during the first week in SAB was partly determined by variation in the CRP gene and partly by presence of deep infection focus. This finding suggests cautiousness in interpreting exceptionally high CRPs from SAB patients and comparison between patients.     

Soluble haemoglobin scavenger receptor (sCD163) in patients with suspected community-acquired infections

The aim of our study was to evaluate soluble haemoglobin scavenger receptor (sCD163) as a molecular marker in patients with community-acquired infections. One hundred and ninety-four adult patients admitted to the Department of Internal Medicine, Odense University Hospital, with suspected community-acquired infection were included in a prospective study. Plasma and serum were sampled from all patients on day of admission and sCD163 and interleukin-6 levels were measured. Demographic data, co-morbidity, microbiological aetiology, biochemical parameters, focus of infection, severity score and mortality on day 28 were recorded. Median age was 68 (range 18-92) years. Mortality rate among infected patients on day 28 was 3.8%. sCD163 concentrations (median and range) were: 2.99 mg/l (1.22-12.65) in non-infected patients, 3.62 mg/l (1.59-74.04) (p=0.08) in infected patients without systemic inflammatory response syndrome, 3.2 mg/l (0.54-22.51) (p=0.4) in patients with sepsis, 3.63 mg/l (1.71-28.4) (p=0.01) in patients with severe sepsis, and 4.9 mg/l (2.66-28.4) (p=0.003) in patients with bacteraemia. In this cohort dominated by mild infections, a moderate elevation of sCD163 was observed only in patients with severe sepsis and/or bacteraemia. sCD163 did not discriminate between infected and non-infected patients.