Tomas Vikerfors

Bacterial or Crystal-associated Arthritis? Discriminating Ability of Serum Inflammatory Markers

A retrospective study of patients with culture-verified septic arthritis (n = 54) and polarizing microscopy verified crystal-associated arthritis (n = 34) was conducted with the objective to identify discriminating laboratory parameters in serum. Serum CRP levels (p = 0.002) and ESR (p = 0.03) were significantly higher on admission in patients with septic arthritis than in those with crystal-associated arthritis. The peripheral WBC counts did not differ between the two groups, nor did the lactoferrin or procalcitonin (PCT) levels. Serum TNFalpha concentrations on admission were higher in patients with septic arthritis than in those with crystal-associated arthritis (p = 0.0008). Significant differences were also found for IL-8 (p = 0.01) and G-CSF (p = 0.002), but not for IL-6 (p = 0.5). However, extensive overlap between the groups was present, resulting in low sensitivity, specificity and predictive value for each test. Determining serum levels of acute phase reactants, including cytokines, does not replace careful synovial fluid examination, including direct microscopy and cultivation.

Use of inflammatory markers for early detection of bacteraemia in patients with febrile neutropenia.

The aim of the study was to evaluate the ability of procalcitonin, C-reactive protein, serum amyloid A, interleukin-6 and interleukin-8 to predict bacteraemia during the 2 first d of fever in neutropenic patients. A total of 94 febrile neutropenic episodes in 60 patients were studied. Plasma samples were analysed at 10-h intervals from the onset of fever. Clinical events were categorized into 4 groups: 1) bacteraemia caused by other agents than coagulase-negative staphylococci (non-CNS bacteraemia) (n=21), 2) coagulase-negative staphylococci bacteraemia (n=15), 3) microbiologically or clinically documented infection without bacteraemia (n=26) and 4) fever of unknown origin (n=32). In non-CNS bacteraemia all markers, except for serum amyloid A, showed significantly higher levels compared to patients with fever of unknown origin (p<0.05). For non-CNS bacteraemia the highest negative predictive value was found for procalcitonin (94%), followed by interleukin-6 (89%), C-reactive protein (88%) and interleukin-8 (87%). Procalcitonin, with a cut-off level of 1.4 ng/ml during 10–20 h after fever onset, showed the highest positive predictive value (67%) for a non-CNS bacteraemia. In conclusion, the value of the analysed markers to predict a non-CNS bacteraemia in neutropenic patients was limited due to low sensitivity and positive predictive value. However, procalcitonin, interleukin-6, C-reactive protein, and interleukin-8 could give useful information for the clinician in excluding a non-CNS bacteraemia.

Dynamics of blood cytokine concentrations in patients with bacteremic infections

Cytokines play a major role in the pathophysiology of sepsis and septic shock. Using enzyme immunoassays the acute serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), granulocyte-colony stimulating factor (G-CSF), interleukin-8 (IL-8), and leukemia inhibitory factor (LIF) were investigated in 90 patients with positive blood cultures and clinical signs of infection. In 27 patients samples were obtained on admission, after 1, 4, 12, 18, and 24 h, and then daily. The acute serum levels of IL-6, TNF-alpha, G-CSF, and IL-8 were significantly higher among patients with severe sepsis. Patients with Gram-negative infection had significantly higher levels of TNF-alpha on admission than did patients with Gram-positive infections (p = 0.0008). The levels of IL-6, G-CSF and, to some extent, TNF-alpha decreased rapidly in survivors within the first 24 h of admission to hospital and institution of treatment. LIF was detected in 8/90 in both survivors and nonsurvivors.

Detection of Specific IgM Antibodies for the Diagnosis of Mycoplasma pneumoniae Infections: A Clinical Evaluation

The diagnostic value of detection of specific IgM antibodies was analysed in Mycoplasma pneumoniae infections. In a retrospective clinical and serological study, M. pneumoniae IgM antibodies were determined by a mu-capture ELISA using enzyme-labelled antigen. The study group consisted of 91 patients with significantly raised titers in paired sera or a single high titer of complement fixation antibodies. About 40% of the patients had been treated with antibiotics ineffective against M. pneumoniae infections prior to admission to hospital. Treatment with erythromycin or tetracycline was shown to give a shorter period of fever compared to if no or ineffective therapy was given. Specific IgM antibodies were detected in about 80% of sera sampled 9 days or more after onset of symptoms. In sera sampled at 7-8 days after onset IgM antibodies were found in about 40% of the sera but only occasionally in sera sampled earlier. In the age group 0-20 years 88% of the patients developed an IgM response. In the higher ages (greater than 60 years) a significantly lower rate of IgM responders was observed.

Assessment of systemic inflammation markers to differentiate a stable from a deteriorating clinical course in patients with febrile neutropenia

In this study, we evaluated the predictive values of procalcitonin (PCT), C‐reactive protein (CRP), interleukin‐6 (IL‐6) and serum amyloid A (SAA) for determining the clinical course in febrile neutropenic patients. Daily plasma analyses during the fever course were performed in 101 episodes with fever and chemotherapy‐induced neutropenia (neutrophil count <0.5 × 109/L). Procalcitonin (PCT) and IL‐6 values were significantly higher in febrile episodes in patients who developed complications. Procalcitonin with a cut‐off value of ≤0.4 ng/mL or IL‐6 ≤50 pg/mL 3 d after fever onset indicated daily high negative predictive values (NPVs) (91–100%) for episodes with complications. No marker could predict deterioration; however, daily low plasma concentrations of PCT or IL‐6 during the first 8 d of fever were found to be a good predictor of no subsequent complications in neutropenic patients and therefore to be a helpful tool for limiting anti‐microbial therapy.

Increased Incidence of Childhood Bacterial Meningitis: A 25-Year Study in a Defined Population in Sweden

In a retrospective study in Orebro, Sweden 1956-1980, 201 cases of bacterial meningitis in children over the age of 1 month were analysed. The aetiology was Haemophilus influenzae in 123 cases, Neisseria meningitidis in 55 cases and Streptococcus pneumoniae in 19 cases. We registered a significant increase in incidence of H. influenzae meningitis from 5.6 (1956-1965) to 13.0 (1971-1980) per 100,000 children and year (p less than 0.01). The mortality decreased from 19% to 4% during the period studied. This decrease was primarily due to a reduced mortality in hospital later than 12 h after admission. Hearing impairment was the most frequent sequel (10%) and no change in frequency was observed during the 25 years studied. Hearing impairment was registered significantly more often in cases with a late admission to hospital (greater than 48 h) as compared to cases with an earlier admission (p less than 0.001).

Febrile Plasmodium falciparum Malaria 4 Years after Exposure in a Man with Sickle Cell Disease

We report a case of symptomatic Plasmodium falciparum malaria that manifested 4 years after a visit to an area of endemicity in an 18-year-old male patient with sickle cell disease. The exceptionally long incubation time raises the questions of how and where P. falciparum parasites can reside for several years before suddenly causing disease.

Secretion of IL-6, IL-8 and G-CSF by human endothelial cells in vitro in response to Staphylococcus aureus and staphylococcal exotoxins

The capacity of endothelial cells to produce and release cytokines (IL‐6, IL‐8 and G‐CSF) in response to exposure to Staphylococcus aureus strains or staphylococcal exotoxins (α‐toxin, enterotoxin A and TSST‐1) was investigated. An endothelial cell culture model of human umbilical vein endothelial cells (HUVEC) was used. Five out of ten clinical isolates of S. aureus were found to induce cytokine production and release from endothelial cells. Four of the five isolates that induce cytokine release produced enterotoxin A, B, C, D and/or TSST‐1, compared with two of those that did not induce release. Purified staphylococcal exotoxins (1 pg/ml – 1 μg/ml) did not act as primary stimuli and induced no detectable cytokine secretion. When endothelial cells were prestimulated with IL‐1β or TNFα at a concentration of 1 ng/ml for 2 h, IL‐1β served as a potent primary stimulus for IL‐6, IL‐8 and G‐CSF production, whereas TNFα did not induce any significant cytokine release during the subsequent 24 h. A further increase in IL‐6 and G‐CSF release, but not of IL‐8, was observed when IL‐1β prestimulated cells were exposed to α‐toxin or TSST‐1. However, to potentiate cytokine production (IL‐6 and IL‐8) by SEA, both IL‐1β and the toxin had to be present simultaneously. Our data show that S. aureus, but not staphylococcal exotoxins, have the capacity to act as primary stimuli of endothelial cells and induce production and release of cytokines. IL‐1β may prime HUVEC to release IL‐6, IL‐8 and G‐CSF prior to subsequent stimulation with staphylococcal exotoxins.

Increased Incidence of Bacteraemia Due to Viridans Streptococci in an Unselected Population of Patients with Acute Myeloid Leukaemia

The aetiology, clinical characteristics and outcome of bacteraemia in patients with acute myeloid leukaemia were studied. All positive blood cultures collected at a haematological ward during 2 7-y periods were evaluated. Altogether, 274 episodes of bacteraemia in 152 patients were recorded, 80 episodes during 1980-86 and 194 during 1990-96. During the 2 periods, trimethoprim-sulfamethoxazol in combination with amikacin was the first-line empirical therapy in patients with neutropaenia and fever. In 1990, antimicrobial prophylaxis with ciprofloxacin and fluconazole was introduced. The incidence of bacteraemia due to viridans streptococci or coagulase-negative staphylococci increased from the first period to the second, whereas the incidence of Enterobacteriaceae decreased. In granulocytopaenic patients during 1990-96, viridans streptococci accounted for 21% of the isolates and in patients treated prophylactically with fluoroquinolone, viridans streptococci accounted for 31%. All viridans streptococci were sensitive to penicillin. At the time of the positive blood cultures, the patients of the second period were granulocytopaenic in 83% of the episodes. The mortality related to septicaemia during the later period was 13% and only 1 of 33 (3%) of the patients with viridans streptococci died. Eight patients (9%) died in relation to septicaemia following curative antileukaemic therapy.The aetiology, clinical characteristics and outcome of bacteraemia in patients with acute myeloid leukaemia were studied. All positive blood cultures collected at a haematological ward during 2 7-y periods were evaluated. Altogether, 274 episodes of bacteraemia in 152 patients were recorded, 80 episodes during 1980-86 and 194 during 1990-96. During the 2 periods, trimethoprim-sulfamethoxazol in combination with amikacin was the first-line empirical therapy in patients with neutropaenia and fever. In 1990, antimicrobial prophylaxis with ciprofloxacin and fluconazole was introduced. The incidence of bacteraemia due to viridans streptococci or coagulase-negative staphylococci increased from the first period to the second, whereas the incidence of Enterobacteriaceae decreased. In granulocytopaenic patients during 1990-96, viridans streptococci accounted for 21% of the isolates and in patients treated prophylactically with fluoroquinolone, viridans streptococci accounted for 31%. All viridans streptococci were sensitive to penicillin. At the time of the positive blood cultures, the patients of the second period were granulocytopaenic in 83% of the episodes. The mortality related to septicaemia during the later period was 13% and only 1 of 33 (3%) of the patients with viridans streptococci died. Eight patients (9%) died in relation to septicaemia following curative antileukaemic therapy.

Interleukin-6, C-reactive protein, lactoferrin and white blood cell count in patients with S. aureus septicemia.

In a prospective study of 65 patients with S. aureus septicemia, the clinical value of measuring serum IL-6 and lactoferrin levels was assessed and compared with CRP levels and WBC count. 20/65 (31%) patients had a CRP value < or = 100 mg/l on admission and 10 (50%) and 11 (55%) of these had serum levels of IL-6 > 100 pg/ml or lactoferrin > 2.0 mg/l, respectively. 41/64 (64%) patients had a WBC count < or = 15.0 x 10(9)/l and the corresponding figures for increased IL-6 and lactoferrin values were 29 (71%) and 21 (51%) patients, respectively. The high concentrations of IL-6 and lactoferrin on admission decreased rapidly during the hospital stay, better reflecting the clinical course than CRP and WBC count. Patients with endocarditis showed higher IL-6 levels and body temperatures both on admission and during the first days of hospitalization compared with patients without endocarditis.