Plasma interleukin-8, interleukin-10, and E-selectin levels in neutropenic and non-neutropenic bacteremic patients

Plasma interleukin-8 (IL-8), interleukin-10 (IL-10), and E-selectin concentrations were studied in 39 neutropenic and 30 non-neutropenic bacteremic patients; 54 nonbacteremic patients were analyzed as controls. Interleukin-8 concentrations were significantly higher in neutropenic than in non-neutropenic bacteremic patients (median 475 vs. 0 pg/ml, p<0.0001). Median IL-8 and IL-10 levels were higher in bacteremic than in non-bacteremic patients (330 vs. 0 pg/ml, p<0.0001 and 20 vs. 0 pg/ml, p=0.04, respectively). In contrast, concentrations of IL-10 were similar in neutropenic and non-neutropenic patients. Median levels of E-selectin were not increased in any of the patient groups. Neutropenic bacteremic patients showed significantly lower concentrations of E-selectin than did non-neutropenic bacteremic patients (p<0.0001). In conclusion, neutropenic bacteremic patients had significantly higher concentrations of IL-8 than non-neutropenic bacteremic patients. Levels of IL-10 were higher in bacteremic than in nonbacteremic patients, but neutropenic and non-neutropenic patients had similar levels of IL-10. Increased levels of E-selectin were not found in any of the patient groups, although neutropenic patients with bacteremia had lower concentrations than did non-neutropenic patients.     

Evaluation of tumor necrosis factor-α, interleukin-6 and C-reactive protein plasma levels as predictors of bacteremia in patients presenting signs of sepsis without shock

Objective: To evaluate the sensitivity of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) plasma measurement to detect bacteremia in patients presenting sepsis signs, and to evaluate the potential benefit of such measurement in terms of early antimicrobial therapy initiation.
Method: Plasma was obtained from 166 hospitalized patients for whom blood cultures were drawn for sepsis. Clinical data and antimicrobial therapies were noted. IL-6, TNF and C-reactive protein (CRP) were measured. The sensitivities of these markers were retrospectively compared with the accuracy of the attending physician in initiating empirical antimicrobial therapy. The setting was an 850-bed university hospital.
Results: Thirty-four bacteremias and 69 non-bacteremic infections were noted. In 63 others, no infection was documented. Median (range) IL-6 plasma levels in the three groups of patients were 462 (15–50 850), 189 (<15–38 300) and 91 (<10–13 750) pg/mL, respectively ( p <0.01). The corresponding TNF-α plasma levels were 37.5 (<15–2400), 15 (<15–240) and 15 (<15–200) pg/mL, respectively ( p <0.01). CRP plasma levels were 10.7 (<0.6–30.2), 10.3 (<0.6–34.4) and 7.3 (<0.6–20.9) mg/dL, respectively ( p =0.12). With respect to these three parameters, IL-6 and TNF-α appear better than CRP for predicting bacteremia. Clinical features resulted in starting empirical antimicrobial therapy in only 62% of the bacteremic patients. On the other hand, 68% of these bacteremic patients had high IL-6 plasma levels (>200 pg/mL). A combination of clinical features and high IL-6 levels would have permitted early treatment for 82% of the bacteremic patients.
Conclusions: IL-6 and TNF-α thus appear to be useful and earlier markers of bacteremia in septic patients. By contrast, CRP is neither sensitive nor specific in this setting.     

Plasma endotoxin and cytokine levels in neutropenic and non-neutropenic bacteremic patients

Plasma endotoxin, tumor necrosis factor- (TNF-), interleukin 1 (IL-1), interleukin 1 receptor antagonist (IL-1ra), and interleukin 6 (IL-6) concentrations in 69 bacteremic patients were compared with those in 54 nonbacteremic patients suffering from suspected bacterial infections. Only three (11%) of the 27 patients with gram-negative bacteremia showed detectable levels of endotoxin. TNF- was detected in 6% of the bacteremic patients and in none of the nonbacteremic patients. Median IL-6 levels were significantly higher in bacteremic than in nonbacteremic patients (55 vs. 0 pg/ml, p=0.0008). IL-6 concentrations were similar in neutropenic and non-neutropenic bacteremic patients (median 55 vs. 74 pg/ml). In contrast, neutropenic bacteremic patients had significantly lower concentrations of tIL-1ra than non-neutropenic bacteremic patients (250 vs. 1,950 pg/ml, p<0.0001). Patients with fatal bacteremia had significantly higher concentrations of IL-6 and IL-1ra than the survivors (median, 450 vs. 40, p=0.012 and 7,600 vs. 420 pg/ml, p=0.0075, respectively). Determinations of endotoxin or TNF- in patients with suspected bacteremia failed to offer clinically relevant data on the prognosis of these patients. IL-6 levels correlated with both the presence of bacteremia and the risk of death. Granulocytopenic patients with bacteremia had lower levels of circulating IL-1ra than patients with normal granulocyte counts, and these levels correlated with poor outcome.     

Inflammatory Responses in Blood Samples of Human Immunodeficiency Virus-Infected Patients with Pulmonary Infections

We analyzed the characteristics of the inflammatory response occurring in blood during pulmonary infections in human immunodeficiency virus (HIV)-infected patients. A prospective study of consecutive hospital admissions of HIV-infected patients with new-onset radiologic pulmonary infiltrates was carried out in a tertiary university hospital from April 1998 to May 2001. Plasma cyclic AMP receptor protein (CRP), interleukin 1β (IL-1β), IL-6, IL-8, IL-10, and tumor necrosis factor alpha (TNF-α) levels were determined at the time of admission and 4, 5, and 6 days later. Patients were included in a protocol addressed to study etiology and outcome of disease. A total of 249 episodes of infection were included, with the main diagnoses being bacterial pneumonia (BP) (118 episodes), Pneumocystis carinii pneumonia (PCP) (41 episodes), and mycobacteriosis (36 episodes). For these three patient groups, at the time of admission the median CRP and cytokine levels were as follows: CRP, 10.2, 3.8 and 5 mg/dl, respectively (P = 0.0001); IL-8, 19, 3, and 2.9 pg/ml (P = 0.045); and TNF-α, 46.4, 44, and 75 pg/ml, respectively (P = 0.029). There were no significant differences in levels of IL-1β, IL-6, or IL-10 among the patient groups. A total of 23 patients died. At the time of admission, HIV-infected patients with BP had higher plasma CRP and IL-8 levels than did PCP and mycobacteriosis patients. TNF-α levels were higher in patients with mycobacteriosis. An elevated IL-8 level (>61 pg/ml) at the time of admission was an independent factor associated with higher mortality (odds ratio, 12; 95% confidence interval, 1.2 to 235.5).     

High serum neopterin and low cytokine values may indicate a non-bacterial etiology for fever of unknown origin in neutropenic patients

Objective: To prospectively evaluate serum neopterin, a marker of cellular immune activation, in relation to blood culture findings and cytokine levels (tumor necrosis factor-α (TNF-α), interleukin (IL)-1 receptor antagonist, interferon-γ (IFN-γ), IL-6, and IL-10) at start of fever in neutropenic patients with hematologic malignancies.
Methods: Serum samples were obtained during the first 24 h after start of fever in 27 episodes of febrile neutropenia seen in 22 patients.
Results: Neopterin levels increased significantly at start of fever (time 0) compared to baseline values (samples obtained within 72 h before start of fever). Neopterin levels peaked at 2–4 h after start of fever and returned to baseline levels after 12 h. At start of fever no differences in neopterin values were seen with regard to blood culture findings (i.e. blood-culture-negative (BCN) fever episodes versus Gram-positive bacteria versus Gram-negative bacteremia). In five of seven BCN fever episodes, in patients without other clinical evidence of infection, a high neopterin/low TNF-α value was observed and the correlation ( r -value) between neopterin/TNF-α was negative in BCN fever episodes (-0.9; p <0.04), as opposed to the bacteremic episodes, where the correlation was positive (0.7; p <0.04).
Conclusion: The results of this study show that febrile neutropenic patients are able to react with increased neopterin values, and that some BCN fever episodes are characterized by high neopterin/low cytokine values which may be due to an occult non-bacterial infection.     

Circulating interleukin 10 and interleukin-6 serum levels in rheumatoid arthritis patients treated with methotrexate or gold salts: Preliminary report

In order to evaluate the relationship between serum concentrations of interleukin-10 (IL-10), IL-6, and acute phase proteins in rheumatoid arthritis (RA) patients treated with methotrexate (MTX) or intramuscular gold (IMG) we determined IL-10, IL-6, C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP) and alpha-1-antichymotrypsin (ACT) in the sera of 35 RA patients. IL-10 and IL-6 levels were evaluated using an enzyme-linked immunoassay (ELISA). AGP and ACT level were measured using rocket immunoelectrophoresis. IL-10 serum level was not increased in RA patients as compared to controls (58.7 ± 18.1 pg/ml vs. 57.2 ± 11.9 pg/ml). IL-6 level was significantly elevated (91.6 ± 46.9 pg/ml vs. 45 ± 19 pg/ml, p < 0.05). CRP was significantly increased as compared to healthy controls (35 ± 19 mg/l vs. 3 ± 2 mg/l, p < 0.05). Patients treated with MTX or IMG presented an increased level of IL-10 and decreased amounts of IL-6, as compared to those treated with NSAID only. However, only changes between patients treated with IMG and NSAID were found to be statistically significant. A good negative correlation between IL-10 and IL-6 serum level was found (r = –0.75, p < 0.05). A positive significant correlation between IL-6 serum level and CRP (r = 0.62, p < 0.05), AGP (r = 0.78, p < 0.05) and ACT (r = 0.45, p < 0.05) was established. On the other hand, a negative correlation between IL-10 and serum level of CRP (r = –0.76, p < 0.05), AGP (r = –0.64, p < 0.05) and ACT (r = –0.38, p < 0.05) was also observed. Moreover, these relationships were maintained when patients treated with MTX, IMG, or NSAID were analyzed independently. According to the data thus far obtained, it seems that IL-10 decreases IL-6 production, and thereby indirectly affects the acute phase response, decreasing CRP, AGP, and ACT concentration in RA patients.Abbreviations ACT -1-antichymotrypsin - AGP ₁-acid glycoprotein - APP acute phase protein - CRP C-reactive protein - CSF colony stimulating factor - IFN interferon - IL interleukin - IMG intramuscular gold - MTX methotrexate - NSAID non-steroidal anti-inflammatory drug - RA rheumatoid arthritis     

Chronic sinusitis refractory to standard management in patients with humoral immunodeficiencies

Chronic refractory sinusitis is a common feature in patients with primary immunodeficiencies. The efficacy of standard therapeutic strategies is questionable. In an open trial we evaluated the efficacy of azithromycin, N-acetylcysteine and topical intranasal beclomethasone (100 μg twice daily for 6 weeks) in 16 patients with primary immunodeficiencies (median age 13.5 years, range 5–32 years). All patients suffered from chronic sinusitis despite regular immunoglobulin replacement therapy every 3 weeks. Magnetic resonance imaging (MRI) scans were performed before and after 6 weeks of treatment to evaluate morphological changes in the paranasal sinuses. Nasal swabs and washings were taken for microbial analysis and measurement of inflammatory mediators (IL-8, tumour necrosis factor-alpha (TNF-α), eosinophilic cationic protein (ECP)) before and post therapy. Inflammatory mediators in nasal secretions were significantly elevated in patients: IL-8 median 2436 pg/ml (range 441–5435 pg/ml), TNF-α 37.3 pg/ml (3.75–524 pg/ml) and ECP 33 ng/ml (1.5–250 ng/ml) versus age-matched healthy controls: IL-8 median 212 pg/ml (99–825 pg/ml), TNF-α 3.77 pg/ml (2.8–10.2 pg/ml) and ECP 1.5 ng/ml (1.5–14.8 ng/ml) (P < 0.0001). Inflammation of the maxillary sinuses was confirmed by MRI scans in all patients, additionally infection of the ethmoidal and frontal sinuses was recorded in five patients. Bacterial growth appeared in 11 out of 16 cultures. In spite of therapy, no improvement in sinal inflammation visualized by MRI was achieved. Moreover, no significant decrease in pathogens and levels of inflammatory mediators could be detected (IL-8 1141 pg/ml, 426–4556 pg/ml; TNF-α 13.9 pg/ml, 4.1–291.6 pg/ml; ECP 32.3 ng/ml, 3.7–58.4 ng/ml). Our results demonstrate that conventional management of sinusitis is of little benefit in patients with chronic refractory sinusitis with an underlying immunodeficiency. More studies are needed to test antibiotic regimens, probably combined with surgical drainage and anti-inflammatory agents.     

Procalcitonin levels in salmonella infection

Aim:

Procalcitonin (PCT) as a diagnostic marker for bacteremia and sepsis has been extensively studied. We aimed to study PCT levels in Salmonella infections whether they would serve as marker for early diagnosis in endemic areas to start empiric treatment while awaiting blood culture report.

Materials and Methods:

BACTEC blood culture was used to isolate Salmonella in suspected enteric fever patients. Serum PCT levels were estimated before starting treatment.

Results:

In 60 proven enteric fever patients, median value of serum PCT levels was 0.22 ng/ml, values ranging between 0.05 and 4 ng/ml. 95% of patients had near normal or mild increase (<0.5 ng/ml), only 5% of patients showed elevated levels. Notably, high PCT levels were found only in severe sepsis.

Conclusion:

PCT levels in Salmonella infections are near normal or minimally increased which differentiates it from other systemic Gram-negative infections. PCT cannot be used as a specific diagnostic marker of typhoid.     

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.     

Inflammatory responses in blood samples of human immunodeficiency virus-infected patients with pulmonary infections

We analyzed the characteristics of the inflammatory response occurring in blood during pulmonary infections in human immunodeficiency virus (HIV)-infected patients. A prospective study of consecutive hospital admissions of HIV-infected patients with new-onset radiologic pulmonary infiltrates was carried out in a tertiary university hospital from April 1998 to May 2001. Plasma cyclic AMP receptor protein (CRP), interleukin 1beta (IL-1beta), IL-6, IL-8, IL-10, and tumor necrosis factor alpha (TNF-alpha) levels were determined at the time of admission and 4, 5, and 6 days later. Patients were included in a protocol addressed to study etiology and outcome of disease. A total of 249 episodes of infection were included, with the main diagnoses being bacterial pneumonia (BP) (118 episodes), Pneumocystis carinii pneumonia (PCP) (41 episodes), and mycobacteriosis (36 episodes). For these three patient groups, at the time of admission the median CRP and cytokine levels were as follows: CRP, 10.2, 3.8 and 5 mg/dl, respectively (P = 0.0001); IL-8, 19, 3, and 2.9 pg/ml (P = 0.045); and TNF-alpha, 46.4, 44, and 75 pg/ml, respectively (P = 0.029). There were no significant differences in levels of IL-1beta, IL-6, or IL-10 among the patient groups. A total of 23 patients died. At the time of admission, HIV-infected patients with BP had higher plasma CRP and IL-8 levels than did PCP and mycobacteriosis patients. TNF-alpha levels were higher in patients with mycobacteriosis. An elevated IL-8 level (>61 pg/ml) at the time of admission was an independent factor associated with higher mortality (odds ratio, 12; 95% confidence interval, 1.2 to 235.5).     

Evaluation of Th1/Th2 cytokines as a rapid diagnostic tool for severe infection in paediatric haematology/oncology patients by the use of cytometric bead array technology

Haematology/oncology children are usually at risk for various infections after intensive chemotherapy. We evaluated the quantification of Th1/Th2 cytokines with a flow cytometric bead array (CBA) in 795 hospitalized haematology/oncology children (309 febrile and 486 afebrile patients) to seek for a diagnostic method for determination of the type and the severity of infection. Three hundred and nine febrile patients developed a total of 505 febrile episodes. Microbiological examination demonstrated a positive blood culture (microbiologically documented infection (MDI)) in 145/505 febrile episodes. The controls included 550 healthy children, 43 haemophagocytic lymphohistiocytosis (HLH) patients, 35 cytomegalovirus infection patients and 19 Epstein–Barr virus infection patients. Interleukin (IL)-4, IL-6, IL-10, tumour necrosis factor (TNF)-α and interferon (IFN)-γ levels in febrile episodes were significantly higher than those in healthy children, and the cytokine profile was different from that of the HLH controls or the viral infection controls. IL-6 levels were much higher in MDI patients (usually >1000.0 pg/mL, 60/145) than in HLH patients (2/43); however, IFN-γ levels were only slightly increased in MDI patients, rarely being more than 100.0 pg/mL (8/145 vs. 39/43 in HLH patients). The median levels of IL-4, IL-6, IL-10, TNF-α and IFN-γ in febrile patients before antibiotic therapy were 3.9, 660.1, 122.7, 6.9 and 11.4 pg/mL, respectively, and returned to 3.3, 22.8, 9.6, 4.1 and 6.4 pg/mL, respectively, after infection was controlled. IL-6 and IL-10 levels were positively associated with septic shock and mortality rates. In conclusion, our results have demonstrated the usefulness of IL-6/IL-10/TNF-α/IFN-γ determination with CBA technology for the early rapid diagnosis, severity evaluation and assessment of therapy effect in febrile haematology/oncology children.     

Procalcitonin Does Not Discriminate Infection from Inflammation after Allogeneic Bone Marrow Transplantation

Procalcitonin (PCT) is an early marker of bacterial infection but little is known about its value in neutropenic allogeneic bone marrow transplant (BMT) recipients. We collected plasma from 12 recipients of T-cell-depleted HLA-matched related BMT recipients who had been treated preemptively with meropenem from the day after BMT for at least 15 days. PCT and C-reactive protein (CRP) concentrations were determined on BMT days 1, 5, 8, 12, and 15, and their relationship to inflammatory events (IE), including mucositis, microbiologically and clinically defined infections, acute graft-versus-host disease (GVDH), and unexplained fever, was then determined. The PCT concentrations were all low and never exceeded 4 μg/liter, unlike CRP concentrations, which spanned the full range up to 350 mg/liter. All patients had mucositis, and there was no significant difference between PCT concentrations associated with mucositis alone and those associated with an additional IE on BMT days 1 to 12. However, on BMT day 15, the mean concentrations of PCT were 0.37 ± 0.05 μg/liter for the 10 patients that had an additional IE, compared with 0.11 ± 0.03 μg/liter for the 2 patients with mucositis only (P = 0.012), and GVHD rather than infection was involved in six cases. PCT was also not a sensitive marker of gram-positive bacteremia or pulmonary aspergillosis. Thus, PCT is of little value in discriminating infections from other inflammatory complications that occur following allogeneic BMT.     

High levels of interleukin 10 in serum are associated with fatality in meningococcal disease.

Interleukin 10 (IL-10) suppresses the production of proinflammatory cytokines in vitro and in murine models of endotoxemia and has been suggested as a candidate for treatment of bacterial septicemia. To investigate the role of IL-10 in meningococcal disease, a sandwich IL-10 enzyme-amplified sensitivity immunoassay was used to quantitate IL-10 in serum and cerebrospinal fluid samples from 41 patients with meningococcal bacteremia or meningitis with or without septic shock. High levels of IL-10 were demonstrated in sera from patients with meningococcal septic shock (mean, 21,221 pg/ml; range, 25 to 64,500 pg/ml). All cases involving fatalities had IL-10 levels in serum of > or = 1,000 pg/ml (mean, 23,058 pg/ml; range, 1,000 to 64,500 pg/ml). Patients with meningococcal meningitis without septic shock had comparably low concentrations of IL-10 in serum (mean, 119 pg/ml; range, 0 to 1,050 pg/ml) but exhibited compartmentalized release of IL-10 in cerebrospinal fluid. Concentrations of IL-10 in serum were positively correlated with the previously reported concentrations of tumor necrosis factor alpha, IL-6, and IL-8 in serum in the same patients. We conclude that IL-10 is extensively activated along with the proinflammatory cytokines during the initial phase of meningococcal septic shock and that IL-10 is associated with fatality in meningococcal disease.     

Plasma procalcitonin levels remain low at the onset of gram-positive bacteremia regardless of severity or the presence of shock: A retrospective analysis of patients with detailed clinical characteristics

ObjectivesProcalcitonin (PCT) is an early diagnosis marker of sepsis/bacteremia. However, some reports refer to its lower responsiveness to gram-positive bacteremia. We retrospectively evaluated the PCT values at the onset of bacteremia in relation to severity index.MethodsPatients with bacteremia caused by two gram-negative bacteria (46 E. coli and 50 Klebsiella pneumoniae) and three gram-positive bacteria (45 S. aureus, 56 S. epidermidis, and 10 S. mitis) were studied. The plasma PCT and C-reactive protein (CRP) levels were compared between species and different Sequential Organ Failure Assessment (SOFA) score groups.ResultsThe median PCT level was higher in gram-negative than in gram-positive bacteremia in overall (13.09 vs. 0.50 ng/mL, p < 0.0001), in SOFA score≥4 group (28.85 vs.1.72 ng/mL, p < 0.0001) and in SOFA<4 group (2.64 vs. 0.42 ng/mL, p < 0.0001). Only 46%, and 11% of patients showed PCT ≥0.5 ng/mL in S. epidermidis, and S. mitis bacteremia, respectively. PCT was significantly better than CRP in discriminating gram-negative from gram-positive bacteremia (AUCROC; 0.828 and 0.634, p < 0.001), but it was low in Staphylococcus epidermidis bacteremia regardless of SOFA scores.ConclusionsPCT levels are lower in gram-positive bacteremia regardless of SOFA scores or the presence of shock. The conventional sepsis cutoff of 0.5 ng/mL may overlook certain proportions of gram-positive bacteremia.     

Human cytomegalovirus, human herpesvirus-6 and human herpesvirus-7 in neutropenic patients with fever of unknown origin

Objective  To investigate the appearance of cytomegalovirus (CMV) DNA, human herpesvirus-6 (HHV-6) DNA and human herpesvirus-7 (HHV-7) DNA in plasma as a sign of reactivation and possible causes of fever of unknown origin (FUO) during neutropenia.
Methods  From 134 patients with febrile neutropenia following cytotoxic chemotherapy during the years 1996–2000, 20 severely neutropenic patients (granulocyte count < 0.1 × 10⁹/L) were selected. Ten were patients with bacteremia and ten were patients with FUO. Five samples from each patient were selected at the start of chemotherapy, at the time of blood culture and fever, after 24 and 48 hours of fever, and, finally, after two to three days without fever. Virus DNA was detected by real-time quantitative and nested polymerase chain reaction (PCR).
Results  CMV-DNA was detected in two out of ten FUO-patients in all samples drawn during fever. From another FUO and during two bacteremia episodes, CMV-DNA was detected after 48 hours of fever. DNA from HHV-6 and HHV-7 was not detected in any of the 20 febrile episodes.
Conclusions  HHV-6 and HHV-7 as a possible explanation for FUO in severely neutropenic patients treated with cytotoxic chemotherapy seems not be very likely. However, CMV was identified in 5/20 patients and the febrile episodes in the two FUO-patients with constant DNA-emia may have been caused by a reactivation of CMV. This implies that CMV infection can be expected not only in transplant patients but also in chemotherapy-treated neutropenic patients.     

Polymicrobial bacteremia

Of 585 bacteremic episodes studied prospectively at Rokach Hospital during a 4-year period (1980–1983), 70 (12%) episodes observed in 67 patients were due to multiple species. A total of 170 strains of microorganisms were involved, 2–5 per bacteremic episode: 130 (76%) were aerobic Gram-negative bacilli, 36 (21%) were Gram-positive cocci (most of them streptococci) and 4 isolates (2%) were Candida. The most common sources of infection were the urinary tract (31 episodes), intra-abdominal foci (22 episodes, half of them from biliary tract), and skin or soft tissue infection (14 episodes). At least one organism was also recovered from a local focus of infection in more than 50% of cases. Many patients had severe underlying diseases in addition to old age. People with biliary infection had, however, a relatively lower frequency of underlying disease. Fifty-six percent of the episodes were hospital-acquired, primarily those related to urinary infection with indwelling catheters, intra-abdominal abscess and infected burns. Twenty-eight patients (42%) died as a result of the bacteremia. Polymicrobial bacteremia was found to be quite common in the population studied, and the urinary tract was the most important portal of entry, especially in the older patients.     

Laboratory markers of systemic inflammation as predictors of bloodstream infection in acutely ill patients admitted to hospital in medical emergency

The aim of the present study was to determine whether the presence of an infectious focus or of fever alone can predict bloodstream infection and whether levels of C-reactive protein, procalcitonin, interleukin (IL)-6, IL-8, and soluble IL-2 receptor (sIL-2R) improve the diagnosis of community-acquired bloodstream infection. Markers of systemic inflammation were studied in 92 patients with community-acquired infection. On admission to hospital, 54 patients had an infectious focus, 25 had fever without an infectious focus, and 13 had neither. The presence of focus or fever predicted bloodstream infection (n=13 patients) with a sensitivity of 100% (95% confidence interval, 75–100), a specificity of 16% (95%CI, 9–26), a negative predictive value of 100% (95%CI, 75–100), and a positive predictive value of 16% (95%CI, 9–26). Positive predictive values of C-reactive protein, procalcitonin, IL-6, IL-8, and sIL-2R, all measured on admission, were also low (33–44%). Eight febrile patients in whom an infectious focus was found during a 3-day follow-up period had higher on-admission IL-6 (P=0.005) and sIL-2R (P=0.046) levels than did 17 febrile patients without an infectious focus. In conclusion, markers of systemic inflammation do not improve the diagnosis of community-acquired bloodstream infection; however, they may aid in identifying patients with fever due to occult infection.     

Plasma levels of procalcitonin and eight additional inflammatory molecules in febrile neutropenic patients

OBJECTIVE:

This study aimed to examine the association between different inflammatory markers and specific clinical endpoints in patients with febrile neutropenia.

METHOD:

We prospectively evaluated the expression of procalcitonin (PCT), interleukin 8 (IL-8), induced protein-10, tumor necrosis factor alpha (TNF-α), two soluble TNF-α receptors (sTNF-R I and sTNF-R II), monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1 alpha, and eotaxin in 37 episodes of febrile neutropenia occurring in 31 hospitalized adult onco-hematologic patients. Peripheral blood samples were collected in the morning at inclusion (day of fever onset) and on days 1, 3, and 7 after the onset of fever. Approximately 2–3 ml of plasma was obtained from each blood sample and stored at -80°C.

RESULTS:

The sTNF-R II level at inclusion (day 1), the PCT level on the day of fever onset, and the change (day 3 - day 1) in the IL-8 and eotaxin levels were significantly higher in patients who died during the 28-day follow-up. A requirement for early adjustment of antimicrobial treatment was associated with higher day 3 levels of IL-8, sTNF-R II, PCT, and MCP-1.

CONCLUSION:

Procalcitonin, sTNF-R II, IL-8, MCP-1, and eotaxin could potentially be used to assess the risk of death and the requirement for early adjustment of antimicrobial treatment in febrile, neutropenic onco-hematologic patients. The levels of the other markers showed no association with any of the evaluated endpoints.