Renaat Peleman

THE POTENTIAL ROLE OF TUMOUR NECROSIS FACTOR ALPHA IN ASTHMA

It has clearly been established over the past few years that asthma is accompanied by airway inflammation [1-3]. This chronic inflammatory state is considered to be intimately related to the pathogenesis of non-speciflc bronchial hyperresponsiveness (BHR), a key feature in asthma [4]. Various aspects in the pathogenesis of the allergic airway inflammation and its precise relationship to bronchial hyperresponsiveness, however, remain unclear. One of the pieces of the puzzle concerns the significance of cytokines in this process. The importance of these cytokines in the orchestration of an allergic inflammatory response is currently emerging. Various cytokines or their mRNA precursors have been shown to be present in bronchial biopsies or bronchoalveolar lavage (BAL) fluid from asthmatics. These include tumour necrosis factor a (TNFa), interleukin-1 (IL-1), IL-2, IL-3, IL-4, IL-5, IL-6 and granulocyte macrophage colony stimulating factor (GMCSF) [5-9]. The exact role of each of these cytokines in the pathogenesis of asthma remains to be fully established.

Colonization status and appropriate antibiotic therapy for nosocomial bacteremia caused by antibiotic-resistant gram-negative bacteria in an intensive care unit.

OBJECTIVE Timely initiation of antibiotic therapy is crucial for severe infection. Appropriate antibiotic therapy is often delayed for nosocomial infections caused by antibiotic-resistant bacteria. The relationship between knowledge of colonization caused by antibiotic-resistant gram-negative bacteria (ABR-GNB) and rate of appropriate initial antibiotic therapy for subsequent bacteremia was evaluated. DESIGN Retrospective cohort study. SETTING Fifty-four-bed intensive care unit (ICU) of a university hospital. In this unit, colonization surveillance is performed through routine site-specific surveillance cultures (urine, mouth, trachea, and anus). Additional cultures are performed when presumed clinically relevant. PATIENTS ICU patients with nosocomial bacteremia caused by ABR-GNB. RESULTS Infectious and microbiological characteristics and rates of appropriate antibiotic therapy were compared between patients with and without colonization prior to bacteremia. Prior colonization was defined as the presence (detected > or = 2 days before the onset of bacteremia) of the same ABR-GNB in colonization and subsequent blood cultures. During the study period, 157 episodes of bacteremia caused by ABR-GNB were suitable for evaluation. One hundred seventeen episodes of bacteremia (74.5%) were preceded by colonization. Appropriate empiric antibiotic therapy (started within 24 hours) was administered for 74.4% of these episodes versus 55.0% of the episodes that occurred without prior colonization. Appropriate therapy was administered within 48 hours for all episodes preceded by colonization versus 90.0% of episodes without prior colonization. CONCLUSION Knowledge of colonization status prior to infection is associated with higher rates of appropriate therapy for patients with bacteremia caused by ABR-GNB.

Importance of lnterleukin-4 and lnterleukin-12 in Allergen-Induced Airway Changes in Mice

T helper 2 (Th2)-like cells are thought to play a crucial role in the pathogenesis of atopic asthma. In this study, we attempted to evaluate the in vivo effect of suppressing Th2 cell development on allergen-induced airway changes. Repeated exposure of actively sensitized C57Bl/6 mice to aerosolized ovalbumin (OA) causes, in comparison to saline-exposed control animals, synthesis of specific IgE, increase of eosinophils in bronchoalveolar lavage fluid and airway hyperresponsiveness. These effects are not observed in OA-exposed, sensitized IL-4-knockout mice. Likewise, these effects are inhibited in OA-exposed C57Bl/6 mice treated with IL-12 during initial antigen exposure. These results suggest that suppressing Th2 cell development in vivo might have profound inhibitory effects on allergen-induced airway changes.

Epidemiology and outcome of nosocomial bloodstream infection in elderly critically ill patients: a comparison between middle-aged, old, and very old patients

Background:We investigated the epidemiology of nosocomial bloodstream infection in elderly intensive care unit (ICU) patients. Methods:In a single-center, historical cohort study (1992–2006), we compared middle-aged (45–64 years; n = 524), old (65–74 years; n = 326), and very old ICU patients (≥75 years; n = 134) who developed a nosocomial bloodstream infection during their ICU stay. Results:Although the total number of ICU admissions (patients aged ≥45 years) decreased by ∼10%, the number of very old patients increased by 33% between the periods 1992–1996 and 2002–2006. The prevalence of bloodstream infection (per 1,000 ICU admissions) increased significantly over time among old (p = 0.001) and very old patients (p = 0.002), but not among middle-aged patients (p = 0.232). Yet, this trend could not be confirmed with the incidence data expressed per 1,000 patient days (p > 0.05). Among patients with bloodstream infection, the proportion of very old patients increased significantly with time from 7.2% (1992–1996) to 13.5% (1997–2001) and 17.4% (2002–2006) (p < 0.001). The incidence of bloodstream infection (per 1000 patient days) decreased with age: 8.4‰ in middle-aged, 5.5‰ in old, and 4.6‰ in very old patients (p < 0.001). Mortality rates increased with age: 42.9%, 49.1%, and 56.0% for middle-aged, old, and very old patients, respectively (p = 0.015). Regression analysis revealed that the adjusted relationship with mortality was borderline significant for old age (hazard ratio, 1.2; 95% confidence interval, 1.0–1.5) and significant for very old age (hazard ratio, 1.8; 95% confidence interval, 1.4–2.4). Conclusion:Over the past 15 years, an increasing number of elderly patients were admitted to our ICU. The incidence of nosocomial bloodstream infection is lower among very old ICU patients when compared to middle-aged and old patients. Yet, the adverse impact of this infection is higher in very old patients.

Sensitization to inhaled antigen by intratracheal instillation of dendritic cells

Airway dendritic cells (DCs) capture and present inhaled antigen. It is not known whether antigen presentation by DCs in the airways is sufficient to induce sensitization to inhaled antigen in vivo.

Infection control in the management of highly pathogenic infectious diseases: consensus of the European Network of Infectious Disease

Summary The European Network for Infectious Diseases (EUNID) is a network of clinicians, public health epidemiologists, microbiologists, infection control, and critical-care doctors from the European member states, who are experienced in the management of patients with highly infectious diseases. We aim to develop a consensus recommendation for infection control during clinical management and invasive procedures in such patients. After an extensive literature review, draft recommendations were amended jointly by 27 partners from 15 European countries. Recommendations include repetitive training of staff to ascertain infection control, systematic use of cough and respiratory etiquette at admission to the emergency department, fluid sampling in the isolation room, and analyses in biosafety level 3/4 laboratories, and preference for point-of-care bedside laboratory tests. Children should be cared for by paediatricians and intensive-care patients should be cared for by critical-care doctors in high-level isolation units (HLIU). Invasive procedures should be avoided if unnecessary or done in the HLIU, as should chest radiography, ultrasonography, and renal dialysis. Procedures that require transport of patients out of the HLIU should be done during designated sessions or hours in secure transport. Picture archiving and communication systems should be used. Post-mortem examination should be avoided; biopsy or blood collection is preferred.

Isolations of Leclercia adecarboxylata from a Patient with a Chronically Inflamed Gallbladder and from a Patient with Sepsis without Focus

ABSTRACT Leclercia adecarboxylata was isolated from a patient with a chronically inflamed gallbladder, together withEnterococcus sp. The organism was considered clinically significant and was susceptible to all antibiotics tested. Another strain of L. adecarboxylata was cultured from blood, together with Escherichia hermannii and E. faecalis, from a patient with sepsis.

The effect of zardaverine, an inhibitor of phosphodiesterase isoenzymes III and IV, on endotoxin‐induced airway changes in rats

Zardaverine is a novel phosphodiesterase III/IV inhibitor, developed as a potential therapeutic agent for asthma. In this study we evaluated the effect of zardaverine in an in vivo animal model of airway inflammation and hyperresponsiveness. Endotoxin exposure in rats causes a transient increase in airway responsiveness and a neutrophilic inflammation of the bronchi, which are both at least partly mediated through the secondary release of tumour necrosis factor a (TNFα), Groups of 10 animals each were pretreated with placebo or zardaverine (1, 10, 30μmol/kg) i.p., 30 min prior to exposure to aerosolized endotoxin (LPS) or saline. Ninety minutes later, airway responsiveness to 5‐HT was assessed and bronchoalveolar lavage (BAL) performed. Zardaverine did not influence basehne lung resistance (RL), but inhibited dose dependently the 5‐HT induced increase in RL in control animals. In placebo pretreated animals LPS exposure caused a signiflcant decrease in PC50RL5‐HT (provocative concentration of 5‐HT causing a 50% increase in RL), compared to the saline exposed control group (1.1 ± 0.1 vs 2.7± 0.4μg/kg) (P<0.01). This decrease in PC50RL‐HT was significantly inhibited by zardaverine 30μmol/kg (5.4 ± 1.8 vs 1.1 ± 0.1μg/kg) (P<0.05). Compared to placebo pre‐treated, LPS exposed animals, zardaverine 30 μmol/kg also significantly inhibited to LPS induced neutrophil increase (193.0 ± 50.0 vs 915.6± 181.3 × 103) (P < 0.05), increase in elastase activity (23 ± 11 vs 54 ± 9 nmol substrate/h/ml) (P<0.05) and TNFα release in BAL fluid (93.1 ± 19.5 vs 229.5 ± 24.8 U/ml BAL fluid) (P<0.01).

Dynamics of C-reactive protein and white blood cell count in critically ill patients with nosocomial Gram positive vs. Gram negative bacteremia: a historical cohort study

BackgroundNosocomial bacteremia is associated with a poor prognosis. Early adequate therapy has been shown to improve outcome. Consequently, rapid detection of a beginning sepsis is therefore of the utmost importance. This historical cohort study was designed to evaluate if different patterns can be observed in either C-reactive protein (CRP) and white blood cell count (WCC) between Gram positive bacteremia (GPB) vs. Gram negative bacteremia (GNB), and to assess the potential benefit of serial measurements of both biomarkers in terms of early antimicrobial therapy initiation.MethodsA historical study (2003–2004) was conducted, including all adult intensive care unit patients with a nosocomial bacteremia. CRP and WCC count measurements were recorded daily from two days prior (d-2) until one day after onset of bacteremia (d+1). Delta (Δ) CRP and Δ WCC levels from the level at d-2 onward were calculated.ResultsCRP levels and WCC counts were substantially higher in patients with GNB. Logistic regression analysis demonstrated that GNB and Acute Physiology and Chronic Health Evaluation (APACHE) II score were independently associated with a CRP increase of 5 mg/dL from d-2 to d+1, and both were also independently associated with an increase of WCC levels from d-2 to d+1 of 5,000 × 103 cells/mm3.ConclusionIncreased levels of CRP and WCC are suggestive for GNB, while almost unchanged CRP and WCC levels are observed in patients with GPB. However, despite the different patterns observed, antimicrobial treatment as such cannot be guided based on both biomarkers.

Two cases of disseminated mucormycosis in patients with hematological malignancies and literature review

Abstract Two cases of disseminated mucormycosis in patients with underlying hematological disease are described. Both patients presented with fever and pulmonary infiltrates which did not respond to empirical treatment with broad-spectrum antibiotics and antifungal agents, and in both patients there was rapid progression with a fatal outcome. All cultures were negative and the diagnosis was made postmortem. A review of the literature revealed only three recent reports of successful treatment of disseminated mucormycosis. Survival correlated with control of the underlying disease and early diagnosis based on histological examination of biopsy specimens from suspected lesions. Therapy consisted of surgical debridement and amphotericin B. Standard therapeutic schedules need to be defined for this infection.