Dirk Vogelaers

Clinical and Economic Outcomes in Critically Ill Patients with Nosocomial Catheter-Related Bloodstream Infections

BACKGROUND Central venous catheters are universally used during the treatment of critically ill patients. Their use, however, is associated with a substantial infection risk, potentially leading to increased mortality and costs. We evaluate clinical and economic outcomes associated with nosocomial central venous catheter-related bloodstream infection (CR-BSI) in intensive care unit (ICU) patients. METHODS A retrospective (1992-2002), pairwise-matched (ratio of case patients to control subjects, 1:2 or 1:1), risk-adjusted cohort study was performed at a 54-bed general ICU at a university hospital. ICU patients with microbiologically documented CR-BSI (n = 176) were matched with control subjects (n = 315) on the basis of disease severity, diagnostic category, and length of ICU stay (equivalent or longer) before the onset of CR-BSI in the index case patient. Clinical outcome was principally evaluated by in-hospital mortality. Economic outcome was evaluated on the basis of duration of mechanical ventilation, length of ICU and hospital stays, and total hospital costs, as derived from the patients hospital invoices. RESULTS The attributable mortality rate for CR-BSI was estimated to be 1.8% (95% confidence interval, -6.4% to 10.0%); in-hospital mortality rates for patients with CR-BSI and matched control subjects were 27.8% and 26.0%, respectively. CR-BSI was associated with significant excesses in duration of mechanical ventilation, duration of ICU and hospital stays, and a significant increase in total hospital cost. Linear regression analysis with adjustment for duration of hospitalization and clinical covariates, revealed that CR-BSI is independently associated with higher costs. CONCLUSIONS In ICU patients, CR-BSI does not result in increased mortality. It is, however, associated with a significant economic burden, emphasizing the importance of continuous efforts in prevention.

Left ventricular systolic and diastolic function in septic shock.

SummaryObjective: The identification of myocardial dysfunction in septic shock has not yet been fully elucidated. We therefore studied patients with persistently vasopressor-dependent septic shock, both with invasive haemodynamic monitoring and transoesophageal two-dimensional and Doppler echocardiography (TEE). Design: Prospective study. Setting: General ICU in University Hospital. Patients and methods: All patients were monitored with arterial and pulmonary artery catheters. Haemodynamics were obtained concomitantly with TEE measurements. TEE was performed at three levels: a) a midpapillary short axis view of the left ventricle (LV) in order to measure end-systolic and end-diastolic areas; b) at the level of both the mitral valve for early (E) and late (A) filling parameters and c) the level of the right upper pulmonary vein for systolic (S) and diastolic (D) filling characteristics. Each parameter was characterised by maximal flow velocity and time velocity integral. Results: Although the measurements of cardiac index demonstrated a wide range, three subsets of patients were identified post hoc after analysis on the basis of different Doppler patterns: first, patients with a LV without regional wall motion abnormalities and both E/A and S/D greater than 1 (group 1); second, patients with a comparable haemodynamic condition, apparently normal LV systolic function but with altered Doppler patterns: S/D less than 1 in conjunction with E/A more than 1 (group 2); finally, patients with compromised global LV systolic function, E/A less than 1 and S/D less than (group 3). Conclusions: Notwithstanding the known various interfering factors which limit the broad applicability of TEE to determine LV function in septic shock, our data suggest that cardiac dysfunction in septic shock shows a continuum from isolated diastolic dysfunction to both diastolic and systolic ventricular failure. These data strengthen the need of including the evaluation of pulmonary venous Doppler parameters in each investigation in order to obtain supplementary information to interpret diastolic function of the LV in septic shock patients.

Severe burn injury in europe: a systematic review of the incidence, etiology, morbidity, and mortality

IntroductionBurn injury is a serious pathology, potentially leading to severe morbidity and significant mortality, but it also has a considerable health-economic impact. The aim of this study was to describe the European hospitalized population with severe burn injury, including the incidence, etiology, risk factors, mortality, and causes of death.MethodsThe systematic literature search (1985 to 2009) involved PubMed, the Web of Science, and the search engine Google. The reference lists and the Science Citation Index were used for hand searching (snowballing). Only studies dealing with epidemiologic issues (for example, incidence and outcome) as their major topic, on hospitalized populations with severe burn injury (in secondary and tertiary care) in Europe were included. Language restrictions were set on English, French, and Dutch.ResultsThe search led to 76 eligible studies, including more than 186,500 patients in total. The annual incidence of severe burns was 0.2 to 2.9/10,000 inhabitants with a decreasing trend in time. Almost 50% of patients were younger than 16 years, and ~60% were male patients. Flames, scalds, and contact burns were the most prevalent causes in the total population, but in children, scalds clearly dominated. Mortality was usually between 1.4% and 18% and is decreasing in time. Major risk factors for death were older age and a higher total percentage of burned surface area, as well as chronic diseases. (Multi) organ failure and sepsis were the most frequently reported causes of death. The main causes of early death (<48 hours) were burn shock and inhalation injury.ConclusionsDespite the lack of a large-scale European registration of burn injury, more epidemiologic information is available about the hospitalized population with severe burn injury than is generally presumed. National and international registration systems nevertheless remain necessary to allow better targeting of prevention campaigns and further improvement of cost-effectiveness in total burn care.

Clinical relevance of Aspergillus isolation from respiratory tract samples in critically ill patients

IntroductionThe diagnosis of invasive pulmonary aspergillosis, according to the criteria as defined by the European Organisation for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG), is difficult to establish in critically ill patients. The aim of this study is to address the clinical significance of isolation of Aspergillus spp. from lower respiratory tract samples in critically ill patients on the basis of medical and radiological files using an adapted diagnostic algorithm to discriminate proven and probable invasive pulmonary aspergillosis from Aspergillus colonisation.MethodsUsing a historical cohort (January 1997 to December 2003), all critically ill patients with respiratory tract samples positive for Aspergillus were studied. In comparison to the EORTC/MSG criteria, a different appreciation was given to radiological features and microbiological data, including semiquantitative cultures and direct microscopic examination of broncho-alveolar lavage samples.ResultsOver a 7 year period, 172 patients were identified with a positive culture. Of these, 83 patients were classified as invasive aspergillosis. In 50 of these patients (60%), no high risk predisposing conditions (neutropenia, hematologic cancer and stem cell or bone marrow transplantation) were found. Typical radiological imaging (halo and air-crescent sign) occurred in only 5% of patients. In 26 patients, histological examination either by ante-mortem lung biopsy (n = 10) or necropsy (n = 16) was performed, allowing a rough estimation of the predictive value of the diagnostic algorithm. In all patients with histology, all cases of clinical probable pulmonary aspergillosis were confirmed (n = 17). Conversely, all cases classified as colonisation had negative histology (n = 9).ConclusionA respiratory tract sample positive for Aspergillus spp. in the critically ill should always prompt further diagnostic assessment, even in the absence of the typical hematological and immunological host risk factors. In a minority of patients, the value of the clinical diagnostic algorithm was confirmed by histological findings, supporting its predictive value. The proposed diagnostic algorithm needs prospective validation.

Promising Role of 18-F-Fluoro-D-Deoxyglucose Positron Emission Tomography in Clinical Infectious Diseases

Abstract.18-F-fluoro-D-deoxyglucose positron emission tomography (FDG PET) has become an established imaging tool in clinical oncology, cardiology and neurology and is now entering the field of clinical infectious diseases. The purpose of this article is to review the currently available, albeit limited, literature on FDG PET in the diagnosis of various infections and fever of unknown origin. Those indications for which FDG PET offers added value over more available techniques like labelled leucocyte scanning, gallium scanning and magnetic resonance imaging are especially highlighted. FDG PET seems to have an incremental value in the assessment of chronic osteomyelitis, especially in the axial skeleton, as well as in the diagnostic workup of fever of unknown origin and HIV complications. Cost-effectiveness studies are needed to define its place in the current diagnostic strategies of these pathologies.

Prevention of ventilator-associated pneumonia with oral antiseptics: a systematic review and meta-analysis

BACKGROUND We did a systematic review and random effects meta-analysis of randomised trials to assess the effect of oral care with chlorhexidine or povidone-iodine on the prevalence of ventilator-associated pneumonia versus oral care without these antiseptics in adults. METHODS Studies were identified through PubMed, CINAHL, Web of Science, CENTRAL, and complementary manual searches. Eligible studies were randomised trials of mechanically ventilated adult patients receiving oral care with chlorhexidine or povidone-iodine. Relative risks (RR) and 95% CIs were calculated with the Mantel-Haenszel model and heterogeneity was assessed with the I(2) test. FINDINGS 14 studies were included (2481 patients), 12 investigating the effect of chlorhexidine (2341 patients) and two of povidone-iodine (140 patients). Overall, antiseptic use resulted in a significant risk reduction of ventilator-associated pneumonia (RR 0.67; 95% CI 0.50-0.88; p=0.004). Chlorhexidine application was shown to be effective (RR 0.72; 95% CI 0.55-0.94; p=0.02), whereas the effect resulting from povidone-iodine remains unclear (RR 0.39; 95% CI 0.11-1.36; p=0.14). Heterogeneity was moderate (I(2)=29%; p=0.16) for the trials using chlorhexidine and high (I(2)=67%; p=0.08) for those assessing povidone-iodine use. Favourable effects were more pronounced in subgroup analyses for 2% chlorhexidine (RR 0.53, 95% CI 0.31-0.91), and in cardiosurgical studies (RR 0.41, 95% CI 0.17-0.98). INTERPRETATION This analysis showed a beneficial effect of oral antiseptic use in prevention of ventilator-associated pneumonia. Clinicians should take these findings into account when providing oral care to intubated patients. FUNDING None.

Fluorine-18 fluorodeoxyglucose-positron emission tomography: A highly accurate imaging modality for the diagnosis of chronic musculoskeletal infections.

Background: The noninvasive diagnosis of chronic musculoskeletal infections remains a challenge. Recent studies have indicated that fluorine-18 fluorodeoxyglucose-positron emission tomography is a highly accurate imaging technique and is significantly more accurate than the combination of a bone scan and a white blood-cell scan for the diagnosis of chronic infection in the central skeleton (p < 0.05). However, patients who had had surgery within the previous two years were excluded from study. It was our aim to evaluate the technique in an unselected, clinically representative population. Methods: Sixty patients with a suspected chronic musculoskeletal infection involving the central skeleton (thirty-three patients) or the peripheral skeleton (twenty-seven patients) were studied with fluorine-18 fluorodeoxyglucose-positron emission tomography. Thirty-five patients had had surgery within the previous two years. The fluorine-18 fluorodeoxyglucose-positron emission tomography studies were read in a blinded, independent manner by two experienced readers. The final diagnosis was based on histopathological studies or microbiological culture (eighteen patients) or on clinical findings after at least six months of follow-up (forty-two patients). Results: On the final composite assessment, twenty-five patients had infection and thirty-five did not. All twenty-five infections were correctly identified by both readers. There were four false-positive findings; in two of these cases, surgery had been performed less than six months prior to the study. The sensitivity, specificity, and accuracy were 100%, 88%, and 93% for the whole group; 100%, 90%, and 94% for the subgroup of patients with a suspected infection of the central skeleton; and 100%, 86%, and 93% for the subgroup of patients with a suspected infection of the peripheral skeleton. Interobserver agreement was excellent (kappa = 0.97). Conclusions: Fluorine-18 fluorodeoxyglucose-positron emission tomography is highly accurate as a single technique for the evaluation of chronic musculoskeletal infections. It is especially valuable in the evaluation of the central skeleton, where white blood-cell scans are less useful. Because of its simplicity and high degree of accuracy, it has the potential to become a standard technique for the diagnosis of chronic musculoskeletal infections. Further studies are needed to assess its ability to identify infections at the sites of total joint replacements and to distinguish infection from aseptic loosening of these prostheses.

The rising problem of antimicrobial resistance in the intensive care unit

Mainly due to its extremely vulnerable population of critically ill patients, and the high use of (invasive) procedures, the intensive care unit (ICU) is the epicenter of infections. These infections are associated with an important rise in morbidity, mortality, and healthcare costs. The additional problem of multidrug-resistant pathogens boosts the adverse impact of infections in ICUs. Several factors influence the rapid spread of multidrug-resistant pathogens in the ICU, e.g., new mutations, selection of resistant strains, and suboptimal infection control. Among gram-positive organisms, the most important resistant microorganisms in the ICU are currently methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. In gram-negative bacteria, the resistance is mainly due to the rapid increase of extended-spectrum Beta-lactamases (ESBLs) in Klebsiella pneumonia, Escherichia coli, and Proteus species and high level third-generation cephalosporin Beta-lactamase resistance among Enterobacter spp. and Citrobacter spp., and multidrug resistance in Pseudomonas aeruginosa and Acinetobacter species. To conclude, additional efforts are needed in the future to slow down the emergence of antimicrobial resistance. Constant evaluation of current practice on basis of trends in MDR and antibiotic consumption patterns is essential to make progress in this problematic matter.

Fungal Infections in Patients with Severe Acute Pancreatitis and the Use of Prophylactic Therapy

Data from an 8-year period for 46 patients with severe acute pancreatitis and infected pancreatic necrosis were analyzed to determine the incidence of fungal infection, to identify risk factors for the development of fungal infection, and to assess the use of early fluconazole treatment. Intraabdominal fungal infection was found in 17 (37%) of 46 patients. Candida albicans was isolated most frequently (15 patients); Candida tropicalis and Candida krusei were found in 1 patient each. Characteristics of patients with fungal infection were not different from patients without fungal infection. The difference in mortality was not statistically significant between patients with fungal infection and patients without fungal infection. Early antifungal therapy (prophylactic or preemptive antifungal therapy) was administered to 18 patients, and only 3 of them developed fungal infection. In this cohort of critically ill patients, no risk factors for fungal infection could be demonstrated, and mortality among patients who received early antifungal therapy was not different. Early treatment with fluconazole seems to prevent fungal infection in these high-risk patients.

A clinical algorithm to diagnose invasive pulmonary aspergillosis in critically ill patients.

RATIONALE The clinical relevance of Aspergillus-positive endotracheal aspirates in critically ill patients is difficult to assess. OBJECTIVES We externally validate a clinical algorithm to discriminate Aspergillus colonization from putative invasive pulmonary aspergillosis in this patient group. METHODS We performed a multicenter (n = 30) observational study including critically ill patients with one or more Aspergillus-positive endotracheal aspirate cultures (n = 524). The diagnostic accuracy of this algorithm was evaluated using 115 patients with histopathologic data, considered the gold standard. Subsequently, the diagnostic workout of the algorithm was compared on the total cohort (n = 524), with the categorization based on the diagnostic criteria of the European Organization for the Research and Treatment of Cancer/Mycoses Study Group. MEASUREMENTS AND MAIN RESULTS Among 115 histopathology-controlled patients, 79 had proven aspergillosis. The algorithm judged 86 of 115 cases to have putative aspergillosis. This diagnosis was confirmed in 72 and rejected in 14 patients. The algorithm judged 29 patients to have Aspergillus colonization. This was confirmed in 22 and rejected in 7 patients. The algorithm had a specificity of 61% and a sensitivity of 92%. The positive and negative predictive values were 61 and 92%, respectively. In the total cohort (n = 524), 79 patients had proven invasive pulmonary aspergillosis (15.1%). According to the European Organization for the Research and Treatment of Cancer/Mycoses Study Group criteria, 32 patients had probable aspergillosis (6.1%) and 413 patients were not classifiable (78.8%). The algorithm judged 199 patients to have putative aspergillosis (38.0%) and 246 to have Aspergillus colonization (46.9%). CONCLUSIONS The algorithm demonstrated favorable operating characteristics to discriminate Aspergillus respiratory tract colonization from invasive pulmonary aspergillosis in critically ill patients.