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1.  What determines health-related quality of life among people living with HIV: an updated review of the literature 
Archives of Public Health  2014;72(1):40.
As infection with the Human Immunodeficiency Virus (HIV) has evolved to a chronic disease, perceived health-related quality of life (HRQoL) is becoming a prominent and important patient-reported outcome measure in HIV care. Literature discusses different factors influencing HRQoL in this population, however, currently no consensus exists about the main determinants. In this review a clear, up-to-date overview of the determinants influencing HRQOL among people living with HIV is provided.
All studies published before July 2013 that identified determinants of HRQoL among people living with HIV in high-income countries, were considered in this narrative review. PubMed, Web of Science and The Cochrane Library were consulted using the keywords ‘determinants’, ‘quality of life’, ‘HIV’ and ‘AIDS’. To be included, studies should have reported overall health and/or physical/mental health scores on a validated instrument and performed multivariable regression analyses to identify determinants that independently influence perceived HRQoL.
In total, 49 studies were included for further analysis and they used a variety of HRQoL instruments: Medical Outcomes Study Short Form-36 or variants, Medical Outcomes Study-HIV, HIV Cost and Services Utilization Study measure, Multidimensional Quality of Life Questionnaire, HIV targeted quality of life instrument, Functional Assessment of Human Immunodeficiency Virus Infection, HIV Overview of Problems Evaluation System, EuroQol, Fanning Quality of Life scale, Health Index and PROQOL-HIV. In this review, the discussed determinants were thematically divided into socio-demographic, clinical, psychological and behavioural factors. Employment, immunological status, presence of symptoms, depression, social support and adherence to antiretroviral therapy were most frequently and consistently reported to be associated with HRQoL among people living with HIV.
HRQoL among people living with HIV is influenced by several determinants. These determinants independently, but simultaneously impact perceived HRQoL. Most HRQoL instruments do not capture all key determinants. We recommend that the choice for an instrument should depend on the purpose of the HRQoL assessment.
Electronic supplementary material
The online version of this article (doi:10.1186/2049-3258-72-40) contains supplementary material, which is available to authorized users.
PMCID: PMC4323115  PMID: 25671112
HIV; Acquired immunodeficiency syndrome; Quality of life; Epidemiologic factors; Review
2.  Disseminated Infection with Mycobacterium tilburgii in a Male Immunocompromised Patient 
Journal of Clinical Microbiology  2014;52(5):1777-1779.
Mycobacterium tilburgii is a nonculturable nontuberculous mycobacterium identifiable only by molecular methods. We report a case of disseminated M. tilburgii infection illustrating the importance of 16S rRNA gene sequencing to determine the responsible mycobacterial pathogen and the difficulties in tailoring antimycobacterial treatment in the absence of a culturable organism.
PMCID: PMC3993618  PMID: 24523470
3.  Prevalence of Arcobacter Species among Humans, Belgium, 2008–2013 
Emerging Infectious Diseases  2014;20(10):1731-1734.
We examined fecal samples from 6,774 patients with enteritis in Belgium, 2008–2013. Members of the genus Arcobacter were the fourth most common pathogen group isolated, and the isolation rate was higher than previously reported. Culturing Arcobacter in a microbiology laboratory is feasible and should thus be tested for in cases of diarrheal disease.
PMCID: PMC4193277  PMID: 25271569
Bacteria; Arcobacter; Campylobacteraceae; Campylobacter; gastroenteritis; enteritis; colitis; septicemia; aerotolerant; diarrhea; zoonoses; food safety; Belgium
4.  Sexual experience and HIV-related knowledge among Belgian university students: a questionnaire study 
BMC Research Notes  2014;7:299.
Adolescents are a risk group for acquiring sexually transmitted diseases, including HIV. Correct knowledge about transmission mechanisms is a prerequisite to taking appropriate precautions to avoid infection. This study aimed at assessing the level of HIV-related knowledge among university students as a first step in developing targeted interventions. We used a self-developed HIV knowledge questionnaire, supplemented with socio-demographic and sexual behaviour questions. The questionnaire was composed of 59 items from different existing questionnaires. It included general statements and statements about prevention, transmission and treatment of HIV.
There were 357 (79.7%) female and 93 (20.3%) male participants and their median age was 20 (IQR 19–21). On average 42/59 (71.2%) questions were answered correctly, 5/59 (8.5%) were answered incorrectly and 12/59 (20.3%) were unknown . The best and worse scores were seen on the prevention questions and the treatment questions, respectively. HIV-related knowledge is higher in older students and in students with a health-related education. Students with sexual experience, with five or more partners and students who have been tested on STDs have a higher HIV-related knowledge.
Knowledge on prevention and transmission of HIV is fairly good among university students and knowledge is higher among students with more sexual experience. They still have some misconceptions (e.g. HIV is spread by mosquitoes) and they are ignorant of a substantial number of statements (e.g. risk for infection through oral sex).
PMCID: PMC4026820  PMID: 24886447
HIV; Acquired Immunodeficiency Syndrome; Knowledge; Sexual behaviour; Adolescent
5.  Comparison of Droplet Digital PCR and Seminested Real-Time PCR for Quantification of Cell-Associated HIV-1 RNA 
PLoS ONE  2014;9(1):e85999.
Cell-associated (CA) HIV-1 RNA is considered a potential marker for assessment of viral reservoir dynamics and antiretroviral therapy (ART) response in HIV-infected patients. Recent studies employed sensitive seminested real-time quantitative (q)PCR to quantify CA HIV-1 RNA. Digital PCR has been recently described as an alternative PCR-based technique for absolute quantification with higher accuracy compared to qPCR. Here, a comparison was made between the droplet digital PCR (ddPCR) and the seminested qPCR for quantification of unspliced (us) and multiply spliced (ms) CA HIV-1 RNA. Synthetic RNA standards and CA HIV-1 RNA from infected patients on and off ART (N = 34) were quantified with both methods. Correlations were observed between the methods both for serially diluted synthetic standards (usRNA: R2 = 0.97, msRNA: R2 = 0.92) and patient-derived samples (usRNA: R2 = 0.51, msRNA: R2 = 0.87). Seminested qPCR showed better quantitative linearity, accuracy and sensitivity in the quantification of synthetic standards than ddPCR, especially in the lower quantification ranges. Both methods demonstrated equally high detection rate of usRNA in patient samples on and off ART (91%), whereas ddPCR detected msRNA in larger proportion of samples from ART-treated patients (p = 0.13). We observed an average agreement between the methods for usRNA quantification in patient samples, albeit with a large standard deviation (bias = 0.05±0.75 log10). However, a bias of 0.94±0.36 log10 was observed for msRNA. No-template controls were consistently negative in the seminested qPCR, but yielded a positive ddPCR signal for some wells. Therefore, the false positive signals may have affected the detection power of ddPCR in this study. Digital PCR is promising for HIV nucleic acid quantification, but the false positive signals need further attention. Quantitative assays for CA HIV RNA have the potential to improve monitoring of patients on ART and to be used in clinical studies aimed at HIV eradication, but should be cross-validated by multiple laboratories prior to wider use.
PMCID: PMC3897572  PMID: 24465831
6.  Socio-economic, behavioural, (neuro)psychological and clinical determinants of HRQoL in people living with HIV in Belgium: a pilot study 
Due to highly active antiretroviral therapy (HAART), HIV-1 infection has evolved from a lethal to a chronic disease. As such, health-related quality of life (HRQoL) has become an important outcome variable. The purpose of this study was to identify socio-economic, behavioural, (neuro)psychological and clinical determinants of HRQoL among people living with HIV (PLHIV).
This study was conducted between 1 January and 31 December 2012 at the AIDS Reference Centre of Ghent University Hospital, a tertiary care referral centre in Belgium. Validated self-report questionnaires were administered to collect socio-demographic data, to assess HRQoL (Medical Outcomes Study-HIV), depressive symptoms (Beck Depression Inventory-II) and adherence to HAART (Short Medication Adherence Questionnaire) and to screen for neurocognitive dysfunction.
A total of 237 people participated, among whom 187 (78.9%) were male. Mean age was 45.8±10.7 years and 144 (63.7%, 144/226) participants were homosexual. Median physical and mental health score (PHS, MHS) were 55.6 (IQR 48.2–60.6) and 52.0 (IQR 44.2–57.9), respectively. Multivariable regression analysis revealed that incapacity to work, depressive symptoms, neurocognitive complaints (NCCs), dissatisfaction with the patient–physician relationship and non-adherence were all negatively associated with HRQoL.
Socio-economic (work status), behavioural (adherence) and (neuro)psychological (depressive symptoms, NCCs) determinants independently impact HRQoL among this cohort of PLHIV. Clinical parameters (viral load, CD4 cell count) were not independently associated with HRQoL.
PMCID: PMC3862978  PMID: 24331754
HIV; AIDS; quality of life; MOS-HIV; psychosocial; outcome
7.  Frequency and Predictors of HIV-1 Co-receptor Switch in Treatment Naive Patients 
PLoS ONE  2013;8(11):e80259.
Determination of HIV-1 co-receptor use is a necessity before initiation of a CCR5 antagonist but the longevity of a CCR5-use prediction remains unknown.
Genotypic co-receptor tropism determination was performed in 225 newly diagnosed individuals consulting an AIDS Reference Centre. Samples were collected at diagnosis and at initiation of antiretroviral therapy or just before closure of the study for patients who did not initiate therapy. For individuals with a discordant tropism prediction on the two longitudinal samples, analysis of intermediate samples and single genome sequencing of proviral DNA was performed to confirm the tropism switch. Deep sequencing was done to identify minor CXCR4 or CCR5-using populations in the initial sample.
Overall, tropism switches were rare (7.6%). Only a geno2pheno false positive rate of <50% at baseline was retained as predictive for a subsequent switch from CCR5-use only to predicted CXCR4-use. Minor CXCR4-using virus populations were detected in the first sample of 9 of the 14 R5-to-X4 switchers but the subsequent outgrowth of these minor populations was documented in only 3.
With the current guidelines for treatment initiation at CD4+ T cell counts of <500 cells/mm3, co-receptor switch between diagnosis and starting antiretroviral therapy is rare. Patients with R5 viruses and a geno2pheno FPR of <50% are more prone to subsequent co-receptor switch than patients with an FPR of >50% and will need repeat tropism testing if initiation of maraviroc is considered and previous testing dates from more than a year before.
PMCID: PMC3820624  PMID: 24244665
8.  Essentials for Selecting Antimicrobial Therapy for Intra-Abdominal Infections 
Drugs  2012;72(6):e17-e32.
Intra-abdominal infection (IAI) is a complex disease entity in which different aspects must be balanced in order to select the proper antimicrobial regimen and determine duration of therapy. A current classification indicates different faces of peritonitis. Primary peritonitis implies an intact gastrointestinal tract without overt barrier disruption. Secondary peritonitis refers to localized or diffuse peritoneal inflammation and abscess formation due to disruption of the anatomical barrier. Tertiary peritonitis includes cases that cannot be solved by a single or even sequential surgical intervention, often in combination with sequential courses of antimicrobial therapy. The most frequently used classification distinguishes ‘uncomplicated’ and ‘complicated’ IAI. In uncomplicated IAI, the infectious process is contained within a single organ, without anatomical disruption. In complicated IAI, disease is extended, with either localized or generalized peritonitis. However, there exists more than a single dimension of complexity in IAI, including severity of disease expression through systemic inflammation. As the currently used classifications of IAI often incite confusion by mixing elements of anatomical barrier disruption, severity of disease expression and (the likelihood of) resistance involvement, we propose an alternative for the current widely accepted classification. We suggest abandoning the terms ‘uncomplicated’ and ‘complicated’ IAI, as they merely confuse the issue. Furthermore, the term ‘tertiary peritonitis’ should likewise be discarded, as this simply refers to treatment failure of secondary peritonitis resulting in a state of persistent infection and/or inflammation. Hence, anatomical disruption and disease severity should be separated into different phenotypes for the same disease in combination with either presence or absence of risk factors for involvement of pathogens that are not routinely covered in first-line antimicrobial regimens (Pseudomonas aeruginosa, enterococci, Candida species and resistant pathogens). Generally, these risk factors can be brought back to recent exposure to antimicrobial agents and substantial length of stay in healthcare settings (5–7 days). As such, we developed a grid based on the different components of the classification: (i) anatomical disruption; (ii) severity of disease expression; and (iii) either community-acquired/early-onset healthcare-associated origin or healthcare-associated origin and/or recent antimicrobial exposure. The grid allows physicians to define the index case of IAI in a more unequivocal way and to select the most convenient empirical antimicrobial regimens. The grid advises on the necessity of covering nosocomial Gram-negative bacteria (including P. aeruginosa), enterococci and yeasts. The basis of antimicrobial therapy for IAI is that both Gram-negative and anaerobic bacteria should always be covered.
In recent years, some newer agents such as doripenem, moxifloxacin and tigecycline have been added to the antimicrobial armamentarium for IAI. For patients in whom the source can be adequately controlled, antimicrobial therapy should be restricted to a short course (e.g. 3–7 days in peritonitis).
PMCID: PMC3585770  PMID: 22480338
9.  Characterization of LEDGF/p75 Genetic Variants and Association with HIV-1 Disease Progression 
PLoS ONE  2012;7(11):e50204.
As Lens epithelium-derived growth factor (LEDGF/p75) is an important co-factor involved in HIV-1 integration, the LEDGF/p75-IN interaction is a promising target for the new class of allosteric HIV integrase inhibitors (LEDGINs). Few data are available on the genetic variability of LEDGF/p75 and the influence on HIV disease in vivo. This study evaluated the relation between LEDGF/p75 genetic variation, mRNA expression and HIV-1 disease progression in order to guide future clinical use of LEDGINs.
Samples were derived from a therapy-naïve cohort at Ghent University Hospital and a Spanish long-term-non-progressor cohort. High-resolution melting curve analysis and Sanger sequencing were used to identify all single nucleotide polymorphisms (SNPs) in the coding region, flanking intronic regions and full 3′UTR of LEDGF/p75. In addition, two intronic tagSNPs were screened based on previous indication of influencing HIV disease. LEDGF/p75 mRNA was quantified in patient peripheral blood mononuclear cells (PBMC) using RT-qPCR.
325 samples were investigated from patients of Caucasian (n = 291) and African (n = 34) origin, including Elite (n = 49) and Viremic controllers (n = 62). 21 SNPs were identified, comprising five in the coding region and 16 in the non-coding regions and 3′UTR. The variants in the coding region were infrequent and had no major impact on protein structure according to SIFT and PolyPhen score. One intronic SNP (rs2737828) was significantly under-represented in Caucasian patients (P<0.0001) compared to healthy controls (HapMap). Two SNPs showed a non-significant trend towards association with slower disease progression but not with LEDGF/p75 expression. The observed variation in LEDGF/p75 expression was not correlated with disease progression.
LEDGF/p75 is a highly conserved protein. Two non-coding polymorphisms were identified indicating a correlation with disease outcome, but further research is needed to clarify phenotypic impact. The conserved coding region and the observed variation in LEDGF/p75 expression are important characteristics for clinical use of LEDGINs.
PMCID: PMC3511443  PMID: 23226247
10.  Impact estimates of nosocomial bloodstream infection: looking from a different angle 
Critical Care  2011;15(3):169.
Mortality associated with nosocomial bloodstream infection is multifactorial. Source of infection, etiology, age, underlying disease, acute illness, and appropriateness of antimicrobial therapy all contribute to the final outcome. As such, estimates of mortality attributable to bloodstream infection may differ largely according to the presence or absence of risk factors in distinct patient populations. The adverse effect of nosocomial bloodstream infection for the individual patient is substantial, with about a doubling of the risk of death. Yet, in settings with a high standard of care in terms of infection prevention and control, the occurrence rate of bloodstream infection is relatively low and therefore its impact on overall ICU mortality rather limited. As a consequence, untargeted interventional studies focused on infection prevention should use occurrence rate of infection rather than mortality as outcome variable.
PMCID: PMC3219020  PMID: 21745423
11.  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.
PMCID: PMC3231873  PMID: 22112929
12.  Severe Drug-induced Liver Injury Associated with Prolonged Use of Linezolid 
Journal of Medical Toxicology  2010;6(3):322-326.
This study aims to describe a patient developing concomitant severe liver failure and lactic acidosis after long-term treatment with linezolid. A 55-year-old Caucasian woman developed concomitant severe liver failure and lactic acidosis after a treatment with linezolid for 50 days because of infected hip prosthesis. Other causes of liver failure and lactic acidosis were excluded by extensive diagnostic workup. A liver biopsy showed microvesicular steatosis. As linezolid toxicity was considered to be the cause of the lactic acidosis and the severe hepatic failure, the antibiotic was withdrawn. After 4 days of supportive therapy and hemodialysis, the serum lactate level returned within normal limits. The prothrombin time ratio and thrombocytes recovered within 2 weeks. Bilirubin levels normalized within 14 weeks. Since no other cause could be identified, liver injury was considered to be drug-related. Resolution of the hepatotoxicity occurred after discontinuation of linezolid, supportive treatment measures, and hemodialysis. Both lactic acidosis and microvesicular steatosis after the use of linezolid are related to mitochondrial dysfunction. The Council for International Organizations of Medical Sciences/Roussel Ucalf Causality Assessment Method scale revealed that the adverse drug event was probable. Prolonged exposure to linezolid may induce severe hepatotoxicity. Clinicians should be aware of this possible adverse effect especially in case of long-term treatment.
PMCID: PMC3550492  PMID: 20358416
Linezolid; Liver failure; Microvesicular steatosis; Lactic acidosis
15.  Comparison of phenotypic and genotypic tropism determination in triple-class-experienced HIV patients eligible for maraviroc treatment 
Determination of HIV-1 tropism is a pre-requisite to the use of CCR5 antagonists. This study evaluated the potential of population genotypic tropism tests (GTTs) in clinical practice, and the correlation with phenotypic tropism tests (PTTs) in patients accessing routine HIV care.
Forty-nine consecutive plasma samples for which an original TrofileTM assay was performed were obtained from triple-class-experienced patients in need of a therapy change. Viral tropism was defined as the consensus of three or more tropism calls obtained from the combination of two independent population PTT assays (Trofile Biosciences, San Francisco, CA, USA, and Virco, Beerse, Belgium), population GTTs and GTTs based on ultra-deep sequencing. If no consensus was reached, a clonal PTT was performed in order to finalize the tropism call. This two-step approach allowed the definition of a reference tropism call.
According to the reference tropism result, 35/49 samples were CCR5 tropic (R5) (patients eligible for maraviroc treatment) and 14/49 were assigned as non-R5 tropic. The non-R5 samples [patients not eligible for maraviroc treatment according to the FDA/European Medicines Agency (EMEA) label] group included both the CXCR4 (X4) samples and the dual and mixed CCR5/CXCR4 (R5/X4) samples. Compared with TrofileTM population PTTs, population GTTs showed a higher sensitivity (97%) and a higher negative predictive value (91%), but almost equal specificity and an equal positive predictive value.
In line with recent reports from clinical trial data, our data support the use of population genotypic tropism testing as a tool for tropism determination before the start of maraviroc.
PMCID: PMC3019088  PMID: 21196489
HIV-1 tropism; genotypic tests; phenotypic tests
16.  Severe burn injury in europe: a systematic review of the incidence, etiology, morbidity, and mortality 
Critical Care  2010;14(5):R188.
Burn 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.
The 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.
The 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.
Despite 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.
PMCID: PMC3219295  PMID: 20958968
17.  Implementation of an evidence-based sepsis program in the intensive care unit: evident or not? 
Critical Care  2009;13(5):193.
Severe sepsis and septic shock are among the most serious health conditions and are associated with unwelcome clinical, social, and economic outcomes. With the introduction of the Surviving Sepsis Campaign guidelines, the campaign leaders aimed to reduce mortality from severe sepsis by at least one quarter by 2009 by means of a six-point action plan, namely, building awareness among health care professionals, improving early and accurate disease recognition and diagnosis, increasing the use of appropriate treatments and interventions, education, getting better post-intensive care unit access, and developing standard processes of care. However, adherence to these recommendations is a first but crucial step in obtaining these goals. A comprehensive evaluation of both, adherence to a sepsis program and whether this results in better outcomes for patients, is therefore essential to guide informed decision-making regarding the implementation of such an evidence-based protocol.
PMCID: PMC2784379  PMID: 19833007
18.  Epidemiological study of phylogenetic transmission clusters in a local HIV-1 epidemic reveals distinct differences between subtype B and non-B infections 
BMC Infectious Diseases  2010;10:262.
The number of HIV-1 infected individuals in the Western world continues to rise. More in-depth understanding of regional HIV-1 epidemics is necessary for the optimal design and adequate use of future prevention strategies. The use of a combination of phylogenetic analysis of HIV sequences, with data on patients' demographics, infection route, clinical information and laboratory results, will allow a better characterization of individuals responsible for local transmission.
Baseline HIV-1 pol sequences, obtained through routine drug-resistance testing, from 506 patients, newly diagnosed between 2001 and 2009, were used to construct phylogenetic trees and identify transmission-clusters. Patients' demographics, laboratory and clinical data, were retrieved anonymously. Statistical analysis was performed to identify subtype-specific and transmission-cluster-specific characteristics.
Multivariate analysis showed significant differences between the 59.7% of individuals with subtype B infection and the 40.3% non-B infected individuals, with regard to route of transmission, origin, infection with Chlamydia (p = 0.01) and infection with Hepatitis C virus (p = 0.017). More and larger transmission-clusters were identified among the subtype B infections (p < 0.001). Overall, in multivariate analysis, clustering was significantly associated with Caucasian origin, infection through homosexual contact and younger age (all p < 0.001). Bivariate analysis additionally showed a correlation between clustering and syphilis (p < 0.001), higher CD4 counts (p = 0.002), Chlamydia infection (p = 0.013) and primary HIV (p = 0.017).
Combination of phylogenetics with demographic information, laboratory and clinical data, revealed that HIV-1 subtype B infected Caucasian men-who-have-sex-with-men with high prevalence of sexually transmitted diseases, account for the majority of local HIV-transmissions. This finding elucidates observed epidemiological trends through molecular analysis, and justifies sustained focus in prevention on this high risk group.
PMCID: PMC2940905  PMID: 20822507
19.  Determinants and impact of multidrug antibiotic resistance in pathogens causing ventilator-associated-pneumonia 
Critical Care  2008;12(6):R142.
The idea that multidrug resistance (MDR) to antibiotics in pathogens causing ventilator-associated pneumonia (VAP) is an independent risk factor for adverse outcome is still debated. We aimed to identify the determinants of MDR versus non-MDR microbial aetiology in VAP and assessed whether MDR versus non-MDR VAP was independently associated with increased 30-day mortality.
We performed a retrospective analysis of a prospectively registered cohort of adult patients with microbiologically confirmed VAP, diagnosed at a university hospital intensive care unit during a three-year period. Determinants of MDR as compared with non-MDR microbial aetiology and impact of MDR versus non-MDR aetiology on mortality were investigated using multivariate logistic and competing risk regression analysis.
MDR pathogens were involved in 52 of 192 episodes of VAP (27%): methicillin-resistant Staphylococcus aureus in 12 (6%), extended-spectrum β-lactamase producing Enterobacteriaceae in 28 (15%), MDR Pseudomonas aeruginosa and other non-fermenting pathogens in 12 (6%). Multivariable logistic regression identified the Charlson index of comorbidity (odds ratio (OR) = 1.38, 95% confidence interval (CI) = 1.08 to 1.75, p = 0.01) and previous exposure to more than two different antibiotic classes (OR = 5.11, 95% CI = 1.38 to 18.89, p = 0.01) as predictors of MDR aetiology. Thirty-day mortality after VAP diagnosis caused by MDR versus non-MDR was 37% and 20% (p = 0.02), respectively. A multivariate competing risk regression analysis showed that renal replacement therapy before VAP (standardised hazard ratio (SHR) = 2.69, 95% CI = 1.47 to 4.94, p = 0.01), the Charlson index of comorbidity (SHR = 1.21, 95% CI = 1.03 to 1.41, p = 0.03) and septic shock on admission to the intensive care unit (SHR = 1.86, 95% CI = 1.03 to 3.35, p = 0.03), but not MDR aetiology of VAP, were independent predictors of mortality.
The risk of MDR pathogens causing VAP was mainly determined by comorbidity and prior exposure to more than two antibiotics. The increased mortality of VAP caused by MDR as compared with non-MDR pathogens was explained by more severe comorbidity and organ failure before VAP.
PMCID: PMC2646301  PMID: 19014695
20.  Discriminating invasive fungal infection from colonization 
Critical Care  2008;12(2):412.
PMCID: PMC2447572  PMID: 18439323
21.  Clinical relevance of Aspergillus isolation from respiratory tract samples in critically ill patients 
Critical Care  2006;10(1):R31.
The 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.
Using 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.
Over 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).
A 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.
PMCID: PMC1550813  PMID: 16507158
22.  Perioperative factors determine outcome after surgery for severe acute pancreatitis 
Critical Care  2004;8(6):R504-R511.
There is evidence that postponing surgery in critically ill patients with severe acute pancreatitis (SAP) leads to improved survival, but previous reports included patients with both sterile and infected pancreatic necrosis who were operated on for various indications and with different degrees of organ dysfunction at the moment of surgery, which might be an important bias. The objective of this study is to analyze the impact of timing of surgery and perioperative factors (severity of organ dysfunction and microbiological status of the necrosis) on mortality in intensive care unit (ICU) patients undergoing surgery for SAP.
We retrospectively (January 1994 to March 2003) analyzed patients admitted to the ICU with SAP. Of 124 patients, 56 were treated surgically; these are the subject of this analysis. We recorded demographic characteristics and predictors of mortality at admission, timing of and indications for surgery, and outcome. We also studied the microbiological status of the necrosis and organ dysfunction at the moment of surgery.
Patients' characteristics were comparable in patients undergoing early and late surgery, and there was a trend toward a higher mortality in patients who underwent early surgery (55% versus 29%, P = 0.06). In univariate analysis, patients who died were older, had higher organ dysfunction scores at the day of surgery, and had sterile necrosis more often; there was a trend toward earlier surgery in these patients. Logistic regression analysis showed that only age, organ dysfunction at the moment of surgery, and the presence of sterile necrosis were independent predictors of mortality.
In this cohort of critically ill patients operated on for SAP, there was a trend toward higher mortality in patients operated on early in the course of the disease, but in multivariate analysis, only greater age, severity of organ dysfunction at the moment of surgery, and the presence of sterile necrosis, but not the timing of the surgical intervention, were independently associated with an increased risk for mortality.
PMCID: PMC1065077  PMID: 15566598
acute necrotizing pancreatitis; infected pancreatic necrosis; multiple organ failure; severe acute pancreatitis
23.  One Case Each of Recurrent Meningitis and Hemoperitoneum Infection with Ralstonia mannitolilytica 
Journal of Clinical Microbiology  2001;39(12):4588-4590.
Two clinical cases of infection with Ralstonia mannitolilytica are described: a recurrent meningitis on an implanted intraventricular catheter and an infected hemoperitoneum as a complication of a cholangiocarcinoma. The strains were first misidentified as Pseudomonas fluorescens and Burkholderia cepacia. Further testing lead to the identification as Ralstonia pickettii biovar 3/“thomasii,” which was recently shown to represent a separate species, R. mannitolilytica (List editor N. Weiss, Int. J. Syst. Evol. Microbiol. 51:795–796, 2001), originally described as R. mannitolytica (De Baere et al., Int. J. Syst. Evol. Microbiol. 51:547–558, 2001). R. mannitolilytica can be distinguished from all described Ralstonia species by its acidification of d-arabitol and mannitol and by its lack of nitrate reduction and of alkalinization of tartrate. In order to determine the true prevalence of infections with this species, colistin-resistant “P. fluorescens” strains and strains growing on B. cepacia selective medium deserve further attention.
PMCID: PMC88597  PMID: 11724893

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