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1.  Microarray-Based Genotyping and Clinical Outcomes of Staphylococcus aureus Bloodstream Infection: An Exploratory Study 
PLoS ONE  2013;8(8):e71259.
The clinical course of Staphylococcus aureus bacteremia varies extensively. We sought to determine the relationship between genetic characteristics of the infecting pathogen and clinical outcomes in an exploratory study. In two study centers, 317 blood culture isolates were analyzed by DNA microarray and spa genotyping. By uni- and multivariate regression analyses associations of genotype data with 30-day all-cause mortality, severe sepsis/septic shock, disseminated disease, endocarditis, and osteoarticular infection were investigated. Univariate analysis showed significant association between S. aureus genes/gene-clusters or clonal complexes and clinical endpoints. For example CC15 was associated with 30-day mortality and CC22 with osteoarticular infection. In multivariate analysis methicillin resistance (mecA, OR 4.8 [1.43–16.06]) and the beta-lactamase-gene (bla, OR 3.12 [1.17–8.30]) remained independently associated with 30-day mortality. The presence of genes for enterotoxins (sed/sej/ser) was associated with endocarditis (OR 5.11 [1.14–18.62]). Host factors such as McCabe classification (OR 4.52 [2.09–9.79] for mortality), age (OR 1.06 [1.03–1.10] per year), and community-acquisition (OR 3.40 [1.31–8.81]) had a major influence on disease severity, dissemination and mortality. Individual genotypes and clonal complexes of S. aureus can only partially explain clinical features and outcomes of S. aureus bacteremia. Genotype-phenotype association studies need to include adjustments for host factors like age, comorbidity and community-acquisition.
PMCID: PMC3743874  PMID: 23967176
2.  Use of a Simple Criteria Set for Guiding Echocardiography in Nosocomial Staphylococcus aureus Bacteremia 
A set of simple clinical prediction criteria for patients with nosocomial Staphylococcus aureus bacteremia was developed to identify patients at low risk of infective endocarditis in whom transesophageal echocardiography might be dispensable and was validated with two independent cohorts.
(see the editorial commentary and Soriano and Mensa, on pages 10–12.)
Background. Infective endocarditis (IE) is a severe complication in patients with nosocomial Staphylococcus aureus bacteremia (SAB). We sought to develop and validate criteria to identify patients at low risk for the development of IE in whom transesophageal echocardiography (TEE) might be dispensable.
Methods. Consecutive patients with nosocomial SAB from independent cohorts in Europe (Invasive S. aureus Infection Cohort [INSTINCT]) and North America (S. aureus Bacteremia Group [SABG]) were evaluated for the presence of clinical criteria predicting an increased risk for the development of IE (ie, prolonged bacteremia of >4 days' duration, presence of a permanent intracardiac device, hemodialysis dependency, spinal infection, and nonvertebral osteomyelitis). Patients were observed closely for clinical signs and symptoms of IE during hospitalization and a 3-month follow-up period.
Results. IE was present in 13 (4.3%) of 304 patients in the INSTINCT cohort and in 40 (9.3%) of 432 patients in the SABG cohort. Within 14 days after the first positive blood culture result, echocardiography was performed in 39.8% and 57.4% of patients in the INSTINCT and SABG cohorts, respectively. In patients with IE, the most common clinical prediction criteria present were prolonged bacteremia (69.2% vs 90% for INSTINCT vs SABG, respectively) and presence of a permanent intracardiac device (53.8% vs 32.5%). In total, 13 of 13 patients in the INSTINCT cohort and 39 of 40 patients in the SABG cohort with documented IE fulfilled at least 1 criterion (sensitivity, 100% vs. 97.5%; negative predictive value, 100% vs 99.2%).
Conclusions. A simple criteria set for patients with nosocomial SAB can identify patients at low risk of IE. Patients who meet these criteria may not routinely require TEE.
PMCID: PMC3149212  PMID: 21653295
3.  Therapy of uncomplicated falciparum malaria in Europe: MALTHER – a prospective observational multicentre study 
Malaria Journal  2012;11:212.
Malaria continues to be amongst the most frequent infectious diseases imported to Europe. Whilst European treatment guidelines are based on data from studies carried out in endemic areas, there is a paucity of original prospective treatment data. The objective was to summarize data on treatments to harmonize and optimize treatment for uncomplicated malaria in Europe.
A prospective observational multicentre study was conducted, assessing tolerance and efficacy of treatment regimens for imported uncomplicated falciparum malaria in adults amongst European centres of tropical and travel medicine.
Between December 2003 and 2009, 504 patients were included in 16 centres from five European countries. Eighteen treatment regimens were reported, the top three being atovaquone-proguanil, mefloquine, and artemether-lumefantrine. Treatments significantly differed with respect to the occurrence of treatment changes (p = 0.005) and adverse events (p = 0.001), parasite and fever clearance times (p < 0.001), and hospitalization rates (p = 0.0066) and durations (p = 0.001). Four recrudescences and two progressions to severe disease were observed. Compared to other regimens, quinine alone was associated with more frequent switches to second line treatment, more adverse events and longer inpatient stays. Parasite and fever clearance times were shortest with artemether-mefloquine combination treatment. Vomiting was the most frequent cause of treatment change, occurring in 5.5% of all patients but 9% of the atovaquone-proguanil group.
This study highlights the heterogeneity of standards of care within Europe. A consensus discussion at European level is desirable to foster a standardized management of imported falciparum malaria.
PMCID: PMC3477029  PMID: 22720832
Imported falciparum malaria; Uncomplicated; Therapy; Treatment change; Parasite clearance time; Fever clearance time; Adverse events; Europe
4.  Differences in Clinical Manifestations of Imported versus Autochthonous Leptospirosis in Austria and Germany 
Leptospirosis, a zoonosis occurring worldwide, has a broad spectrum of clinical manifestations. Recently, various countries observed an increase of severe anicteric cases. In Austria and Germany, growing numbers of imported cases are notified in addition to autochthonous infections. The aim of this study was to assess whether imported and autochthonous cases differ in clinical manifestations and outcome. We retrospectively analyzed 24 imported and 35 autochthonous cases treated in six infectious disease units between 1998 and 2008. To compare disease severity, patients were classified according to established independent risk factors for fatal outcome. Although severe leptospirosis (i.e., presence of ≥ 1 independent risk factors for death) occurred in similar proportions of imported (67%) and autochthonous (86%) infections (P = 0.1), imported cases were significantly fewer icteric (13% versus 69%; P < 0.0001). In conclusion, an increasing incidence of severe anicteric imported cases of leptospirosis should be anticipated with rising global travel activities.
PMCID: PMC2911179  PMID: 20682876
5.  Paenibacillus larvae Bacteremia in Injection Drug Users 
Emerging Infectious Diseases  2010;16(3):487-489.
Paenibacillus larvae causes American foulbrood in honey bees. We describe P. larvae bacteremia in 5 injection drug users who had self-injected honey-prepared methadone proven to contain P. larvae spores. That such preparations may be contaminated with spores of this organism is not well known among pharmacists, physicians, and addicts.
PMCID: PMC3322038  PMID: 20202425
Paenibacillus larvae; bacteremia; bacteria; intravenous drug abuse; honey; methadone substitution; American foulbrood; dispatch
6.  Molecular surveillance of the antifolate-resistant mutation I164L in imported african isolates of Plasmodium falciparum in Europe: sentinel data from TropNetEurop 
Malaria Journal  2003;2:17.
Malaria parasites that carry the DHFR-mutation I164L are not only highly resistant to sulfadoxine-pyrimethamine but also to the new antimalarial drug chlorproguanil-dapsone. The spread of this mutation in Africa would result in a public health disaster since there is a lack of effective alternatives that are both affordable and safe. Up to now, this mutation has only been described in Asian and Latin-American countries. The objective of this study was to assess the prevalence of this mutation in African isolates of Plasmodium falciparum that have been imported into Europe through travellers.
TropNetEurop is a network for the surveillance of travel-associated diseases and seems to cover approximately 12% of all malaria cases imported into Europe. Within this network we screened 277 imported African isolates of P. falciparum with the help of PCR- and enzyme-digestion-methods for the antifolate-resistant mutation I164L.
The I164L mutation was not detected in any of the isolates tested.
Continuous molecular surveillance of mutations in P. falciparum, as it is practised within TropNetEurop, is an essential tool for the understanding and early detection of the spread of antimalarial drug resistance in Africa.
PMCID: PMC166141  PMID: 12869209
7.  Molecular surveillance of drug resistance through imported isolates of Plasmodium falciparum in Europe 
Malaria Journal  2002;1:11.
Results from numerous studies point convincingly to correlations between mutations at selected genes and phenotypic resistance to antimalarials in Plasmodium falciparum isolates. In order to move molecular assays for point mutations on resistance-related genes into the realm of applied tools for surveillance, we investigated a selection of P. falciparum isolates that were imported during the year 2001 into Europe to study the prevalence of resistance-associated point mutations at relevant codons. In particular, we tested for parasites which were developing resistance to antifolates and chloroquine. The screening results were used to map the prevalence of mutations and, thus, levels of potential drug resistance in endemic areas world-wide.
337 isolates have been tested so far. Prevalence of mutations that are associated with resistance to chloroquine on the pfcrt and pfmdr genes of P. falciparum was demonstrated at high levels. However, the prevalence of mutations associated with resistance to antifolates at the DHFR and DHPS genes was unexpectedly low, rarely exceeding 60% in endemic areas.
Constant screening of imported isolates will enable TropNetEurop to establish a screening tool for emerging resistance in endemic areas.
PMCID: PMC140139  PMID: 12423552

Results 1-7 (7)