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Biomedical subjects

R Marre

Publications and source records attributed to R Marre.

At least 19 recordsLinked to original sources
PubMed2006

Moxifloxacin prophylaxis in neutropenic patients.

OBJECTIVES: Recent studies have shown a beneficial impact of fluoroquinolones on infection-related morbidity and mortality for patients with haematological malignancies during neutropenia. Among the fluoroquinolones moxifloxacin currently provides one of the broadest spectra of antibacterial activity and may be suitable for prophylaxis during neutropenia. PATIENTS AND METHODS: In this controlled before and after observational study, moxifloxacin chemoprophylaxis was used during prolonged neutropenia in haemato-oncological patients (period 2; 282 episodes). Data were compared with two periods with levofloxacin prophylaxis, one preceding period (period 1; 399 episodes) and a post-observational period (period 3; 53 episodes). Endpoints for evaluation were the rates of Gram-negative and Gram-positive bacteraemia and infection-related mortality. RESULTS: We found similar survival rates as compared with levofloxacin. The rate of Gram-negative bacteraemia was higher during prophylaxis with moxifloxacin (11%) when compared with levofloxacin (6% for period 1 and 6% for period 3). In addition we observed a marked increase in diarrhoea associated with Clostridium difficile toxin A (CDAD) after a formula change from levofloxacin to moxifloxacin (attack rate 6% versus 33%). A decrease was attained after changing back to levofloxacin and reinforcing hygienic measures (13%). CONCLUSIONS: During moxifloxacin prophylaxis, we observed a significantly increased incidence of Gram-negative bacteraemia and CDAD. Careful attention must be paid not to trade the particularly beneficial effects of fluoroquinolones in the neutropenic setting for such disadvantageous effects. Until further data are obtained, caution is warranted when applying fluoroquinolones with high anaerobic activity in the neutropenic setting.

Anti-Infective Agents↗
PubMed2006

Antibiotic resistant fecal isolates of Enterococci among unselected patients outside the clinical sector: an epidemiological study from Southern Germany.

PURPOSE: The aim of the study was to assess the prevalence and determinants of antibiotic-resistant Enterococci in a large group of outpatients in Southern Germany. METHODS: Stool samples were collected from 497 unselected patients aged 40-75 years attending general practitioners. Enterococcus faecium (E. faecium) and Enterococcus faecalis (E. faecalis) were cultured and minimal inhibitory concentrations of antibiotics used inside and outside the clinical sector were tested. RESULTS: E. faecium and E. faecalis could be identified and cultured in 60 (12.4%) and 205 (41.2%) of the stool samples, respectively. Under non-selective culture conditions no vancomycin-resistant Enterococcus (VRE) isolate was found. Only E. faecium isolates showed resistance to fluoroquinolones, 40% were resistant to ciprofloxacin. The prevalences of E. faecium resistance to ampicillin and doxycycline were 3.3% and 13.3%, respectively, whereas 0.5% and 29.6% of the E. faecalis isolates were resistant to ampicillin and doxycycline, respectively. Antibiotic use during the last 3 months was significantly associated with antibiotic resistance (to either ampicillin, imipenem, or doxycycline) of E. faecalis isolates (OR: 2.9; CI: 1.2-6.8). CONCLUSIONS: Prevalences of resistance were generally lower than and patterns of resistance were quite different from previous investigations in the clinical setting. Recent antibiotic use was associated with increased colonization with resistant strains.

Adult↗
PubMed2006

CRB-65 predicts death from community-acquired pneumonia.

OBJECTIVE: The study was performed to validate the CURB, CRB and CRB-65 scores for the prediction of death from community-acquired pneumonia (CAP) in both the hospital and out-patient setting. DESIGN: Data were derived from a large multi-centre prospective study initiated by the German competence network for community-acquired pneumonia (CAPNETZ) which started in March 2003 and were censored for this analysis in October 2004. SETTING: Out- and in-hospital patients in 670 private practices and 10 clinical centres. SUBJECTS: Analysis was done for n = 1343 patients (n = 208 out-patients and n = 1135 hospitalized) with all data sets completed for the calculation of CURB and repeated for n = 1967 patients (n = 482 out-patients and n = 1485 hospitalized) with complete data sets for CRB and CRB-65. INTERVENTION: None. 30-day mortality from CAP was determined by personal contacts or a structured interview. RESULTS: Overall 30-day mortality was 4.3% (0.6% in out-patients and 5.5% in hospitalized patients, P < 0.0001). Overall, the CURB, CRB and CRB-65 scores provided comparable predictions for death from CAP as determined by receiver-operator-characteristics (ROC) curves. However, in hospitalized patients, CRB misclassified 26% of deaths as low risk patients. Availability of the CRB-65 score (90%) was far superior to that of CURB (65%), due to missing blood urea nitrogen values (P < 0.001). CONCLUSIONS: Both the CURB and CRB-65 scores can be used in the hospital and out-patients setting to assess pneumonia severity and the risk of death. Given that the CRB-65 is easier to handle, we favour the use of CRB-65 where blood urea nitrogen is unavailable.

Adolescent↗
PubMed2005

[New therapeutic strategies for community acquired pneumonia].

Community Acquired Pneumonia (CAP) is the most important infectious disease in Germany. In the acute phase, lethality is almost 10%, and in the six months follow up period following the acute infection, lethality is more than 15%. Problems with resistances had not been found in Germany, except for a decreasing susceptibility of S. pneumoniae against macrolides. The CRB-65 score allows a reliable discrimination between patients with a high and low risk of dying. The new S3 guideline for diagnosis and treatment of community acquired pneumonia recommends a risk adapted treatment. Low risk patients shall receive a monotherapy with e. g. amoxicillin, high risk patients should be treated with a broad spectrum combination therapy (beta-lactam and macrolide).

Anti-Bacterial Agents↗
PubMed2005

Fluoroquinolone resistance of Escherichia coli at a cancer center: epidemiologic evolution and effects of discontinuing prophylactic fluoroquinolone use in neutropenic patients with leukemia.

The aim of the present study was to investigate the epidemiologic evolution of fluoroquinolone resistance of E. coli clinical isolates from patients admitted to a hematology-oncology service where fluoroquinolone prophylaxis during neutropenia was recommended as the standard of care for many years but was then discontinued in a trial conducted in patients with acute leukemia. Fluoroquinolones had been shown to decrease the incidence of gram-negative bacteremia in cancer patients with neutropenia, yet it was thought that the emergence of resistance in Escherichia coli and other gram-negative bacteria may have caused a progressive lack of efficacy of fluoroquinolone prophylaxis. Epidemiologic surveillance of fluoroquinolone resistance of E. coli clinical isolates at our cancer center since 1992 showed a continuing influx of new clones not previously observed in the population of cancer patients, an increase in the number of cancer patients per year colonized and/or infected by fluoroquinolone-resistant E. coli (1992-1994, 10-16 patients; 1995-1997, 24-27 patients), and a resistance rate of >50% among E. coli bloodstream isolates of hematology-oncology patients. A 6-month fluoroquinolone prophylaxis discontinuation intervention trial in 1998 suggested that despite increasing resistance among E. coli isolates, fluoroquinolone prophylaxis in acute leukemia patients was still effective in the prevention of gram-negative bacteremia (incidence rates, 8% during the pre-intervention period vs. 20% after discontinuation; p<0.01). The resumption of fluoroquinolone prophylaxis in acute leukemia patients thereafter decreased the incidence of gram-negative bacteremia to the pre-intervention level (9%; p=0.03), while the proportion of in vitro fluoroquinolone resistance in E. coli bacteremia isolates again increased (from 15% during the intervention period to >50% in the post-intervention period). Relative rates of resistance thus were a poor indicator of the potential clinical benefits associated with fluoroquinolone prophylaxis in cancer patients.

Adolescent↗
PubMed2004

[Competence network "community acquired pneumonia" (CAPNETZ). A first interim report].

Community acquired pneumonia (CAP) is a disease with high morbidity and mortality in Germany. However, no reliable data are available about spectrum and resistance of pathogens, course of the disease, evidence based guidelines for treatment, and pathogen-host interactions. The German Ministry of Education and Research recognized these deficits and therefore decided to fund CAPNETZ, a network of competence for community acquired pneumonia. CAPNETZ integrates components of health research as well as clinical and basic research (horizontal network) on one hand and supports cooperation among general practitioners, community hospitals and universities (vertical network). Since October 2002, 1547 patients with CAP have been recruited within the network. First results indicate, that new observations made in terms of symptoms, spectrum of pathogens involved, and treatment modalities will impact on the formulation of new guidelines for the management of community acquired pneumonia.

Biomedical Research↗
PubMed2004

Prevalence and determinants of nasal colonization with antibiotic-resistant Staphylococcus aureus among unselected patients attending general practitioners in Germany.

Although the great majority of antibiotics are prescribed outside hospitals, little is known about the prevalence and determinants of antibiotic resistance in the group of outpatients. Nasal swabs were taken from 627 consecutive patients aged 40 years or above attending general practitioners in Southern Germany. Staphylococcus aureus was cultured and minimal inhibitory concentrations to various antibiotics were tested. Nasal swabs of 152 patients were positive for S. aureus. Prevalence of resistance was 68.3, 8.3 and 0.7% for penicillin G, erythromycin, and oxacillin respectively. Antibiotic use within the last month was associated with erythromycin resistance [adjusted odds ratio (OR) 7.4; 95 % confidence interval (CI) 1.0-53]. Besides a high prevalence of resistance to penicillinase-instable antibiotics we found only one (0.7%) methicillin-resistant S. aureus. Recent antibiotic use was associated with increased resistance to erythromycin.

Adult↗
PubMed2003

Rapid and standardized detection of Chlamydia pneumoniae using LightCycler real-time fluorescence PCR.

In order to meet the need of many microbiological laboratories for a standardized system for detecting Chlamydia pneumoniae in respiratory specimens, a hybridization probe-based LightCycler (Roche Diagnostics, Germany) PCR assay was developed. The assay's analytical sensitivity and specificity were evaluated according to the recommendations of the Centers for Disease Control and Prevention (USA) and Laboratory Centre for Disease Control (Canada). Seventy-four bacterial species other than Chlamydia pneumoniae, including strains of Chlamydia trachomatis, Chlamydia psittaci, and Chlamydia pecorum, tested negative. Six of six representative Chlamydia pneumoniae strains tested positive. An analytical sensitivity of 1 inclusion forming unit per ml of bronchoalveolar lavage fluid, corresponding to 0.02 inclusion forming units per PCR reaction, was observed. The assay showed 100% specificity and sensitivity for Chlamydia pneumoniae when testing DNA preparations from 12 specimens of patients with known pulmonary Chlamydia pneumoniae infection and from 78 specimens of patients with respiratory tract disease of other origin. The newly developed LightCycler assay may contribute to the urgently needed standardization of laboratory diagnosis of Chlamydia pneumoniae.

Bacteriological Techniques↗
PubMed2003

[CAPNet--network of competence for community acquired pneumonia: structures and aims].

Community Acquired Pneumonia (CAP) is a disease with high morbidity and mortality in Germany. Apart from the importance of CAP, no reliable data is available about infective germs, resistance of germs, course of the disease, or evidence based treatment. Also basic research should be improved in this field. The German State Ministry for Research (BMBF) has recognised these deficits and supports CAPNet, the network of competence for Community Acquired Pneumonia since 2002.

Community-Acquired Infections↗
PubMed2002

Interaction of fibronectin and aggregation substance promotes adherence of Enterococcus faecalis to human colon.

This in vitro study investigates the interaction between aggregation substance (AS), a virulence factor of Enterococcus faecalis, and colonic mucosal fibronectin in normal colon and colon from patients with Crohn's disease. Fibronectin was found to be overexpressed in Crohn's disease compared to normal colon. Compared to E. faecalis OG1X:pAM944 (AS-negative), E. faecalis OG1X:pAM721 (expressing AS) showed a significantly enhanced adhesion to human colonic mucosa in normal colon and in colon from patients with Crohn's disease. Double-staining of fibronectin and AS-positive enterococci showed that colocalization of bacteria and fibronectin was significantly more frequent in Crohn's disease than in normal colon. Preincubation of bacteria with soluble fibronectin caused a significant reduction in the adherence to fibronectin. In conclusion, the interaction between AS and fibronectin plays is an important factor that mediates adhesion of Enterococcus faecalis to colonic mucosa. This might be one of the mechanisms responsible for bacterial translocation of Enterococcus faecalis.

Bacterial Adhesion↗
PubMed2001

Aggregation substance-mediated adherence of Enterococcus faecalis to immobilized extracellular matrix proteins.

Aggregation substance (AS) of Enterococcus faecalis (E. faecalis), a sex pheromone plasmid encoded cell surface protein, mediates the formation of bacterial aggregates, thereby promoting plasmid transfer. The influence of pAD1-encoded AS, Asa1, on binding to immobilized extracellular matrix proteins was studied. The presence of AS increased enterococcal adherence to fibronectin more than eight-fold, to thrombospondin more than four-fold, to vitronectin more than three-fold, and to collagen type I more than two-fold (P<0.001). In contrast, binding to laminin and collagen type IV occurred independently of AS. Adherence of the constitutively AS expressing E. faecalis OG1X(pAM721) to immobilized fibronectin was found to be approximately five times higher than that of Staphylococcus aureus Cowan and approximately 30 times higher than that of Streptococcus bovis. Investigation of strains with various deletions within the structural gene of asa1 suggests that attachment to immobilized fibronectin is mainly mediated by amino acids within the variable region or by neighbouring residues. Thus, AS may promote adherence to injured epithelium and endothelium, where extracellular matrix proteins are exposed, thereby facilitating colonization and infection.

Bacterial Proteins↗
PubMed2001

Overexpresssion of a Legionella pneumophila homologue of the E. coli regulator csrA affects cell size, flagellation, and pigmentation.

Legionella pneumophila is an inhabitant of the aquatic environment and the causative agent of a bacterial pneumonia. We identified the presence of an L. pneumophila homologue of csrA of E. coli and rsmA of Erwinia carotovora, genes which regulate gene expression by destabilising mRNA and which have been shown to relate to environmental fitness and pathogenicity. The Legionella csrA was able to complement a csrA-negative mutant of E. coli. Overproduction of csrA in L. pneumophila lead to a reduction of flagellation and pigmentation and an increase in bacterial cell size. csrA overproduction was associated with a reduction of fliA and flaA transcripts. This suggests that similar to E. coli and Erwinia, L. pneumophila csrA is a regulator of gene expression and may contribute to the capability of the pathogen to rapidly adapt to changing environments.

Amino Acid Sequence↗
PubMed2001

Detection of legionellae in hospital water samples by quantitative real-time LightCycler PCR.

Contamination of hospital water systems with legionellae is a well-known cause of nosocomial legionellosis. We describe a new real-time LightCycler PCR assay for quantitative determination of legionellae in potable water samples. Primers that amplify both a 386-bp fragment of the 16S rRNA gene from Legionella spp. and a specifically cloned fragment of the phage lambda, added to each sample as an internal inhibitor control, were used. The amplified products were detected by use of a dual-color hybridization probe assay design and quantified with external standards composed of Legionella pneumophila genomic DNA. The PCR assay had a sensitivity of 1 fg of Legionella DNA (i.e., less than one Legionella organism) per assay and detected 44 Legionella species and serogroups. Seventy-seven water samples from three hospitals were investigated by PCR and culture. The rates of detection of legionellae were 98.7% (76 of 77) by the PCR assay and 70.1% (54 of 77) by culture; PCR inhibitors were detected in one sample. The amounts of legionellae calculated from the PCR results were associated with the CFU detected by culture (r = 0.57; P < 0.001), but PCR results were mostly higher than the culture results. Since L. pneumophila is the main cause of legionellosis, we further developed a quantitative L. pneumophila-specific PCR assay targeting the macrophage infectivity potentiator (mip) gene, which codes for an immunophilin of the FK506 binding protein family. All but one of the 16S rRNA gene PCR-positive water samples were also positive in the mip gene PCR, and the results of the two PCR assays were correlated. In conclusion, the newly developed Legionella genus-specific and L. pneumophila species-specific PCR assays proved to be valuable tools for investigation of Legionella contamination in potable water systems.

Bacterial Proteins↗
PubMed2001

Survival of Chlamydia pneumoniae-infected Mono Mac 6 cells is dependent on NF-kappaB binding activity.

The respiratory tract pathogen Chlamydia pneumoniae has been associated with atherosclerosis. Monocytes are supposed to serve as a vehicle for systemic dissemination of intracellular C. pneumoniae from the lung to the artery vessel wall. We were therefore interested in pathogen-induced cellular events associated with NF-kappaB, a crucial transcription factor for both inflammatory cytokines and antiapoptotic molecules. In this study we demonstrate by electrophoretic mobility shift assay that C. pneumoniae infection of the human monocytic cell line Mono Mac 6 induces activation of NF-kappaB over 48 h, with a maximum level at 1 h postinfection. As shown by supershift assay, the activated NF-kappaB complex consists of the subunits RelA (p65) and NF-kappaB1 (p50). Apoptotic host cells were not detected during the early stages of the infection when maximal activation of NF-kappaB was detected. Pretreatment of Mono Mac 6 with the antioxidant and NF-kappaB inhibitor PDTC (pyrrolidine dithiocarbamate) induced activation of caspase-3 and led to apoptotic cell death. The C. pneumoniae-induced activation of the NF-kappaB complex was reduced by PDTC, which in parallel resulted in an increased apoptosis, as quantified by annexin V labeling and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling reaction. In the complete absence of activated NF-kappaB, when Mono Mac 6 cells were pretreated with the more potent NF-kappaB inhibitors MG-132 and parthenolide a C. pneumoniae-mediated rescue of cells from induced apoptosis could not be achieved. Our results indicate that activation of NF-kappaB in C. pneumoniae-infected Mono Mac 6 cells is associated with protection of Mono Mac 6 cells against apoptosis and might thereby contribute to systemic spread of the pathogen.

Apoptosis↗