When a Picasso is a "Picasso": the entry point in the identification of visual art.

We investigated whether art is distinguished from other real world objects in human cognition, in that art allows for a special memorial representation and identification based on artists' specific stylistic appearances. Testing art-experienced viewers, converging empirical evidence from three experiments, which have proved sensitive to addressing the question of initial object recognition, suggest that identification of visual art is at the subordinate level of the producing artist. Specifically, in a free naming task it was found that art-objects as opposed to non-art-objects were most frequently named with subordinate level categories, with the artist's name as the most frequent category (Experiment 1). In a category-verification task (Experiment 2), art-objects were recognized faster than non-art-objects on the subordinate level with the artist's name. In a conceptual priming task, subordinate primes of artists' names facilitated matching responses to art-objects but subordinate primes did not facilitate responses to non-art-objects (Experiment 3). Collectively, these results suggest that the artist's name has a special status in the memorial representation of visual art and serves as a predominant entry point in recognition in art perception.

Clinical and bacteriologic efficacy of telithromycin in patients with bacteremic community-acquired pneumonia.

This retrospective analysis was performed to determine the clinical and bacteriologic efficacy of the ketolide antibacterial telithromycin in patients with community-acquired pneumonia (CAP) with pneumococcal bacteremia. Patients 13 years old with radiologically confirmed CAP and a positive blood culture for Streptococcus pneumoniae at screening were analyzed from eight multicenter Phase III/IV clinical trials. In four open-label, non-comparative studies, patients received telithromycin 800 mg once daily for 7-10 days. In four randomized, controlled, double-blind, comparative studies, patients received telithromycin 800 mg once daily for 5-10 days or a comparator antimicrobial (amoxicillin 1000 mg three times daily, clarithromycin 500 mg twice daily, or trovafloxacin 200 mg once daily) for 7-10 days. In total, 118 patients (telithromycin, 94/1061 [8.9%]; comparator, 24/244 [9.8%]) had documented pneumococcal bacteremia. Those who were treated with telithromycin achieved a clinical cure rate of 90.2% (74/82, per-protocol population); S. pneumoniae was eradicated in 77/82 (93.9%) bacteremic patients who received telithromycin and 15/19 (78.9%) comparator-treated patients. Clinical cure was also observed among telithromycin-treated bacteremic patients who were infected with penicillin- or erythromycin-resistant strains of S. pneumoniae (5/7 and 8/10, respectively). In conclusion, telithromycin achieves high clinical and bacteriologic cure rates in CAP patients with pneumococcal bacteremia.

Liens entre résistance et échec dans les infections respiratoires communautaires.

Resistance is one of failure's reasons. We tried, through clinical experience, to approach the magnitude and nature of the links, between phenotypically defined acquired resistance and clinical failure, in community acquired respiratory infections. An efficient resistance mecanism, able to suppress antibiotic action, is clearely associated to a risk of clinical failure (e.g. betalactamase secretion, target modification using methilation for macrolides, target mutation for fluoroquinoles). Resistance mecanism due to reduction of target affinity (pneumococcus and betalactams) progressively decreasing beta lactam activity depending on its expression, is at present time, not clearely associeted with clinical failure. Critical concentration, defining phenotypical resistance, is predictive of failure if it identifies a bacterial population owning an efficient resistance mecanism. It will not be predictive of failure if that concentration do not detect the resistance mecanism (e.g. parC mutation and levofloxacin) or if the link between antibiotic and resistant bacteria is not binary but depends also on pharmacokinetic parameters (pneumococcus and betalactam). Using resistance as a parametre for antibiotic choice, must integrate several elements: presence or not of a resistance mecanism, type and efficiency of the mecanism, links with clinical failure and antibiotic concentration, type and site of infection. Critical concentration is not allways the magic number that predict failure or success.

[Link between resistance and failure in community-acquired respiratory infections]. / Liens entre résistance et echec dans les infections respiratoires communautaires.

Resistance is one of failure's reasons. We tried, through clinical experience, to approach the magnitude and nature of the links, between phenotypically defined acquired resistance and clinical failure, in community acquired respiratory infections. An efficient resistance mecanism, able to suppress antibiotic action, is clearely associated to a risk of clinical failure (e.g. betalactamase secretion, target modification using methilation for macrolides, target mutation for fluoroquinoles). Resistance mecanism due to reduction of target affinity (pneumococcus and betalactams) progressively decreasing beta lactam activity depending on its expression, is at present time, not clearely associeted with clinical failure. Critical concentration, defining phenotypical resistance, is predictive of failure if it identifies a bacterial population owning an efficient resistance mecanism. It will not be predictive of failure if that concentration do not detect the resistance mecanism (e.g. parC mutation and levofloxacin) or if the link between antibiotic and resistant bacteria is not binary but depends also on pharmacokinetic parameters (pneumococcus and betalactam). Using resistance as a parametre for antibiotic choice, must integrate several elements: presence or not of a resistance mecanism, type and efficiency of the mecanism, links with clinical failure and antibiotic concentration, type and site of infection. Critical concentration is not allways the magic number that predict failure or success.

Continuing professional development and clinical governance: the role of scientific societies.

To date, the rules and state of development of the processes of continuing education and the evaluation of skills and competence vary considerably from one European Member State to another. The recognition of the freedom of establishment of health professionals throughout Europe must be made conditional upon the possession of a given qualification, and also the demonstration of maintained level of expertise, knowledge and skills. This appears to be of primary importance in order to maintain a good quality of care and to improve the performances and responsibilities of the infection of specialists, within the healthcare system. The role of scientific societies such as the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) can be envisaged as follows: (1) to play a key role in the coordination of the processes; definition of the main topics and visions, accreditation of the teaching courses and modalites of evaluation (which supposes a high level of cooperation with the platform for professional qualification) (2) to manage training courses (e.g., ESCMID School, postgraduate courses, technical workshops, educational activities within congresses). In order to make the system clearer and easier to apply, a proposal for a single, comprehensive directive is highly necessary.

Report of working group 3: specialist training and continuing medical education/professional development in the infection disciplines.

The European Union of Medical Specialists (UEMS) core curricula for training in infectious diseases and medical microbiology are adequate with the exception of one deficiency which is the absence of training in epidemiology, public health and infection control. Infectious disease curricula should include training in HIV, tuberculosis, hepatitis and sexually transmitted diseases. There is a need for a core curriculum in infection control. Infection control should have a basis in both medical microbiology and infectious diseases, and should become a specialty dealing with healthcare hygiene in hospitals, in outpatient clinics and also in institutions for the elderly. In the UK, a specialty training in infection is offered and includes internal medicine, clinical infectious diseases and medical microbiology for a total of 9 years. The UEMS should be contacted about the creation of a single specialty of infection, allowing for various degrees of sub-specialisation in infectious diseases or medical microbiology. It is unlikely that a European board examination validating the training of specialists will become a reality soon. Meanwhile, national systems should be created, documenting the content of the training and evaluating the quality of the training institutions. A medical specialist has a constant need for further education. This is generally a national matter, with requirements varying throughout Europe. It should be possible to accumulate continuing medical education/continuing professional development merits on a European level as well as on a national one. With the expansion of the European Union, it is important that the quality and content of specialist training can be verified and training curricula be harmonised. The UEMS should assist in this, in collaboration with scientific societies such as the ESCMID.

A pooled analysis of telithromycin in the treatment of community-acquired respiratory tract infections in adults.

BACKGROUND: Thirteen multinational, Phase III studies were conducted to establish the efficacy of telithromycin 800 mg once daily in the treatment of community-acquired respiratory tract infections (RTIs). PATIENTS AND METHODS: Data were analyzed from 4,743 adult patients participating across four indications: community-acquired pneumonia (CAP) of mild to moderate severity, acute exacerbations of chronic bronchitis (AECB), acute maxillary sinusitis (AMS) and tonsillitis/pharyngitis. RESULTS: Treatment with telithromycin for either 5 days (AECB, AMS and tonsillitis/pharyngitis) or 7-10 days (CAP and AMS) provided high rates of clinical and bacteriologic cure (5-day, 87.0% and 86.0%, respectively; 7 to 10-days, 90.3% and 90.5%, respectively) that were equivalent to those of a 10-day course of comparator antibacterials (86.5% and 86.5%, respectively). The clinical efficacy of telithromycin extended to high-risk CAP and AECB patients and to all key respiratory pathogens, including Streptococcus pneumoniae strains resistant to penicillin or erythromycin and atypical/intracellular pathogens. Telithromycin was generally well-tolerated across patient groups. CONCLUSION: These findings support the use of telithromycin as an effective therapy for the treatment of community-acquired RTIs.

Telithromycin 800 mg once daily for seven to ten days is an effective and well-tolerated treatment for community-acquired pneumonia.

OBJECTIVE: This open, multinational study examined the efficacy and tolerability of telithromycin (HMR 3647), the first ketolide antibacterial agent, at an oral dose of 800 mg once daily for seven to ten days (further validated using pharmacokinetic analysis) as an empiric therapy in adults with mild to moderate community-acquired pneumonia (CAP). METHODS: A total of 240 patients (aged 18-79 years; median 40 years) with clinical signs and symptoms of CAP (radiologically confirmed) were enrolled in the study and received at least one dose of study medication. Sputum and blood samples for bacteriologic documentation were collected within 48 h prior to enrollment. Clinical and bacteriological outcomes were assessed 17-21 days (test of cure visit) and 31-36 days (late post-therapy visit) after treatment initiation. Adverse events were assessed by spontaneous reporting and investigator observation. RESULTS: At the test of cure visit, 92.9% (95% CI: 88.4-96.1; n= 197) of patients achieved clinical cure in the per-protocol (PP) population. In the modified intent-to-treat (mITT) population, the cure rate was 79.6% (95% CI: 73.9-84.5; n= 240), including 12.5% of undetermined cases categorized as failures. Clinical cure (PP population) remained high in patients >/=65 years (85.7%), and in patients with a Fine score >/=III (92.1%). Among those patients for whom bacteriologic data were available, the majority had a satisfactory outcome (88.9% in the bacteriologic PP; n= 45). Bacterial eradication rates were similarly high (85.5% and 82.7% for the mITT and PP populations, respectively). All patients with infections as a result of atypical/intracellular pathogens Chlamydophila (Chlamydia) pneumoniae, Mycoplasma pneumoniae or Legionella pneumophila had a clinical outcome of cure. Treatment was well tolerated. Adverse events were mainly gastrointestinal in origin and mild in intensity. CONCLUSION: An oral dose of telithromycin 800 mg once daily for seven to ten days is an effective and well-tolerated first-line treatment for mild to moderate CAP in adults.

Telithromycin in the treatment of community-acquired pneumonia: a pooled analysis.

The efficacy of telithromycin has been assessed in six Phase III studies involving adults with mild to moderate community-acquired pneumonia (CAP) with a degree of severity compatible with oral therapy. Patients received telithromycin 800 mg once daily for 7-10 days in three open-label studies (n=870) and three randomized, double-blind, comparator-controlled studies (n=503). Comparator antibacterials were amoxicillin 1000 mg three-times daily, clarithromycin 500 mg twice daily and trovafloxacin 200 mg once daily. Clinical and bacteriological outcomes were assessed 7-14 days post-therapy. Among telithromycin-treated patients, per-protocol clinical cure rates were 93.1 and 91.0% for the open-label and comparative studies, respectively. Telithromycin treatment was as effective as the comparator agents. High eradication and clinical cure rates were observed for infections caused by key pathogens: Streptococcus pneumoniae including isolates resistant to penicillin G and/or erythromycin A (95.4%), Haemophilus influenzae (89.5%) and Moraxella catarrhalis (90%). Telithromycin was also highly effective in patients with infections caused by atypical and/or intracellular pathogens and those at increased risk of morbidity. Telithromycin was generally well tolerated. Telithromycin 800 mg once daily for 7-10 days offers a convenient and well-tolerated first-line oral therapy for the empirical treatment of mild to moderate CAP.

Impact of elements containing glycopeptide resistance genes on expression of virulence in Enterococcus faecalis peritonitis: a pilot study with rats.

The relationship between virulence and chromosomal elements containing glycopeptide resistance genes was experimentally assessed for two transconjugant strains of Enterococcus faecalis (VanA and VanB phenotypes) and compared to that for a susceptible wild-type strain. Microbiologic and inflammatory effects were assessed in a polymicrobial rat model of peritonitis. Mean peritoneal enterococcus concentrations +/- standard deviations at day 1 were 2.1 +/- 1.9, 1.3 +/- 1.1, and 1.7 +/- 2.0 log(10) CFU/ml for susceptible, VanA, and VanB strains, respectively (P < 0.05). At day 3 also there were lower concentrations of glycopeptide-resistant enterococcal strains in peritoneal fluid (3.2 +/- 3.4, 1.8 +/- 1.8, and 2.1 +/- 2.4 log(10) CFU/ml for susceptible, VanA, and VanB strains, respectively [P < 0.05]). Transconjugant glycopeptide-resistant strains were associated with increased peritoneal cell counts at the different evaluation times of the experiment (P < 0.001). Plasma alpha1-acid glycoprotein concentrations were lower in the presence of the susceptible strain (667 +/- 189 mg/liter) than in the presence of the VanA or VanB strain (1,193 +/- 419 or 1,210 +/- 404 mg/liter, respectively [P < 0.05]), while concentrations of tumor necrosis factor alpha and interleukin-6 in peritoneal fluid remained similar for the strains. These results suggest a trend toward variation of virulence of transconjugant strains compared to the wild-type strain in this peritonitis model.

Moving from recommendation to implementation and audit: part 2. Review of interventions and audit.

There are multiple interventions available that may help to control the development and spread of resistance to antimicrobial agents in bacteria implicated in community-acquired respiratory tract infections. Unfortunately, very few studies have assessed the effectiveness of these interventions using objective end-points, such as reduction in resistance rates and improvement in clinical outcomes. Most interventions are centered on reducing inappropriate or unnecessary use of antibiotics; others focus on reducing disease burden and bacterial colonization. With regard to antibiotic use, efforts should be concentrated at both the prescriber and consumer levels. Interventions that target prescribers include: provision of educational materials; strategies and tools to improve diagnosis; implementation of practice guidelines; personalized interactive sessions with feedback on the practice profile; and use of delayed prescription and alternative prescribing strategies. Optimal results are usually obtained when these interventions are combined with consumer education. Regulatory interventions (e.g. licensing regulations and controlled access to drugs), restrictions in the use of agents for growth promotion in animals, and use of nonantimicrobial therapies (e.g. probiotics) may help further to reduce inappropriate antibiotic use and thereby decrease the selective pressure for development of resistance. Infection-control strategies, public health measures, vaccination programs, and new antibiotics all have a role in minimizing the spread of resistant organisms. Ideally, resistance-control programs should include predefined criteria for success and integral audit processes based on objective end-points (antibiotic use, resistance trends, and health outcomes). Standardization of data collection is imperative so that the relative merits of various interventions can be compared. Effective implementation and audit of interventions is often difficult in developing countries owing to poor health-care infrastructures, lack of resources, poor education/training, and minimal regulatory controls on the supply and quality of antimicrobials. Substantial support from governments and health-care organizations across the globe is required to initiate and sustain effective intervention programs to control antimicrobial resistance.

[Prosthetic valve endocarditis due to Coxiella burnetii: six cases]. / Endocardites à Coxiella burnetii sur prothèse: six observations.

PURPOSE: Prosthetic valve endocarditis is a dangerous complication of valvular surgery (3-6%). Among involved pathogens, Coxiella burnetii is an occasional agent, though isolated with increasing frequency. We report our experience with this peculiar endocarditis and lay stress on specific diagnostic and therapeutic difficulties. METHODS: Between 1990 and 1995, six patients retrospectively met the diagnosis criteria for definite endocarditis due to Coxiella burnetii. RESULTS: Five Algerian men and one French woman presented with prosthetic valve endocarditis with negative blood cultures (on bioprosthesis: four cases, on mechanical valve: two cases). The main clinical and biological feature was febrile congestive heart failure with hepatomegaly, splenomegaly, hepatic and renal abnormalities, inflammatory syndrome, hypergammaglobulinemia, anemia and lymphopenia. Serological testing for Coxiella burnetii provided diagnosis in all cases. Echocardiography displayed vegetations in all cases. Valvular replacement was performed in four patients. With antibiotic therapy including doxycycline or/and hydroxychloroquine, quinolones or rifampicine, all patients experienced complete clinical, biological and echographic remission. CONCLUSION: Q fever prosthetic valve endocarditis presents as a systemic disorder occurring in patients with valvular heart disease. From now on, early diagnosis and efficient medical treatment may provide permanent prosthetic sterilization.

Optimal treatment strategies for community-acquired pneumonia: high-risk patients (geriatric and with comorbidity).

The four major factors predisposing individuals to community-acquired pneumonia (CAP) are chronic obstructive pulmonary disease, congestive heart failure, diabetes, and a high alcohol intake. The elderly are also at increased risk of severe infection. The introduction of fluoroquinolones with increased activity against Streptococcus pneumoniae and other CAP pathogens has been an important development, with recent guidelines recommending the use of respiratory fluoroquinolones as a first-line choice in outpatients with modifying factors, nursing home residents, and hospitalised patients in medical wards. Of the fluoroquinolones currently available that have antipneumococcal activity, levofloxacin is well tolerated and effective. It has been approved by the Food and Drug Administration (FDA) for treatment of CAP and widespread use has shown it to be very safe.

Consequences of VanE-type resistance on efficacy of glycopeptides in vitro and in experimental endocarditis due to Enterococcus faecalis.

The consequences on glycopeptide activity of low-level resistance to vancomycin due to VanE-type resistance were evaluated in vitro and in experimental endocarditis caused by Enterococcus faecalis BM4405 (MICs of vancomycin and teicoplanin: 16 and 0.5 microg/ml, respectively), its susceptible derivative BM4405-1, and susceptible E. faecalis JH2-2. After 24 h of incubation, vancomycin at 8 microg/ml was not active against E. faecalis BM4405 whereas it was bacteriostatic against strains BM4405-1 and JH2-2. Against all three strains, vancomycin at 30 microg/ml and teicoplanin at 8 or 30 microg/ml were bacteriostatic but bactericidal when combined with gentamicin. In rabbits with aortic endocarditis due to VanE-type resistant strain BM4405, treatment with a standard dose of vancomycin generated subinhibitory plasma concentrations (i.e., peak of 36.3 +/- 2.1 microg/ml and trough of 6.0 +/- 2.2 microg/ml) and led to no significant reduction in mean aortic valve vegetation counts compared to no treatment of control animals. In contrast, a higher dosing regimen of vancomycin (i.e., resulting in a peak of 38.3 +/- 5.2 microg/ml and a trough of 15.0 +/- 8.3 microg/ml), providing plasma concentrations above the MIC for the entire dosing interval, led to significant and similar activities against all three strains, which were enhanced by combination with gentamicin. Treatment with teicoplanin led to results similar to those obtained with vancomycin at a high dose. No subpopulations with increased resistance to glycopeptides were selected in vitro or in vivo. In conclusion, the use of a high dose of vancomycin was necessary for the treatment of experimental enterococcal endocarditis due to VanE-type strains.

Comparison of side effects of levofloxacin versus other fluoroquinolones.

The side-effect profile of levofloxacin was compared with that of other fluoroquinolones based on European and international data from approximately 130 million prescriptions. Levofloxacin was found to be very safe with a low rate of hepatic abnormalities (1/650,000). In contrast, 140 trovafloxacin-treated patients developed hepatic problems, 14 of which were severe, and 8 required transplantation. The main CNS problems associated with fluoroquinolones include dizziness, convulsions, psychosis, and insomnia. Levofloxacin, ofloxacin, and moxifloxacin reportedly have the lowest potential of inducing central nervous system (CNS) adverse events among the fluoroquinolones currently available. Cardiovascular problems were seen in 1/15 million levofloxacin prescriptions compared to 1-3% of sparfloxacin patients having QTc prolongation of greater than 500 msec. Moxifloxacin was also associated with QTc prolongation when compared to non-fluoroquinolone comparators. Nausea, vomiting, and diarrhoea remain the main adverse drug reactions (ADRs) associated with levofloxacin. However, the ADR rate for levofloxacin is still one of the lowest of any fluoroquinolone at 2% (compared to 2-10% for other fluoroquinolones). Ofloxacin and levofloxacin have a very low phototoxic potential, whereas this is a problem for sparfloxacin, enoxacin, and pefloxacin. The tolerance profile of levofloxacin can be considered to be very good, and better than most, if not all of the fluoroquinolones available.