Azithromycin to prevent Pseudomonas aeruginosa ventilator-associated pneumonia by inhibition of quorum sensing: a randomized controlled trial.

Purpose: Anti-virulence strategies have not been evaluated for the prevention of bacterial infections. Prolonged colonization of intubated patients with Pseudomonas aeruginosa isolates producing high-levels of the quorum sensing (QS)-regulated virulence factor rhamnolipids has been associated with ventilator-associated pneumonia (VAP). In this pathogen, azithromycin reduces QS-regulated virulence.

Rifampin-bonded vascular grafts and postoperative infections.

Postoperative wound and graft infections remain a major challenge for vascular surgeons. The bonding of antimicrobial substances on the graft material has been considered for many years, but the demonstration of safety and efficacy of these techniques is far from evident. Among the different proposed options, bonding of rifampin to the grafts has been the most evaluated technique, both experimentally and clinically.

Effect of clarithromycin in patients with sepsis and ventilator-associated pneumonia.

Background: Because clarithromycin provided beneficiary nonantibiotic effects in experimental studies, its efficacy was tested in patients with sepsis and ventilator-associated pneumonia (VAP).

Methods: Two hundred patients with sepsis and VAP were enrolled in a double-blind, randomized, multicenter trial from June 2004 until November 2005. Clarithromycin (1 g) was administered intravenously once daily for 3 consecutive days in 100 patients; another 100 patients were treated with placebo.

A global survey of antibiotic leftovers in the outpatient setting.

We performed a global survey of outpatients who had taken self-administered antibiotics within the last 12 months in order to identify factors that lead to possession of leftover antibiotics in the community. The study included 4,514 subjects aged 18-99 years. Of 4,192 respondents not currently taking antibiotics, 53.

Non-compliance with antibiotic therapy for acute community infections: a global survey.

A global patient survey of non-compliance with antibiotic therapy for acute community infections included 4514 adult respondents (aged 18-99 years) in 11 countries. Admitted non-compliance (ANC) was reported in 912/4088 (22.3%) of cases but varied widely between countries.

[The physician, patient and antibiotics].

More than 3.000 randomized patients, who received an antibiotic course for a mild respiratory infection in the last 2 months have been interviewed in 4 European countries about their perceptions of antibiotic therapy and the doctor's skills. Six attitudinal dimensions related to the doctor identified 4 patients type: Involved (30 %), Deferents (23%), Ignored (13%) and Critical (17%).

[How bacteria resist antibiotics: a primary form of collective intelligence?].

Bacteria produce inhibitory enzymes (beta-lactamases, etc), block antibiotic attachment to target molecules (MRSA, etc.), extrude antibiotics from the cell by active efflux systems (multidrug resistant pseudomonas, etc) or limit antibiotic penetration through the outer membrane in Gram negatives. Genetically, resistance occurs after mutation or horizontal transfers (transformation, transduction, conjugation) of mobile genetic elements (integrons, transposons, phages, plasmids), associated with a risk of epidemic spread.

Regulatory effects of macrolides on bacterial virulence: potential role as quorum-sensing inhibitors.

Pseudomonas aeruginosa is an opportunistic pathogen, and this organism is a major cause of pulmonary damage and mortality in patients with cystic fibrosis (CF), diffuse panbronchiolitis (DPB) and other forms of bronchiectasis. A break-through in the treatment of DPB and associated chronic P. aeruginosa pulmonary infection was realized when a patient with DPB improved dramatically after treatment with erythromycin for years.

Community-acquired pneumonia: new management strategies for evolving pathogens and antimicrobial susceptibilities.

Community-acquired pneumonia (CAP) is still one of the leading causes of mortality and morbidity. The most common bacterial cause of CAP is Streptococcus pneumoniae. The increase in antimicrobial resistance has raised concerns about the efficacy of available therapies, and a call for the reassessment of both existing and newer therapeutic agents.

Activities of garenoxacin against quinolone-resistant Streptococcus pneumoniae strains in vitro and in a mouse pneumonia model.

Garenoxacin is a novel des-F(6) quinolone with enhanced in vitro activities against both gram-positive and gram-negative bacteria. We compared the activity of garenoxacin with that of trovafloxacin (TVA) against Streptococcus pneumoniae, together with their efficacies and their capacities to select for resistant mutants, in a mouse model of acute pneumonia. In vitro, garenoxacin was more potent than TVA against wild-type S.

The Pseudomonas aeruginosa autoinducer N-3-oxododecanoyl homoserine lactone accelerates apoptosis in macrophages and neutrophils.

Quorum-sensing systems are critical regulators of the expression of virulence factors of various organisms, including Pseudomonas aeruginosa. Las and Rhl are two major quorum-sensing components, and they are regulated by their corresponding autoinducers, N-3-oxododecanoyl homoserine lactone (3-oxo-C(12)-HSL) and N-butyryl-L-homoserine lactone (C(4)-HSL). Recent progress has demonstrated the potential of quorum-sensing molecules, especially 3-oxo-C(12)-HSL, for modulation of the host immune system.

Attitudinal classification of patients receiving antibiotic treatment for mild respiratory tract infections.

The aim of this study was to determine patients' perceptions of antibiotic therapy and the doctor's skill in the management of ambulatory respiratory tract infections. Standardized face-to-face interviews were used with more than 3000 randomized patients or parents from four European countries. Attitudinal dimensions relating to their doctor identified four patient types: Involved (30%), Deferent (23%), Ignored (13%) and Critical (17%).

The antibacterial activity of topical retinoids: the case of retinaldehyde.

Background: Retinoids such as retinoic acid (RA), retinol (ROL) and retinaldehyde (RAL) are currently used in many formulations and indications ranging form acne to skin aging. Most if not all their pharmacological activities occur through binding to nuclear receptors with subsequent modulation of the activities of several genes. Little attention has been given to the many other potential actions on the surface of the skin.

Amino acid residues essential for function of the MexF efflux pump protein of Pseudomonas aeruginosa.

At least four broad-spectrum efflux pumps (Mex) are involved in elevated intrinsic antibiotic resistance as well as in acquired multidrug resistance in Pseudomonas aeruginosa. Substrate specificity of the Mex pumps has been shown to be determined by the cytoplasmic membrane component (MexB, MexD, MexF, and MexY) of the tripartite efflux pump system. Alignment of their amino acid sequences with those of the homologous AcrB and AcrD pump proteins of Escherichia coli showed conservation of five charged amino acid residues located in or next to transmembrane segments (TMS).

Rotating antibiotics in the intensive care unit: feasible, apparently beneficial, but questions remain.

Rotating antibiotics in the intensive care unit may result in less infections caused by resistant organisms and in even less mortality. The selection of super-resistant organisms associated with the rotation strategy cannot be excluded, however, and many practical issues will have to be addressed before antibiotic rotation can be routinely recommended.

Detection of Pseudomonas aeruginosa cell-to-cell signals in lung tissue of cystic fibrosis patients.

Chronic Pseudomonas aeruginosa infections lead to progressive lung tissue destruction in cystic fibrosis (CF) patients. Two bacterial cell-to-cell signals, 3-oxo-C(12)-HSL and C(4)-HSL are required for the production of several extracellular virulence factors. 3-oxo-C(12)-HSL is also required for the development of a differentiated biofilm, induces IL-8 production by epithelial cells and possesses immunomodulatory activities.

Influence of previous exposure to antibiotic therapy on the susceptibility pattern of Pseudomonas aeruginosa bacteremic isolates.

Many patients who present with Pseudomonas aeruginosa bacteremia have been previously exposed to antibiotics. To assess whether resistance of bacteremic strains to antipseudomonal antibiotics (piperacillin, ceftazidime, imipenem, ciprofloxacin, or aminoglycosides) is associated with previous exposure to these drugs, a case-control study including 267 cases of P. aeruginosa bacteremia was conducted.

New perspectives on macrolide antibiotics.

Macrolides are not used exclusively for the treatment of community-acquired respiratory tract infections. Their ability to penetrate cells makes them highly suitable for the treatment of diseases caused by intracellular pathogens, such as non-gonococcal urethritis and trachoma. Azithromycin is approved for these indications.

Macrolide resistance mechanisms in Gram-positive cocci.

Two principal mechanisms of resistance to macrolides have been identified in Gram-positive bacteria. Erythromycin-resistant methylase is encoded by erm genes. Resultant structural changes to rRNA prevent macrolide binding and allow synthesis of bacterial proteins to continue.

Overexpression, refolding, and purification of the histidine-tagged outer membrane efflux protein OprM of Pseudomonas aeruginosa.

This paper describes the overproduction and purification of the C-terminus polyhistidine-tagged outer membrane protein OprM, which is a part of the MexA-MexB-OprM active efflux system of Pseudomonas aeruginosa. Renaturation of the protein from inclusion bodies of Escherichia coli was achieved using guanidine-HCl as denaturing agent and n-octylpolyoxyethylene (C8POE) and n-octyltetraoxyethylene (C8E4) as nonionic detergents. The refolded protein was purified by ion-exchange and nickel-affinity chromatography.