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Nordmann P.,French Institute of Health and Medical Research | Picazo J.J.,Servicio de Microbiologia Clinica | Mutters R.,Institute For Medizinische Mikrobiologie Und Hygiene | Korten V.,Marmara University | And 5 more authors.
Journal of Antimicrobial Chemotherapy

Objectives: Doripenem is a new carbapenem recently introduced into Europe. The COMParative Activity of Carbapenem Testing (COMPACT) study compared the susceptibility of common Gram-negative bacilli causing serious infections in hospitalized patients with doripenem, imipenem and meropenem. Methods: Gram-negative isolates (4498 total: 2171 Pseudomonas species; 1910 Enterobacteriaceae; and 417 other Gram-negative bacilli) were collected from 80 centres in 16 countries in Europe, the Middle East and Africa during 2008-09. The MICs of doripenem, imipenem and meropenem were determined using Etest methodology and broth microdilution. Susceptibility was interpreted according to CLSI, EUCAST and FDA breakpoints. Results: The MIC 90s of doripenem, imipenem and meropenem for all isolates were 8, ≥64 and 32 mg/L, respectively. Doripenem had the lowest MIC 90 for Pseudomonas species at 16 mg/L, with imipenem and meropenem values of ≥64 mg/L. Enterobacteriaceae were highly susceptible to all three carbapenems, with MIC 90s of doripenem, imipenem and meropenem of 0.06, 0.5 and 0.12 mg/L, respectively. Other Gram-negative isolates, predominantly Acinetobacter baumannii, were resistant to all three carbapenems (MIC 90 ≥64 mg/L). Susceptibility to doripenem was observed in 14.9% of isolates resistant to imipenem and/or meropenem. Conclusions: Doripenem showed excellent activity against Gram-negative isolates; generally it was more active than imipenem and at least as good as meropenem. Against Pseudomonas species, doripenem was more active than both imipenem and meropenem, with doripenem susceptibility observed for some imipenemand/or meropenem-resistant isolates. © The Author 2011. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. Source

Luck C.,Institute For Medizinische Mikrobiologie Und Hygiene
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz

Legionellae are environmental bacteria that can be frequently isolated from technical water supply systems. The most prevalent species is Legionella pneumophila, especially serogroup 1. In the environment, legionellae multiply in amoebae. Since Legionella pneumonias cannot be distinguished from pneumonias caused by other microbial pathogens, special microbiological tests, e.g., urinary antigen assays, are essential to detect Legionella infections. All water supply systems to which the patient is exposed during the incubation time of 2 to 10 days might be the source of the infection. This can be confirmed or excluded by molecular typing of isolates from patients and the environment. The most commonly used techniques are monoclonal antibody typing and sequence-based typing (SBT). Some sequence types (ST) are frequently found among clinical strains but are seldom isolated from the environment, e.g., ST 23, 42, 47, 62, and 146. It is safe to assume that such strains are highly virulent. Conversely, it does not seem to be justified to dedicate the same awareness to all environmental Legionella strains. © 2011 Springer Medizin Verlag. Source

Littlewood K.J.,Mapi Consultancy | Higashi K.,Mapi Consultancy | Jansen J.P.,Mapi Consultancy | Capkun-Niggli G.,Novartis | And 4 more authors.
Journal of Cystic Fibrosis

Background: Various inhaled antibiotics are currently used for treating chronic Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) patients, however their relative efficacies are unclear. We compared the efficacy of the inhaled antibiotics tobramycin (TIP, TIS-T, TIS-B), colistimethate sodium (colistin) and aztreonam lysine for inhalation (AZLI) based on data from randomised controlled trials. Methods: In the base case, efficacies of antibiotics were compared using a network meta-analysis of seven trials including change from baseline in forced expiratory volume in 1second (FEV1) % predicted, P. aeruginosa sputum density and acute exacerbations. Results: The tobramycin preparations, AZLI and colistin, showed comparable improvements in efficacy in terms of FEV1% predicted at 4. weeks; the difference in % change from baseline (95%CrI) for TIP was compared to TIS-T (- 0.55, -3.5;2.4), TIS-B (-0.64, -7.1;5.7), AZLI (3.64, -1.0;8.3) and colistin (5.77, -1.2;12.8). Conclusion: We conclude that all studied antibiotics have comparable efficacies for the treatment of chronic P. aeruginosa lung infection in CF. © 2012 European Cystic Fibrosis Society.. Source

Niederbichler A.D.,Medizinische Hochschule Hanover | Jokuszies A.,Medizinische Hochschule Hanover | Claassen L.,Medizinische Hochschule Hanover | Dodic T.,Medizinische Hochschule Hanover | And 2 more authors.
Zeitschrift fur Wundheilung

Bacterial contamination of the burn wound is frequently encountered during the care of thermally injured patients. Protection against systemic invasion and sepsis is key to efficient treatment and patient survival. Surgical source control and local antiseptic measures are the primary therapeutic cornerstones in burn wound infection prophylaxis and treatment. In case of invasive burn wound infection, systemic antibiotic therapy in many cases needs to be initiated prior to the receipt of microbiologic evaluations of the isolated microbes. To add on to the current knowledge base, we retrospectively analyzed our data with regard to resistance of the isolated microbes to available antibiotics. The data acquired from 05/2001 to 10/2006 was analyzed. Grampositive and gramnegative microbes were differentiated and assessed. Overall, n=10780 resistance tests of gramnegative bacteria and n=8993 resistance tests of grampositive bacteria were analyzed. Among the most effective antibiotics were acylaminopenicillins plus ß-lactamase-inhibitors in grampositive and fluorochinolones in gramnegative microbes. Meropenem was one of the most effective antibiotics for both grampositive and gramnegative bacteria. In summary, the initiation of calculated systemic antibiotic therapy needs to be thoughtfully adapted to the clinical situation and re-evaluation of the used antibiotic after microbiologic assessment represents a mandatory process in the care of burn wound infections. Adequate measures to establish surgical source control and local antiseptic therapy must be maintained during systemic antibiotic prophylaxis in thermally injured patients. © DGfW. Source

Albesa-Jove D.,Imperial College London | Bertrand T.,Imperial College London | Carpenter E.P.,Imperial College London | Swain G.V.,Imperial College London | And 11 more authors.
Journal of Molecular Biology

Clostridium difficile is a nosocomial bacterial pathogen causing antibiotic-associated diarrhea and fatal pseudomembranous colitis. Key virulence factors are toxin A and toxin B (TcdB), two highly related toxins that are members of the large clostridial toxin family. These large multifunctional proteins disrupt cell function using a glucosyltransferase domain that is translocated into the cytosol after vesicular internalization of intact holotoxin. Although substantial information about the biochemical mechanisms of intoxication exists, research has been hampered by limited structural information, particularly of intact holotoxin. Here, we used small-angle X-ray scattering (SAXS) methods to obtain an ab initio low-resolution structure of native TcdB, which demonstrated that this molecule is monomeric in solution and possesses a highly asymmetric shape with a maximum dimension of ~275 Å. Combining this SAXS information with crystallographic or modeled structures of individual functional domains of TcdB reveals for the first time that the three-dimensional structure of TcdB is organized into four distinct structural domains. Structures of the N-terminal glucosyltransferase, the cysteine protease, and the C-terminal repeat region can be aligned within three domains of the SAXS envelope. A fourth domain, predicted to be involved in the translocation of the glucosyltransferase, appears as a large solvent-exposed protrusion. Knowledge of the shapes and relative orientations of toxin domains provides new insight into defining functional domain boundaries and provides a framework for understanding how potential intra-domain interactions enable conformational changes to propagate between domains to facilitate intoxication processes. © 2010 Elsevier Ltd. Source

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