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Antimicrobial Drugs (antimicrobial + drug)
Terms modified by Antimicrobial Drugs Selected AbstractsA century of the synthesis of dapsone: its anti-infective capacity now and thenINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 10 2000Ronni Wolf MD Background Although dapsone was first synthesized in 1908, a quarter of a century was to pass before it was used in the treatment of bacterial infections. Dapsone was, however, too toxic for humans (because of the excess dosage which was administered at that time) and was thus considered to be of no value in the treatment of common bacterial infections. Since the early 1950s, dapsone has been recognized as being uniquely effective against a number of noninfectious, inflammatory diseases and, today, this is its main indication. Thus, the reason why dapsone was first introduced into medicine, namely the treatment of bacterial infections, has been set aside and its main current applications are the treatment of noninfectious, inflammatory, autoimmune, and bullous diseases. Objective To study the anti-infective capacity of dapsone against common bacterial infections. As many patients who receive dapsone for the treatment of noninfectious, inflammatory diseases have a concomitant bacterial infection or a superinfection of their skin disease, we thought that, if dapsone proved to be effective against common bacterial infections, it may obviate the need for an additional antimicrobial drug in these patients. Methods Three bacterial ATCC> strains (Streptococcus pyogenes, Staphylococcus aureus, and Escherichia coli) were tested by a macrodilution minimal inhibitory concentration (MIC) test for dapsone. Dapsone concentrations were between 0.06 and 1125 ,g/mL. Results Even the highest concentration of dapsone of 1125 ,g/mL did not inhibit bacterial growth. Conclusions Our results indicate that dapsone has no antibacterial effects whatsoever. Even at very high concentrations, it does not suppress the growth of most susceptible strains of bacteria. The story of dapsone (i.e. the long time that elapsed between its synthesis to its use for the chemotherapy of infectious diseases) will not repeat itself this time. [source] Comparison of Salmonella enterica serotype Infantis isolates from a veterinary teaching hospitalJOURNAL OF APPLIED MICROBIOLOGY, Issue 6 2007M. Dunowska Abstract Aims:, To compare Salmonella enterica serotype Infantis isolates obtained from patients or the environment of a veterinary teaching hospital over a period of 9 years following a nosocomial outbreak to determine whether isolates were epidemiologically related or represented unrelated introductions into the hospital environment. Methods and Results:, Fifty-six S. Infantis isolates were compared based on their phenotypic (antimicrobial drug [AMD] susceptibility pattern) and genotypic (pulsed-field gel electrophoresis [PFGE] pattern and presence of integrons) characteristics. Epidemiologically unrelated S. Infantis isolates clustered separately from all but two of the hospital isolates, and several isolates from different years and various sources were indistinguishable from each other in cluster analysis of two-enzyme PFGE results. A high percentage of isolates (80·3%) were resistant to at least one AMD, with 67·8% showing resistance to >5 AMD. The majority (74·1%) of isolates tested contained type 1 integrons. Conclusion:, Results strongly suggest that there was nosocomial transmission of S. Infantis during the initial outbreak, and that contamination arising from this outbreak persisted across years despite rigorous hygiene and biosecurity precautions and may have led to subsequent nosocomial infections. Significance and Impact of the Study:, Evidence of persistence and transmission of Salmonella clones across years, even in the face of rigorous preventive measures, has important implications for other facilities that have experienced outbreaks of Salmonella infections. [source] A systematic review of prophylactic antimicrobials in PEG placementJOURNAL OF CLINICAL NURSING, Issue 7 2009Allyson Lipp Aim., To establish whether prophylactic systemic antimicrobials reduce the risk of peristomal infection in placement of percutaneous endoscopic gastrostomies. Background., Percutaneous endoscopic gastrostomies, placed surgically through the anterior abdominal wall, maintain nutrition in the short or long term. Those undergoing percutaneous endoscopic gastrostomy placement are often vulnerable to infection. The increasing incidence of methicillin-resistant Staphylococcus aureus contributes an additional risk to the debate surrounding antibiotic prophylaxis. The aim of antimicrobial prophylaxis is to establish a bactericidal concentration of an antimicrobial drug in the patient, during placement. Design., Systematic review. Methods., We searched the Cochrane Wounds Group Specialised Register (July 2006); The Cochrane Central Register of Controlled Trials (The Cochrane Library 2006, Issue 2); handsearched wound care journals, relevant conference proceedings and bibliographies of publications identified, and contacted manufacturers and distributors of percutaneous endoscopic gastrostomy products. Randomised controlled trials were selected evaluating the use of prophylactic antimicrobials for percutaneous endoscopic gastrostomy placement, with no restrictions for language, date or publication status. Both authors performed data extraction and assessment of study quality. Meta-analysis was performed where appropriate. Results., Ten eligible randomised controlled trials were identified evaluating prophylactic antimicrobials in 1100 patients. All trials reported peristomal infection as an outcome and a pooled analysis resulted in a statistically significant reduction in the incidence of peristomal infection with prophylactic antibiotics (pooled OR 0·31, 95% CI 0·22,0·44). The relative reduction in risk of infection for those given antibiotics was 19% with the need to treat 5·8 patients to prevent one infection , NNT. Conclusions., Administration of systemic prophylactic antibiotics for percutaneous endoscopic gastrostomy placement reduces peristomal infection. Relevance to clinical practice., The nurse's role in endoscopy is expanding rapidly and demands that practice is based on the best available evidence. This systematic review seeks to make a contribution to best practice in percutaneous endoscopic gastrostomy placement. [source] Preparation of antimicrobial sutures by preirradiation grafting onto polypropylene monofilamentPOLYMERS FOR ADVANCED TECHNOLOGIES, Issue 12 2008Bhuvanesh Gupta Abstract Antimicrobial sutures were prepared by the radiation grafting of acrylonitrile monomer onto polypropylene (PP) monofilament. The grafted sutures were subsequently hydrolyzed to transform nitrile groups into carboxylic groups for the immobilization of antimicrobial drug, tetracycline hydrochloride (TC). The modified sutures show continuous release of drug for a period of 4,5 days. The antimicrobial activity of the sutures was determined against both Gram positive and Gram negative bacteria by the zone of inhibition technique. Zone of inhibition was observed around the drug-containing sutures in the plate inoculated with Escherichia coli (E. coli), Klebsiella pneumonea (K. pneumonea), and Staphylococcus aureus (S. aureus). The results of infection studies in albino rats against S. aureus showed no infection even after fourth postoperative day of surgery. This is because of the release of the TC drug at the site of injury, which inhibits the bacterial growth. Copyright © 2008 John Wiley & Sons, Ltd. [source] RECENT PROGRESS IN ENDOSCOPY-BASED DIAGNOSIS OF HELICOBACTER PYLORI INFECTIONDIGESTIVE ENDOSCOPY, Issue 1 2001Tadashi Sato Numerous invasive and non-invasive tests are available in the detection of Helicobacter pylori. Endoscopy-based tests that include rapid urease test, histological examination and culture are important generally in the assessment of H. pylori status before eradication therapy. Recently, several new endoscopy-based diagnostic methods have been developed aiming at rapid and accurate detection of the organisms. It would be possible to diagnose H. pylori infection in treated patients by using these new highly sensitive tests. Although the diagnosis of H. pylori infection itself is possible by using non-invasive diagnostic tests, endoscopy-based tests provide not only the diagnosis of the organisms, but also the exclusive information such as treatment indications and the susceptibility for the antimicrobial drugs. Recently, new triple therapy including clarithromycin has been widely performed in Japan. Along with an increase in the prevalence of the antibiotic-resistant strains, culture may become a more important diagnostic method in the future. The inappropriate application of the tests may increase the potential risk of the misdiagnosis and the treatment failures. The diagnostic method should be selected by taking into account the circumstances in which a diagnosis is to be performed. [source] Overview of the use of antimicrobials for the treatment of bacterial infections in horsesEQUINE VETERINARY EDUCATION, Issue 8 2008E. F. Haggett Summary Use of antimicrobial drugs is central to the treatment of primary and secondary bacterial infection in horses. When selecting an antimicrobial to treat confirmed or suspected bacterial infection multiple factors should be considered, including: the likely infectious agent; distribution and dosage of selected drugs; mechanisms of action; and potential side effects. Many of these issues will be covered in subsequent articles in this series. The aim of this paper is to aid the clinician in the rational selection of antimicrobials by reviewing the mode of action, spectrum of activity, pharmacokinetics, pharmacodynamics, indications and potential side effects of the main classes of antimicrobial drugs. Extralabel use of drugs is common in veterinary medicine due to a lack of licensed products. This increases the importance of a thorough understanding of antimicrobials and their possible adverse effects. [source] Inhibition of pneumococcal choline-binding proteins and cell growth by esters of bicyclic aminesFEBS JOURNAL, Issue 2 2007Beatriz Maestro Streptococcus pneumoniae is one of the major pathogens worldwide. The use of currently available antibiotics to treat pneumococcal diseases is hampered by increasing resistance levels; also, capsular polysaccharide-based vaccination is of limited efficacy. Therefore, it is desirable to find targets for the development of new antimicrobial drugs specifically designed to fight pneumococcal infections. Choline-binding proteins are a family of polypeptides, found in all S. pneumoniae strains, that take part in important physiologic processes of this bacterium. Among them are several murein hydrolases whose enzymatic activity is usually inhibited by an excess of choline. Using a simple chromatographic procedure, we have identified several choline analogs able to strongly interact with the choline-binding module (C-LytA) of the major autolysin of S. pneumoniae. Two of these compounds (atropine and ipratropium) display a higher binding affinity to C-LytA than choline, and also increase the stability of the protein. CD and fluorescence spectroscopy analyses revealed that the conformational changes of C-LytA upon binding of these alkaloids are different to those induced by choline, suggesting a different mode of binding. In vitro inhibition assays of three pneumococcal, choline-dependent cell wall lytic enzymes also demonstrated a greater inhibitory efficiency of those molecules. Moreover, atropine and ipratropium strongly inhibited in vitro pneumococcal growth, altering cell morphology and reducing cell viability, a very different response than that observed upon addition of an excess of choline. These results may open up the possibility of the development of bicyclic amines as new antimicrobials for use against pneumococcal pathologies. [source] An overview of factors affecting the disposition of intramammary preparations used to treat bovine mastitisJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2006R. GEHRING The administration of antimicrobial drugs by the intramammary route offers a convenient option for the treatment of bovine mastitis. The goal of antimicrobial treatment is to achieve effective drug concentrations at the site of infection. Drug concentrations must also decrease to safe levels before the milk is harvested for human consumption. The rate of change of drug concentrations in the milk and udder tissues over time is dependent on the physicochemical characteristics of the drug and how these interact with the biological environment, affecting the rate and extent of absorption, distribution and elimination. Studies reported in the literature have identified various pathophysiological and pharmaceutical factors that may influence these processes. This review summarizes current understanding of factors affecting the disposition of drugs following intramammary administration. Areas of incomplete knowledge requiring further research have been identified. [source] Principles of pharmacodynamics and their applications in veterinary pharmacologyJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2004P. LEES Pharmacodynamics (PDs) is the science of drug action on the body or on microorganisms and other parasites within or on the body. It may be studied at many organizational levels , sub-molecular, molecular, cellular, tissue/organ and whole body , using in vivo, ex vivo and in vitro methods and utilizing a wide range of techniques. A few drugs owe their PD properties to some physico-chemical property or action and, in such cases, detailed molecular drug structure plays little or no role in the response elicited. For the great majority of drugs, however, action on the body is crucially dependent on chemical structure, so that a very small change, e.g. substitution of a proton by a methyl group, can markedly alter the potency of the drug, even to the point of loss of activity. In the late 19th century and first half of the 20th century recognition of these facts by Langley, Ehrlich, Dale, Clarke and others provided the foundation for the receptor site hypothesis of drug action. According to these early ideas the drug, in order to elicit its effect, had to first combine with a specific ,target molecule' on either the cell surface or an intracellular organelle. It was soon realized that the ,right' chemical structure was required for drug,target site interaction (and the subsequent pharmacological response). In addition, from this requirement, for specificity of chemical structure requirement, developed not only the modern science of pharmacology but also that of toxicology. In relation to drug actions on microbes and parasites, for example, the early work of Ehrlich led to the introduction of molecules selectively toxic for them and relatively safe for the animal host. In the whole animal drugs may act on many target molecules in many tissues. These actions may lead to primary responses which, in turn, may induce secondary responses, that may either enhance or diminish the primary response. Therefore, it is common to investigate drug pharmacodynamics (PDs) in the first instance at molecular, cellular and tissue levels in vitro, so that the primary effects can be better understood without interference from the complexities involved in whole animal studies. When a drug, hormone or neurotransmitter combines with a target molecule, it is described as a ligand. Ligands are classified into two groups, agonists (which initiate a chain of reactions leading, usually via the release or formation of secondary messengers, to the response) and antagonists (which fail to initiate the transduction pathways but nevertheless compete with agonists for occupancy of receptor sites and thereby inhibit their actions). The parameters which characterize drug receptor interaction are affinity, efficacy, potency and sensitivity, each of which can be elucidated quantitatively for a particular drug acting on a particular receptor in a particular tissue. The most fundamental objective of PDs is to use the derived numerical values for these parameters to classify and sub-classify receptors and to compare and classify drugs on the basis of their affinity, efficacy, potency and sensitivity. This review introduces and summarizes the principles of PDs and illustrates them with examples drawn from both basic and veterinary pharmacology. Drugs acting on adrenoceptors and cardiovascular, non-steroidal anti-inflammatory and antimicrobial drugs are considered briefly to provide a foundation for subsequent reviews in this issue which deal with pharmacokinetic (PK),PD modelling and integration of these drug classes. Drug action on receptors has many features in common with enzyme kinetics and gas adsorption onto surfaces, as defined by Michaelis,Menten and Langmuir absorption equations, respectively. These and other derived equations are outlined in this review. There is, however, no single theory which adequately explains all aspects of drug,receptor interaction. The early ,occupation' and ,rate' theories each explain some, but not all, experimental observations. From these basic theories the operational model and the two-state theory have been developed. For a discussion of more advanced theories see Kenakin (1997). [source] Antimicrobial resistance in livestockJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2003B. Catry Antimicrobial resistance may become a major problem in veterinary medicine as a consequence of the intensive use and misuse of antimicrobial drugs. Related problems are now arising in human medicine, such as the appearance of multi-resistant food-borne pathogens. Product characteristics, dose, treatment interval and duration of treatment influence the selection pressure for antimicrobial drug resistance. There are theoretical, experimental and clinical indications that the emergence of de novo resistance in a pathogenic population can be prevented by minimizing the time that suboptimal drug levels are present in the infected tissue compartment. Until recently, attention has been focused on target pathogens. However, it should be kept in mind that when antimicrobial drugs are used in an individual, resistance selection mainly affects the normal body flora. In the long term, this is at least equally important as resistance selection in the target pathogens, as the horizontal transfer of resistance genes converts almost all pathogenic bacteria into potential recipients for antimicrobial resistance. Other factors contributing to the epidemiology of antimicrobial resistance are the localization and size of the microbial population, and the age, immunity and contact intensity of the host. In livestock, dynamic herd-related resistance patterns have been observed in different animal species. [source] Synthesis, in-vitro Antimicrobial and Cytotoxic Studies of Novel Azetidinone DerivativesARCHIV DER PHARMAZIE, Issue 4 2010Rangappa S. Keri Abstract Developing novel antimicrobial drugs is increasingly important in the modern pharmaceutical industry. A series of novel 3-chloro-4-[4-(2-oxo-2H -chromen-4-ylmethoxy)phenyl]-1-phenylazetidin-2-ones 5a,o have been synthesized from 4-bromomethylcoumarins 1a,e and 4-aryliminomethyl-phenols 3a,c. These compounds were screened for their in-vitro antibacterial activity against two Gram-positive (Staphylococcus aureus and Vancomycin resistant enteroccoccus) and two Gram-negative (Escherichia coli and Shigella dysentery) bacterial strains and antifungal activity against Aspergillus fumigatus, Candida albicans, and Penicillium. Results revealed that compounds 5c, 5f, 5h, 5j, and 5m showed excellent activity against a panel of microorganisms. The brine-shrimp bioassay was also carried out to study their in-vitro cytotoxic properties and two compounds, 5h and 5m, possessing LD50 = 7.154×10,4 M and 5.782×10,4 M, respectively, displayed potent cytotoxic activity against Artemia salina. The presence of a chlorine group in the coumarin moiety, its effect on their antibacterial, antifungal, and cytotoxic activities is discussed. All newly synthesized compounds were characterized by elemental analysis, IR, 1H-NMR, 13C-NMR, and MS. [source] Crystallization and preliminary crystallographic analysis of the recombinant N-terminal domain of riboflavin synthaseACTA CRYSTALLOGRAPHICA SECTION D, Issue 9 2001Winfried Meining Riboflavin synthase catalyzes the final step in the biosynthesis of riboflavin. Animals and humans lack this enzyme, whereas many bacteria and certain yeasts are absolutely dependent on endogenous riboflavin synthesis. Riboflavin synthase is therefore an attractive target for chemotherapy. The N-terminal domain of riboflavin synthase forms a dimer in solution and is capable of strongly binding riboflavin. It can serve as a model for the binding site of the native enzyme. Structural information obtained from this domain at high resolution will be helpful in the determination of the binding mode of riboflavin and thus for the development of antimicrobial drugs. Here, the crystallization and preliminary crystallographic analysis of the N-terminal domain of riboflavin synthase are reported. The crystals belong to the space group C2221, with unit-cell parameters a = 50.3, b = 104.7, c = 85.3,Å, , = , = , = 90°, and diffract to 2.6,Å resolution. [source] A double mutation of Escherichia coli 2C -methyl- d -erythritol-2,4-cyclodiphosphate synthase disrupts six hydrogen bonds with, yet fails to prevent binding of, an isoprenoid diphosphateACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 7 2005Tanja Sgraja The essential enzyme 2C -methyl- d -erythritol-2,4-cyclodiphosphate (MECP) synthase, found in most eubacteria and the apicomplexan parasites, participates in isoprenoid-precursor biosynthesis and is a validated target for the development of broad-spectrum antimicrobial drugs. The structure and mechanism of the enzyme have been elucidated and the recent exciting finding that the enzyme actually binds diphosphate-containing isoprenoids at the interface formed by the three subunits that constitute the active protein suggests the possibility of feedback regulation of MECP synthase. To investigate such a possibility, a form of the enzyme was sought that did not bind these ligands but which would retain the quaternary structure necessary to create the active site. Two amino acids, Arg142 and Glu144, in Escherichia coli MECP synthase were identified as contributing to ligand binding. Glu144 interacts directly with Arg142 and positions the basic residue to form two hydrogen bonds with the terminal phosphate group of the isoprenoid diphosphate ligand. This association occurs at the trimer interface and three of these arginines interact with the ligand phosphate group. A dual mutation was designed (Arg142 to methionine and Glu144 to leucine) to disrupt the electrostatic attractions between the enzyme and the phosphate group to investigate whether an enzyme without isoprenoid diphosphate could be obtained. A low-resolution crystal structure of the mutated MECP synthase Met142/Leu144 revealed that geranyl diphosphate was retained despite the removal of six hydrogen bonds normally formed with the enzyme. This indicates that these two hydrophilic residues on the surface of the enzyme are not major determinants of isoprenoid binding at the trimer interface but rather that hydrophobic interactions between the hydrocarbon tail and the core of the enzyme trimer dominate ligand binding. [source] Problems associated with potential massive use of antimicrobial agents as prophylaxis or therapy of a bioterrorist attackCLINICAL MICROBIOLOGY AND INFECTION, Issue 8 2002E. Navas In addition to the direct sanitary damage of a terrorist attack caused by biological weapons, the consequences of the massive stockpiling and consumption of antimicrobial agents in order to treat or prevent the disease under a potential epidemic due to pathogenic bacteria must also be considered. Bacillus anthracis, Francisella tularensis and Yersinia pestis are the bacteria most likely to be used as terrorist weapons. Tetracyclines, quinolones and aminoglycoside are the antibiotics of choice against these microorganisms. The recent terrorist attack with anthrax spores in the USA caused a substantial increase in the sales of ciprofloxacin, as thousands of citizens received antibiotic prophylaxis for either confirmed or suspected exposure to anthrax, and many others stockpiled antibiotic supplies at their homes under a panic scenario. The massive consumption of antimicrobial drugs may lead to the selection of antibiotic resistant strains, and to the appearance of undesirable side effects, such as anaphylaxis or teratogenesis. National health authorities must develop realistic protocols in order to detect, treat and prevent mass casualties caused by biological weapons. An antibiotic stockpile has to be planned and implemented, and home stockpiling of antibiotics must be strongly discouraged. [source] | |||||||||||||