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Bacterial Resistance (bacterial + resistance)
Selected AbstractsI PREVENT Bacterial Resistance.DERMATOLOGIC SURGERY, Issue 10 2009An Update on the Use of Antibiotics in Dermatologic Surgery BACKGROUND AND OBJECTIVES Prophylaxis may be given to prevent a surgical wound infection, infective endocarditis (IE), or infection of a prosthetic joint, but its use before cutaneous surgery is controversial. Our aim was to review the current literature and provide a mnemonic to assist providers in appropriately prescribing prophylactic antibiotics. METHODS AND MATERIALS We reviewed the current literature, including the new guidelines provided by the American Heart Association (AHA). RESULTS The new AHA guidelines recommend prophylaxis for patients with high risk of an adverse outcome from IE instead of high risk of developing IE. The American Academy of Orthopedic Surgeons and the American Dental Association also provide guidelines. Given the paucity of conclusive studies, prophylaxis against a surgical wound infection is based more on clinical judgment. CONCLUSION The mnemonic we propose, "I PREVENT," represents: Immunosuppressed patients; patients with a Prosthetic valve; some patients with a joint Replacement; a history of infective Endocarditis; a Valvulopathy in cardiac transplant recipients; Endocrine disorders such as uncontrolled diabetes mellitus; Neonatal disorders including unrepaired cyanotic heart disorders (CHDs), repaired CHD with prosthetic material, or repaired CHD with residual defects; and the Tetrad of antibiotics: amoxicillin, cephalexin, clindamycin, and ciprofloxacin. [source] Purification, crystallization and preliminary X-ray analysis of the ,-lactamase Oih-1 from Oceanobacillus iheyensisACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 6 2009Marta Toth Bacterial resistance to the ,-lactam family of antibiotics is primarily the result of the deactivation of the drugs by ,-lactamase enzymes. The gene encoding the proficient ,-lactamase Oih-1 from the alkaliphilic and halotolerant Gram-positive bacterium Oceanobacillus iheyensis has been cloned and the mature wild-type protein (comprising 274 amino-acid residues) has been expressed in Escherichia coli and subsequently purified to homogeneity. Oih-1 crystallized in two crystal forms both belonging to the trigonal space group P3121 but with distinctly different unit-cell parameters. Synchrotron diffraction data were collected to high resolution (1.65,1.75,Å) from both crystal forms on beamlines BL7-1 and BL11-1 at SSRL (Stanford, California, USA). [source] Adaptive drug resistance mediated by root,nodulation,cell division efflux pumpsCLINICAL MICROBIOLOGY AND INFECTION, Issue 2009C. Daniels Abstract Bacterial resistance to antibiotics is a major therapeutic problem. Bacteria use the same mechanisms for developing resistance to antibiotics as they do for developing resistance to biocide compounds present in some cleaning and personal care products. Root,nodulation,cell division (RND) family efflux pumps are a common means of multidrug resistance, and induction of their expression can explain the observed cross-resistance found between antibiotics and biocides in laboratory strains. Hence, there is a relationship between the active chemicals used in household products, organic solvents and antibiotics. The widespread use of biocide-containing modern-day household products may promote the development of microbial resistance and, in particular, cross-resistance to antibiotics. [source] Coselection for microbial resistance to metals and antibiotics in freshwater microcosmsENVIRONMENTAL MICROBIOLOGY, Issue 9 2006Ramunas Stepanauskas Summary Bacterial resistances to diverse metals and antibiotics are often genetically linked, suggesting that exposure to toxic metals may select for strains resistant to antibiotics and vice versa. To test the hypothesis that resistances to metals and antibiotics are coselected for in environmental microbial assemblages, we investigated the frequency of diverse resistances in freshwater microcosms amended with Cd, Ni, ampicillin or tetracycline. We found that all four toxicants significantly increased the frequency of bacterioplankton resistance to multiple, chemically unrelated metals and antibiotics. An ampicillin-resistant strain of the opportunistic human pathogen Ralstonia mannitolilytica was enriched in microcosms amended with Cd. Frequencies of antibiotic resistance were elevated in microcosms with metal concentrations representative of industry and mining-impacted environments (0.01,1 mM). Metal but not antibiotic amendments decreased microbial diversity, and a weeklong exposure to high concentrations of ampicillin (0.01,10 mg l,1) and tetracycline (0.03,30 mg l,1) decreased microbial abundance only slightly, implying a large reservoir of antibiotic resistance in the studied environment. Our results provide first experimental evidence that the exposure of freshwater environments to individual metals and antibiotics selects for multiresistant microorganisms, including opportunistic human pathogens. [source] Topical Antibacterial Agents for Wound Care: A PrimerDERMATOLOGIC SURGERY, Issue 6 2003Candace Thornton Spann MD Although often overlooked, topical antibiotic agents play an important role in dermatology. Their many uses include prophylaxis against cutaneous infections, treatment of minor wounds and infections, and elimination of nasal carriage of Stapylococcus aureus. For these indications, they are advantageous over their systemic counterparts because they deliver a higher concentration of medication directly to the desired area and are less frequently implicated in causing bacterial resistance. The ideal topical antibiotic has a broad spectrum of activity, has persistent antibacterial effects, and has minimal toxicity or incidence of allergy. [source] Molecular basis of bacterial resistance to chloramphenicol and florfenicolFEMS MICROBIOLOGY REVIEWS, Issue 5 2004Stefan Schwarz Abstract Chloramphenicol (Cm) and its fluorinated derivative florfenicol (Ff) represent highly potent inhibitors of bacterial protein biosynthesis. As a consequence of the use of Cm in human and veterinary medicine, bacterial pathogens of various species and genera have developed and/or acquired Cm resistance. Ff is solely used in veterinary medicine and has been introduced into clinical use in the mid-1990s. Of the Cm resistance genes known to date, only a small number also mediates resistance to Ff. In this review, we present an overview of the different mechanisms responsible for resistance to Cm and Ff with particular focus on the two different types of chloramphenicol acetyltransferases (CATs), specific exporters and multidrug transporters. Phylogenetic trees of the different CAT proteins and exporter proteins were constructed on the basis of a multisequence alignment. Moreover, information is provided on the mobile genetic elements carrying Cm or Cm/Ff resistance genes to provide a basis for the understanding of the distribution and the spread of Cm resistance , even in the absence of a selective pressure imposed by the use of Cm or Ff. [source] Prescribing antibiotics in odontology and stomatology.FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2003Recommendations by the French Health Products Safety Agency Abstract In order to limit the onset of adverse effects and the increasing emergence of bacterial resistance, the prescription of antibiotics must be reserved strictly for situations where their efficacy has been demonstrated. The French Health Products Safety Agency (Afssaps) has updated recommendations concerning the use of antibiotic treatment in odontology and stomatology. The general strategy for the prescription of antibiotics proposed by the present recommendations relies on a professional consensus. The full-length, discussed and referenced text is available at the web site of Afssaps (http://www.afssaps.sante.fr) in the ,Documentation et publications' rubric. [source] Diagnosis of Helicobacter pylori InfectionHELICOBACTER, Issue 2004Athanasios Makristathis ABSTRACT While there are some attempts to improve culture of Helicobacter pylori, molecular methods have been the main focus of this interest. Their main application concerns the development of rapid tests also allowing the determination of bacterial resistance, i.e. real-time polymerase chain reaction (PCR) or fluorescence in situ hybridization (FISH), or to genotype the strains. Attempts to improve, simplify or explain the discrepancies of urea breath test results have been made and new generation of stool antigen test with monoclonal antibodies either using the standard ELISA format or rapid immunoenzymatic detection have confirmed their value. With regard to serology, studies have mainly focused on the distinction of infections with more pathogenic strains and the ability to diagnose atrophic gastritis with the Gastropanel. [source] Antimicrobial therapy in DermatologyJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 1 2006Cord Sunderkötter Antiseptika; Antibiotika; ,-Laktam-Resistenz; Weichteilinfektion Summary The extensive and sometimes indiscriminate use of antibiotics sometimes without strict indications has led to increases in both bacterial resistance and sensitization of patients. Systemic antibiotics in skin infections are indicated when a severe local infection occurs which spreads into the surrounding tissue or when there are signs of systemic infection. There are special indications in patients with peripheral arterial occlusive disease,diabetes or immunosuppression. Topical use of antibiotics should be abandoned and replaced by antiseptics. The ,-lactam antibiotics are the antibiotics of first choice for many skin infections. They are usually effective, have a well-defined profile of adverse events and most are affordable. Penicillin G or V are the first line treatment for erysipelas. Infections with Staphylococcus aureus are usually treated with isoxazolyl penicillins or second generation cephalosporins. In mixed infections in patients with diabetes or peripheral arterial occlusive disease,the treatment of choice is metronidazole plus ,-lactam-/,-lactamase inhibitor antibiotics, but quinolones or second generation cephalosporins can also be used, once again with metronidazole. The aim of this review is to define the indications for antibiotics in dermatology, to highlight their modes of action and adverse effects and to make suggestions for rational antibiotic therapy in cutaneous infections frequently encountered in the practice of dermatology. Zusammenfassung Der bisweilen unkritische Einsatz von Antibiotika hat die Resistenzentwicklung beschleunigt und die Sensibilisierungsrate bei Patienten erhöht. Systemische Antibiotika sind bei kutanen Superinfektionen in der Regel dann indiziert, wenn eine schwere lokale Infektion mit Ausbreitung in das umgebende Gewebe vorliegt oder wenn sich gleichzeitig Zeichen einer systemischen Infektion einstellen. Bei peripherer arterieller Verschlusskrankheit, Diabetes mellitus oder Immunsuppression kann die Indikation auch früher gestellt werden. Lokale Antibiotika sollten in der Regel gemieden und durch moderne Antiseptika ersetzt werden. ,-Laktam-Antibiotika stellen für viele bakterielle Infektionserkrankungen in der ambulanten und klinischen Dermatologie die Antibiotika der ersten Wahl dar. Sie sind häufig ausreichend wirksam, besitzen ein gut definiertes Nebenwir-kungsprofil und sind zumeist preisgünstig. So wird das klassische Streptokokken-Erysipel mit Penicillin G oder V therapiert, bei Infektionen durch S. aureus kommen primär Isoxazolyl-Penicilline oder Zweit-Generations-Cephalosporine zum Einsatz. Im Falle von Mischinfektionen bei Diabetes mellitus oder pAVK sind ,-Laktam/,-Laktamaseinhibitoren indiziert, alternativ auch Chinolone oder Zweitgenerations-Cephalosporine, jeweils in Kombination mit Metronidazol. Diese Übersicht möchte die Indikationen für Antibiotika in der Dermatologie aufzeigen, das Wichtigste zu deren Wirkungsweise und Nebenwirkungen aufzählen und Therapievorschläge für häufige Infektionen der Haut in der dermatologischen Praxis geben. [source] Intrinsic and acquired resistance to quaternary ammonium compounds in food-related Pseudomonas spp.JOURNAL OF APPLIED MICROBIOLOGY, Issue 4 2003S. Langsrud Abstract Aims: To determine the sensitivity of a strain used for disinfectants testing (Pseudomonas aeruginosa ATCC 15442) and food-associated isolates to benzalkonium chloride and didecyl dimethylammonium chloride (DDAC). To determine whether the increase in bacterial resistance after adaptation to DDAC can be associated with phenotypic changes. To test the activity of alternative disinfectants to eliminate resistant Pseudomonas spp. Methods and Results:Pseudomonas aeruginosa ATCC 15442 was among the most resistant strains tested using a bactericidal suspension test. Growth of a sensitive Ps. fluorescens in gradually higher concentrations of DDAC resulted in stable higher resistance and to some cross-resistance to several antibacterial agents, with the exception of disinfectants containing chloramine T, glutaraldehyde or peracetic acid. It was shown by microscopy that adaptation was followed by loss of flagella, and slime formation. Removal of the slime by sodium dodecyl sulphate resulted in partial loss of the acquired resistance. Conclusions:Pseudomonas spp. may adapt to survive against higher concentrations of quaternary ammonium compounds (QACs), but resistant strains can be eliminated with chemically unrelated disinfectants. Significance and Impact of the Study: The work supports the rotation of disinfectants in food processing environments for avoiding the development of bacterial resistance to QACs. The alternating disinfectants should be chosen carefully, because of possible cross-resistance. [source] Ototoxic eardrops and tympanic membrane perforations: Time for a change?JOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 8 2005Harvey Coates Abstract: Until recently the only available antibiotic eardrops for treatment of the discharging middle ear and mastoid cavity have been potentially ototoxic. With the advent of non-ototoxic fluoroquinolone eardrops, consensus panels in the USA, Canada and the UK have advocated the preferential use of these agents in the open middle ear. However, in Australia, no fluoroquinolone topical agent is approved for use with tympanic membrane perforations, and when used as an ,off label' eardrop, none is on the Pharmaceutical Benefits Scheme. This creates an ethical dilemma, particularly with best practice management of chronic suppurative otitis media in indigenous children. Despite concerns regarding resistance issues with ototopical use of systemic antibiotics, bacterial resistance has not been documented in major studies. For equity and ethical reasons, Australian regulatory authorities should consider approving a sterile non-ototoxic eardrop for use in the open middle ear. [source] The pharmacology of radiolabeled cationic antimicrobial peptidesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 5 2008Carlo P.J.M. Brouwer Abstract Cationic antimicrobial peptides are good candidates for new diagnostics and antimicrobial agents. They can rapidly kill a broad range of microbes and have additional activities that have impact on the quality and effectiveness of innate responses and inflammation. Furthermore, the challenge of bacterial resistance to conventional antibiotics and the unique mode of action of antimicrobial peptides have made such peptides promising candidates for the development of a new class of antibiotics. This review focuses on antimicrobial peptides as a topic for molecular imaging, infection detection, treatment monitoring and additionally, displaying microbicidal activities. A scintigraphic approach to studying the pharmacokinetics of antimicrobial peptides in laboratory animals has been developed. The peptides were labeled with technetium-99m and, after intravenous injection into laboratory animals, scintigraphy allowed real-time, whole body imaging and quantitative biodistribution studies of delivery of the peptides to the various body compartments. Antimicrobial peptides rapidly accumulated at sites of infection but not at sites of sterile inflammation, indicating that radiolabeled cationic antimicrobial peptides could be used for the detection of infected sites. As the number of viable micro-organisms determines the rate of accumulation of these peptides, radiolabeled antimicrobial peptides enabled to determine the efficacy of antibacterial therapy in animals to be monitored as well to quantify the delivery of antimicrobial peptides to the site of infection. The scintigraphic approach provides to be a reliable method for investigating the pharmacokinetics of small cationic antimicrobial peptides in animals and offers perspective for diagnosis of infections, monitoring antimicrobial therapy, and most important, alternative antimicrobial treatment infections with multi-drug resistant micro-organisms in humans. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci [source] Do Biocides Select for Antibiotic Resistance?,JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 2 2000A. D. RUSSELL Some similarities exist between bacterial resistance to antibiotics and to biocides, and gram-negative bacteria that have developed resistance to cationic biocides may also be insusceptible to some antibiotics. Outer membrane changes are believed to be responsible for this non-specific increase in resistance. Efflux, another important resistance mechanism, is associated with the qacA/B gene system in staphylococci that confers low-level resistance to cationic agents including chlorhexidine salts and quaternary ammonium compounds. It has been proposed that the introduction into clinical practice of Chlorhexidine and quaternary ammonium compounds has resulted in the selection of staphylococci containing qacA genes on multiresistance plasmids. A linkage between low-level resistance to triclosan and to antibiotics has recently been claimed to occur in Escherichia coli, with the bisphenol selecting for chromosomally-mediated antibiotic resistance. A key issue in many studies has been the use of biocides at concentrations significantly below those used clinically. It remains to be determined how an increase to low-level resistance to cationic biocides can be held responsible for the selection of antibiotic-resistant bacteria. [source] A guide to antibiotic resistance in bacterial skin infectionsJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 5 2005G Perera ABSTRACT The emergence of bacterial resistance to commonly used antibiotics is not new. In this review we have tried to cover the ever increasing problems facing the treatment and containment of bacterial skin infections. We have tried to give an overview of the varied mechanisms by which bacteria gain and spread antimicrobial resistance, whilst dealing with the patterns of resistance exhibited by some of the commonly encountered organisms. Where there is evidence, we have formulated an approach on how to tackle antibiotic resistance. Where there is a lack of evidence we have formulated what we perceive to be appropriate guidelines. [source] Review article: rifaximin, a minimally absorbed oral antibacterial, for the treatment of travellers' diarrhoeaALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11 2010P. LAYER Aliment Pharmacol Ther,31, 1155,1164 Summary Background, Travellers' diarrhoea, a common problem worldwide with significant medical impact, is generally treated with anti-diarrhoeal agents and fluid replacement. Systemic antibiotics are also used in selected cases, but these may be associated with adverse effects, bacterial resistance and drug,drug interactions. Aim, To review the clinical evidence supporting the efficacy and safety of the minimally absorbed oral antibiotic rifaximin in travellers' diarrhoea. Methods, PubMed and the Cochrane Register of Controlled Clinical Trials (to January 2010) and International Society of Travel Medicine congress abstracts (2003,2009) were searched to identify relevant publications. Results, A total of 10 publications were included in the analysis. When administered three times daily for 3 days, rifaximin is superior to placebo or loperamide; it is at least as effective as ciprofloxacin in reducing duration of illness and restoring wellbeing in patients with travellers' diarrhoea, both with and without identification of a pathogen, as well as in diarrhoea caused by Escherichia coli infection. Rifaximin demonstrates only minimal potential for development of bacterial resistance and for cytochrome P450-mediated drug,drug interactions, and its tolerability profile is similar to that of placebo. Conclusion, When antibiotic therapy is warranted in uncomplicated travellers' diarrhoea, rifaximin may be considered as a first-line treatment option because of its favourable efficacy, tolerability and safety profiles. [source] Bioequivalence of four preparations of enrofloxacin in poultryJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2001L. H. Sumano In various parts of the world, many 10% enrofloxacin commercial preparations for water medication of chicken are being employed. To avoid the development of bacterial resistance to this agent, the original trademark and similar preparations must be bioequivalent. To assess whether or not bioequivalence exists among the pioneer vs. three commercial preparations of enrofloxacin, a controlled pharmacokinetic study was conducted. The following variables were compared: maximal plasma concentration (Cpeak), time to Cpeak, bioavailability (expressed as the area under the concentration vs. time curve), elimination half-life, and the shapes of the respective time-serum concentrations of enrofloxacin profiles. Results indicate that all three similar commercial preparations had lower Cpeak values than the reference formulation, being 39.62 to 67.77% of the corresponding Cpeak reference. Additionally, bioavailability of enrofloxacin in the pioneer product was statistically higher (P < 0.05). Based upon these results, we conclude that although all preparations were formulated as water-soluble products, bioequivalence studies are mandatory for the analogue formulations to ensure product comparability. Lack of product bioequivalence could facilitate the development of bacterial resistance and limit the useful life span of the product. [source] Clinical trial: randomized study of clarithromycin versus placebo in active Crohn's diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2008K. LEIPER Summary Background, Crohn's disease is characterized by defective innate immune responses to intestinal bacteria. Clarithromycin is a broad-spectrum antibiotic that has good penetration into macrophages. Aim, To assess the efficacy of clarithromycin in active Crohn's disease. Methods, Patients with Crohn's disease activity index > 200 and serum C-reactive protein , 10 mg/L were randomized to receive clarithromycin 1 g o.d. or placebo for 3 months. Patients taking more than 10 mg/day prednisolone or 3 mg/day budesonide were excluded. Primary outcome was remission (CDAI , 150) or response (fall in CDAI , 70 from pre-treatment level) at 3 months. Results, The trial was stopped after 41 patients had been recruited because of poor overall efficacy. There was no difference in combined remission or response rates at 3 months between clarithromycin: 26% (five of 19) and placebo: 27% (six of 22) (P = 1.00). The mean (s.d.) fall in Crohn's disease activity index was 35 (80) clarithromycin and ,2 (114) placebo (P = 0.24). However, post hoc analysis showed a significant difference in response/remission determined by Crohn's disease activity index after 1 month: 53% (10 of 19) clarithromycin vs. 14% (three of 22) placebo (P = 0.01). Conclusion, Clarithromycin 1 g for 3 months is ineffective in active Crohn's disease but possible benefit was observed at 1 month, suggesting that an initial effect may be attenuated by subsequent bacterial resistance. [source] Progress in type II dehydroquinase inhibitors: From concept to practiceMEDICINAL RESEARCH REVIEWS, Issue 2 2007Concepción González-Bello Abstract Scientists are concerned by an ever-increasing rise in bacterial resistance to antibiotics, particularly in diseases such as malaria, toxoplasmosis, tuberculosis, and pneumonia, where the currently used therapies become progressively less efficient. It is therefore necessary to develop new, safe, and more efficient antibiotics. Recently, the existence of the shikimic acid pathway has been demonstrated in certain parasites such as the malaria parasite. These types of parasites cause more than a million casualties per year, and their effects are particularly strong in people with a compromised immune system such as HIV patients. In such cases it is possible that inhibitors of this pathway could be active against a large variety of microorganisms responsible for the more opportunistic infections in HIV patients. Interest in this pathway has resulted in the development of a wide variety of inhibitors for the enzymes involved. This review covers recent progress made in the development of inhibitors of the third enzyme of this pathway, i.e., the type II dehydroquinase. The X-ray crystal structures of several dehydroquinases (Streptomyces coelicolor, Mycobacterium tuberculosis, etc.) with an inhibitor bound in the active site have recently been solved. These complexes identified a number of key interactions involved in inhibitor binding and have shed light on several aspects of the catalytic mechanism. These crystal structures have also proven to be a useful tool for the design of potent and selective enzyme inhibitors, a feature that will also be discussed. © 2006 Wiley Periodicals, Inc. Med Res Rev [source] A glutamate-alanine-leucine (EAL) domain protein of Salmonella controls bacterial survival in mice, antioxidant defence and killing of macrophages: role of cyclic diGMPMOLECULAR MICROBIOLOGY, Issue 5 2005Katherine B. Hisert Summary Signature-tagged transposon mutagenesis of Salmonella with differential recovery from wild-type and immunodeficient mice revealed that the gene here named cdgR[for c-diguanylate (c-diGMP) regulator] is required for the bacterium to resist host phagocyte oxidase in vivo. CdgR consists solely of a glutamate-alanine-leucine (EAL) domain, a predicted cyclic diGMP (c-diGMP) phosphodiesterase. Disruption of cdgR decreased bacterial resistance to hydrogen peroxide and accelerated bacterial killing of macrophages. An ultrasensitive assay revealed c-diGMP in wild-type Salmonella with increased levels in the CdgR-deficient mutant. Thus, besides its known role in regulating cellulose synthesis and biofilm formation, bacterial c-diGMP also regulates host,pathogen interactions involving antioxidant defence and cytotoxicity. [source] Carcinoembryonic antigen-related cell adhesion molecule (CEACAM)-binding recombinant polypeptide confers protection against infection by respiratory and urogenital pathogensMOLECULAR MICROBIOLOGY, Issue 5 2005Darryl J. Hill Summary The human-specific pathogens Neisseria meningitidis, N. gonorrhoea, Haemophilus influenzae and Moraxella catarrhalis share the property of targeting the carcinoembryonic antigen (CEA)-related cell adhesion molecules (CEACAMs) expressed on human epithelia. CEACAMs are signalling receptors implicated in cell adhesion and regulation of several physiological functions. Their targeting by pathogens can lead to tissue invasion. Although the CEACAM-binding ligands of the bacteria are structurally diverse, they target a common site on the receptor. We have generated a recombinant polypeptide that blocks the interactions of the mucosal pathogens with human epithelial cells and antibodies against it inhibit M. catarrhalis interactions with the receptor. As such, it is a potential antimicrobial agent to prevent infection via a strategy unlikely to promote bacterial resistance and a vaccine candidate against M. catarrhalis. In addition, it could serve more widely as a novel research tool and as a potential therapeutic agent in CEACAM-based physiological disorders. [source] Regulation of Salmonella typhimurium virulence gene expression by cationic antimicrobial peptidesMOLECULAR MICROBIOLOGY, Issue 1 2003Martin W. Bader Summary Cationic antimicrobial peptides (CAMP) represent a conserved and highly effective component of innate immunity. During infection, the Gram-negative pathogen Salmonella typhimurium induces different mechanisms of CAMP resistance that promote pathogenesis in animals. This study shows that exposure of S. typhimurium to sublethal concentrations of CAMP activates the PhoP/PhoQ and RpoS virulence regulons, while repressing the transcription of genes required for flagella synthesis and the invasion-associated type III secretion system. We further demonstrate that growth of S. typhimurium in low doses of the ,-helical peptide C18G induces resistance to CAMP of different structural classes. Inducible resistance depends on the presence of PhoP, indicating that the PhoP/PhoQ system can sense sublethal concentrations of cationic antimicrobial peptides. Growth of S. typhimurium in the presence of CAMP also leads to RpoS-dependent protection against hydrogen peroxide. Because bacterial resistance to oxidative stress and CAMP are induced during infection of animals, CAMP may be an important signal recognized by bacteria on colonization of animal tissues. [source] Structural mechanisms of multidrug recognition and regulation by bacterial multidrug transcription factorsMOLECULAR MICROBIOLOGY, Issue 4 2002Maria A. Schumacher Summary The increase in bacterial resistance to multiple drugs represents a serious and growing health risk. One component of multidrug resistance (MDR) is a group of multidrug transporters that are often regulated at the transcriptional level by repressors and/or activators. Some of these transcription factors are also multidrug-binding proteins, frequently recognizing the same array of drugs that are effluxed by the transporters that they regulate. How a single protein can recognize such chemically disparate compounds is an intriguing question from a structural standpoint and an important question in future drug development endeavours. Unlike the multidrug transporters, the cytosolic multidrug-binding regulatory proteins are more tractable systems for structural analyses. Here, we describe recent crystallographic studies on MarR, BmrR and QacR, three bacterial transcription regulators that are also multidrug-binding proteins. Although our understanding of multidrug binding and transcriptional regulation by MarR is in its initial stages, the structure of a BmrR,TPP+,DNA complex has revealed important insights into the novel transcription activation mechanism of the MerR family, and the structures of a QacR,DNA complex and QacR bound to six different drugs have revealed not only the mechanism of induction of this repressor but has afforded the first view of any MDR protein bound to multiple drugs. [source] Antibiotic use in five children's hospitals during 2002,2006: the impact of antibiotic guidelines issued by the Chinese Ministry of Health,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 3 2008Wenshuang Zhang Abstract Purpose To investigate the pattern of antibiotic use in five Chinese children's hospitals from 2002 to 2006. To see if the Guidelines to encourage rational use of antibiotics issued by the Ministry of Health in October 2004 have any impact on the use. Methods The Anatomical Therapeutic Chemical Classification/Defined Daily Doses (ATC/DDD) methodology was used. Aggregate data on antibiotic use (ATC code-J01) were expressed in numbers of DDD/100 bed-days for inpatients. Results Total 56 different substances of systemic antibiotics were used. The overall consumption of antibiotic drugs was 68.2, 58.4, 65.8, 65.6 and 49.9 DDD/100 bed-days for the years 2002,2006, respectively. The top antibiotics used were third-generation cephalosporins. There was considerable variation in both type and amount of antibiotics used in the five hospitals. In 2002, some hospitals had twice the antibiotic use compared to others. While the overall antibiotic use in 2005 was largely unchanged compared with previous years, by 2006 antibiotic use had decreased by 22.6% and the variation in use between hospitals was also reduced. Conclusions The ATC/DDD methodology proved useful for studying overall antibiotic usage in children's hospitals. The decline in antibiotic usage found in 2006 (and the reduced variation between hospitals) may be attributed to the impact of the Ministry of Health guidelines which took some time to be promulgated to individual staff members. Further research will focus on compliance of antibiotic use in these five hospitals with particular guideline recommendations for specific clinical problems such as bacterial resistance and surgical antibiotic prophylaxis. Copyright © 2007 John Wiley & Sons, Ltd. [source] Latest news and product developmentsPRESCRIBER, Issue 21 2007Article first published online: 3 DEC 200 NSAIDs and SSRIs increase GI bleeding Taking an NSAID and an SSRI increases the risk of GI bleeding more than six-fold compared with taking neither drug, a meta-analysis shows (Aliment Pharmacol Ther online: 5 Oct 2007; doi:10.1111/j.1365-2036.20 07.03541.x). The analysis included four observational studies involving a total of 153 000 patients, and 101 cases reported in postmarketing surveillance. Compared with nonuse, the odds ratio for upper GI haemorrhage in patients taking an SSRI alone was 2.36; the number needed to harm (NNH) was 411 for one year's treatment in patients aged over 50 with no risk factors. For those taking an SSRI and an NSAID, it was 6.33 (NNH 106). Of 22 cases where treatment duration was known, the median time to onset of bleeding was 25 weeks and five occurred within one month. The MHRA warns of this interaction in its latest issue of Drug Safety Update, noting: ,corticosteroids, antiplatelet agents, and SSRIs may increase the risk of GI ulceration or bleeding. NSAIDs may enhance the effects of anticoagulants, such as warfarin'. MHRA warning on NSAID safety The MHRA reminds prescribers of new restrictions on prescribing piroxicam and the risks associated with ketorolac and ketoprofen in its latest Drug Safety Update (2007;1:Issue 3). Treatment with piroxicam should now only be initiated by a specialist as a second-line drug; patients currently taking it should be reviewed at the next routine appointment. Piroxicam is no longer indicated for any acute indications. These restrictions do not apply to topical piroxicam (Feldene gel). Ketorolac and ketoprofen are associated with a higher risk of adverse GI effects than other NSAIDs. The MHRA advises prescribers to adhere to the licensed indications that limit oral ketorolac therapy to seven days (two days for continuous iv or im use) and the maximum dose of ketoprofen to 100-200mg. Inhaled steroids may increase the risk of pneumonia in patients with COPD. In the TORCH study (N Engl J Med 2007;356:775-89), fluticasone (Flixotide) and fluticasone plus salmeterol (Seretide) were associated with a significantly increased risk compared with salmeterol alone. The MHRA recommends vigilance for signs of pneumonia or bronchitis in patients with COPD who are treated with inhaled steroids; affected patients should have their treatment reconsidered. Other issues reviewed in Drug Safety Update include: a more intense reaction after revaccination with the pneumococcal vaccine, Pneumovax II; exacerbation of osteonecrosis of the jaw by dental surgery in patients taking a bisphosphonate; a lower maximum dose for lorazepam (4mg for severe anxiety, 2mg for severe insomnia) rare reactions with botulinum toxin; and the cardiovascular safety and risk of fractures with the glitazones. Antibiotic resistance GPs who reduce their antibiotic prescribing achieve a significant reduction in bacterial resistance, a study from Wales has shown (Br J Gen Pract 2007;57:785-92). The analysis of 164 225 coliform isolates from urine samples submitted from 240 general practices found a 5.2 per cent decrease in ampicillin resistance in practices with the greatest reductions in total antibiotic prescribing. Overall, ampicillin resistance decreased by 1 per cent for every reduction of 50 amoxicillin prescriptions per 1000 patients. Trimethoprim resistance showed a similar trend. Mortality risk with discontinuing statins Patients who discontinue statin therapy after acute stroke are almost three times more likely to die than those who do not, an Italian study shows (Stroke 2007;38:2652-7). Follow-up of 631 patients discharged after acute stroke revealed that 39 per cent discontinued statin therapy. The hazard ratio for all-cause mortality in the first 12 months was 2.78 compared with those who continued treatment; this compared with a hazard ratio of 1.81 for stopping antiplatelet therapy. The authors argue that patient care should be improved during the transition from hospital to outpatient primary care. ACEI ± ARB = ADRs Combining an ACE inhibitor and an angiotensin-II receptor blocker increases the risk of adverse effects in patients with symptomatic left ventricular dysfunction, according to a US study (Arch Intern Med 2007;167:1930-6). Meta-analysis of four trials involving a total of 17 337 patients followed up for about two years showed that, compared with therapy including an ACE inhibitor, combined treatment increased the risk of stopping treatment due to adverse events by 38 per cent in patients with heart failure and by 17 per cent in patients with MI. The authors estimate that, for every 1,000 patients treated, 25 will discontinue treatment due to adverse effects and 17 will develop renal dysfunction. WOSCOPS: statin protection continues Pravastatin reduces the risk of death years after treatment has stopped, according to a follow-up of the WOSCOPS study (N Engl J Med 2007;357:1477-86). The West of Scotland Coronary Prevention Study originally randomised men with hypercholesterolaemia but no history of myocardial infarction (MI) to treatment with pravastatin or placebo. After five years, the combined incidence of death from CHD or nonfatal MI was reduced from 7.9 to 5.5 per cent in the treatment group. During the 10 years after completion of the trial, the incidence of the combined end-point was 8.6 per cent in those originally assigned to pravastatin and 10.3 per cent in the placebo group. All- cause mortality was also reduced over the entire 15-year period. The proportions of patients still taking a statin in the middle of this period, ie five years after the trial ended, were 39 per cent of the placebo group. Prescribing policies on HRT need reappraisal Health authorities should reconsider their policy on prescribing HRT, the International Menopause Society (IMS) says. In an open letter, the IMS says current safety concerns over HRT use are founded, but have been misinterpreted in observational studies, such as the Women's Health Initiative, that led to changes in guidelines. The IMS says HRT is the most effective treatment for vasomotor and urogenital symptoms and the risk:benefit profile is favourable until age 60. Low-dose oestrogen or the transdermal route of administration may lead to a more favourable risk profile. Flu vaccine does cut morbidity and mortality Following The Lancet's commentary doubting the effectiveness of flu vaccination (Lancet Infectious Diseases 2007;7:658-66), a US cohort study has found that it does reduce morbidity and mortality (N Engl J Med 2007;357:1373-81). The observational study included 713 872 person-seasons in older people living in the community over a 10year period from 1990 to 2000. Vaccination was associated with a 48 per cent reduction in the risk of death and a 27 per cent reduction in admission for pneumonia or flu. These benefits changed little in subgroups or with age. Copyright © 2007 Wiley Interface Ltd [source] Analysis of the plasticity of location of the Arg244 positive charge within the active site of the TEM-1 ,-lactamasePROTEIN SCIENCE, Issue 10 2009David C. Marciano Abstract A large number of ,-lactamases have emerged that are capable of conferring bacterial resistance to ,-lactam antibiotics. Comparison of the structural and functional features of this family has refined understanding of the catalytic properties of these enzymes. An arginine residue present at position 244 in TEM-1 ,-lactamase interacts with the carboxyl group common to penicillin and cephalosporin antibiotics and thereby stabilizes both the substrate and transition state complexes. A comparison of class A ,-lactamase sequences reveals that arginine at position 244 is not conserved, although a positive charge at this structural location is conserved and is provided by an arginine at positions 220 or 276 for those enzymes lacking arginine at position 244. The plasticity of the location of positive charge in the ,-lactamase active site was experimentally investigated by relocating the arginine at position 244 in TEM-1 ,-lactamase to positions 220, 272, and 276 by site-directed mutagenesis. Kinetic analysis of the engineered ,-lactamases revealed that removal of arginine 244 by alanine mutation reduced catalytic efficiency against all substrates tested and restoration of an arginine at positions 272 or 276 partially suppresses the catalytic defect of the Arg244Ala substitution. These results suggest an evolutionary mechanism for the observed divergence of the position of positive charge in the active site of class A ,-lactamases. [source] Microbiology of Recurrent Acute RhinosinusitisTHE LARYNGOSCOPE, Issue 1 2004Itzhak Brook MD Abstract Objective We undertook to evaluate the microbiology of recurrent acute rhinosinusitis. Methods Repeated aspirations of maxillary sinus secretions by endoscopy were performed in eight patients over a period of 98 to 185 days. Results Bacteria were recovered for all 25 aspirates. A total of 31 isolates,14 Streptococcus pneumoniae, 11 Haemophilus influenzae, 5 Moraxella catarrhalis, and 1 Staphylococcus aureus,were recovered. The organism persisted in consecutive cultures in 13 instances and were eliminated in 8, and new organisms emerged in 6 instances. An increase in antimicrobial resistance was noted in 5 instances (3 in S. pneumoniae and 2 H. influenzae). Conclusions This study illustrates the microbial dynamics of recurrent acute rhinosinusitis, with the changes in microbial findings and increased bacterial resistance that occurs over time. [source] Synthesis and Biological Evaluation of 2-Mercapto-1,3-benzothiazole Derivatives with Potential Antimicrobial ActivityARCHIV DER PHARMAZIE, Issue 10 2009Carlo Franchini Abstract The enhancement of bacterial resistance of pathogens to currently available antibiotics constitutes a serious public health threat. So, intensive efforts are underway worldwide to develop new antimicrobial agents. To identify compounds with a potent antimicrobial profile, we designed and synthesized low molecular weight 2-mercaptobenzothiazole derivatives 2a,2l and 3a,3l. Both series were screened for in-vitro antibacterial activity against the representative panel of Gram-positive and Gram-negative bacteria strains. The biological screening identified compounds 2e and 2l as the most active ones showing an interesting antibacterial activity with MIC values of 3.12 ,g/mL against Staphylococcus aureus and 25 ,g/mL against Escherichia coli, respectively. The replacement of the S-H by the S-Bn moiety resulted in considerable loss of the antibacterial action of the 3a,3l series. The antibiotic action of compounds 2e and 2l was also investigated by testing their activity against some clinical isolates with different antimicrobial resistance profile. Moreover, the involvement of the NorA efflux pump in the antibacterial activity of our molecules was evaluated. Finally, in this paper, we also describe the cytotoxic activity of the most interesting compounds by MTS assay against HeLa and MRC-5 cell lines. [source] Crystallization of type I chloramphenicol acetyltransferase: an approach based on the concept of ionic strength reducersACTA CRYSTALLOGRAPHICA SECTION D, Issue 1 2000Antonina E. Andreeva Chloramphenicol acetyltransferase (CAT) is responsible for bacterial resistance to chloramphenicol. It catalyzes inactivation of the antibiotic by acetyl-group transfer from acetyl CoA to one or both hydroxyl groups of chloramphenicol. Type I CAT possesses some unique properties which are not observed in other CAT variants. Type I CAT overexpressed in Escherichia coli was purified and crystals with a resolution limit of 2.22,Å have been obtained using a novel procedure which is based on the concept of `ionic strength reducers'. The crystals have the symmetry of space group P1 and unit-cell parameters a = 96.46, b = 113.86, c = 114.21,Å, , = 119.9, , = 94.1, , = 98.6°. These dimensions are consistent with four to six trimers per unit cell, corresponding to a solvent fraction ranging from 65 to 47%. [source] Purification, crystallization and preliminary X-ray analysis of Enterococcus casseliflavus aminoglycoside-2,,-phosphotransferase-IVaACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 1 2010Marta Toth The deactivation of aminoglycoside antibiotics by chemical modification is one of the major sources of bacterial resistance to this family of therapeutic compounds, which includes the clinically relevant drugs streptomycin, kanamycin and gentamicin. The aminoglycoside phosphotransferases (APHs) form one such family of enzymes responsible for this resistance. The gene encoding one of these enzymes, aminoglycoside-2,,-phosphotransferase-IVa [APH(2,,)-IVa] from Enterococcus casseliflavus, has been cloned and the protein (comprising 306 amino-acid residues) has been expressed in Escherichia coli and purified. The enzyme was crystallized in three substrate-free forms. Two of the crystal forms belonged to the orthorhombic space group P212121 with similar unit-cell parameters, although one of the crystal forms had a unit-cell volume that was approximately 13% smaller than the other and a very low solvent content of around 38%. The third crystal form belonged to the monoclinic space group P21 and preliminary X-ray diffraction analysis was consistent with the presence of two molecules in the asymmetric unit. The orthorhombic crystal forms of apo APH(2,,)-IVa both diffracted to 2.2,Å resolution and the monoclinic crystal form diffracted to 2.4,Å resolution; synchrotron diffraction data were collected from these crystals at SSRL (Stanford, California, USA). Structure determination by molecular replacement using the structure of the related enzyme APH(2,,)-IIa is proceeding. [source] Fighting infections due to multidrug-resistant Gram-positive pathogensCLINICAL MICROBIOLOGY AND INFECTION, Issue 3 2009G. Cornaglia Guest Editor Growing bacterial resistance in Gram-positive pathogens means that what were once effective and inexpensive treatments for infections caused by these bacteria are now being seriously questioned, including penicillin and macrolides for use against pneumococcal infections and,in hospitals,oxacillin for use against staphylococcal infections. As a whole, multidrug-resistant (MDR) Gram-positive pathogens are rapidly becoming an urgent and sometimes unmanageable clinical problem. Nevertheless, and despite decades of research into the effects of antibiotics, the actual risk posed to human health by antibiotic resistance has been poorly defined; the lack of reliable data concerning the outcomes resulting from antimicrobial resistance stems, in part, from problems with study designs and the methods used in resistence determination. Surprisingly little is known, too, about the actual effectiveness of the many types of intervention aimed at controlling antibiotic resistance. New antibiotics active against MDR Gram-positive pathogens have been recently introduced into clinical practice, and the antibiotic pipeline contains additional compounds at an advanced stage of development, including new glycopeptides, new anti-methicillin-resistant Staphylococcus aureus (MRSA) ,-lactams, and new diaminopyrimidines. Many novel antimicrobial agents are likely to be niche products, endowed with narrow antibacterial spectra and/or targeted at specific clinical problems. Therefore, an important educational goal will be to change the current, long-lasting attitudes of both physicians and customers towards broad-spectrum and multipurpose compounds. Scientific societies, such as the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), must play a leading role in this process. 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