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Methicillin-resistant S. Aureus (methicillin-resistant + s._aureu)
Selected AbstractsStaphylococcus aureus as source of catheter-related bloodstream infection evaluated by PFGE and rep-PCR typing in a Brazilian hospital,APMIS, Issue 11 2008GERALDO SADOYAMA Staphylococci are a common cause of catheter-related bloodstream infection (CR-BSI), and epidemiological typing is an important tool for effective infection control. This study evaluated by PFGE and rep-PCR whether Staphylococcus aureus strains isolated from skin and catheter tips were related to specimens isolated from blood. A prospective observational study, carried out in a clinical surgical ward at a Brazilian hospital between September 2000 and November 2002, investigated non-tunneled central venous catheters from 179 patients. S. aureus isolates were mainly obtained from blood (41.4%), while coagulase-negative staphylococci strains were more often isolated from the skin at the catheter insertion site (49.7%) and from the catheter tip (57.5%). Among the 21 strains isolated from 9 patients at 2 or 3 sites simultaneously, 9 were methicillin-resistant S. aureus (MRSA) and 12 were methicillin-susceptible S. aureus (MSSA). Seven patients harbored the same S. aureus strain isolated from the skin, blood and/or catheter tip cultures. MRSA isolates belonged to one PFGE pattern (type A- subtypes A1, A2 and A3), and to two rep-PCR patterns (a and b). MSSA isolates were distinguished in five PFGE (B to F) and in three rep-PCR (c, d and e) patterns. Both PFGE and rep-PCR methods indicated that the skin at the catheter insertion site was the origin of CR-BSI caused by S. aureus. [source] Synthesis and In Vitro Antibacterial Activity of 7-(3-Alkoxyimino-4-methyl-4-methylaminopiperidin-1-yl)-fluoroquinolone DerivativesARCHIV DER PHARMAZIE, Issue 3 2010Yi-Bin Zhang Abstract A series of novel 7-(3-alkoxyimino-4-methyl-4-methylaminopiperidin-1-yl)fluoroquinolone derivatives were designed, synthesized, and characterized by 1H-NMR, MS, and HRMS. These fluoroquinolones were evaluated for their in-vitro antibacterial activity against representative Gram-positive and Gram-negative strains. Generally, all of the target compounds have considerable antibacterial activity against the tested forty strains, and exhibit exceptional potency in inhibiting the growth of methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) ATCC33591 (MICs: 0.06 to 2 ,g/mL). In particular, compounds 14, 19, 28, and 29 are fourfold more potent than ciprofloxacin against MSSA 08-49. Compounds 23, 26, and 27 are twofold more potent than ciprofloxacin against MRSA ATCC33591 and MSSA ATCC29213. In addition, compound 14 exhibits excellent activity (MIC: 0.06 ,g/mL) against Acinetobactes calcoaceticus, which is two- to 16-fold more potent than the reference drugs gemifloxacin, levofloxacin, and ciprofloxacin. [source] Synthesis and Antistaphylococcal Activity of N -Substituted-1H -benzimidazole-sulphonamidesARCHIV DER PHARMAZIE, Issue 1 2010M. Orhan Püsküllü Abstract A series of N -substituted-1H -benzimidazole-5(6)-sulfonamides and 3-(5,6-dichloro-1H -benzimidazol-2-yl)- N -substituted benzensulfonamides were synthesized and evaluated for antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA). Certain compounds inhibit bacterial growth with low MIC (,g/mL) values. The most active compounds 30, 31, and 32 have the lowest MIC values with 0.39 to 0.19 ,g/mL. Among the compounds having sulfonamido moities, 16, 23, and 24 exhibited the strongest antibacterial activity with 1.56 ,g/mL MIC values. [source] Inhibitory properties and X-ray crystallographic study of the binding of AR-101, AR-102 and iclaprim in ternary complexes with NADPH and dihydrofolate reductase from Staphylococcus aureusACTA CRYSTALLOGRAPHICA SECTION D, Issue 8 2009Christian Oefner Iclaprim is a novel dihydrofolate reductase (DHFR) inhibitor belonging to the 2,4-diaminopyrimidine class of antibiotics, of which trimethoprim (TMP) is the most well known representative. Iclaprim exhibits potent bactericidal activity against major Gram-positive pathogens, notably methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) phenotypes, including TMP-resistant strains. The inhibition properties of racemic iclaprim and of the two enantiomers, termed AR-101 and AR-102, towards S. aureus wild-type DHFR and TMP-resistant F98Y mutant DHFR were determined and compared. Similar to TMP, AR-101, AR-102 and iclaprim are all competitive inhibitors with respect to the substrate dihydrofolate. Iclaprim, AR-101 and AR-102 demonstrated little or no difference in activity towards these enzymes and were significantly more potent than TMP. The crystal structures of S. aureus DHFR and F98Y mutant DHFR were determined as ternary complexes with NADPH and either AR-101, AR-102 or iclaprim. The binding modes of the inhibitors were analysed and compared. The X-ray crystallographic data explain the binding modes of all molecules well and can be used to rationalize the equipotent affinity of AR-101, AR-102 and iclaprim, which is also reflected in their antibacterial properties. [source] Structure of Staphylococcus aureus cytidine monophosphate kinase in complex with cytidine 5,-monophosphateACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 8 2006Jingshan Ren The crystal structure of Staphylococcus aureus cytidine monophosphate kinase (CMK) in complex with cytidine 5,-monophosphate (CMP) has been determined at 2.3,Å resolution. The active site reveals novel features when compared with two orthologues of known structure. Compared with the Streptococcus pneumoniae CMK solution structure of the enzyme alone, S. aureus CMK adopts a more closed conformation, with the NMP-binding domain rotating by ,16° towards the central pocket of the molecule, thereby assembling the active site. Comparing Escherichia coli and S. aureus CMK,CMP complex structures reveals differences within the active site, including a previously unreported indirect interaction of CMP with Asp33, the replacement of a serine residue involved in the binding of CDP by Ala12 in S. aureus CMK and an additional sulfate ion in the E. coli CMK active site. The detailed understanding of the stereochemistry of CMP binding to CMK will assist in the design of novel inhibitors of the enzyme. Inhibitors are required to treat the widespread hospital infection methicillin-resistant S. aureus (MRSA), currently a major public health concern. [source] Key considerations in the treatment of complicated staphylococcal infectionsCLINICAL MICROBIOLOGY AND INFECTION, Issue 2008R. N. Jones Abstract Substantial increases in antimicrobial resistance among Gram-positive pathogens, particularly Staphylococcus aureus, are compromising traditional therapies for serious bacterial infections. There has been an alarming increase in the rates of methicillin-resistant S. aureus (MRSA) over the past two decades, and the more recent emergence of heterogenous vancomycin-intermediate (hVISA), vancomycin-intermediate (VISA) and vancomycin-resistant S. aureus (VRSA) strains limits the use of vancomycin, the current standard of care for MRSA infections. Tolerance to vancomycin, which represents a lack of bactericidal activity of vancomycin, is another troublesome property of some S. aureus strains that can adversely affect the outcome of antimicrobial therapy. Increasing MICs of vancomycin for staphylococci, poor tissue penetration by the drug and a slow rate of bactericidal action of the drug have also raised concerns about its efficacy in the contemporary treatment of MRSA infections. There is an increasingly apparent need for new agents for the treatment of staphylococcal infections, ideally with potent bactericidal activity against MRSA, hVISA, VISA and VRSA and with superior susceptibility profiles as compared with glycopeptides. [source] Empirical therapy for diabetic foot infections: are there clinical clues to guide antibiotic selection?CLINICAL MICROBIOLOGY AND INFECTION, Issue 4 2007B. A. Lipsky Abstract Initial antibiotic therapy for diabetic foot infections is usually empirical. Several principles may help to avoid selecting either an unnecessarily broad or inappropriately narrow regimen. First, clinically severe infections require broad-spectrum therapy, while less severe infections may not. Second, aerobic Gram-positive cocci, particularly Staphylococcus aureus (including methicillin-resistant S. aureus (MRSA) for patients at high-risk) should always be covered. Third, therapy should also be targeted at aerobic Gram-negative pathogens if the infection is chronic or has failed to respond to previous antibiotic therapy. Fourth, anti-anaerobe agents should be considered for necrotic or gangrenous infections on an ischaemic limb. Parenteral therapy is needed for severe infections, but oral therapy is adequate for most mild or moderate infections. [source] Detection of low-level oxacillin resistance in mecA -positive Staphylococcus aureusCLINICAL MICROBIOLOGY AND INFECTION, Issue 4 2007W. Witte Abstract Detection of low-level oxacillin-resistant Staphylococcus aureus is a problem that needs special attention, particularly in relation to methicillin-resistant S. aureus (MRSA) strains in the community that belong to clonal lineage ST80. This study compared different phenotypic methods for the detection of 74 low-level oxacillin-resistant S. aureus strains (oxacillin MIC ,1 mg/L), 46 MRSA strains (oxacillin MIC ,2 mg/L) and 117 methicillin-susceptible S. aureus strains. Determination of microbroth dilution MICs for oxacillin was wholly unsatisfactory, and gave a limited specificity for cefoxitin. The sensitivity of disk-diffusion performed according to CLSI recommendations was 92% with an oxacillin 1-µg disk, and 96% with a cefoxitin 30-µg disk; use of a 10-µg cefoxitin disk and a semi-confluent inoculum (breakpoint for resistance <18 mm zone diameter) gave a sensitivity of 97%. When disk-diffusion was performed on IsoSensitest agar with a zone diameter breakpoint for resistance of <22 mm (as recommended by the Swedish Reference Group for Antibiotics), the sensitivity was 95%. [source] | |||||||||||||