Sievert, D. M. et al. Vancomycin-resistant Staphylococcus aureus in the United States, 2002-2006. Clin. Infect. Dis. 46, 668-674
Michigan Department of Community Health, Lansing, USA. Clinical Infectious Diseases
(Impact Factor: 8.89).
04/2008; 46(5):668-74. DOI: 10.1086/527392
This report compares the clinical characteristics, epidemiologic investigations, infection-control evaluations, and microbiologic findings of all 7 of the cases of vancomycin-resistant Staphylococcus aureus (VRSA) infection in the United States during the period 2002-2006.
Epidemiologic, clinical, and infection-control information was collected. VRSA isolates underwent confirmatory identification, antimicrobial susceptibility testing, pulsed-field gel electrophoresis, and typing of the resistance genes. To assess VRSA transmission, case patients and their contacts were screened for VRSA carriage.
Seven cases were identified from 2002 through 2006; 5 were reported from Michigan, 1 was reported from Pennsylvania, and 1 was reported from New York. All VRSA isolates were vanA positive and had a median vancomycin minimum inhibitory concentration of 512 microg/mL. All case patients had a history of prior methicillin-resistant S. aureus and enterococcal infection or colonization; all had several underlying conditions, including chronic skin ulcers; and most had received vancomycin therapy prior to their VRSA infection. Person-to-person transmission of VRSA was not identified beyond any of the case patients. Infection-control precautions were evaluated and were consistent with established guidelines.
Seven patients with vanA-positive VRSA have been identified in the United States. Prompt detection by microbiology laboratories and adherence to recommended infection control measures for multidrug-resistant organisms appear to have prevented transmission to other patients.
- "MRSA infection has spread in the past few decades and is treated by vancomycin, the " drug of last resort " . Unfortunately, vancomycin-resistant strains (VRSA) were isolated in June 2002  and there is therefore an urgent need to continuously discover new drugs to combat S. aureus. The type II fatty acid biosynthesis pathway (Fig. 1a), which is usually found in plants and bacteria, is responsible for the de novo production of lipids for incorporation into the bacterial cell membrane . "
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ABSTRACT: The pharmacokinetics (PK) and pharmacodynamics (PD) of PT119, a potent Staphylococcus aureus enoyl-ACP reductase (saFabI) inhibitor with a Ki value of 0.01 nM and a residence time of 750 min on the enzyme target, has been evaluated in mice. PT119 was found to have promising antibacterial activity in two different S. aureus infection models: it caused a 3 log reduction in the CFU's in a mouse thigh muscle infection model and increased the survival rate from 0% to 50% in a mouse systemic infection model. PT119 was then radiolabeled with carbon-11 to evaluate its biodistribution and PK in both healthy and S. aureus infected mice using positron emission tomography (PET). The biodistribution of [(11)C]PT119 and/or its labeled metabolites did not differ significantly between the healthy group and the infected group, and PT119 was found to distribute equally between serum and tissue during the ∼1 h of analysis permitted by the carbon-11 half life. This approach provides important data for PK/PD modeling and is the first step in identifying radiotracers that can non-invasively image bacterial infection in vivo.
European Journal of Medicinal Chemistry 09/2014; 88. DOI:10.1016/j.ejmech.2014.09.008 · 3.45 Impact Factor
Available from: Prashanth Shastrula
- "In 2008, a report on isolates from Kolkata (India) was published. There are many reports of VRSA worldwide; most recently the transfer of vanA to MRSA was also reported in Pennsylvania     "
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ABSTRACT: The emergence of multidrug-resistant and vancomycin-resistant enterococci during the last decade has made it difficult to treat nosocomial infections. Although various enterococcal species have been identified, only two (Enterococcus faecalis and Enterococcus faecium) are responsible for the majority of human infections. Vancomycin is an important therapeutic alternative against multidrug-resistant enterococci but is associated with a poor prognosis. Resistance to vancomycin dramatically reduces the therapeutic options for enterococcal infections. The bacterium develops resistance by modifying the C-terminal d-alanine of peptidoglycan to d-lactate, creating a d-Ala-d-Lac sequence that effectively reduces the affinity of vancomycin for the peptidoglycan by 1000-fold. Moreover, the resistance genes can be transferred from enterococci to Staphylococcus aureus, thereby posing a threat to patient safety and also a challenge for treating physicians. Judicious use of vancomycin and broad-spectrum antibiotics must be implemented, but strict infection control measures must also be followed to prevent nosocomial transmission of these organisms. Furthermore, improvements in clinical practice, rotation of antibiotics, herbal drugs, nanoantibiotics and the development of newer antibiotics based on a pharmacogenomic approach may prove helpful to overcome dreadful vancomycin-resistant enterococcal infections.
Journal of Global Antimicrobial Resistance 05/2014; 2(4). DOI:10.1016/j.jgar.2014.04.002 · 1.09 Impact Factor
Available from: Floris Bikker
- "Staphylococcus aureus is a Gram-positive pathogen that is the leading cause of skin, soft tissue, lower respiratory tract and bloodstream infections . Its emerging multiple resistance to antibiotic treatment is becoming a major public health concern , . Multiple resistant S. aureus strains, such as MRSA (methicillin resistant S. aureus), have become endemic in many parts of the world . "
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ABSTRACT: The majority of Staphylococcus aureus virulence- and colonization-associated surface proteins contain a pentapeptide recognition motif (LPXTG). This motif can be recognized and cleaved by sortase A (SrtA) which is a membrane-bound transpeptidase. After cleavage these proteins are covalently incorporated into the peptidoglycan. Therefore, SrtA plays a key role in S. aureus virulence. We aimed to generate a substrate mimicking this SrtA recognition motif for several purposes: to incorporate this substrate into the S. aureus cell-wall in a SrtA-dependent manner, to characterize this incorporation and to determine the effect of substrate incorporation on the incorporation of native SrtA-dependent cell-surface-associated proteins. We synthesized substrate containing the specific LPXTG motif, LPETG. As a negative control we used a scrambled version of this substrate, EGTLP and a S. aureus srtA knockout strain. Both substrates contained a fluorescence label for detection by FACScan and fluorescence microscope. A spreading assay and a competitive Luminex assay were used to determine the effect of substrate treatment on native LPXTG containing proteins deposition in the bacterial cell-wall. We demonstrate a SrtA-dependent covalent incorporation of the LPETG-containing substrate in wild type S. aureus strains and several other Gram-positive bacterial species. LPETG-containing substrate incorporation in S. aureus was growth phase-dependent and peaked at the stationary phase. This incorporation negatively correlated with srtA mRNA expression. Exogenous addition of the artificial substrate did not result in a decreased expression of native SrtA substrates (e.g. clumping factor A/B and protein A) nor induced a srtA knockout phenotype.
PLoS ONE 02/2014; 9(2):e89260. DOI:10.1371/journal.pone.0089260 · 3.23 Impact Factor
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