Vancomycin-resistant Staphylococcus aureus

The prototypical lantibiotic, nisin, was discovered in 1928 for its antibacterial properties and has been used as a preservative in dairy products since the 1950s (1). Nisin and other lantibiotics exhibit nanomolar efficacy against many Gram-positive strains of bacteria (2), which include methicillin resistant Staphylococcus aureus, vancomycin resistant enterococci, and oxacillin resistant bacteria. On the other hand, some lantibiotics function as morphogenetic peptides rather than antibiotics and are important for spore formation in streptomycetes (3). Since the structural elucidation of nisin in the early 1970s, extensive research efforts have been directed at understanding the biosynthesis and mode of action of various lantibiotics. 

Recently, a water-based polymer synthesised from N-chloro-2,2,6,6-tetramethyl-4-pipridinyl methacrylate (Cl-TMPM) was prepared via emulsion polymerisation (Figure 10.3). Furthermore, the addition of this antimicrobial material to commercial water-based latex paints led to antimicrobial activity against methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococcus, Escherichia coli, Candida tropicalis, bacteriophage MS2 virus and Staphylococcus chartarum [53]. 

C. beijerinckii is also a producer of clostrubin, an exceptional polyphenolic polyketide antibiotic [26]. Small doses (0.12-0.97 pM minimal inhibitory concentration (MIC)) of clostrubin inhibit growth ofvarious pathogenic bacteria, such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and mycobacteria [26]. 

Tabarez, M. R. 7-O-malonyl macrolactm A, a new macrolactm antibiotic from Bacillus sub-tilis active against methiciUm-resistant Staphylococcus aureus, vancomycin-resistant Enterococci, and a smaU-colony variant of Burkholderia cepacia. Antimicrob Agents Ch. 2005, 50(5), 1701-1709. 

Methidllin-resistant Staphylococcus aureus. Vancomycin-resistant enterococcus. 

Acute Staphylococcus aureus Vancomycin + gentamicin Penicillinase-resistant penicillin1 + gentamicin... 

While many natural products have been tested against hundreds of different strains of bacteria, the most common bacteria used in susceptibility tests include Bacillus cereus, Bacillus subtillis, Chlamydia pneumonia, Enterococcus faecalis, Escherichia coli, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pneumoniae, Klebsiella pneumoniae, vancomycin-resistant Enterococcus (VRE), Pseudomonas aeruginosa and Helicobacter pylori [18, 19], As the amount of published data describing the in vitro, in vivo and clinical antibacterial activities of natural products is so vast it could easily fill a book (or two), this review focuses only on natural products for which there is in vitro, in vivo and some clinical antibacterial data, as well as a plausible mechanism of action. 

As recently as 1970, only about 30 naturally occurring organohalogen compounds were known. It was simply assumed that chloroform, halogenated phenols, chlorinated aromatic compounds called PCBs, and other such substances found in the environment were industrial pollutants. Now, only a third of a century later, the situation js quite different. More than 5000 organohalogen compounds have been found to occur naturally, and tens of thousands more surely exist. From a simple compound like chloromethane to an extremely complex one like vancomycin, a remarkably diverse range of organohalogen compounds exists in plants, bacteria, and animals. Many even have valuable physiological activity. Vancomycin, for instance, is a powerful antibiotic produced by the bacterium Amycolatopsis orientalis and used clinically to treat methicillin-resistant Staphylococcus aureus (MRSA). 

Problems of recent years involving listeriosis, salmonellosis, giardiasis and Legionnaire s disease have received attention, as have the re-emergence of tuberculosis and the importance of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). 

Infections acquired from an external source are referred to as exogenous infections. These infections may occur as a result of human-to-human transmission, contact with exogenous bacterial populations in the environment, and animal contact. Resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus spp. 

Methicillin-resistant Staphylococcus aureus (MRSA) is a common hospital-acquired pathogen and is also increasing in the community. MRSA has presented a problem in the past because it required treatment with vancomycin. Community-acquired MRSA presents a major therapeutic challenge. MRSA can cause pneumonia, cellulitis, and other infections. Clinicians should be aware of the rate of hospital and community MRSA in your geographic area. New treatment options are available for MRSA. They include linezolid, tigecycline, and daptomycin. Prospective clinical trials have not demonstrated benefits of these agents over vancomycin.36-37... 

Joint replacement S. aureus, S. epidermidis Cefazolin 1 gx 1 preoperatively, then every 8 hours x 2 more doses Vancomycin reserved for penicillin-allergic patients or where institutional prevalence of methicillin-resistant Staphylococcus aureus warrants use IA... 

The combined synergistic effects of cyclo(Leu-Pro) and cyclo(Phe-Pro) were effective against five vancomycin-resistant enterococci (VRE) strains Enterococcus faecium (K-99-38), E. faecalis (K-99-17), E. faecalis (K-99-258), E. faecium (K-01-312), and E. faecalis (K-01-511) with MIC values of 0.25—1 mgl . It also showed activity against E. coli, Staphylococcus aureus. Micrococcus luteus, Candida albicans, and Cryptococcus neoformans with MIC values of 0.25—0.5 mg 1. This combination also showed mutagenic activity against Salmonella typhimurium TA98 and TAIOO strains in a Salmonella mutation assay. ... 

Dhawan B, Gadepalli R, Kapil A. (2009) In vitro activity of daptomycin against Staphylococcus Aureus and vancomycin-resistant Enterococcus Faecium isolates associated with skin and soft tissue infections First results from India. Diagn Microbiol Infect Dis 65 196-198. 

Recently, the piperazine intermediate 15 for the total synthesis of (—)-lemon-omycin (9) was reported by Fukuyama et al. [14], (—)-Lemonomycin possesses interesting antibiotic activity against methiciUin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium, as well as cytotoxicity against the human colon tumor cell line HCT-116 [15]. The reaction of 2-isocyanoethyl phenyl carbonate 11 gave Ugi product 14, which was further transformed to a piperazine intermediate 15 (Scheme 2). 

MRSA = methicillin-resistant Streptococcus aureus, MRSE = methicillin-resistant Staphylococcus epidermitis, PRSP = peniciUin-resistant Streptococcus pneumoniae, and VRE = vancomycin-resistant enterococci. 

Hiramatsu K., H. Hanaki, T. Ino, K. Yahuta, T. Oguri, and F.C. Tenover (1997). MethiciUin-resistant Staphylococcus aureus chnical strains with reduced vancomycin susceptihihty. Journal of Antimicrobial Chemotherapy 40 135-136. 

S. A. Roberts, J. Robson, K. Read, N. Bak, J. Hurley, P.D.R. Johnson, A.J. Morris, B.C. Mayall, and M.L. Grayson (2004). Treatment outcomes for serious infections caused by methicillin-resistant Staphylococcus aureus with reduced vancomycin susceptibility. Clinical Infectious Diseases 38 521-528. 

Howe R.A., A. Monk, M. Wootton, T.R. Walsh, and M.C. Enright (2004). Vancomycin susceptibility within methicillin-resistant Staphylococcus aureus lineages. Emerging Infectious Diseases 10 855-857. 

Miller D., V. Urdaneta, and A. Weltman (2002). Vancomycin-resistant Staphylococcus aureus—Pennsylvania, 2002. Morbidity and Mortality Weekly Report 51 509. 

Noble W.C., Z. Virani, and R.G. Cree (1992). Co-transfer of vancomycin and other resistance genes from Enterococcus faecalis NCTC to Staphylococcus aureus. FEMS Microbiology Letters 72 195-198. 

Tenover F.C., L.M. Weigel, P.C. Appelbaum, L.K. McDougal, J. Chaitram, S. McAllister, N. Clark, G. Killgore, C.M. O Hara, L. Jevitt, J.B. Patel, and B. Bozdogan (2004). Vancomycin-resistant Staphylococcus aureus isolate from a patient in Pennsylavania. Antimicrobial Agents and Chemotherapy 48 275-280. 

Whitener C.J., S.Y. Park, F.A. Browne, L.J. Parent, K. Julian, B. Bozdogan, P.C. Appelbautn, J. Chaitram, L.M. Weigel, J. Jemigan, L.K. McDougal, F.C. Tenover, and S.K. Fridkin (2004). Vancomycin-resistant Staphylococcus aureus in the absence of vancomycin exposure. Clinical Infectious Diseases 38 1049-1055. 

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