Vancomycin-intermediate

Resistance to vancomycin in enterococci is due to modification of the D-Ala-D-Ala binding site of the peptidoglycan building block in which the terminal D-Ala is replaced by D-lactate. This results in the loss of a critical hydrogen bond that facilitates high-affinity binding of vancomycin to its target and loss of activity. This mechanism is also present in vancomycin-resistant S aureus strains (MIC s32. ug/mL), which have acquired the enterococcal resistance determinants. The mechanism for reduced vancomycin susceptibility of vancomycin-intermediate strains (MICs = 8-16 g/mL) is not known. 

Staphylococcus aureus is one of the major resistant pathogens. Found on the mucous membranes and the skin of around a third of the population, it is extremely adaptable to antibiotic pressure. MRS A was first detected in the early 1960s and is now quite common in hospitals. Strains with intermediate (4-8 J,g/ml) levels of resistance, termed glycopeptide intermediate Staphylococcus aureus (GISA) or vancomycin intermediate Staphylococcus aureus (VISA), began appearing in the late 1990s the first documented strain with complete (> 16 ag/ml) resistance to vancomycin, termed vancomycin-resistant Staphylococcus aureus (VRSA), appeared in 2002. 

In vitro activities of daptomycin, vancomycin, linezolid, and quinupristin-dalfopristin against staphylococci and enterococci, including vancomycin-intermediate and -resistant strains. Antimicrob Agents Chemother... 

Aeschlimann JR, Allen GP, Hershberger E, Rybak MJ. Activities of LY333328 and vancomycin administered alone or in combination with gentamicin against three strains of vancomycin-intermediate Staphylococcus aureus in an in vitro pharamacodynamic infection model. Antimicrob Agents Chemother 2000 44 2991-2998. 

The most relevant of the coagulase-positive species is Staphylococcus aureus subsp. aureus (further S. aureus), pathogenic to both humans and animals. It is an extraordinary versatile pathogen and the major causative agent of numerous hospital-and community acqnired infections. The spread, survival and prevalence of antibiotic resistant clones of S. aureus are immensely important problems for human health. Major antibiotic resistance problems are typically associated with methicillin (oxacillin) resistant S. aureus strains (MRSA) and, more recently, vancomycin-intermediate (VISA) and vancomycin-resistant (VRSA) strains. Up to 30% of the hnman population carries S. aureus without any symptoms. In most cases, however, the colonizing strain serves as an endogenous reservoir for clinical infections (von Eiff et al. 2004). The disease spectrum includes abscesses, bacteremia, central nervons... 

Infections caused by intermediate strains have failed to resporul to vancomycin. Prior treatment courses and low vancomycin levels may predispose patients to infection with such vancomycin-intermediate strains, which typically are resistant to methicillin and multiple other antibiotics. Their emergence is a major concern because vancomycin has been the only antibiotic to which staphylococci were reliably susceptible. 

ANTIBACTERIAL ACTIVITY Because of its unique mechanism of action, linezolid is active against strains that are resistant to multiple other agents, including penicilhn-resistant strains of S. pneumoniae, methicillin-resistant, vancomycin-intermediate and vancomycin-resistant strains of staphylococci and vancomycin-resistant strains of enterococci. 

MSSA, methicilUn-sensitive S. aureus MRSA, methiciUin-resistant S. aureus StrR, streptomycin resistant VISA, vancomycin intermediate susceptibility. 

Vancomycin intermediate 5. aureus, first isolated in Japan in May 1996, then subsequently in the eastern United States (2,3), may be an example of transfer of exogenous genetic material. Transfer of vancomycin resistance from vancomycin-resistant enterococci (VRE) to S. aureus has been demonstrated in the laboratory (4,5). Because S. aureus is a leading cause of nosocomial pneumonia, 37.5% of which have become methicillin resistant (6), the threat of an increasing prevalence of VISA and the eventual appearance of vancomycin-resistant 5. aureus (VRSA) have sobering implications. Detection of VISA will ensure proper isolation to prevent nosocomial spread and initiate appropriate, albeit less than optimal, therapy. 

Fridkin, S. K. Vancomycin-intermediate and resistant what the infec-... 

Hanaki, H., Hososaka, Y, Yanagisawa, C., Otsuka, Y, Nagasawa, Z., Nakae, T, Suna-kawa, K. Occurrence of vancomycin-intermediate-resistant Staphylococcus aureus in Japan. J Infection Chemoth. 2007, 13(2), 118-121. 

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