Costs of healthcare-associated methicillin-resistant Staphylococcus aureus and its control

Staphylococcus aureus is a major human and veterinary pathogen worldwide. Methicillin-resistant S. aureus (MRSA) poses a significant and enduring problem to the treatment of infection by such strains. Resistance is usually conferred by the acquisition of a nonnative gene encoding a penicillin-binding protein (PBP2a), with significantly lower affinity for β-lactams. This resistance allows cell-wall biosynthesis, the target of β-lactams, to continue even in the presence of typically inhibitory concentrations of antibiotic. PBP2a is encoded by the mecA gene, which is carried on a distinct mobile genetic element (SCCmec), the expression of which is controlled through a proteolytic signal transduction pathway comprising a sensor protein (MecR1) and a repressor (MecI). Many of the molecular and biochemical mechanisms underlying methicillin resistance in S. aureus have been elucidated, including regulatory events and the structure of key proteins. Here we review recent advances in this area.

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“…The morbidity and mortality caused by MRSA result in significant economic and societal costs (14,15).…”

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confidence: 99%

Mechanisms of Methicillin Resistance in Staphylococcus aureus

Peacock

Paterson

2015

Annu. Rev. Biochem.

500

371

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“…1,2 It is a principal cause of hospital infections, the most frequent and serious of which are bacteremia and endocarditis in hospitalized patients. 3–6 This organism has become resistant to many different classes of antibiotics. 7,8 Of special concern are the strains designated as methicillin-resistant S. aureus (MRSA), which are broadly resistant to most β-lactam antibiotics, agents of historic choice for treatment of infections by S. aureus .…”

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confidence: 99%

Exploration of the structure–activity relationship of 1,2,4-oxadiazole antibiotics

Ding

Boudreau

Leemans

et al. 2015

Bioorganic & Medicinal Chemistry Letters

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We have recently disclosed the discovery of the class of 1,2,4-oxadiazole antibiotics, which emerged from in silico docking and scoring efforts. This class of antibacterials exhibits Gram-positive activity, particularly against Staphylococcus aureus. We define the structure-activity relationship (SAR) of this class of antibiotics with the synthesis and evaluation of a series of 59 derivatives with variations in the C ring or C and D rings. A total of 17 compounds showed activity against S. aureus. Four derivatives were evaluated against a panel of 16 Gram-positive strains, inclusive of several methicillin-resistant S. aureus strains. These compounds are broadly active against Gram-positive bacteria.

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“…1 The continual rise in multiple antibiotics resistance among S. aureus isolates further complicates treatment of these diseases and increases the economic burden associated with treatment in both the medical and veterinary fields. 2,3 Additionally, S. aureus mastitis infections are generally subclinical, further exasperating the loss in milk yield and treatment costs. 4 Identifying and classifying isolates of S. aureus is a common laboratory practice and is important epidemiologically to determine colonality and prevalence of isolates and follow outbreaks.…”

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confidence: 99%