Abstract

Staphylococcus aureus is a notorious human pathogen that causes superficial and invasive infections both in nosocomial and community-acquired settings. The prevalence of staphylococcal infections became more challenging after emerging resistance against topical antibiotics. S. aureus evolved resistance to β-lactam antibiotics due to modification and expression of penicillin-binding proteins (PBP), inactivation of drug by β-lactamase synthesis, limiting uptake of drug by biofilm formation, and reducing uptake by expression of efflux pump. The wave of resistance was first observed in penicillin by β-lactamase production and PBPs modification. The second wave of resistance emerged to methicillin by appearing methicillin-resistant S. aureus (MRSA) strains. Cephalosporin has long been used as the last resort for preventing MRSA infections, but resistant strains appeared during treatment. In progression to control MRSA or related infections, carbapenems have been used but strains developed resistance. S. aureus is among the high-priority resistance organisms that need renewed efforts for the research and development of new antibiotics and innovative preventive approaches. However, a lot of toiling is involved in devising an effective treatment against drug resistant S. aureus. This chapter aim is to retrospectively determine the progression of resistance in S. aureus, against different β-lactam antibiotics and their challenges of medication.

Highlights

  • IntroductionInfections caused by a variety of bacterial, fungal, viral, and other infectious microorganisms are considered to be the world’s most leading problem

  • We focus on emerging trends of drug resistance in S. aureus to the different β-lactam antibiotics (β-LA)

  • The phenomenon of drug resistance was first observed when β-lactam antibiotics became ineffective after indiscriminative uses and plasmidresponsive β-lactamase synthesis

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Summary

Introduction

Infections caused by a variety of bacterial, fungal, viral, and other infectious microorganisms are considered to be the world’s most leading problem. In 2013, Center for Disease Control and Prevention (CDC) reported more than 11,000 deaths in the USA had a methicillin-resistant S. aureus (MRSA)-related infection (CDC 2013) This represents almost 50% of all causalities caused by antibiotic-resistant bacteria. Similar to penicillin or other β-lactams, cephalosporins target to bind penicillin-binding proteins (PBPs) to inhibit peptidoglycan formation in bacteria These are effectively used in the treatment of superficial (skin and soft tissue) infections, and nosocomial and community-acquired pneumonia. Ceftaroline is active against methicillin-resistant S. aureus (MRSA) and has been successfully used for the treatment of different invasive bacterial infections with low adverse effects. This potent third-generation drug was found resistance in MRSA-ST293 strain in different geographical regions. Alteration of the promoter sequence of PBP4 by mutation increases PBP4 production that leads to resistance to ceftaroline [46]

Carbapenem-resistance
Future perspective
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