title: Drug delivery approaches to overcome bacterial resistance to beta-lactam antibiotics.
abstract: BACKGROUND
  Since its landmark discovery in 1928, penicillin has had a profound impact on the quality of human life. The ability to treat and cure deadly infections and bacterial diseases has forever changed our medical profession and way of life, providing unprecedented relief from pain, suffering, and death due to microbial infection. Penicillin and its many derivatives have dominated the field of antibiotics research and development, while demonstrating unprecedented success as a therapeutic used around the world. The beta-lactams, as a family of more than six structural variants all having the 2-azetidinone ring, have worked extremely well against a wide variety of disease-causing pathogens, while exerting little if any toxicity towards mammalian cells. Penicillin has truly been a wonder drug. However, over the last 60 years, drug resistance to the penicillins has steadily been increasing in frequency and severity, to the point where today there are grave concerns that the beta-lactams will soon no longer be able to stop deadly bacterial infections.
  
  
  OBJECTIVE
  The aim of this discussion is to present what has been investigated as a means to enhance the performance of beta-lactam antibiotics against drug-resistant bacteria, and what is currently being explored or is likely to prove useful in the future.
  
  
  METHODS
  This review provides a descriptive overview of the various published ways to enhance the clinical effectiveness of beta-lactam antibiotics, beginning with the early and ongoing search for more powerful beta-lactam derivatives, penicillinase-stable variants, beta-lactam prodrugs, intracellular delivery approaches, nanocarrier-based strategies, and new beta-lactams with an alternative mechanism of action.
  
  
  CONCLUSIONS
  Of the progress made so far to develop approaches to overcome bacterial resistance to beta-lactams, the use of drug carriers such as liposomes and nanoparticles seems to hold significant promise, as do structural variants that operate through different biological modes of action.
authors.affiliation: University of South Florida, Center for Molecular Diversity in Drug Design, Discovery, and Delivery, Department of Chemistry, Tampa, FL 33620, USA.
authors.forename: Sampath C
authors.initials: SC
authors.lastname: Abeylath
authors.forename: Edward
authors.initials: E
authors.lastname: Turos