Title:PEGylated Liposomal Vancomycin: A Glimmer of Hope for Improving Treatment Outcomes in MRSA Pneumonia
Volume: 7
Issue: 3
Author(s): Andrew S. Pumerantz
Affiliation:
Keywords:
Liposomal, lung, MRSA, PEGylated, pneumonia, vancomycin, FORMIDABLE PATHOGEN, PEGYLATED LIPOSOMAL, lipophilic drugs
Abstract: Methicillin-resistant Staphylococcus aureus (MRSA) plays a significant role in the pandemic of multidrug resistant
bacterial infections and is a major cause of hospital-acquired pneumonia. MRSA pneumonia carries a high morbidity
and mortality rate especially in elderly diabetics with chronic kidney disease. S. aureus is highly virulent and successful
respiratory pathogen. Vancomycin and linezolid are the only two antimicrobial agents FDA-approved to treat MRSA
pneumonia. Standard vancomycin dosing is associated with high clinical failure rates and higher dosages are associated
with increased nephrotoxicity. Pharmacokinetic and pharmacodynamic limitations are major contributors to poor outcomes
with vancomycin. New agents are needed to improve treatment outcomes with MRSA pneumonia. Recently released
antimicrobials with in vitro activity are not FDA-approved for treating MRSA pneumonia. Other novel agents are
being investigated though none are in late-stage development. Pharmaceutical industry perception of low returns on investment,
a Sisyphean regulatory environment, and obstacles to patentability have contributed to declining interest in both
the development of novel antibiotics and the improvement of existing generic formulations. Despite decades of investigation
into liposomal encapsulation as a drug delivery system that would increase efficacy and decrease toxicity, only
liposomal amphotericin B and doxorubicin are commercially available. In this article, the pharmacokinetics and biodistribution
of a novel PEGylated liposomal vancomycin formulation along with passive targeting and the enhanced permeability
and retention effect of liposomal drug delivery; the pathogenesis of MRSA pneumonia; and recent patents of novel
anti-MRSA agents, including inhalational liposomal vancomycin, are reviewed.
