Abstract
In recent years, the emergence of newly identified acute and chronic infectious disorders caused by diverse combinations of pathogens, termed polymicrobial diseases, has had catastrophic consequences for humans. Antimicrobial agents have been clinically proven to be effective in the pharmacological treatment of polymicrobial diseases. Unfortunately, an increasing trend in the emergence of multi-drug-resistant pathogens and limited options for delivery of antimicrobial drugs might seriously impact humans’ efforts to combat polymicrobial diseases in the coming decades. New antimicrobial agents with novel mechanism(s) of action and new pharmaceutical formulations or delivery systems to target infected sites are urgently required. In this review, we discuss the prospective use of novel antimicrobial compounds isolated from natural products to treat polymicrobial infections, mainly via mechanisms related to inhibition of biofilm formation. Drug-delivery systems developed to deliver antimicrobial compounds to both intracellular and extracellular pathogens are discussed. We further discuss the effectiveness of several biofilm-targeted delivery strategies to eliminate polymicrobial biofilms. At the end, we review the applications and promising opportunities for various drug-delivery systems, when compared to conventional antimicrobial therapy, as a pharmacological means to treat polymicrobial diseases.
Highlights
Microorganisms commonly grow in multifaceted polymicrobial biofilm communities in nature, attached to host mucosal sites and environmental surfaces [1]
This study showed that the antibacterial activity of ciprofloxacin increased significantly when formulated in PLGA NPs
Polymicrobial infections are resistant to antibacterial agents and usually present delivery barriers at the infection sites, leading to the unsuccessful use of antibiotics
Summary
Microorganisms commonly grow in multifaceted polymicrobial biofilm communities in nature, attached to host mucosal sites and environmental surfaces [1]. Using culture-independent community analysis methodologies, several diseases have been characterized as polymicrobial infections, such as oral cavity disease, otitis media, chronic infection in the cystic fibrosis lung, and diabetic foot wound infections In those polymicrobial-related infections, severity and disease outcomes can be predicted from the microbial composition. Increasing cases of multi-drug-resistant pathogens, the small selection of effective antimicrobials, and limitations to antimicrobial drug delivery hamper treatment of these diseases [8,9,10] In this Review, we present the pharmacological approaches available and readily used to treat mono- and polymicrobial diseases and the challenges facing the field. We discuss several newly developed drug-delivery systems targeting intracellular and extracellular pathogenic microbes and their potential applications in the pharmacological treatment of polymicrobial diseases. These promising pharmaceutical technologies may provide important advances in the treatment of polymicrobial diseases
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