Current State and Promising Opportunities on Pharmaceutical Approaches in the Treatment of Polymicrobial Diseases

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.

Keywords: antimicrobials; biofilms; drug delivery system; natural products; pharmacological approach; polymicrobial diseases.

Figure 1

Sites of action for different types of antibiotics.

Figure 2

The zone of inhibition of ciprofloxacin and its nanoparticle (NP) formulation against P. aeruginosa (A) and illustrative results after normalization to released amount of ciprofloxacin NPs compared to free ciprofloxacin (B) [192]. TEM images of the Esc NPs (C) [184]. All figures are reprinted with permission of the publishers.

Figure 3

TEM images of chitosan (CS)–silver NPs (A) and illustrative images of macroscopic appearance of the in vivo wounds healing studies after the administration of CS–Ag NPs gels compared to different type of treatments (B) [177]. All figures are reprinted with permission of the publishers.

Figure 4

SEM images of different type of microparticles (MPs) laden with silver NPs (A–E). In vitro release of silver NPs from MPs without (F) and with the presence of Staphylococcus aureus (G) and Pseudomonas aeruginosa (H) [206]. All figures are reprinted with permission of the publishers.