**1. Introduction**

Antimicrobial resistance refers to the evolutionary capacity developed by microorganisms such as bacteria, fungi, viruses, and parasites to fight and neutralize an antimicrobial agent. According to the World Health Organization (WHO) [1], the intensive use and misuse of antimicrobials has led to an expansion of the number and types of resistant organisms. Moreover, the use of sub-therapeutic antibiotic doses to prevent diseases in animal breeding to improve animal growth can select resistant microorganisms, which can possibly disseminate to humans [2].

The number of pathogens presenting multidrug resistance has had an exponential increase in recent times and is considered an important problem for public health [3]. A wide number of bacteria have been reported as multidrug-resistant (MDR), and they present a high cost of management, including medicines, staff capacity, isolation materials [4], and productivity loss [5]. For instance, in the USA, the cost of conventional tuberculosis treatment for the drug-susceptible bacterium is \$17,000 and up to \$482,000 for the treatment of the MDR bacterium [5]. In 2017, WHO published the first list of antibiotic-resistant pathogens offering risk to human health and, as such, the development of new drugs is crucial. Priority 1 (critical) microorganisms are carbapenem-resistant *Acinetobacter baumannii*; carbapenem-resistant *Pseudomonas aeruginosa*; and carbapenem-resistant, ESBL-producing *Enterobacteriaceae*. Accounting for priority 2 (high) are vancomycin-resistant *Enterococcus faecium*; methicillin-resistant, vancomycin-intermediate and resistant *Staphylococcus aureus*; clarithromycinresistant *Helicobacter pylori*; fluoroquinolone-resistant *Campylobacter* spp.; fluoroquinolone-resistant *Salmonellae*; and cephalosporin-resistant, fluoroquinolone-resistant *Neisseria gonorrhoeae*. In priority 3

(medium) are penicillin-non-susceptible *Streptococcus pneumoniae*, ampicillin-resistant *Haemophilus influenzae*, and fluoroquinolone-resistant *Shigella* spp. [6].

The use of drugs combinations, two or more antimicrobial drugs to combat MDRB [7], is already employed in cancer therapy [8], HIV-patients [9], and malaria patients [10]. On the other hand, research groups around the globe are suggesting innovative solutions to treat resistant organisms. Xiao et al. [11] synthesized the block copolymer poly (4-piperidine lactone-b-ω-pentadecalactone) with high antibacterial activity against *E. coli* and *S. aureus*, and low toxicity to NIH-3T3 cells, and suggested that cationic block copolymer biomaterials can be employed in medicine and implants. Zoriasatein et al. [12] showed that a derivative peptide from the snake (*Naja naja*) has an antimicrobial effect against *S. aureus*, *B. subtilis*, *E. coli*, and *P. aeruginosa*. Al-Gbouri and Hamzah [13] reported that an alcoholic extract of *Phyllanthus emblica* exhibits antimicrobial activity against *E. coli*, *S. aureus*, and *P. aeruginosa* and it inhibits biofilm formation of *P. aeruginosa*. Naqvi et al. [14] suggested the combined use of biologically synthesized silver nanoparticles (AgNPs) and antibiotics to combat the MDRB.

The increasing utilization and in-depth studies of nanomaterials have brought new perspectives towards new antimicrobial materials and nanocomposites that could add-in to the MDRB pandemic that we are currently facing. Nanoparticles and nanocomposites comprising zinc oxide [15], copper oxide [16], iron oxide [17], and, especially, silver, have been widely used in textiles [18,19], dental care [20], packaging [21], paints [22], and in a whole myriad of applications. Silver nanoparticles are one of the most exploited nanomaterials for this end, as they have been used for over a century in the healing of wounds and burns. Although chemical methods were successfully employed for AgNPs synthesis, with the need to use sustainable and non-toxic methods in chemistry, a biocompatible modality of AgNPs synthesis came about by using biological routes for nanoparticle synthesis (Figure 1). Biosynthesis or bio-based synthesis of AgNPs may occur through three routes: fungal, bacterial, or by plants, for the reduction of Ag+ to Ag0. The saturation of Ag<sup>0</sup> monomers in suspension eventually leads to a burst-nucleation process [23] in which nanoclusters of metallic silver are produced and stabilized by biomolecules from the biological extracts.

**Figure 1.** Biological extracts may be prepared from any part of plant material, or via extracellular/ intracellular processes using fungi and bacteria cultures. The extracts are rich in biomolecules such as sugars, proteins, nucleic acids, and metabolites that either have a stabilizing potential or reducing and stabilizing potential for the formation of silver nanoparticles.

The demand of products for the combat of MDR bacterial strains such as *Pseudomonas aeruginosa*, methicillin-resistant *Staphylococcus aureus* (MRSA), vancomycin-resistant *Staphylococcus aureus* (VRSA), erythromycin-resistant *Streptococcus pyogenes*, and ampicillin-resistant *Escherichia coli* [24] has led to the design of powerful antimicrobial materials that are reinforced with silver nanoparticles [25]. Today, in medicinal practice, there are wound dressings, contraceptive devices, surgical instruments, bone prostheses, and dental implants which are coated or embedded with nanosilver [26–31]. In daily life, consumers may find nanosilver in room sprays, laundry detergents, water purification devices and paints [26,32,33]. In the final part of this review, some of the recent advances in patented technologies containing AgNPs that establish viable grounds for the development of biogenic AgNPs-containing products for MDRB eradication purposes are cited and discussed.
