## 5 Copper Nanoparticles and Their Antibacterial Role
### Resistance to Antibiotics  
At the beginning of 2017, the World Health Organization (WHO) published a list of a dozen bacteria which possess a very high resistance to antibiotics and who became threatening to human health. The bacteria were split into three categories, according to their urgency (Table 5).  
Figure 1: Antibiotics timeline [62].  
It is noticeable that the above list underlines the threat that Gram-negative bacteria pose, the _Enterobacteriaceae_ in particular. From the total of 12 bacteria mentioned above, nine of them are Gram-negative: _Acinetobacter baumannii_, _Pseudomonas aeruginosa_, _Enterobacteriaceae_, _Helicobacter pylori_, _Campylobacter_ spp., _Salmonella_ spp., _Neisseria gonorrhoeaeae_, _Haemophilus influenzae_, _Shigella_ spp.--and three of them are part of the _Enterobacteriaceae_ family.  
If we are to think about medication-resistant bacteria, Gram-negative are the bacteria which are most common in human infections. Researchers from the European Center for Disease Prevention and Control quantified Gram-negative bacteria being responsible for more than half a million infections out of a total number of over 650,000 and more than 24,000 deaths out of 33,000 during a time span of a year. On the other hand, the World Health Organization released communications mentioning that Gram-negative bacteria have developed and increased characteristics and abilities to find ways to increase resistance to treatments and transmit their genetic material to other bacteria, determining them to become resistant as well [62].  
During the 1980s awareness emerged regarding the glycoptide's (Vancomycin) resistance in Enterococcus [63]. The main risk here was that there was a possibility for this resistance to transfer to Staphylococcus as well--the Staphylococcus aureus infections already started to become a problem, at least in the United States. As a result, this was the first case of concern of antimicrobial resistance.  
Moreover, since Gram-negative bacteria are more resistant and more numerous compared to Gram-positive bacteria, there are limitations in treating infections caused by GNBs.  
This urgency has determined medical professionals to turn to old molecules to treat these drug-resistant bacteria infections, such as colistin. However, the situation improved during recent years, as other substances meeting the criteria of fighting against GNBs have emerged, among which are ceftolozane, ceftazidime and meropenem.  
Since antimicrobial resistance is not a new subject and bacteria has always been able to adapt and develop, medicine was forced to react and research for new antibacterial molecules, such as copper- and silver nanoparticles. The role of copper nanoparticles against bacteria is discussed in the next section.  
\begin{table}
\begin{tabular}{c c c} \hline
**Priority 1: Critical Urgency** & **Priority 2: High Urgency** & **Priority 3: Medium Urgency** \\ \hline \multicolumn{3}{c}{_Enterococcus_} \\ _faecium_—vancomycin-resistant & \\ _Staphylococcus_ & _aureus_—methicillin-resistant, \\ _baumantii_—carbapenem resistant & vancomycin-erin intermediate and resistant & _Streptococcus_ \\ _Pseudomonas_ & _pylori_—clarithmomycin-resistant & _pneumonia_—penicillin-non-susceptible \\ _Haemophilus_ & _Haemophilus_ & \\ _influencezae_—ampicillin-resistant & \\ _Salgella_ spp.—fluoroquinolone-resistant & _Stigella_ spp.—fluoroquinolone-resistant & \\ _Neisseria gonorrhoeaea_—3 rd generation & \\ _cephalosporin-resistant & & \\ _fluoroquinolone-resistant & \\ \hline \end{tabular}
\end{table}
Table 5: WHO criticality on pathogens and resistance to antibiotics.