**7. Concluding remarks**

*Antimicrobial Resistance - A One Health Perspective*

*P. aeruginosa* [129].

**6. Mitigation of resistance**

species.

The National Nosocomial Infection Surveillance System (NNIS) also conducted the study for statistical analysis of the resistance developed by the hospital strains of *P. aeruginosa* and define that the hospital samples are more resistive to various groups of antibiotic classes [128]. The resistance to various classes of antibiotic by *P. aeruginosa* is a new threat to our defence system as once compromised it will be a difficult task to control the spread and infection of the bacteria among the living system. It has been also reported that the bacteraemia was not in control by the administration of antibiotics as it was spread by the antibiotic-resistant strains of

Due to hospitalization for a significant period of time in the ICU [130] of a patient suffering from respiratory disorder [110], kidney disease [89] and other diseases which needs the ventilator along with the medical device installation are more prone to the infection of *P. aeruginosa* [131]. The administration of various drugs makes the *Pseudomonas* strain more resistive due to mechanisms like multidrug-resistance (MDR), efflux systems, and loss of porin proteins from the outer membrane. Extensive research work is necessary to understand the infection mechanism and the development of resistance in the bacteria, the suitable combination of antibiotic molecules which will overcome the resistant behaviour and eradication of the bacterial biofilm without affecting the other processes in the living beings.

The eradication of the resistance is highly necessary for the prevention followed by cure to *Pseudomonas* infection for healthy sustenance. So, research is still going on to overcome the resistance by the organism and combinational therapeutic approach is found to be an effective tool against the resistance of the *Pseudomonas*

Cross-infection through hospital personnel gives rise to 30–40% of infection so irrespective of cost and time use of masks, cloths, gloves, antiseptics for the proper isolation can minimize the resistant developed in the pathovars [132]. It was observed that usual laboratory methods failed to detect the Antimicrobial-Drug resistance hence new testing methods, standards and guidelines implemented by various national and international clinical research groups for the early detection and control its outbreak [133]. The synergistic of two or more anti-bactericidal molecules is found to be an effective than monotherapy to overcome the resistance. The combination of polymixin with tobramycin is found to be an effective antimicrobial for inhibition in the formation of biofilms [134]. The combinational administration of tobramycin with aminoglycoside and macrolide clarithromycin shows a devastating effect against the biofilm [79]. Likewise, the integration of azithromycin with the tobramycin helped to destroy the bacterial biofilm when treated with *in vitro* condition [135]. The use of nitric oxide (NO) was reported to trigger the downstream of signal processing in quorum sensing and hence the production of cyclic-di-GMP decreases hence the extracellular matrix of biofilm get destroyed [136]. The introduction of deoxyribonuclease (DNAse) directly into the biofilm of the bacterial colony as it digests the environmental DNA (eDNA) enzymatically. The *P. aeruginosa* contains a molecule known as acyl-homoserine lactones (AHL), the blockage of signaling of this molecule prevents the formation of biofilms [137]. The *rsaL* gene expression acts as a negative regulator of the *lasI* gene expression which is responsible for the quorum sensing in the strains of *P. aeruginosa* [138]. The *PmrAB* and *PhoPQ* can alter the permeability of the outer membrane as the level of divalent ions decrease it increase the extracellular DNA in the biofilms and shows resistance to cationic bactericidal peptides and polymyxins [139]. Due to this phenomenon, the addition of amino

**58**

*P. aeruginosa* as an emerging human pathogen causes an array of diseases in immunocompromised patients, newborns as well as healthy persons. The infection as a biofilm is much more severe than monoculture. Various antimicrobial/ antibiotics treatment leads to not only increases the resistance in different strains of *P. aeruginosa* but also increase the disease incidence. The present chapter clearly enlightens various mechanisms of infection of *P. aeruginosa*, its biofilms and resistance pathways/mechanisms, global impact due to infections which further paves the way for various remediation in future through improved implementations of genetic engineering and advances nanotechnology tools.
