**5. Treatment and future aspects**

Drugs that are discussed to be used for MRSA infections are Daptomycin and Linezolid. Daptomycin is a synthetic drug that is the class of antibiotics that destroy the cell membrane ability by a calcium-dependent binding phenomenon which leads to bactericidal activity in a concentration-dependent way. So, one of the widely used antibiotics and which shows good efficacy even more than methicillin and vancomycin. Therefore, for any MRSA bacteremia, Daptomycin is considered to be very effective [38–40]. There were many topical drugs used against the MRSA strains. These anti MRSA drugs were quite effective. Mupirocin, is one of the anti MRSA topical drug which is applied on the skin for curing skin infections caused by *S. aureus* [41]. The mechanism of Mupirocin is, it binds to the isoleucyl t-RNA synthetase which inhibits the protein synthesis of the organisms resulting in the destruction of the organism [42]. Fusidic acid is another topical drug used against staphylococcal infections and it was reported effective as well. Fusidic acid binds to the elongation factor G of bacteria and interferes with the translocation process resulting in the inhibition of the protein synthesis [28].

Similarly, Linezolid which belongs to the oxazolidinones class predominantly inhibits the protein synthesis in the 50S ribosome of the cell. Linezolid shows a good amount of efficacy against several toxin-producing strains such as toxic shock syndrome toxin, Panton-Valentine leukocidin, α-hemolysin [38]. But the resistance against Linezolid was also observed. So, the combinatorial theory was taken into account. Combinatorial theory helps to mix multiple compounds to balance the inadequate conditions of other compounds and increase efficacy of drugs. The combinatorial theory started with Vancomycin and it shows synergistic interaction with β-lactams widely. Studies cleared that the capacity of clearing the MRSA infection-causing strains was not high in amount when the patients were only subjected to Vancomycin but in combination with β-lactams the clearance efficiency was much higher in amount. Combination with Vancomycin shows a specific effect named as Sea-Saw Effect where if the susceptibility of the vancomycin is decreased which results in decrease of transcription of the *mec A* gene and this increases the susceptibility of the β- lactams [43–46]. Combination with the Daptomycin has also been applied to check the outcome. This combination was to some extent very much successful as it enhanced the destruction of both Daptomycin-susceptible as well as Daptomycin-non-susceptible strains of MRSA. This combination showed high efficacy against the clearance of the bacteremia from the patient's body [47, 48].

Few drugs are in development such as Dalbavancin, Oritavancin, Tigecycline. Tigecycline inhibits protein synthesis and it shows broad-spectrum antibiotic activity. These are the possible treatments upon which the work is going on to reduce the resistance against the invasive MRSA. The prospect of the medication for *S. aureus* infections also lies in traditional medicines. The traditional herbal medicines are believed to have anti-MRSA activity. The bioactive phytoconstituents present in the plants such as Mansonone *F* from *Ulmus davidiana*, β-asarone from *Acorus calamus* rhizome, Prenylated flavonoids from *Desmodium caudatum* root, galloylated flavonol rhamnosides from *Calliandra tergemina* leaves, eupomatenoid-5 from *Piper regnellii* leaves are important for the MRSA treatment as they constitute anti-MRSA activity [49]. Some of the new relevant information regarding the treatment of AMR in *S. aureus* has come forward. Quinopristin-dalfopristin and Linezolid are another set of antimicrobial agents which have come up with activity against the resistance in *S. aureus*. Both these agents are protein inhibiting agents and Quinopristin-dalfopristin mainly exhibits bactericidal effects and Linezolid is bacteriostatic. Current studies against the treatment of this disease deal with the

various combinations of antimicrobial agents [50]. Several compounds are known to inhibit the synthesis of fatty acid in bacteria and with this, two antibacterial agents have shown greater efficiency against *S. aureus*. Triclosan and Isoniazid are the two antimicrobial agents which target the FabI in the *S. aureus.* Fab I is one of the essential enzymes utilized in fatty acid elongation and it plays a major role in *S. aureus.* High throughput screening of the FabI inhibitors has led to come up with a new molecule AFN-1252 also called Affinium Pharmaceuticals was identified and proved to be efficient against the MRSA strains [51]. Multiple combinations were analyzed and several limitations emerged from those. Vancomycin and Rifampicin were in great demand for diagnosing MRSA infections but later on, Rifampicin proved not to be a better option for treating the disease as this drug is the primary drug given against one of the concerned diseases named Tuberculosis. This combination has exhibited higher possibilities of rising the resistance against Rifampicin and this was the major reason for the failure of the Vancomycin-Rifampicin combination against *S. aureus*. Similarly, Trimethoprim/Sulfamethoxazole and Rifampicin was a major failure because of the poor efficacy along with multiple side effects. Also, it was found to be resistant to infections. Among all this, Vancomycin is the only drug that is still either used in combinations or as monotherapy for treating MRSA infections but some of the new antibiotics such as Ceftaroline, Tedizolid, Plazomicin are proved to be successful among other antibiotics and are under research and development for further studies of treating the MRSA infections [52]. Other explored combinations with vancomycin have shown adverse nephrotoxicity. So, it is said that intensive research is required for novel approaches against the treatment of resistance to *S. aureus*. Above all the discussed conventional therapies for the treatment, either majority of them were proved to be ineffective or have shown severe side effects in the patients.

According to the future perspective, there is an immense need for an alternative strategy for treating the resistance against *S. aureus*. Treatment methods such as using nanoparticles are one of the efficient ways of delivering the drug directly to the patients. Under the nanoparticle treatment strategy, there is a unique feature of using ligands that are target specific for certain receptors in bacteria. AuNPs were surface modified by Vancomycin helps in reducing the bacterial growth and also the iron oxide nanoparticles are modified with the porphyrin platinum and Vancomycin which results in thermal degradation of the resistance strain of *S. aureus*. Another very interesting aspect is the usage of SiRNA therapy which enhances the MRSA inhibition. Vancomycin nanocomplexes are proved to have effective anti-MRSA effects which are very new to the study of alternative strategies [53].

The major limitation or failure that rises is intrinsic mechanisms of bacterial resistance and the target-specific antibiotics or drugs have disappointed to come up with any useful product. Another unique novel approach has come forth which combines the genomic information on the drug target and undergo chemical modifications along with efficacy testing [50].

### **6. Conclusion**

*Staphylococcus aureus* is a major cause of bacterial infection in humans, which has been able to acquire resistance to a variety of antibiotics. MSRA is an emerging issue globally because apart from causing nosocomial infection also emerged as one of the key causative agents of community-acquired infections. Antibiotic resistance in *S. aureus* involves various mechanisms which are drug efflux, expression, or mutation of target proteins, leading to its rapid evolution which requires innovative approaches to develop novel treatment methodologies. A very limited amount of

*Antimicrobial Resistance in* Staphylococcus aureus *DOI: http://dx.doi.org/10.5772/intechopen.96888*

treatments are available for MRSA and this has become the reason for increasing the mortality rates. Appropriate use of the antimicrobial agents as the MDR is a very natural phenomenon and handling this type of phenomenon needs extra care to minimize the growth rate of resistant MRSA isolates further in the future. The development of new drugs is also in progress so that the resistance can be reduced. Anti MRSA topical drugs are extensively in use for treating skin infections. The new approaches have been initiated by the use of Fusidic acid, Linozolid against *Staphylococcal* infections.
