**Author details**

populations has increased but within the susceptible range. This phenomenon is referred to as vancomycin MIC creep. There has been poor response to vancomycin therapy in patients infected with vancomycin-susceptible MRSA isolates which had vancomycin MIC at the higher end of susceptible range (2 mg/L) [121, 122]. Optimizing the dose regimen and drug delivery, in order to achieve the desired blood plasma concentration which would give the clinical efficacy is the way forward in preserving the clinical utility of vancomycin [91, 92].

The problem of MRSA infections in hospitals and lack of effective antibiotics other than vancomycin to treat them necessitated the discovery of novel anti-MRSA drugs. The continued efforts of researchers in discovering novel anti-MRSA drugs fructified resulting in arrival of number of newer anti-MRSA drugs for clinical use in the last 15 years [78, 123–125]. The following **Table 3** lists the newer anti-MRSA drugs that were approved by U.S. FDA for clinical use.

Apart from chemotherapeutic approach to tackle the *S. aureus* infection, alternatives such as agents which inhibit the virulent factors expression and vaccines have been investigated. Various phytochemical are also found to have anti-MRSA activity. All these are at investigational stages and more research is necessary to bring promising candidates for clinical usage.

Clinical use of agents which are not conventional antibiotics but able to inhibit the expression or function of the virulence factors, rendering the bacteria non-pathogenic is considered an alternative approach to tackle MRSA. Stripping microorganisms of their virulence properties without threatening their existence may offer a reduced selection pressure for drug-resistant mutations. Virulence-specific therapeutics would also avoid the undesirable dramatic altera-

Accessory gene regulator (*agr*)-mediated quorum sensing system of *S. aureus* plays a central role in pathogenesis of Staphylococci. Scientists identified small molecules which inhibited the *agr* system [144–146]. Active and passive immunization strategies targeting the virulence

Plants have immune system and other defensive mechanisms against microorganisms that cause plant diseases. Hence, the plants with huge diversity provide a vast source for exploration of anti-MRSA phytochemicals. *In vitro* Anti-MRSA activity of crude extracts of medicinal plants has been extensively reported [148]. Various phytochemicals such as β-asarone, Mansonone F, prenylated flavonoids and thymoquinone showed *in vitro* anti-MRSA activity [149–152].

tions of the host microbiota that are associated with current antibiotics [142, 143].

*6.2.2. Newer anti-MRSA drugs*

**7.1. Anti-virulence agents**

**7.2. Plants**

**7. Alternative therapeutic approach**

factors of *S. aureus* have also been explored [147].

Arumugam Gnanamani1 \*, Periasamy Hariharan<sup>2</sup> and Maneesh Paul-Satyaseela2,3

