**6. Therapeutic approach**

Therapeutic approach to *S. aureus* infections depends on the type of infection, patient age, clinical manifestation of the disease, co-morbidity, antibacterial susceptibility of infecting organism and hospitalization. Various drugs as single agent and drug combinations have been used to treat *S. aureus* infection. In general, management of infections due to MRSA is difficult compared to that of MSSA. There are guidelines and reviews to help in the treatment of community and hospital infections of MRSA.

#### **6.1. Topical anti-MRSA drugs**

#### *6.1.1. Mupirocin*

Mupirocin is used as topical antibiotic to treat impetigo due to *S. aureus* and *S. pyogenes* [103]. The drug is also used for nasal decolonization of *S. aureus* [27]. Mupirocin belongs to monoxycarbolic acid class and it exerts antibacterial action by binding to isoleucyl t-RNA synthetase, thereby, inhibiting the protein synthesis [104]. The antibiotic shows excellent activity against Staphylococci and most Streptococci [105]. Clinical efficacy of mupirocin ointment in treating *S. aureus* superficial skin infections and wound infections was established [106–108]. Various reports also demonstrated effectiveness of mupirocin in nasal decolonization of *S. aureus* [25, 109, 110] that is a risk factor for MRSA infections in nosocomial settings.

#### *6.1.2. Fusidic acid*

Fusidic acid is an antibiotic, which belongs to a class referred to as fusidanes. Chemically it is a tetracyclic triterpenoid [111] and it binds to bacterial elongation factor G (EF-G), which results in impaired translocation process and inhibition of protein synthesis [112]. It has potent activity against *S. aureus* and clinically used in treatment of mild to moderately severe skin and soft-tissue infections, for example, impetigo, folicullitis, erythrasma, furunculosis, abscesses and infected traumatic wounds [113]. The efficacy of fusidic acid ointment in treatment of *S. aureus* infections is widely reported [114, 115]. The drug has also been used systemically to treat invasive *S. aureus* infections but its efficacy was questioned [116].

#### **6.2. Systemic anti-MRSA drugs**

#### *6.2.1. Vancomycin*

As discussed earlier, vancomycin remained the mainstay of therapy against MRSA infections in hospitalized patients for decades. Though the antibiotic was available for clinical use since 1958, it gained prominence among clinicians only after the surge in nosocomial MRSA infections in 1980s [73, 75]. Numerous reports documented the clinical efficacy of vancomycin in treating various MRSA infections in hospitalized patients [116–120]. The emergence and spread of hVISA and VISA strains has threatened the clinical utility of vancomycin. In addition, over the years, the mean MIC of vancomycin against susceptible MRSA


**6. Therapeutic approach**

**6.1. Topical anti-MRSA drugs**

*6.1.1. Mupirocin*

*6.1.2. Fusidic acid*

*6.2.1. Vancomycin*

**6.2. Systemic anti-MRSA drugs**

of community and hospital infections of MRSA.

Therapeutic approach to *S. aureus* infections depends on the type of infection, patient age, clinical manifestation of the disease, co-morbidity, antibacterial susceptibility of infecting organism and hospitalization. Various drugs as single agent and drug combinations have been used to treat *S. aureus* infection. In general, management of infections due to MRSA is difficult compared to that of MSSA. There are guidelines and reviews to help in the treatment

Mupirocin is used as topical antibiotic to treat impetigo due to *S. aureus* and *S. pyogenes* [103]. The drug is also used for nasal decolonization of *S. aureus* [27]. Mupirocin belongs to monoxycarbolic acid class and it exerts antibacterial action by binding to isoleucyl t-RNA synthetase, thereby, inhibiting the protein synthesis [104]. The antibiotic shows excellent activity against Staphylococci and most Streptococci [105]. Clinical efficacy of mupirocin ointment in treating *S. aureus* superficial skin infections and wound infections was established [106–108]. Various reports also demonstrated effectiveness of mupirocin in nasal decolonization of *S. aureus*

Fusidic acid is an antibiotic, which belongs to a class referred to as fusidanes. Chemically it is a tetracyclic triterpenoid [111] and it binds to bacterial elongation factor G (EF-G), which results in impaired translocation process and inhibition of protein synthesis [112]. It has potent activity against *S. aureus* and clinically used in treatment of mild to moderately severe skin and soft-tissue infections, for example, impetigo, folicullitis, erythrasma, furunculosis, abscesses and infected traumatic wounds [113]. The efficacy of fusidic acid ointment in treatment of *S. aureus* infections is widely reported [114, 115]. The drug has also been used systemically to treat invasive *S. aureus* infections but its efficacy was questioned [116].

As discussed earlier, vancomycin remained the mainstay of therapy against MRSA infections in hospitalized patients for decades. Though the antibiotic was available for clinical use since 1958, it gained prominence among clinicians only after the surge in nosocomial MRSA infections in 1980s [73, 75]. Numerous reports documented the clinical efficacy of vancomycin in treating various MRSA infections in hospitalized patients [116–120]. The emergence and spread of hVISA and VISA strains has threatened the clinical utility of vancomycin. In addition, over the years, the mean MIC of vancomycin against susceptible MRSA

[25, 109, 110] that is a risk factor for MRSA infections in nosocomial settings.

**Table 3.** Newer anti-MRSA drugs. 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].

#### *6.2.2. Newer anti-MRSA drugs*

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.
