**3.2 Emerging therapies**

In the recent years there have been a few significant developments of new antibiotics. Ceftaroline, often referred to as a 5th generation cephalosporin, has shown activity against multidrug resistant gram positive bacteria (Bazan et al., 2009; Steed & Ryback, 2010).

Ceftaroline fosamil is a prodrug form which is rapidly converted to the active form after administered (Bazan et al., 2009). Like other cephalosporins, it binds to penicillin binding proteins (PBP), but differs from other β-lactams in that it has a high affinity for PBP2a, which is unique to *MRSA* (Steed & Ryback, 2010). Ceftaroline has been successfully used for the treatment of skin and skin structure infections caused by methicillin resistant *S. aureus, S. pyogenes, S. agalactiae, E. coli, K. oxytoca,* and *K. pneumoniae* (Bazan et al., 2009; Product insert, 2010; Saravolatz et al., 2010a, 2011b; Snydman et al., 2010; Steed & Ryback, 2010). The most common side effects reported were diarrhea, nausea, constipation, vomiting, increased transaminases, hyperkalemia, rash, and phlebitis (Hester et al., 2011).

Another recent addition to approved antibiotics is telavancin. Telavancin is a lipoglycopeptide derivative of vancomycin that inhibits bacterial cell wall synthesis (Saravolatz et al., 2009). When compared to vancomycin, talavancin has demonstrated effectiveness in treatment of skin and skin structure infections caused by methicillin resistant *S. aureus, S. pyogenes, S. agalactiae, S. pneumoniae,* and vancomycin resist*ant E. faecalis* (Stryjewski et al., 2006a, 2006b, 2008c). The drug has also been explored for use in hospital acquired pneumonia (Rubinstein et al., 2011). The most common side effects reported included: nausea, vomiting, foamy urine, and disturbance in taste (Medical Letter, 2010).

A recent carapenem, doripenem, has demonstrated a broad spectrum of antimicrobial activity against gram positive and negative bacteria including *P. aeruginosa* (included some cabapenems resistant strains) (Jones et al., 2004; Lister, 2007; Mushtaq et al., 2004). Doripenem is indicated for complicated intra-abdominal and urinary tract infections due to enterococci, anaerobes, and *P. aeruginosa* as well as hospital acquired pneumonia resulting from *Klebsiella, Enterobacter, Acinetobacter,* and *Serratia* species or in some cases *S. aureus* (Medical Letter, 2007; Solomkin et al., 2003). Aside from allergic reactions, the most commonly reported side effects included: headache, nausea, diarrhea, rash, and phlebitis (Horiuchi et al., 2006).

Retapamulin is a recently approaved topical antibiotic effective for treatment of impetigo due to *S. pyogenes* and methicillin-susceptible *S. aureus* (Rittenhouse et al., 2006). Activity against *MRSA* has been observed *in vitro* (Rittenhouse et al., 2006). This antibiotic is derived from fermentation of fungi and represents the first in a class of antibiotics known as pleuromutilins. Drugs from this class interfere with bacterial protein synthesis by acting on the 50S subunit of the ribosome (Yan et al., 2006). Reported side effects are minimal and included only site irritation (Parish et al., 2008; Parish et al., 2006).

Lastly, consideration of some not yet approved but promising antibiotics is warranted. In early 2011, results of a phase 3 clinical trial for a new antibiotic called fidaxomicin were published (Louie et al., 2011). Fidaxomicin starts a new class of antibiotics referred to as macrocycles. The drug offers a narrow range of activity as it is designed specifically for *C. difficile* (Louie et al., 2011). The clinical studies reported that fidaxomicin treated patients had

In the recent years there have been a few significant developments of new antibiotics. Ceftaroline, often referred to as a 5th generation cephalosporin, has shown activity against

Ceftaroline fosamil is a prodrug form which is rapidly converted to the active form after administered (Bazan et al., 2009). Like other cephalosporins, it binds to penicillin binding proteins (PBP), but differs from other β-lactams in that it has a high affinity for PBP2a, which is unique to *MRSA* (Steed & Ryback, 2010). Ceftaroline has been successfully used for the treatment of skin and skin structure infections caused by methicillin resistant *S. aureus, S. pyogenes, S. agalactiae, E. coli, K. oxytoca,* and *K. pneumoniae* (Bazan et al., 2009; Product insert, 2010; Saravolatz et al., 2010a, 2011b; Snydman et al., 2010; Steed & Ryback, 2010). The most common side effects reported were diarrhea, nausea, constipation, vomiting, increased

Another recent addition to approved antibiotics is telavancin. Telavancin is a lipoglycopeptide derivative of vancomycin that inhibits bacterial cell wall synthesis (Saravolatz et al., 2009). When compared to vancomycin, talavancin has demonstrated effectiveness in treatment of skin and skin structure infections caused by methicillin resistant *S. aureus, S. pyogenes, S. agalactiae, S. pneumoniae,* and vancomycin resist*ant E. faecalis* (Stryjewski et al., 2006a, 2006b, 2008c). The drug has also been explored for use in hospital acquired pneumonia (Rubinstein et al., 2011). The most common side effects reported included: nausea, vomiting, foamy urine, and disturbance in taste (Medical Letter,

A recent carapenem, doripenem, has demonstrated a broad spectrum of antimicrobial activity against gram positive and negative bacteria including *P. aeruginosa* (included some cabapenems resistant strains) (Jones et al., 2004; Lister, 2007; Mushtaq et al., 2004). Doripenem is indicated for complicated intra-abdominal and urinary tract infections due to enterococci, anaerobes, and *P. aeruginosa* as well as hospital acquired pneumonia resulting from *Klebsiella, Enterobacter, Acinetobacter,* and *Serratia* species or in some cases *S. aureus* (Medical Letter, 2007; Solomkin et al., 2003). Aside from allergic reactions, the most commonly reported side effects included: headache, nausea, diarrhea, rash, and phlebitis

Retapamulin is a recently approaved topical antibiotic effective for treatment of impetigo due to *S. pyogenes* and methicillin-susceptible *S. aureus* (Rittenhouse et al., 2006). Activity against *MRSA* has been observed *in vitro* (Rittenhouse et al., 2006). This antibiotic is derived from fermentation of fungi and represents the first in a class of antibiotics known as pleuromutilins. Drugs from this class interfere with bacterial protein synthesis by acting on the 50S subunit of the ribosome (Yan et al., 2006). Reported side effects are minimal and

Lastly, consideration of some not yet approved but promising antibiotics is warranted. In early 2011, results of a phase 3 clinical trial for a new antibiotic called fidaxomicin were published (Louie et al., 2011). Fidaxomicin starts a new class of antibiotics referred to as macrocycles. The drug offers a narrow range of activity as it is designed specifically for *C. difficile* (Louie et al., 2011). The clinical studies reported that fidaxomicin treated patients had

included only site irritation (Parish et al., 2008; Parish et al., 2006).

multidrug resistant gram positive bacteria (Bazan et al., 2009; Steed & Ryback, 2010).

transaminases, hyperkalemia, rash, and phlebitis (Hester et al., 2011).

**3.2 Emerging therapies** 

2010).

(Horiuchi et al., 2006).

fewer recurrent episodes of *C. difficle* infection than patients taking vancomycin (Louie et al., 2011). Another potential antibiotic worth considering is referred to as kibdelomycin, which was selected based on screening against multiple engineered strains of S. aureus. Although the structure identified was unique, it was found to function as a type II topoisomerase inhibitor and has demonstrated activity primarily against gram positive bacteria. Although it functions as a topoisomerase inhibitor, it is unique in the fact that it specifically inhibits the ATPase activity of bacterial type II topoisomerases (Phillips et al., 2011). Another promising publication in *Nature* suggests that a new inhibitor (GSK299423) has demonstrated broad spectrum activity by inhibiting DNA gyrase. The promising detail about this inhibitor is that crystal structures have indicated that the inhibitor binds to a noncatalytic site on the DNA gyrase, as compared to the binding site for most fluoroquinolones, thus representing a new class of antibiotics and making this a prime target for further development (Bax et al., 2010).
