Ceftaroline: A New Cephalosporin with Activity Against Methicillin-Resistant Staphylococcus aureus (MRSA)

Abstract

Microbial resistance has reached alarming levels, threatening to outpace the ability to counter with more potent antimicrobial agents. In particular, methicillin-resistant Staphylococcus aureus (MRSA) has become a leading cause of skin and soft-tissue infections and PVL-positive strains have been associated with necrotizing pneumonia. Increasing reports of growing resistance to glycopeptides have been noted, further limiting the efficacy of standard antibiotics, such as vancomycin. Ceftaroline is a novel fifth-generation cephalosporin, which exhibits broad-spectrum activity against Gram-positive bacteria, including MRSA and extensively-resistant strains, such as vancomycin-intermediate S. aureus (VISA), heteroresistant VISA (hVISA), and vancomycinresistant S. aureus (VRSA). In addition to being an exciting new agent in the anti-MRSA armamentarium, ceftaroline provides efficacy against many respiratory pathogens including Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Ceftaroline (600 mg intravenously every 12 hours) has been shown effective in phase III studies in the treatment of complicated skin and soft tissue infections and community-acquired pneumonia. To date, this unique antibiotic exhibits a low propensity for inducing resistance and has a good safety profile, although further post-marketing data and clinical experience are needed. In summary, ceftaroline provides an additional option for the management of complex multidrug resistant infections, including MRSA.

Molecular Characterization of Methicillin Resistant Staphylococcus aureus in West Bank-Palestine

“…It is one of the major human pathogens that can cause broad variety of human diseases ranging from mild skin and soft tissue infections (SSTIs) to severe life-threatening invasive infections; such as: endocarditis, osteomyelitis, necrotizing pneumonia, bacteremia, septicemia, meningitis, food poisoning, and toxic shock syndrome (1–5). Methicillin resistance is caused by an alteration in the penicillin-binding protein (PBP2a) which has a lower affinity to the β-lactam antibiotics; including: all penicillins, all cephalosporins (except the fifth generation ceftaroline), and carbapenems (6, 7). It is encoded by the mecA gene carried on a staphylococcal chromosomal cassette (SCC mec ).Thus; the therapeutic options of MRSA strains are lowered and limited.…”

The Continuing Threat of Methicillin-Resistant Staphylococcus aureus

“…Ceftaroline (Teflaro ® [US], Zinforo ® [EU]; 600 mg/12 h) and ceftobiprole (Zevtera ® [US], Mabelio ® [EU]; 500 mg/8 h) are broad-spectrum cephalosporins with pronounced bactericidal activity against MRSA, VISA, daptomycin-resistant S. aureus, and vancomycin-resistant E. faecalis [154,155,156,157,158,159,160,161]. For this reason, they are sometimes termed anti-MRSA cephalosporins, or fifth generation cephalosporins [49,79].…”

“…For this reason, they are sometimes termed anti-MRSA cephalosporins, or fifth generation cephalosporins [49,79]. It is important to note that these drugs are hydrolyzed by ESBL-enzymes, therefore they may not be appropriate for mixed infections involving Gram-positive and Gram-negative pathogens [156]. They have low minimum inhibitory concentrations for MRSA, which corresponds to their high affinity to the PBP2a/c proteins [154,155,156,157,158,159,160].…”

“…It is important to note that these drugs are hydrolyzed by ESBL-enzymes, therefore they may not be appropriate for mixed infections involving Gram-positive and Gram-negative pathogens [156]. They have low minimum inhibitory concentrations for MRSA, which corresponds to their high affinity to the PBP2a/c proteins [154,155,156,157,158,159,160]. Ceftaroline and ceftobiprole are both approved for the treatment of cSSTI, CAP, and HAP (excluding ventilator-associated pneumonia), with ceftaroline being additionally approved for MRSA bacteremia [154,155,156,157,158,159,160].…”

Identification of novel pyrazole and benzimidazole based derivatives as PBP2a inhibitors: Design, synthesis, and biological evaluation

“…1) [5]. Ceftaroline, an approved β-lactam antibiotic, has an exceptional affinity for PBP2a due to its ability to bind noncovalently to the allosteric site that predisposes the enzyme to inhibition by a second molecule of antibiotic at 60 A ο distance [6,7]. Also, ceftobiprole is another cephalosporin βlactam antibiotic that exhibits good anti-MRSA activity by inhibiting its antibiotic resistance determinant PBP2a [8].…”