above image explains why gram negative bacteria are more difficult and pose serious threats as compared to gram positive bacteria.
The cephalosporins (sg. /ˌsɛfələˈspɔːrɪn, ˌkɛ-, -loʊ-/[1][2]) are a class of β-lactam antibiotics originally derived from the fungus Acremonium, which was previously known as Cephalosporium.[3]
Together with cephamycins, they constitute a subgroup of β-lactam antibiotics called cephems. Cephalosporins were discovered in 1945, and first sold in 1964.
Cephalosporins are bactericidal and, like other β-lactam antibiotics, disrupt the synthesis of the peptidoglycan layer forming the bacterial cell wall. The peptidoglycan layer is important for cell wall structural integrity. The final transpeptidation step in the synthesis of the peptidoglycan is facilitated by penicillin-binding proteins (PBPs). PBPs bind to the D-Ala-D-Ala at the end of muropeptides (peptidoglycan precursors) to crosslink the peptidoglycan. Beta-lactam antibiotics mimic the D-Ala-D-Ala site, thereby irreversibly inhibiting PBP crosslinking of peptidoglycan.
Third-generation cephalosporins have a broad spectrum of activity and further increased activity against gram-negative organisms. They may be particularly useful in treating hospital-acquired infections, although increasing levels of extended-spectrum beta-lactamases are reducing the clinical utility of this class of antibiotics. They are also able to penetrate the central nervous system, making them useful against meningitis caused by pneumococci, meningococci.
Ceftobiprole has been described as “fifth-generation” cephalosporin,[34][35] though acceptance for this terminology is not universal. Ceftobiprole has anti-pseudomonal activity and appears to be less susceptible to development of resistance. Ceftaroline has also been described as “fifth-generation” cephalosporin, but does not have the activity against Pseudomonas aeruginosa or vancomycin-resistant enterococci that ceftobiprole has.[36] Ceftolozane is an option for the treatment of complicated intra-abdominal infections and complicated urinary tract infections. It is combined with the β-lactamase inhibitor tazobactam, as multi-drug resistant bacterial infections will generally show resistance to all β-lactam antibiotics unless this enzyme is inhibited
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