Penicillinase resistant penicillin (methicillin), MRSA and Ceftaroline

 

Ø In gram positive bacteria, peptidoglycan residues cross link to form cell wall.

Ø Cross linking occurs by transpeptidation of glycine with D-alanine of two adjacent peptidoglycan residues.

Ø Beta lactam antibiotics inhibit the enzyme transpeptidase that cross links peptidoglycan residues.

Ø Penicillinase (beta lactamase) producing gram positive bacteria destroy beta lactam ring and become resistant to beta lactam antibiotics.

Ø Penicillinase resistant penicillin (methicillin) are not destroyed by penicillinase producing bacteria. So, such bacteria are sensitive to methicillin and known as Methicillin Sensitive Staph aureus (MSSA).

Ø Methicillin Resistant Staph aureus (MRSA) produce altered transpeptidase (PBP2a). PBP2a do not bind with beta lactam antibiotics and therefore MRSA is resistant to all beta lactam antibiotics.

Ø Therefore, non-beta lactam antibiotics like sulfonamides, tetracyclines, clindamycin, vancomycin, linezolid etc are used in the treatment of MRSA. Vancomycin and linezolid have proven efficacy in treatment of MRSA.

Ø Vancomycin was discovered in the 1950s but seldom used in therapeutics because of adverse effects.

Ø When MRSA were reported in 1960s, vancomycin rapidly became popular for treatment of MRSA. No beta lactam was effective against MRSA at that time.

Ø Only after many years of research, the first beta lactam antibiotic with clinically significant anti-MRSA activity was approved in 2010. The name of the beta lactam antibiotic effective against MRSA is ceftaroline.