Over the last few decades, β-lactams are the most widely used and favored antimicrobials worldwide, because of their efficacy, broad spectra and low toxicity. They inhibit the bacterial penicillin-binding proteins (PBPs), which are the enzymes that catalyze the final cross-linking of the bacterial cell wall polymer, peptidoglycan. However, due to heavy use of β-lactams antibiotics, bacteria developed various mechanism of resistance. Modification or substitution of the PBPs is important mechanism in gram-positive cocci , while production of β-lactamases is main cause of resistance among gram-negative bacilli . Mostly plasmid harbors the resistance gene and therefore, is crucial in disseminating resistance into previously susceptible species. Throughout the 1960s and 1970s there was a relentless rise in reports of resistance to β-lactams as a consequence of the selection of bacteria that produce β-lactamases.