For example, resistance to vancomycin in S. aureus is due to additional peptidoglycan synthesis that makes the cell wall much thicker preventing effective penicillin entry. Resistance in Gram-negative bacteria is due to mutational variations in the structure and number of porins. In bacteria like Pseudomonas aeruginosa, there is reduced number of porins; whereas in bacteria like Enterobacter species, Escherichia coli and Klebsiella pneumoniae, there are modified porins such as non-specific porins (such as OmpC and OmpF groups) that cannot transport penicillin.Resistance due to PBP alterations is highly varied. A common case is found in Streptococcus pneumoniae where there is mutation in the gene for PBP, and the mutant PBPs have decreased binding affinity for penicillins. There are six mutant PBPs in S. pneumoniae, of which PBP1a, PBP2b, PBP2x and sometimes PBP2a are responsible for reduced binding affinity. S. aureus can activate a hidden gene that produces a different PBP, PBD2, which has low binding affinity for penicillins. There is a different strain of S. aureus named methicillin-resistant S. aureus (MRSA) which is resistant not only to penicllin and other β-lactams, but also to most antibiotics. The bacterial strain developed after introduction of methicillin in 1959. In MRSA, mutations in the genes (mec system) for PBP produce a variant protein called PBP2a (also termed PBP2), while making four normal PBPs. PBP2a has poor binding affinity for penicillin and also lacks glycosyltransferase activity required for complete peptidoglycan synthesis (which is carried out by the four normal PBPs).
In 2012, BioMarin began the first clinical trial on affected patients using their recombinant DNA technology cerliponase alfa which is synthesized using Chinese hamster ovarian (CHO) cell lines. After the success of this clinical trial, the U.S. FDA approved the marketing of cerliponase alfa to patients with CLN2 disease. The approval only applied to patients three years or older as the FDA wants to have more data available on children under the age of three before approving it for younger patients. A ten-year study is being performed to assess the long term effects of continued use of this drug. Cerliponase alfa is developed by BioMarin Pharmaceutical and the drug application was granted both orphan drug designation to provide incentives for rare disease research and the tenth Rare Pediatric Disease Priority Review Voucher. Cerliponase alfa was also approved by European Medicines Agency (EMA) on 30 May 2017. In the United Kingdom NICE evaluated cerliponase alfa for the treatment of CLN2 and deemed it not cost-effective. BioMarin announced that the price per infusion is $27,000, coming to $702,000 per year for treatment, though using Medicaid can decrease the cost.In March 2018, cerliponase alfa was approved in the United States as a treatment for a specific form of Batten disease.