Editing Methicillin (section)

== Medical uses ==

Compared to other penicillins that face [[antimicrobial resistance]] due to [[beta-lactamase|β-lactamase]], it is less active, can be administered only [[Route of administration#Parenteral|parenterally]], and has a higher frequency of [[interstitial nephritis]], an otherwise-rare [[adverse effect]] of penicillins. However, selection of methicillin depended on the outcome of [[antibiotic sensitivity|susceptibility testing]] of the sampled infection, and since it is no longer produced, it is also not routinely tested for any more. It also served a purpose in the [[laboratory]] to determine the antibiotic sensitivity of ''[[Staphylococcus aureus]]'' to other penicillins facing β-lactam resistance; this role has now been passed on to other penicillins, namely ''[[cloxacillin]]'', as well as [[genetic testing]] for the presence of ''[[mecA]]'' gene by ''[[Polymerase chain reaction|PCR]]''.{{cn|date=March 2023}}

=== Spectrum of activity ===
At one time, methicillin was used to treat infections caused by certain [[gram-positive bacteria]] including ''Staphylococcus aureus'', ''Staphylococcus epidermidis'', ''Streptococcus pyogenes'', and ''Streptococcus pneumoniae''. Methicillin is only effective against ''Staphylococcus aureus'' 50% of the time.

Resistance to methicillin is conferred by activation of a new bacterial [[penicillin binding protein]] (PBP) ''[[mecA (gene)|mecA gene]]''. This encodes protein PBP2a. PBP2a works in a similar manner to other PBPs, but it binds β-lactams with very low affinity, meaning they do not compete efficiently with the natural substrate of the enzyme and will not inhibit cell wall biosynthesis.

These susceptibility data are given on a few medically significant bacteria:
* ''Staphylococcus aureus'': 0.125 – >100&nbsp;μg/ml
* [[Methicillin resistant Staphylococcus aureus]] (MRSA): 15.6 – >1000&nbsp;μg/ml
* ''Streptococcus pneumoniae'': 0.39&nbsp;μg/ml<ref>{{cite web | title = Methicillin Sodium Susceptibility and Concentration (MIC) Data | url = http://www.toku-e.com/Assets/MIC/Methicillin%20sodium.pdf | work = TOKU-E }}</ref>