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Concept
Methicillin
Summary
Methicillin (USAN), also known as meticillin (INN), is a narrow-spectrum β-lactam antibiotic of the penicillin class.
Methicillin was discovered in 1960.
Compared to other penicillins that face antimicrobial resistance due to β-lactamase, it is less active, can be administered only 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 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 PCR.
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. 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. Expression of PBPA2 confers resistance to all β-lactams.
These susceptibility data are given on a few medically significant bacteria:
Staphylococcus aureus - 0.125 - >100 μg/ml
Methicillin resistant Staphylococcus aureus (MRSA) - 15.6 - >1000 μg/ml
Streptococcus pneumoniae 0.39 μg/ml
β-Lactam antibiotic
Like other beta-lactam antibiotics, methicillin acts by inhibiting the synthesis of bacterial cell walls. It inhibits cross-linkage between the linear peptidoglycan polymer chains that make up a major component of the cell wall of gram-positive bacteria.
Official source
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