Methicillin: Effects, Uses & Risks

Methicillin is an antibiotic from the penicillin group of active ingredients. It is only effective against Gram-positive bacteria such as Staphylococcus aureus and thus has a very narrow spectrum of activity. Today, it no longer serves as a drug, but is used only as an indicator substance in MRSA resistance testing.

What is methicillin?

Methicillin is an antibiotic from the penicillin group of drugs. It is effective only against Gram-positive bacteria such as Staphylococcus aureus. Methicillin is considered to be the first penicillin for which resistance to bacterial penicillinase has been established. The characteristic feature of methicillin is a beta-lactam ring that is sterically shielded against external destruction. The enzyme penicillinase degrades this beta-lactam ring of penicillins, rendering them ineffective. However, methicillin has a side chain that impedes the enzyme’s access to the beta-lactam ring. Therefore, methicillin raised many hopes of being an effective penicillin against Gram-positive bacteria. In 1959 it was developed by the pharmaceutical company “Beecham”. Initially, it was able to effectively combat infections with the bacterium Staphylococcus aureus. However, more and more resistance developed. Methicillin had to be administered parenterally (not via the digestive system) because it is acid-sensitive and would therefore be destroyed in the stomach. Later, methicillin was replaced by the penicillins oxacillin or flucloxacillin, which are also resistant to penicillinase, because they are acid-resistant and can therefore also be administered orally. At the same time, they also lead to fewer side effects than methicillin. The belief that methicillin cannot lead to resistance in bacterial strains has also been disproved. Today, the term MRSA (methicillin-resistant Staphylococcus aureus) stands for the dangerous multidrug-resistant hospital germ.

Pharmacologic effect

The antibacterial effect of methicillin against Gram-positive germs is based on disruption of the buildup of a murein layer. Existing bacteria are not attacked by methicillin. However, their cell profiling is hindered because the cell wall of the bacteria cannot form due to the disturbed structure of the murein layer. Murein is a peptidoglycan that is essential for the construction of the bacterial cell wall. In contrast to gram-negative bacteria, gram-positive bacteria in particular have a thick murein layer. Therefore, methicillin is only effective against Gram-positive germs. Gram-negative bacteria, however, are resistant to methicillin. The murein layer is built up with the help of the bacterial enzyme transpeptidase. The enzyme transpeptidase ensures that N-acetylmuramic acid is combined with N-acetylglucosamine to form murein. However, transpeptidase is sensitive to all beta-lactam antibiotics. The beta-lactam antibiotics inhibit the enzyme by forming a tight bond. As part of this reaction, the beta-lactam ring opens and can bind amino acids in the active site of the enzyme in this form, causing the transpeptidase to lose its effectiveness. However, ongoing mutations have made the transpeptidase increasingly stable against the action of beta-lactam antibiotics. Thus, resistance to beta-lactam antibiotics such as methicillin has developed at an early stage.

Medical application and use

Beginning in the late 1950s, methicillin was used as an antibiotic against Gram-positive bacteria. It found particular application in the control of infections with Staphylococcus aureus. Normally, this bacterium is harmless. It is found everywhere on the skin and mucous membranes of humans and animals. However, it can cause serious infections in immunocompromised individuals. The spread of these germs could be stopped by methicillin. However, since methicillin is acid-sensitive, it had to be administered by infusion. Over time, methicillin was ultimately replaced by the acid-resistant beta-lactam antibiotics oxacillin, flucloxacillin and dicloxacillin. They act in the same way as methicillin but cause fewer side effects. Today, methicillin is only used as an indicator substance alongside oxacillin and other antibiotics in the context of MRSA resistance testing. Originally, methicillin was used as the lead antibiotic for this test. This is also the origin of the name MRSA for the multi-resistant hospital germs.In addition to the term MRSA, ORSA (oxacillin-resistant Staphylococcus aureus) has now also become established for hospital germs, as oxacillin is now frequently used as an indicator substance. The real medical importance of methicillin is based on the fact that it was the first penicillin resistant to penicillinase to find application. It was a narrow-spectrum antibiotic against Gram-positive germs.

Risks and side effects

The increased use of methicillin has contributed to the development of multidrug-resistant germs, among other things. At the beginning of its use in the late 1950s, methicillin was ruled out as a source of resistance. However, antibiotic-resistant germs developed in the early years. Today, MRSA or ORSA is considered the most important representative of multi-resistant germs. Since the use of methicillin began very early, the first resistance to antibiotics was associated with methicillin. However, it became apparent that these germs also developed resistance to other beta-lactam antibiotics, as their mode of action is comparable. Methicillin was used especially in hospitals, other medical facilities or nursing homes, because most infections with Staphylococcus aureus occurred there, due to many immunocompromised patients treated here. As a result, the germs initially developed resistance to beta-lactam antibiotics and later, in some cases, to other antibiotics as well. The emergence of multidrug-resistant germs in hospitals, other medical facilities, and nursing homes today poses major challenges to the health care system. For example, mass indiscriminate treatment with antibiotics, and especially with methicillin, has led to diseases that did not exist in the past. In addition, it is now increasingly difficult to control Staphylococcus aureus infections in immunocompromised individuals as resistance to certain antibiotics continues to emerge.