Methicillin
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Methicillin
Methicillin (USAN), also known as meticillin (INN), is a narrow-spectrum β-lactam antibiotic of the penicillin class. Methicillin was discovered in 1960. Medical uses 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''. Spectrum of activity At one time, methicillin was used to tr ...
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Methicillin Resistant Staphylococcus Aureus
Methicillin-resistant ''Staphylococcus aureus'' (MRSA) is a group of Gram-positive bacteria that are genetically distinct from other strains of ''Staphylococcus aureus''. MRSA is responsible for several difficult-to-treat infections in humans. It caused more than 100,000 deaths attributable to antimicrobial resistance in 2019. MRSA is any strain of ''S. aureus'' that has developed (through natural selection) or acquired (through horizontal gene transfer) a multiple drug resistance to beta-lactam antibiotics. Beta-lactam (β-lactam) antibiotics are a broad-spectrum group that include some penams (penicillin derivatives such as methicillin and oxacillin) and cephems such as the cephalosporins. Strains unable to resist these antibiotics are classified as methicillin-susceptible ''S. aureus'', or MSSA. MRSA is common in hospitals, prisons, and nursing homes, where people with open wounds, invasive devices such as catheters, and weakened immune systems are at greater risk of healt ...
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Staphylococcus Aureus
''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often positive for catalase and nitrate reduction and is a facultative anaerobe that can grow without the need for oxygen. Although ''S. aureus'' usually acts as a commensal of the human microbiota, it can also become an opportunistic pathogen, being a common cause of skin infections including abscesses, respiratory infections such as sinusitis, and food poisoning. Pathogenic strains often promote infections by producing virulence factors such as potent protein toxins, and the expression of a cell-surface protein that binds and inactivates antibodies. ''S. aureus'' is one of the leading pathogens for deaths associated with antimicrobial resistance and the emergence of antibiotic-resistant strains, such as methicillin-resistant ''S. aureus'' (MRSA ...
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Penicillin
Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from ''Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum using deep tank fermentation and then purified. A number of natural penicillins have been discovered, but only two purified compounds are in clinical use: penicillin G (intramuscular or intravenous use) and penicillin V (given by mouth). Penicillins were among the first medications to be effective against many bacterial infections caused by staphylococci and streptococci. They are still widely used today for different bacterial infections, though many types of bacteria have developed resistance following extensive use. 10% of the population claims penicillin allergies but because the frequency of positive skin test results decreases by 10% with each year of avoidance, 90% of these patients can tolerate penicillin. Additionally, those with ...
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MecA
''mecA'' is a gene found in bacterial cells which allows them to be resistant to antibiotics such as methicillin, penicillin and other penicillin-like antibiotics. The bacteria strain most commonly known to carry ''mecA'' is methicillin-resistant ''Staphylococcus aureus'' (MRSA). In '' Staphylococcus'' species, ''mecA'' is spread through the staphylococcal chromosome cassette SCC''mec'' genetic element. Resistant strains cause many hospital-acquired infections. ''mecA'' encodes the protein PBP2A (penicillin-binding protein 2A), a transpeptidase that helps form the bacterial cell wall. PBP2A has a lower affinity for beta-lactam antibiotics such as methicillin and penicillin than DD-transpeptidase does, so it does not bind to the ringlike structure of penicillin-like antibiotics. This enables transpeptidase activity in the presence of beta-lactams, preventing them from inhibiting cell wall synthesis. The bacteria can then replicate as normal. History Methicillin resistance f ...
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MecA (gene)
''mecA'' is a gene found in bacterial cells which allows them to be resistant to antibiotics such as methicillin, penicillin and other penicillin-like antibiotics. The bacteria strain most commonly known to carry ''mecA'' is methicillin-resistant ''Staphylococcus aureus'' (MRSA). In ''Staphylococcus'' species, ''mecA'' is spread through the staphylococcal chromosome cassette SCC''mec'' genetic element. Resistant strains cause many hospital-acquired infections. ''mecA'' encodes the protein PBP2A (penicillin-binding protein 2A), a transpeptidase that helps form the bacterial cell wall. PBP2A has a lower affinity for beta-lactam antibiotics such as methicillin and penicillin than DD-transpeptidase does, so it does not bind to the ringlike structure of penicillin-like antibiotics. This enables transpeptidase activity in the presence of beta-lactams, preventing them from inhibiting cell wall synthesis. The bacteria can then replicate as normal. History Methicillin resistance firs ...
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Flucloxacillin
Flucloxacillin, also known as floxacillin, is an antibiotic used to treat skin infections, external ear infections, infections of leg ulcers, diabetic foot infections, and infection of bone. It may be used together with other medications to treat pneumonia, and endocarditis. It may also be used prior to surgery to prevent '' Staphylococcus'' infections. It is not effective against methicillin-resistant ''Staphylococcus aureus'' (MRSA). It is taken by mouth or given by injection into a vein or muscle. Common side effects include an upset stomach. Other side effects may include muscle or joint pains, shortness of breath, and liver problems. It appears to be safe during pregnancy and breastfeeding. It should not be used in those who are allergic to penicillin. It is a narrow-spectrum beta-lactam antibiotic of the penicillin class. It is similar in effect to cloxacillin and dicloxacillin, being active against penicillinase forming bacteria. Flucloxacillin was patented in 1961 ...
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Antimicrobial Resistance
Antimicrobial resistance (AMR) occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials. All classes of microbes can evolve resistance. Fungi evolve antifungal resistance. Viruses evolve antiviral resistance. Protozoa evolve antiprotozoal resistance, and bacteria evolve antibiotic resistance. Those bacteria that are considered extensively drug resistant (XDR) or totally drug-resistant (TDR) are sometimes called "superbugs".A.-P. Magiorakos, A. Srinivasan, R. B. Carey, Y. Carmeli, M. E. Falagas, C. G. Giske, S. Harbarth, J. F. Hinndler ''et al''Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria... Clinical Microbiology and Infection, Vol 8, Iss. 3 first published 27 July 2011 ia Wiley Online Library Retrieved 28 August 2020 Although antimicrobial resistance is a naturally-occurring process, it is often the result of improper usage of the drugs and management of the infections. Antibiotic resistance is a major subset o ...
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Beecham (pharmaceutical Company)
The Beecham Group plc was a British pharmaceutical company. It was once a constituent of the FTSE 100 Index. Beecham, after having merged with American pharmaceutical company SmithKline Beckman to become SmithKline Beecham, merged with Glaxo Wellcome to become GlaxoSmithKline (GSK). GSK still uses the Beechams brand name in the UK for its over-the-counter cold and flu relief products. Early history Beecham began as the family business of Thomas Beecham (1820–1907), a chemist. (Beecham would become the grandfather of music conductor Thomas Beecham, 1879–1961). As a boy, Beecham worked as a shepherd, selling herbal remedies as a sideline. He later became a travelling salesman or peddler full time. His first product was Beecham's Pills, a laxative, in 1842. Subsequent success enabled him to open a shop in Wigan in 1847. Beecham opened its first factory in 1849 in St Helens, Lancashire, for the rapid production of medicines. Under his son, Sir Joseph Beecham, 1st Baronet (184 ...
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β-lactam Antibiotic
β-lactam antibiotics (beta-lactam antibiotics) are antibiotics that contain a beta-lactam ring in their chemical structure. This includes penicillin derivatives (penams), cephalosporins and cephamycins (cephems), monobactams, carbapenems and carbacephems. Most β-lactam antibiotics work by inhibiting cell wall biosynthesis in the bacterial organism and are the most widely used group of antibiotics. Until 2003, when measured by sales, more than half of all commercially available antibiotics in use were β-lactam compounds. The first β-lactam antibiotic discovered, penicillin, was isolated from a rare variant of ''Penicillium notatum'' (since renamed ''Penicillium chrysogenum)''. Bacteria often develop resistance to β-lactam antibiotics by synthesizing a β-lactamase, an enzyme that attacks the β-lactam ring. To overcome this resistance, β-lactam antibiotics can be given with β-lactamase inhibitors such as clavulanic acid. Medical use β-lactam antibiotics are indicated for ...
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Oxacillin
Oxacillin (trade name Bactocill) is a narrow-spectrum beta-lactam antibiotic of the penicillin class developed by Beecham. It was patented in 1960 and approved for medical use in 1962. Medical uses Oxacillin is a penicillinase-resistant β-lactam. It is similar to methicillin, and has replaced methicillin in clinical use. Other related compounds are nafcillin, cloxacillin, dicloxacillin, and flucloxacillin. Since it is resistant to penicillinase enzymes, such as that produced by ''Staphylococcus aureus'', it is widely used clinically in the US to treat penicillin-resistant ''Staphylococcus aureus''. However, with the introduction and widespread use of both oxacillin and methicillin, antibiotic-resistant strains called methicillin-resistant and oxacillin-resistant ''Staphylococcus aureus'' (MRSA/ORSA) have become increasingly prevalent worldwide. MRSA/ORSA can be treated with vancomycin or other new antibiotics. Contraindications The use of oxacillin is contraindicated in ...
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Interstitial Nephritis
Interstitial nephritis, also known as tubulointerstitial nephritis, is inflammation of the area of the kidney known as the renal interstitium, which consists of a collection of cells, extracellular matrix, and fluid surrounding the renal tubules. In addition to providing a scaffolding support for the tubular architecture, the interstitium has been shown to participate in the fluid and electrolyte exchange as well as endocrine functions of the kidney. There are a variety of known factors that can provoke the inflammatory process within the renal interstitium, including pharmacologic, environmental, infectious and systemic disease contributors. The spectrum of disease presentation can range from an acute process to a chronic condition with progressive tubular cell damage and renal dysfunction. Signs and symptoms Interstitial nephritis may present with a variety of signs and symptoms, many of these nonspecific. Fever is the most common, occurring in 30-50% of patients, particularly ...
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Steric Hindrance
Steric effects arise from the spatial arrangement of atoms. When atoms come close together there is a rise in the energy of the molecule. Steric effects are nonbonding interactions that influence the shape ( conformation) and reactivity of ions and molecules. Steric effects complement electronic effects, which dictate the shape and reactivity of molecules. Steric repulsive forces between overlapping electron clouds result in structured groupings of molecules stabilized by the way that opposites attract and like charges repel. Steric hindrance Steric hindrance is a consequence of steric effects. Steric hindrance is the slowing of chemical reactions due to steric bulk. It is usually manifested in ''intermolecular reactions'', whereas discussion of steric effects often focus on ''intramolecular interactions''. Steric hindrance is often exploited to control selectivity, such as slowing unwanted side-reactions. Steric hindrance between adjacent groups can also affect torsional ...
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